Whole-body integration of gene expression and single-cell morphology.

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.

Exploring Reversible Redox Behavior in the 6H-BaFeO3-δ (0 < δ < 0.4) System: Impact of Fe3+/Fe4+ Ratio on CO Oxidation.

This work is devoted to evaluating the relationship between the oxygen content and catalytic activity in the CO oxidation process of the 6H-type BaFeO3-δ system. Strong evidence is provided about the improvement of catalytic performance with increasing Fe average oxidation state, thus suggesting the involvement of lattice oxygen in the catalytic process. The compositional and structural changes taking place in both the anionic and cationic sublattices of the catalysts during redox cycles have been determined by temperature-resolved neutron diffraction. The obtained results evidence a structural transition from hexagonal (P63/mmc) to orthorhombic (Cmcm) symmetry. This transition is linked to octahedra distortion when the Fe3+ concentration exceeds 40% (δ values higher than 0.2). The topotactical character of the redox process is maintained in the δ range 0 < δ < 0.4. This suggests that the cationic framework is only subjected to slight structural modifications during the oxygen exchange process occurring during the catalytic cycle.

Relevance of CT for the detection of septic foci: diagnostic performance in a retrospective cohort of medical intensive care patients.

AIM: To analyse the diagnostic yield of computed tomography (CT) in septic patients from a medical intensive care unit (ICU). MATERIALS AND METHODS: A full-text search of the department's radiological information system (RIS) retrieved 227 body CT examinations undertaken to search for a septic focus in 2018 from medical ICU patients. CT reports were categorised according to the identified foci. Clinical and laboratory information was gathered. Data were analysed statistically using descriptive statistics, diagnostic test quality criteria, binomial tests and chi-square test. RESULTS: A total of 227 CT examinations from 165 septic patients detected 264 foci, which were distributed as follows: 58.3% (n=154/264) chest, 26.5% (n=70/264) abdomen, 5.3% (n=14/264) genitourinary system, and 9.8% (n=26/264) other body regions. In 15.9% (n=36/227) no focus was identified on CT. Based on CT reports, 37.5% (n=99/264) of foci were graded as certain, 18.9% (n=50/264) as likely, and 15.9% (n=42/264) as possible infectious sources. Septic foci were detected using CT with 75.8% sensitivity (95% confidence interval [CI] 69.6-81.9%) and 59.46% specificity (95% CI 42.9-76.1%). The positive predictive value was 90.6% (95% CI 86-95.2%), with a negative predictive value of 32.4% (95% CI 21-43.8%). CONCLUSION: The present results confirm that body CT is a suitable rule-in test for septic patients in medical intensive care, although it cannot reliably rule out a septic focus. Follow-up CT examinations may reveal a septic source in the further course of a patient's hospital stay.

Automated Insulin Delivery: The Artificial Pancreas Technical Challenges.

BACKGROUND: The automation of glucose control has been an important goal of diabetes treatment for many decades. The first artificial pancreas experiences were in-hospital, closely supervised, small-scale, and short-term studies that demonstrated their superiority over continuous subcutaneous insulin infusion therapy. At present, long-term outpatient studies are being conducted in free-living scenarios. AREAS OF UNCERTAINTY: The integration of multiple devices increases patients' burden and the probability of technical risks. Control algorithms must be robust to manage disturbance variables, such as physical exercise, meal composition, stress, illness, and circadian variations in insulin sensitivity. Extra layers of safety could be achieved through remote supervision. Dual-hormone systems reduce the incidence and duration of hypoglycemia, but the availability of stable pumpable glucagon needs to be solved. Faster insulin analogues are expected to improve all types of artificial pancreas. THERAPEUTIC ADVANCES: Artificial pancreas safety and feasibility are being demonstrated in outpatient studies. Artificial pancreas use increases the time of sensor-measured glucose in near-normoglycemia and reduces the risk of hyperglycemia and hypoglycemia. The benefits are observed both in single- and dual-hormone algorithms and in full- or semi-closed loop control. A recent meta-analysis including 41 randomized controlled trials showed that artificial pancreas use achieves a reduction of time in hyperglycemia (2 hours less than control treatment) and in hypoglycemia (20 minutes less); mean levels of continuous glucose sensor fell by 8.6 mg/dL over 24 hours and by 14.6 mg/dL overnight. The OpenAPS community uses Do It Yourself artificial pancreas in the real world since 2013, and a recent retrospective cross-over study (n = 20) compared continuous glucose sensor readings before and after initiation: mean levels of blood glucose fell by 7.4 mg/dL over 24 hours and time in range increased from 75.8% to 82.2% (92 minutes more). CONCLUSIONS: The outpatient use of artificial pancreas is safe and improves glucose control in outpatients with type 1 diabetes compared with the use of any type of insulin-based treatment. The availability of open-source solutions and data sharing is needed to foster the development of new artificial pancreas approaches and to promote the wide use of Big Data tools for knowledge discovery, decision support, and personalization.

Switching to dual antiretroviral regimens is associated with improvement or no changes in activation and inflammation markers in virologically suppressed HIV-1-infected patients: the TRILOBITHE pilot study.

OBJECTIVES: While the use of dual antiretroviral therapies could reduce the toxicity of antiretroviral treatment in treatment-experienced HIV-1-infected patients, it is crucial to know if reducing the number of drugs could lead to an adverse increase in inflammation and activation markers. METHODS: This was a cross-sectional pilot study conducted at the HIV-1 Unit at the Tertiary University Hospital in Madrid, Spain, evaluating biomarkers of activation [interferon-γ-induced protein 10 (IP10), high-sensitivity C-reactive protein (hs-CRP), soluble CD14 (sCD14) and sCD163], inflammation [interleukin-6 (IL-6)], blood coagulation (d-dimer), and immune response [interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-4] in three groups of suppressed HIV-1-infected patients: patients continuing on triple therapy (26 patients), and patients who switched from triple to dual therapy, at 24 or 48 weeks after switching (13 and 36 patients, respectively). RESULTS: Demographic and immunovirological parameters were similar in the three groups of patients. IL-6 and sCD14 levels were lower in patients at 48 weeks after switching to dual therapy compared with those found in patients who continued to receive triple therapy (P = 0.012 and P = 0.001, respectively), with no differences in the levels of the remaining biomarkers. Among patients with nadir CD4 count ≤ 200 cells/µL, sCD14 levels were lower in patients who had been on dual therapy for 48 weeks (14 patients) compared with those found in patients who received ongoing triple therapy (11 patients; P = 0.029), with no differences in the levels of the other biomarkers. CONCLUSIONS: HIV-1-infected patients receiving dual regimens showed similar or even lower levels of inflammatory and activation markers compared with those found in patients who received ongoing triple therapy. Of note, similar data were obtained in patients with low nadir CD4 count.

History-driven population structure and asymmetric gene flow in a recovering large carnivore at the rear-edge of its European range.

Understanding the mechanisms and patterns involved in population recoveries is challenging and important in shaping conservation strategies. We used a recovering rear-edge population of brown bears at their southernmost European range in Greece as a case study (2007-2010) to explore the recovery genetics at a species' distribution edge. We used 17 microsatellite and a mitochondrial markers to evaluate genetic structure, estimate effective population size and genetic diversity, and infer gene flow between the identified subpopulations. To understand the larger picture, we also compared the observed genetic diversity of each subpopulation with other brown bear populations in the region. The results indicate that the levels of genetic diversity for bears in western Greece are the lowest recorded in southeastern Europe, but still higher than those of other genetically depauperate bear populations. Apart from a complete separation of bear populations in eastern and western Greece, our results also indicate a considerable genetic sub-structuring in the West. As bear populations in Greece are now recovering, this structure is dissolving through a "recovery cascade" of asymmetric gene flow from South to North between neighboring subpopulations, mediated mainly by males. Our study outlines the importance of small, persisting populations, which can act as "stepping stones" that enable a rapid population expansion and recovery. This in turn makes their importance much greater than their numeric or genetic contribution to a species as a whole.

Design and Technical Validation of a Telemedicine Service for Rural Healthcare in Ecuador.

BACKGROUND: Telemedicine is becoming increasingly important in Ecuador, especially in areas such as rural primary healthcare and medical education. Rural telemedicine programs in the country need to be strengthened by means of a technological platform adapted to local surroundings and offering advantages such as access to specialized care, continuing education, and so on, combined with modest investment requirements. INTRODUCTION: This present article presents the design of a Telemedicine Platform (TMP) for rural healthcare services in Ecuador and a preliminary technical validation with medical students and teachers. MATERIALS AND METHODS: An initial field study was designed to capture the requirements of the TMP. In a second phase, the TMP was validated in an academic environment along three consecutive academic courses. Assessment was by means of user polls and analyzing user interactions as registered automatically by the platform. The TMP was developed using Web-based technology and open code software. RESULTS: One hundred twenty-four students and 6 specialized faculty members participated in the study, conducting a total of 262 teleconsultations of clinical cases and 226 responses, respectively. CONCLUSION: The validation results show that the TMP is a useful communication tool for the documentation and discussion of clinical cases. Moreover, its usage may be recommended as a teaching methodology, to strengthen the skills of medical undergraduates. The results indicate that implementing the system in rural healthcare services in Ecuador would be feasible.

[Impact of medium-term outcomes of inappropriate prescribing in older patients discharged from a short stay unit]. / Impacto de los resultados a medio plazo de la prescripción inadecuada en los pacientes ancianos dados de alta desde una unidad de corta estancia.

OBJECTIVE: To study the association between the potential inappropriate prescriptions (PIP) and the 30 and 180-day adverse event rate after discharge from a Short Stay Unit (SSU). METHODOLOGY: A retrospective cohort observational study was conducted on patients aged ≥75years discharged from an SSU from February to April, 2014. STOPP-START criteria version2 was used. The main outcome was 30 and 180-day adverse event rate after being discharged. RESULTS: A total of 179 patients, with a mean age of 84 (SD5) years were included. The presence of ≥1PIP after being discharged was not associated with a 30 and 180-day composite adverse event. Patients with ≥1PIP related to a cerebro-cardiovascular process were at higher risk of an adverse event at 30 days after discharge (adjusted OR, 2.1; 95%CI: 1.0-3.2; P=.045), those with ≥1PIP related to neuropsychiatric process and risk of fall were at higher risk of increased 30-day functional impairment (adjusted OR, 6.3; 95%CI: 1.7-22.5; P=.005), and those with ≥1PIP related to omission of cardiovascular system were at higher risk of 180-day hospital readmission (adjusted OR, 3.6; 95%CI: 1.5-8.3; P=.003). CONCLUSIONS: The presence of adverse events in older patients discharged from SSU may be associated with PIP, identified by STOPP-START criteria, and more specifically with drugs related to cardiovascular, neuropsychiatric disorders, and falls.

Atomically Resolved Short-Range Order at the Nanoscale in the Ca-Mn-O System.

The elucidation of the reaction mechanisms involving redox processes in functional transition-metal oxides, which usually start in areas of very few nanometers in size, is yet a challenge to be satisfactorily achieved. Atomically resolved HAADF and EELS have provided both chemical and structural information at the nanoscale, which reveal the preservation of short-range cationic order in areas of 2-3 nm length as the driving force behind the reversibility of the Ca2Mn3O8-Ca2Mn3O5 redox process. Oxygen evolution is accommodated by cationic diffusion along the Ca and Mn layers of the cation-deficient Ca2Mn3O8 delafossite related structure, whereas Mn remains octahedrally coordinated.

Cluster analysis of adult individuals with type 1 diabetes: Treatment pathways and complications over a five-year follow-up period.

AIMS: To identify subgroups of adults with type 1 diabetes and analyse their treatment pathways and risk of diabetes-related complications over a 5-year follow-up. METHODS: We performed a k-means cluster analysis using the T1DExchange Registry (n = 6,302) to identify subgroups based on demographic and clinical characteristics. Annual reassessments linked treatment trajectories with these clusters, considering drug and technology use. Complication risks were analysed using Cox regression. RESULTS: Five clusters were identified: 1) A favourable combination of all variables (31.67 %); 2) Longer diabetes duration (22.63 %); 3) Higher HbA1c levels (13.28 %); 4) Higher BMI (15.25 %); 5) Older age at diagnosis (17.17 %). Two-thirds of patients remained in their initial cluster annually. Technology adoption showed improved glycaemic control over time. Cox proportional hazards showed different risk patterns: Cluster 1 had low complication risk; Cluster 2 had the highest risk for retinopathy, coronary artery disease and autonomic neuropathy; Cluster 3 had the highest risk for albuminuria, depression and diabetic ketoacidosis; Cluster 4 had increased risk for multiple complications; Cluster 5 had the highest risk for hypertension and severe hypoglycaemia, with elevated coronary artery disease risk. CONCLUSIONS: Clinical characteristics can identify subgroups of patients with T1DM showing differences in treatment and complications during follow-up.

Le fort I osteotomy with or without concomitant removal of upper third molars: A prospective cohort study of intraoperative findings, related complications, and level of pterygomaxillary separation after down-fracture.

The main objective of our study was to assess the clinical implications of concomitant intraoperative removal of maxillary third molars (M3M) with the Le Fort I osteotomy 'twist' technique (LF1twist). A prospective comparative study was carried out regarding the necessity of bone trimming around the pedicle, intra- and postoperative complications, surgery time, and the level of pterygomaxillary junction (PMJ) separation following LF1twist with concomitant intraoperative removal of M3M (test group) versus LF1twist alone (control group). Outcome parameters were assessed from clinical and radiographic measurements. In total, 100 surgery sites were included (50 in each group). The mean surgery time was 53.4 ± 7.8 min, with nonsignificant differences between groups. The frequency of intraoperative complications was negligible, with no significant differences between groups - though all bleeding events (n = 4) occurred when M3M was not removed concomitantly. No postoperative complications were recorded. Percentages of disarticulations occurring at the PMJ were similar in both groups. In conclusion, the results demonstrate that removal of M3M in conjunction with LF1twist does not imply additional surgery time, or differences regarding the level of PMJ separation or perioperative complications. Furthermore, the concomitant procedure reduces the amount of maxillary and palatal bone in the disjunction area, which facilitates down-fracture and field clearing for maxillary repositioning.

Precision nutrition impact on metabolic health and quality of life in aging population after a 3-month intervention: A randomized intervention.

OBJECTIVES: Innovative precision dietary procedures are required to promote healthy aging. This study aimed to evaluate the effects of a personalised strategy based on the inclusion of individualised foods and digital tools on overall health status and quality of life within a follow-up of 3 months in older adults with overweight or obesity. METHODS: 127 men and women aged between 50 and 80 years with overweight/obesity participated in the study-between January 2020 and September 2020 at the Center for Nutrition Research-University of Navarra and IMDEA-ALIMENTACIÓN-and were randomly assigned to a usual-care group (standard recommendations) or precision group (precision nutrition strategy based on the inclusion of individualised foods and a mobile application). Anthropometry, body fat percentage, biochemical parameters, diet, and quality of life (SF-36 Health Survey) were assessed at baseline and after 3 months. RESULTS: Both strategies were found to improve overall metabolic health; however, the precision approach demonstrated significantly better outcomes. The precision strategy reduced body weight at 3 months (-4.3 kg; p < 0.001) with significant improvements in body fat percentage, blood pressure and general metabolic health (glycated haemoglobin; alanine aminotransferase; aspartate aminotransferase; hepatic steatosis index) in comparison with the standard recommendations. The precision approach significantly enhanced the quality of life (SF-36) of individuals, with additional improvements in emotional well-being (p = 0.024) and vitality (p = 0.008). Adherence to the Mediterranean diet was significantly associated with a higher quality of life and vitality. CONCLUSION: These results support the benefit of precision nutrition approaches for promoting healthy aging and emotional well-being, enhancing the quality of life in aging populations, during the COVID-19 pandemic.

Investigation of Galaxolide degradation products generated under oxidative and irradiation processes by liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry.

RATIONALE: Polycyclic musks have become a concern due to their bioaccumulation potential and ecotoxicological effects. The HHCB transformation product (TP) (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta[γ]-2-benzopyran; HHCB-lactone) is the most stable intermediate generated and it is frequently detected in river waters. The aim of this work was the identification of relevant TPs generated from UV irradiation and ozone treatments. METHODS: Identification of HHCB TPs was carried out by liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (LC/ESI-QTOF-MS) and two-dimensional gas chromatography/electron impact time-of-flight mass spectrometry (GC×GC-EI-TOF-MS). With LC/ESI-QTOF-MS, TPs were characterized by means of mass accuracy in both full-scan and MS/MS modes through information-dependent acquisition (IDA) and direct injection on-column. With stir bar sorptive extraction (SBSE)-GC×GC-EI-TOF-MS, identification was based on the enhanced separation capacity and screening of unknowns through the acquisition of full-range mass spectra. RESULTS: The effectiveness of these complementary techniques allowed a detailed evaluation of the main TPs. Eighteen TPs were elucidated based on mass accuracy, in both full-scan and MS/MS modes using LC/ESI-QTOF-MS with mass errors below 5 ppm and 10 ppm (mostly), respectively. Most of the TPs had not been analytically identified in previous studies. Separation of the enantiomeric species (R) and (S) of HHCB-lactone, and the identification of other relevant TPs, was performed using SBSE-GC×GC-EI-TOF-MS. CONCLUSIONS: LC/ESI-QTOF-MS and GC×GC-EI-TOF-MS analysis provides the best alternative for TP identification of chemicals of concern, which have a wide range of polarities and isobaric compounds. A prediction of PBT (persistence, bioaccumulation and toxicity) using the PBT Profiler program suggested a classification of 'very persistent' and 'very toxic' for most of the TPs identified.

Qualitative and quantitative analysis of poly(amidoamine) dendrimers in an aqueous matrix by liquid chromatography-electrospray ionization-hybrid quadrupole/time-of-flight mass spectrometry (LC-ESI-QTOF-MS).

This work introduces a liquid chromatography-electrospray ionization-hybrid quadrupole/time-of-flight mass spectrometry (LC-ESI-QTOF-MS)-based method for qualitative and quantitative analysis of poly(amidoamine) (PAMAM) dendrimers of generations 0 to 3 in an aqueous matrix. The multiple charging of PAMAM dendrimers generated by means of ESI has provided key advantages in dendrimer identification by assignation of charge state through high resolution of isotopic clusters. Isotopic distribution in function of abundance of isotopes (12)C and (13)C yielded valuable and complementarity data for confident characterization. A mass accuracy below 3.8 ppm for the most abundant isotopes (diagnostic ions) provided unambiguous identification of PAMAM dendrimers. Validation of the LC-ESI-QTOF-MS method and matrix effect evaluation enabled reliable and reproducible quantification. The validation parameters, limits of quantification in the range of 0.012 to 1.73 µM, depending on the generation, good linear range (R > 0.996), repeatability (RSD < 13.4%), and reproducibility (RSD < 10.9%) demonstrated the suitability of the method for the quantification of dendrimers in aqueous matrices (water and wastewater). The added selectivity, achieved by multicharge phenomena, represents a clear advantage in screening aqueous mixtures due to the fact that the matrix had no significant effect on ionization, with what is evidenced by an absence of sensitivity loss in most generations of PAMAM dendrimers. Fig Liquid chromatography-electrospray ionization-hybrid quadrupole/time of flight mass spectrometry (LC-ESI-QTOF-MS) based method for qualitative and quantitative analysis of PAMAM dendrimers in aqueous matrix.

'Pillow technique' to improve lip support in the context of zygoma implant rehabilitation.

This study proposes a simple, off-the-shelf ancillary method for application in the dental rehabilitation of severe maxillary atrophy with zygoma implants, allowing simultaneous improvement of lip support in cases with a moderate lack of premaxillary projection. Three consecutive patients with an atrophic maxilla were evaluated retrospectively. All were treated with a fixed rehabilitation over four zygomatic implants and the pillow technique. The study variables included radiological assessment of the premaxilla volume, upper lip and perinasal soft tissue changes, clinical complications, and subjective evaluation of functional and aesthetic patient satisfaction based on a visual analogue scale. All of the zygomatic implants showed osseointegration. The survival rate was 100%. The immediate postoperative course was uneventful, and no surgical complications were noted at the follow-up visits. Radiological assessment of the premaxilla volume enhancement showed a final mean skeletal projection improvement of +9.4 mm, while the nasolabial angle decreased an average of + 0.6 mm. On the other hand, only small changes in nasal width were detected. Patient satisfaction with the functional and aesthetic outcomes at the 1-year follow-up was excellent. The pillow graft is an easy-to-handle technique that can be included in the armamentarium for moderately incrementing the maxillary sagittal dimension and enhancing lip support in the context of zygoma implant rehabilitation.

Transmucosal pterygomaxillary disjunction using a piezoelectric device, in the context of the minimally invasive Le Fort I osteotomy protocol.

The aim of this study was to assess the accuracy and clinical implications of pterygomaxillary junction (PMJ) disjunction with a transmucosal PMJ osteotomy using a piezoelectric hand-piece device, in the context of Le Fort I osteotomy, by evaluating the level of PMJ disarticulation and the need for bone trimming around the pedicle. An ambidirectional 1-month follow-up cohort study was designed involving consecutive patients undergoing minimally invasive maxillary Le Fort I osteotomy through the twist technique. Two cohorts were defined according to whether or not the transmucosal PMJ osteotomy was performed. The site of PMJ disjunction was analysed radiographically. A total of 114 patients were included in the study, 57 in each group. The overall accuracy of the PMJ disjunction path was higher in the test group (43.9%) than in the control group (15.8%). Multiple logistic regression analysis identified the need for bone trimming (odds ratio 0.02; P < 0.001) and removal of the upper third molar (odds ratio 0.17; P < 0.001) as relevant factors. In conclusion, compared with the originally described twist technique, combination of the latter with the PMJ osteotomy increased its accuracy at the level of the PMJ. As a result, there is a decrease in resistance during down-fracture and decrease in the need for bone trimming around the pedicle, with preservation of the minimally invasive concept.

Three-dimensional evaluation of postoperative stability: a comparative study between surgery-first and surgery-late protocols.

The main objective of this study was to compare the stability of the surgery-first and surgery-late approaches according to the standardized centre protocols, by three-dimensional evaluation after 1 year of follow-up. A retrospective study was designed that included a test group (surgery-first protocol) and a control group (surgery-late protocol), with a follow-up period of at least 1 year (average 14 months; range 12-24 months). Stability was evaluated using linear and angular measurements by superimposing cone beam computed tomography images obtained at specific points in time: preoperatively, 1 month after surgery, and at the end of the orthodontic treatment. A total of 56 patients with a mean age of 32.2 ± 11.1 years were included in the study. After surgery there were significant changes in all of the measurements in at least one dimension in both groups (except for the transverse maxillary dimension), which remained stable at the end of the treatment, with no statistically significant differences between the two groups. At the 1-year follow-up, both groups presented a SNA angle relapse; this relapse was more significant in the surgery-late group (P = 0.031) and was present only in Class III patients (P = 0.013). In conclusion, an equivalent three-dimensional stability between surgery-first and surgery-late protocols was demonstrated after 1 year of follow-up when eligibility criteria were strictly adhered to.

Does orthognathic surgery have an incidentally beneficial effect on mild or asymptomatic sleep apnoea?

A prospective study was performed to assess the effect of orthognathic surgery on mild obstructive sleep apnoea (OSA) in patients with an underlying dentofacial deformity treated for occlusal and/or aesthetic reasons. As the main outcome variables, changes in upper airway volume and apnoea-hypopnoea index (AHI) were evaluated at 1 and 12 months of follow-up, in patients undergoing orthognathic surgery with widening movements of the maxillomandibular complex. Descriptive, bivariate, and correlation analyses were performed; significance was set at P < 0.05. Eighteen patients diagnosed with mild OSA were enroled (mean age 39.8 ± 10.0 years). An overall upper airway volume widening of 46.7% after orthognathic surgery was observed at 12 months of follow-up. The AHI decreased significantly from a median 7.7 events/hour preoperatively to 5.0 events/h at 12 months postoperative (P = 0.045), and the Epworth Sleepiness Scale score decreased from a median 9.5 preoperatively to 7 at 12 months postoperative (P = 0.009). A cure rate of 50% was obtained at 12 months of follow-up (P = 0.009). Despite the limited sample size, this study provides evidence that in patients with an underlying retrusive dentofacial deformity and mild OSA, a slight decrease in AHI is obtained after orthognathic surgery due to upper airway enlargement, which could be added as a beneficial effect of orthognathic surgery.

In vitro dose-response effects of poly(amidoamine) dendrimers [amino-terminated and surface-modified with N-(2-hydroxydodecyl) groups] and quantitative determination by a liquid chromatography-hybrid quadrupole/time-of-flight mass spectrometry based method.

This article presents a dose-response study of the effects of two types of third-generation (G3) and fourth-generation poly(amidoamine) (PAMAM) dendrimers on two cell lines (RTG-2 and H4IIE) by in vitro cytotoxicity assays with 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red uptake (NRU), and lactate dehydrogenase (LDH) assays. We particularly investigated the potential cytotoxic effect of positive surface charge, which a cationic amino-terminated PAMAM dendrimer can display, on the marked ability of PAMAM dendrimers to cross the cell membrane compared with PAMAM dendrimers functionalized with chains of N-(2-hydroxydodecyl). Quantification of dose-response effects was performed by use of mass spectrometry analysis. The analytical method using liquid chromatography-hybrid quadrupole/time-of-flight mass spectrometry that we developed allowed characterization of defective dendrimers instead of "ideal structures." Identification was based on accurate mass measurement, assignment of elemental composition, and the fully resolved (13)C/(12)C isotopic clusters of the multiply charged ions of PAMAM dendrimers. Validation of the liquid chromatography-mass spectrometry method made possible reliable and reproducible quantification of the extracellular and intracellular concentration of dendrimers at a micromolar level (limits of detection from 0.14 to 1.34 µM and from 0.43 to 1.82 µM in standard and culture medium, respectively). A higher cytotoxicity was found with the H4IIE cell line for surface-modified PAMAM dendrimers. The LDH assay was significantly more sensitive than the MTT and NRU assays, with half-maximal inhibitory concentrations (IC(50)) of 12.96 and 38.31 µg mL(-1) for surface-modified G3 and G4 dendrimers, respectively. No cytotoxic effects, in terms of IC(50), of amino-terminated PAMAM dendrimers were observed on both H4IIE and RTG-2 cells when the concentration was below 500 µg mL(-1) for G3 and G4 dendrimers.