Docosahexaenoic Acid Controls Pulmonary Macrophage Lipid Raft Size and Inflammation.

BACKGROUND: Docosahexaenoic acid (DHA) controls the biophysical organization of plasma membrane sphingolipid/cholesterol-enriched lipid rafts to exert anti-inflammatory effects, particularly in lymphocytes. However, the impact of DHA on the spatial arrangement of alveolar macrophage lipid rafts and inflammation is unknown. OBJECTIVES: The primary objective was to determine how DHA controls lipid raft organization and function of alveolar macrophages. As proof-of-concept, we also investigated DHA's anti-inflammatory effects on select pulmonary inflammatory markers with a murine influenza model. METHODS: MH-S cells, an alveolar macrophage line, were treated with 50 µM DHA or vehicle control and were used to study plasma membrane molecular organization with fluorescence-based methods. Biomimetic membranes and coarse grain molecular dynamic (MD) simulations were employed to investigate how DHA mechanistically controls lipid raft size. qRT-PCR, mass spectrometry, and ELISAs were used to quantify downstream inflammatory signaling transcripts, oxylipins, and cytokines, respectively. Lungs from DHA-fed influenza-infected mice were analyzed for specific inflammatory markers. RESULTS: DHA increased the size of lipid rafts while decreasing the molecular packing of the MH-S plasma membrane. Adding a DHA-containing phospholipid to a biomimetic lipid raft-containing membrane led to condensing, which was reversed with the removal of cholesterol. MD simulations revealed DHA nucleated lipid rafts by driving cholesterol and sphingomyelin into rafts. Downstream of the plasma membrane, DHA lowered the concentration of select inflammatory transcripts, oxylipins, and IL-6 secretion. DHA lowered pulmonary Il6 and Tnf-α mRNA expression and increased anti-inflammatory oxylipins of influenza-infected mice. CONCLUSIONS: The data suggest a model in which the localization of DHA acyl chains to nonrafts is driving sphingomyelin and cholesterol molecules into larger lipid rafts, which may serve as a trigger to impede signaling and lower inflammation. These findings also identify alveolar macrophages as a target of DHA and underscore the anti-inflammatory properties of DHA for lung inflammation.

Same-Admission Microvascular Maxillofacial Ballistic Trauma Reconstruction Using Virtual Surgical Planning: A Case Series and Systematic Review.

Study Design: Retrospective case series; systematic review. Objective: It is unknown whether the use of virtual surgical planning (VSP) to facilitate same-admission microsurgical reconstruction of the mandible following acute maxillofacial ballistic trauma (MBT) is sufficient to achieve definitive reconstruction and functional occlusion. Methods: A single-center retrospective analysis was conducted for patients who underwent microsurgical reconstruction of the mandible using VSP after acute MBT. The PubMed/MEDLINE, Embase, ScienceDirect, and Scopus databases were systematically reviewed using blinded screening. Studies were evaluated via thematic analysis. Results: Five patients were treated by same-admission and microsurgical reconstruction of the mandible using VSP. We observed an average of 16.4 ± 9.1 days between initial presentation and reconstruction, an average length of stay of 51.6 ± 17.9 days, 6.2 ± 2.8 operations, and 1.6 ± 0.9 free flaps per patient. Four types and 8 total flaps were employed, most commonly the anterior lateral thigh flap (37.5%). Care yielded complete flap survival. Each patient experienced at least 1 minor complication. All patients achieved centric occlusion, oral nutrition, and an approximation of their baseline facial aesthetic. Follow up was 191.0 ± 183.9 weeks. Systematic review produced 8 articles that adhered to inclusion criteria. Consensus themes in the literature were found for clinical goal and function of VSP when practicing MBT reconstruction, yet disagreement was found surrounding optimal treatment timeline. Conclusions: Same-admission microsurgical reconstruction after MBT is safe and effective to re-establish mandibular form and function. VSP did not delay reconstruction, given the need for preparation prior to definitive reconstruction.

Electronic portal image enhancement based on nonuniformity correction in wavelet domain.

PURPOSE: Electronic portal images are one of the most important tools to verify the ongoing radiotherapy treatment through comparison with a reference image generated during treatment planning. In this procedure, two images are geometrically matched by means of visible bone or other landmarks of interest such as implanted fiducials. However, the intrinsically poor contrast and low spatial resolution of portal images can limit image quality. METHODS: In this study, we have provided a multiresolution approach to enhance the quality of portal images acquired from the pelvis treatment fields. The main idea behind this work aims at removing some of the image artifacts that conceal the anatomical information. For this purpose, we have applied the homomorphic filtering on the approximation sub-band of wavelet decomposition to enhance local information. Moreover, in order to sharpen the bone edges, wavelet detail sub-bands were weighted to amplify important image details in the reconstruction of the desired enhanced image. The most appropriate image quality measure was chosen according to the image's characteristics in the spatial domain. By considering the characteristics of portal images as the random and nonperiodic texture, high level of noise, and a nonuniform background, three suitable quality measures of images were assessed: edge content, measure of enhancement, and measure of enhancement by entropy. RESULTS: The higher values of these measures indicate the quality improvement in the processed images through our proposed algorithm. Moreover, the subjective evaluation results indicate that the proposed multiresolution approach significantly enhances the perceived quality of images in comparison with original and the similar approach ( p < 0.001 $p < 0.001$ ). CONCLUSIONS: Our proposed wavelet-based enhancement algorithm successfully reduced image intensity nonuniformity and enhanced anatomical featured information, which drastically improved the objective metrics values. Subjective evaluation of enhanced image confirmed this quality improvement.

Advanced Three-Dimensional Technologies in Craniofacial Reconstruction.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the evolution of three-dimensional computer-aided reconstruction and its current applications in craniofacial surgery. 2. Recapitulate virtual surgical planning, or computer-assisted surgical simulation, workflow in craniofacial surgery. 3. Summarize the principles of computer-aided design techniques, such as mirror-imaging and postoperative verification of results. 4. Report the capabilities of computer-aided manufacturing, such as rapid prototyping of three-dimensional models and patient-specific custom implants. 5. Evaluate the advantages and disadvantages of using three-dimensional technology in craniofacial surgery. 6. Critique evidence on advanced three-dimensional technology in craniofacial surgery and identify opportunities for future investigation. SUMMARY: Increasingly used in craniofacial surgery, virtual surgical planning is applied to analyze and simulate surgical interventions. Computer-aided design and manufacturing generates models, cutting guides, and custom implants for use in craniofacial surgery. Three-dimensional computer-aided reconstruction may improve results, increase safety, enhance efficiency, augment surgical education, and aid surgeons' ability to execute complex craniofacial operations. Subtopics include image analysis, surgical planning, virtual simulation, custom guides, model or implant generation, and verification of results. Clinical settings for the use of modern three-dimensional technologies include acquired and congenital conditions in both the acute and the elective settings. The aim of these techniques is to achieve superior functional and aesthetic outcomes compared to conventional surgery. Surgeons should understand this evolving technology, its indications, limitations, and future direction to use it optimally for patient care. This article summarizes advanced three-dimensional techniques in craniofacial surgery with cases highlighting clinical concepts.

Extending the Reach of Craniofacial Free Flaps Using the Descending Branch of the Lateral Circumflex Femoral Vessels.

SUMMARY: Craniofacial free tissue transfer is sometimes complicated by insufficient pedicle length and/or paucity of recipient vessels. A saphenous vein graft can be used to reach the high-flow, large-caliber vessels of the neck, but because of the vein's taper and thick wall, there is often a mismatch. Following the principle of like-for-like, the authors prefer the descending branch of the lateral circumflex femoral vessels to achieve a more anatomical pedicle extension for free tissue transfer in complex craniofacial reconstruction. The authors' experience using the descending branch of the lateral circumflex femoral pedicle extender from 2010 to 2019 was reviewed. Indications, patient characteristics, reconstruction site, flap type, pedicle length, recipient vessels, and vascular complications were noted. The authors reviewed two strategies for implementation of the pedicle extender: in some cases, the flap was first transferred and allowed to perfuse on the descending branch of the lateral circumflex femoral vessels in the thigh, and then transferred to the recipient vessels (double-ischemia transfer); and in other cases, the flap and pedicle extender were transferred such that the flap underwent a single period of ischemia (single-ischemia transfer). The descending branch of the lateral circumflex femoral pedicle extender was used in 17 craniofacial cases. Indications included tumor, trauma, osteoradionecrosis, and congenital. Double-ischemia transfer was used in eight cases and single-ischemia transfer in nine. The longest pedicle extender in the series was 15 cm. Arterial thrombosis occurred in one case. This case series demonstrates that the descending branch of the lateral circumflex femoral pedicle extender is a viable option for complex craniofacial free tissue transfer cases. It provides ample length and excellent vessel match, following the like-for-like principle. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Copper(I) and silver(I) complexes of anthraldehyde thiosemicarbazone: synthesis, structure elucidation, in vitro anti-tuberculosis/cytotoxic activity and interactions with DNA/HSA.

A reaction of copper(i) halides (X = I, Br, Cl) and silver(i) halides with 9-anthraldehyde thiosemicarbazone (9-Hanttsc, H1L) and triphenylphosphine produced halogen-bridged dinuclear complexes, [M2(µ2-X)2(η1-S-9-Hanttsc)2(Ph3P)2] (M = Cu, X = Cl, 1; Br, 2; I, 3; M = Ag, X = Cl, 4; Br, 5). A similar reaction of 9-anthraldehyde-N1-methyl thiosemicarbazone (9-Hanttsc-N1-Me, H2L) with Ph3P and silver(i) halides yielded sulfur-bridged dimers, [Ag2X2(µ2-S-9-Hanttsc-N1-Me)2(Ph3P)2] (X = Cl, 9; Br, 10), however with copper(i) halides insoluble compounds were formed, which upon the addition of one extra mole of Ph3P gave mononuclear complexes of the formula [CuX(η1-S-9-Hanttsc-N1-Me)(Ph3P)2] (X = Cl, 6; Br, 7; I, 8). All of the complexes have been characterized by elemental analysis, NMR (1H, 13C) spectroscopy and single crystal X-ray crystallography (2, 5, 6, and 9). Both the ligands (H1L and H2L) and their complexes (1-10) were tested for their anti-tubercular and anticancer activities. The interactions of the ligands and their complexes (copper and silver) with calf thymus DNA (ct-DNA) and human serum albumin (HSA) were examined through UV-visible and fluorescence spectroscopy. Results showed that copper complex 2 displayed strong interactions with ct-DNA and HSA having binding constant values of 6.66 × 104 M-1 and 3.28 × 104 M-1, respectively, followed by silver complex 10 which gave binding constant values of 4.60 × 104 M-1 and 3.06 × 104 M-1, respectively. All of the complexes also showed good interactions with DNA in docking studies.

Ascorbic acid: The chemistry underlying its antioxidant properties.

Ascorbic acid (vitamin C) is an unusual antioxidant in that it donates a single reducing equivalent, and the radical it forms, monodehydroascorbate, reacts preferentially with radicals instead of with non-radical compounds. This happens because removal of an electron from monodehydroascorbate would create a tricarbonyl structure that is energetically unfavored. Instead of forming this structure, ascorbic acid oxidizes only to monodehydroascorbate, and monodehydroascorbate reacts with other radicals, oxidizing by mechanisms that may circumvent formation of this unfavored structure. Ironically, this tricarbonyl compound, which we suggest be called pseudodehydroascorbate, is commonly and mistakenly cited as the real product of ascorbic acid oxidation. In fact, it has been known for over 40 years that dehydroascorbate has a bicyclic hemiketal structure, and kinetic considerations suggest that it may be produced and reduced without forming pseudodehydroascorbate as an intermediate. This and other significant questions about the chemical basis of the antioxidant properties of ascorbic acid are obscured by this misconception about its oxidation product, dehydroascorbate.

Early Diagnosis and Intervention for Airway-Obstructing Neonatal Plexiform Neurofirbomatosis.

BACKGROUND: Respiratory distress is a frequent occurrence in neonates, typically caused by a variety of pulmonary conditions. Accurate diagnosis of the cause is vital to appropriately treat neonates and prevent long-term complications. Neck masses rarely cause respiratory distress in this setting but should be considered when clinical signs indicate. METHODS: The authors present the patient with a neonate born at term who developed stertor, respiratory distress requiring intubation, and repeated failure to extubate. RESULTS: Physical examination showed right-sided lower and midface enlargement with a firm mass mostly over the parotid and right neck. Both computerized and magnetic resonance tomography demonstrated a right-sided neck mass. Surgical exploration revealed extensive tumor burden emanating from the great auricular, hypoglossal, and other nerves of the neck, including invasion of the carotid sheath encasing the artery. Excisional biopsy showed plexiform neurofibroma, and pathognomonic for neurofibromatosis type 1. The decision was made to pursue medical management, as complete excision would have resulted in increased morbidity due to the involvement of multiple cranial nerves. The patient underwent microlaryngoscopy, bronchoscopy, and tracheostomy and was started on Trametinib chemotherapy. CONCLUSION: Neonatal airway obstruction can rarely be caused by unanticipated mass lesion, such as plexiform neurofibroma. A high index of suspicion must be maintained for early onset mass lesions causing respiratory obstruction to inhibit early disease progression and avoid potentially fatal sequelae.

Characterization and comparison of oxidative potential of real-world biodiesel and petroleum diesel particulate matter emitted from a nonroad heavy duty diesel engine.

Little is known regarding the oxidative potential of biodiesel particulate matter (PM) relative to diesel PM emitted from heavy duty diesel (HDD) nonroad engines generated in real-world occupational settings. The composition of biodiesel and diesel PM can include transition metals, polar, and nonpolar organic species which can increase oxidative potential via production of reactive oxygen species (ROS). Elevated ROS can lead to oxidative stress and induce antioxidant defense, inflammation, and toxicity. This study characterized the chemical composition of PM (water soluble organic carbon and elemental metals) collected in a real-world occupational setting. ROS production in a human epithelial cell line (BEAS-2B) treated with biodiesel and diesel PM extracts was compared to oxidative potential measured by an acellular dithiothreitol (DTT) assay. The oxidative potential (DTT consumption rate) of diesel PM was 21% greater than biodiesel PM at the highest treatment concentration (60 µg/mL), yet the ROS generated in vitro were similar between fuel types. Average concentrations of Cu, Cr and Zn were higher in diesel PM compared to biodiesel PM. Additionally, there was a significant correlation between DTT consumption and Cu in diesel PM (r = 0.98), but not B20 PM. There was a strong correlation between WSOC content in diesel PM and ROS generated in vitro (r = 0.83), but no correlation between WSOC content in biodiesel PM and ROS. Taken together, the results indicate the influence of fuel type on the chemical composition and oxidative potential of PM generated by a nonroad HDD engine operated at a recycling center. While acknowledging the potential influence of other species of interest not measured (i.e., quinones), real-world petroleum diesel PM emissions had higher oxidative potential compared to biodiesel PM suggesting that biodiesel use may reduce risk to human health.

Enhancement in anti-tubercular activity of indole based thiosemicarbazones on complexation with copper(I) and silver(I) halides: Structure elucidation, evaluation and molecular modelling.

A series of monomeric tetrahedral complexes of stoichiometry, [MX(HL)(Ph3P)2] (In case of M = Cu, H1L, X = I, 1; Br, 2; Cl, 3; H3L, X = I, 4; Br, 5; Cl, 6; H4L, X = I, 7; Br, 8; Cl, 9 and in case of M = Ag, H1L, X = Cl, 13; Br, 14; H2L, X = Cl, 15, Br 16; H3L, X = Cl, 17, Br, 18) were synthesized by the reaction of copper (I) or silver (I) halides with indole-3-thiosemicarbazone (H1L) or 5-methoxy indole-3-thiosemicarbazone (H2L) or 5-methoxy indole-N1-methyl-3-thiosemicarbazone (H3L), whereas dimers of stoichiometry, [Cu2(µ-X)2(η1-S-H2L)2(Ph3P)2] (X = I, 10; Br, 11; Cl, 12) were obtained by the reaction of copper (I) halides with indole-N1-methyl-3-thiosemicarbazone (HIntsc-N1-Me, H2L). The synthesized complexes were characterized using NMR (1H and 13C) and single crystal X-ray diffraction (H2L, 3, 7, 8, 10, 11 and 13) as well as elemental analysis. Anti- M. tuberculosis activity of ligands (H1L-H4L) and their metal complexes (1-18) were evaluated against M. tuberculosis H37RV strain ATCC 27294. It has been observed that there is unusual enhancement in anti TB activity of these ligands on complexation with copper (I) and silver (I). Molecular modelling studies in the active binding site are also giving complementary theoretical support for the experimental biological data acquired.

Effect of biodiesel fuel on "real-world", nonroad heavy duty diesel engine particulate matter emissions, composition and cytotoxicity.

Biodiesel is regarded by many as a "greener" alternative fuel to petroleum diesel with potentially lower health risk. However, recent studies examining biodiesel particulate matter (PM) characteristics and health effects are contradictive, and typically utilize PM generated by passenger car engines in laboratory settings. There is a critical need to analyze diesel and biodiesel PM generated in a "real-world" setting where heavy duty-diesel (HDD) engines and commercially purchased fuel are utilized. This study compares the mass concentrations, chemical composition and cytotoxicity of real-world PM from combustion of both petroleum diesel and a waste grease 20% biodiesel blend (B20) at a community recycling center operating HDD nonroad equipment. PM was analyzed for metals, elemental/organic carbon (EC/OC), polycyclic aromatic hydrocarbons (PAHs), and nitro-polycyclic aromatic hydrocarbons (N-PAHs). Cytotoxicity in a human lung epithelial cell line (BEAS-2B) following 24h exposure to the real-world particles was also evaluated. On average, higher concentrations for both EC and OC were measured in diesel PM. B20 PM contained significantly higher levels of Cu and Mo whereas diesel PM contained significantly higher concentrations of Pb. Principal component analysis determined Mo, Cu, and Ni were the metals with the greatest loading factor, suggesting a unique pattern related to the B20 fuel source. Total PAH concentration during diesel fuel use was 1.9 times higher than during B20 operations; however, total N-PAH concentration was 3.3 times higher during B20 use. Diesel PM cytotoxicity was 8.5 times higher than B20 PM (p<0.05) in a BEAS-2B cell line. This study contributes novel data on real-world, nonroad engine sources of metals, PAH and N-PAH species, comparing tailpipe PM vs. PM collected inside the equipment cabin. Results suggest PM generated from burning petroleum diesel in nonroad engines may be more harmful to human health, but the links between exposure, composition and toxicity are not straightforward.

Prediction of Cognitive and Functional Decline Using the Telephone-Administered Minnesota Cognitive Acuity Screen.

OBJECTIVES: To examine whether a telephone-based cognitive assessment-the Minnesota Cognitive Acuity Screen (MCAS)-is effective in predicting cognitive and functional decline in older adults with mild cognitive impairment (MCI) and conversion to dementia. DESIGN: Longitudinal. SETTING: Academic medical center. PARTICIPANTS: Individuals aged 60 to 84 with MCI (N = 61). MEASUREMENTS: An initial office visit consisting of a neurological examination, Clinical Dementia Rating Scale (CDR), and neuropsychological testing using the Dementia Rating Scale-2 (DRS-2), followed by the MCAS within 1 month. Participants completed up to three follow-up in-office neuropsychological assessments, originally scheduled 1 year apart. A multidisciplinary consensus group determined diagnosis (MCI, dementia) at each assessment. RESULTS: Higher baseline MCAS total scores emerged as a significant predictor of slower functional decline (P = .002) and dementia conversion (P = .02). An increase in score from 43 to 50 points (1st to 3rd quartile) was associated with a 0.59-point (95% confidence interval (CI) = 0.23-0.95) lower CDR score at follow-up, and a 71% (95% CI = 1.11-2.63) increase in median time to dementia conversion from 2 years to 3.5 years. Of the MCAS subscales, delayed word recall predicted functional decline alone (P < .001), whereas computation was nominally associated with cognitive (P = .01) and functional (P = .01) decline. CONCLUSION: The brief telephone-administered MCAS provides valuable information about future cognitive and functional decline in older adults with MCI and predicted conversion from MCI to dementia. These findings provide additional support for use of MCAS in clinical and research settings. The instrument may be particularly valuable in settings in which an office visit is difficult.

Posterior cranial vault distraction osteogenesis: evolution of technique.

The rapid growth of the brain in the first few years of life drives the expansion of the cranial vault. This expansion occurs primarily at the cranial sutures; premature fusion of these results in growth restriction perpendicular to the axis of the suture. The result of this is physical deformation of the cranial and facial skeleton, as well as the distortion of the underling brain and its physiology. These patients can present with symptoms of raised intracranial pressure, neurodevelopmental delay, as well as the morphological features of craniosynostosis. Acquired conditions such as the slit ventricle syndrome may also result in cephalocranial disproportion with these clinical features. Traditional vault remodeling surgery is able to correct the physical abnormalities as well as correcting cephalocranial disproportion. Its limitations include the degree of scalp expansion achievable as well as resulting defects in the bone. The use of distraction osteogenesis of the cranial vault permits a controlled expansion in a predetermined vector in a gradual manner. When used in the calvarium, this combines the benefits of tissue expansion on the scalp, as well as stimulating the production of new bone, reducing the defects resulting from expansion. In this review, the authors describe some of the surgical considerations important to the use of this technique. This includes the relevant anatomy and technical aspects illustrated with the use of clinical cases. Finally, they present a summary of their experience and discuss the complications associated with cranial vault distraction osteogenesis.

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

Resorption of PDLLA plates as a nidus for recurrent langerhans cell histiocytosis.

Resorbable plating systems have been adapted into routine use for craniofacial reconstruction in children. After implantation in some patients, the area around the plates can develop palpable and visible fibrous capsules, with underlying bone resorption and a significant foreign-body giant cell reaction. The reaction is usually self-limited. We report a case in which Langerhans cell histiocytosis was resected, and then recurred at the sites of resorbing plate and screw placement in association with a foreign-body giant cell reaction.