Physical Medicine Rehabilitation

Gait variability in women with hip osteoarthritis before and after total hip replacement: A prospective cohort study Objective Gait variability changes before and after total hip arthroplasty (THA) are unclear. This study aimed to investigate gait variability changes in hip osteoarthritis (OA) patients before and after THA and to examine the relationships between gait variability changes and hip function. Design Twenty-three female patients with hip OA (61.0±7.1 years) and 10 healthy female participants (57.8±3.9 years) were assessed 1 month before and 12 months after surgery. Heel and lower trunk accelerations were measured using two triaxial accelerometers. The coefficient of variation (CV) of stride time for gait variability of lower limb motions and the harmonic ratio (HR) for trunk variability were calculated. Radiographic leg-length discrepancy, hip abductor strength, hip abduction, extension range of motion (ROM), and pain level during gait were measured. Results CV was significantly decreased after THA and was comparable to that in healthy individuals. While postoperative HRs were greater than preoperative HRs, they were not comparable with those in healthy individuals. CV changes were associated with pain relief during gait. HR changes were associated with hip abductor strength, extension ROM, and limb lengthening. Conclusion Gait variability improved after THA due to improved hip function. However, trunk variability was insufficient compared to that in healthy individuals. Correspondence: Osamu Wada, Anshin Hospital, 1-4-12, Minatojima Minamimachi, Chuo-ku, Kobe City, Hyogo, Japan. Tel: +81-78-304-5252. Email: osamuw19841013@gmail.com Author Disclosures Funding or grants: None Financial benefits: None Previous presentation: None Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Bone Marrow Edema: A Case of Regional Migratory Osteoporosis Bone marrow edema represents a typical pattern on magnetic resonance imaging consisting of an area of abnormal bone signal with low to intermediate intensity on T1 weighted images and a high intensity on fat suppressed T2 weighted images. Bone marrow edema syndromes are a group of entities characterized by idiopathic bone marrow edema and osteoporosis. Regional migratory osteoporosis is a bone marrow edema syndrome characterized by a self-limited migrating arthralgia of the lower limbs not related to trauma or other events. Its clinical presentation is variable and may include a less frequent form of migration of the bone marrow edema within the same joint, illustrated here by means of a case report. Conservative treatment is the preferred approach to this condition and usually it resolves completely and with no sequelae. Physicians should be made aware of this condition in order to avoid unnecessary and costly diagnostic and therapeutic measures. Correspondence: All correspondence and requests for reprints should be addressed to: Tiago Pimenta, Department of Physical Medicine & Rehabilitation, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PORTUGAL.E-mail: tiago.pmt@gmail.com. Phone number: (+351) 22 551 2100 Disclosures: no conflicts of interest related to the manuscript have been reported by the authors or by any individuals in control of the content of this article. No funding or equipment was provided for the project from any source. There are no financial benefits to the authors. This manuscript has not been previously submitted to any other publication. Authorship has been granted only to those individuals who have contributed substantially to the manuscript. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Pathological thoracic spine scoliosis due to ganglioneuroma No abstract available

Head Motion Predicts Transient Loss of Consciousness in Human Head Trauma: a Case-Control Study of Mixed Martial Artists Objective Concussion with transient loss of consciousness (tLOC) is a commonly observed but poorly understood phenomenon with mounting clinical significance. This study aimed to examine the relationship between head motion in varying planes and tLOC in athletes with brain injuries. Study Design A case-control design was utilized. The Ultimate Fighting Championship database was screened for events ending with knockouts (KO) from 2013 to 2016. Time of strike, striking implement, strike location, and head motion were recorded for all KO strikes (cases), and for a subset of non-KO strikes (controls). Characteristics of winners and losers were compared using 2-tailed t-tests. Multivariate logistic regression was used to determine odds ratios for strike characteristics associated with tLOC. The Kaplan-Meier estimate was used to describe the temporal distribution of KO's. Results 136 fights were identified and 110 videos were included. Head motion in the axial plane was strongly associated with tLOC (OR, 45.3; 95% CI, 20.8 - 98.6). Other predictors of tLOC were head motion in sagittal and coronal planes, non-fist striking implements and strikes to the mandible or maxilla. The Kaplan-Meier survival curve demonstrated a decreasing rate of KO's through time. Conclusion Rotational head acceleration, particularly in the axial plane, is strongly associated with tLOC. CORRESPONDENCES: Alexandra Fogarty, Washington University, PM&R Division, 4444 Forest Park Avenue, St Louis, MO. Tel: (314) 319-9807, alexandra.fogarty@wustl.edu DISCLOSURES: The authors have no competing interests. No funding, grants or equipment was provided for the project from any source. There were no financial benefits to the authors. The manuscript has not been previously presented or published. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Rapid Onset of Femoral Head Osteonecrosis after a Single Intraarticular Hip Joint Injection of Corticosteroid – A Case Report We outline a case in which osteonecrosis of the femoral head developed in temporal association with a single intraarticular injection of corticosteroid (triamcinolone acetonide) in a 72 year old woman, resulting in a total hip arthroplasty. We conclude that the risk of developing osteonecrosis after a single intraarticular injection of corticosteroid needs to be considered in the informed consent process. Corresponding Author: Erik Ensrud, MD, Sam Jackson Hall, Suite 2360, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239. ph. 503-494-5661. fax. 503-494-5050. ensrud@ohsu.edu Sources of Funding: No funding was received. Disclosures: Authors AT and EE have nothing to disclose. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Extracorporeal shock wave therapy immediately affects Achilles tendon structure and widespread pressure pain thresholds in healthy people: a repeated-measures observational study Objectives Extracorporeal shockwave therapy (ESWT) is a common clinical treatment for tendinopathy, yet negative effects on tendon structure have been shown in animal studies. This study aimed to investigate the effect of ESWT in healthy participants (i.e. no Achilles tendon pain or pathology). Design This study examined the effect of three helpbouts of weekly ESWT over 3-weeks in 13 healthy participants. Outcomes measures assessed were; (1) Achilles tendon structure, quantified using ultrasound tissue characterisation (before and 3-hours post ESWT), (2) pressure pain thresholds, over the Achilles tendon and common extensor tendon origin (before, immediately after and 3-hours post ESWT) and (3) hop pain (before and immediately post ESWT). Results There was a significant reduction in echo-type-I (p<0.05) and increase in echo-type-II (p<0.05) at 3-hours after the first ESWT session that recovered to baseline levels before week 2. There were no significant changes in UTC echopattern observed in subsequent sessions. There were increased pressure pain thresholds (PPTs) immediately following ESWT at the common extensor tendon origin but no significant change at the Achilles tendon. PPTs returned to baseline at 3-hours after ESWT. There were no significant changes in PPT in subsequent sessions. Conclusions ESWT resulted in transient changes to tendon structure and widespread hyperalgesia. Disclosures Conflicts of Interest: None Funding or financial benefits: None Corresponding author: Dr. Ebonie Rio, 03 9479 3785, La Trobe Sport & Exercise Medicine Research Centre, La Trobe University, Bundoora VIC 3086, Australia. e.rio@latrobe.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Does a web-based exercise programming system improve home exercise adherence for people with musculoskeletal conditions? Randomized controlled trial Objective To evaluate whether a web-based exercise programming system improves adherence to a home exercise program for people with musculoskeletal conditions. Design Eligible patients with a musculoskeletal condition presenting to a physical therapist in private practice were randomised to: 1) control (home exercise prescribed by therapist's usual methods), or 2) intervention (home exercise prescribed using a web-based exercise programming system). The primary outcome was self-rated exercise adherence measured at week 3 via 11-point numeric rating scales (NRS). Secondary outcomes were satisfaction with exercise delivery and confidence in ability to undertake prescribed exercise. Process measures were also included. Results We enrolled 305 participants, with loss-to-follow-up of 14.5% (22/152) and 13.7% (21/153) in intervention and control groups, respectively. Compared with controls, the intervention group reported higher exercise adherence (mean difference NRS units (95% confidence intervals): adherence overall -1.0 (-1.6,-0.3) and regarding number of exercises in session -0.7 (-1.3,-0.1), number of repetitions -0.8 (-1.4,-0.2) and number of sessions -1.0 (-1.6,-0.3)). The intervention group showed greater confidence to exercise than control, with no difference in satisfaction. Conclusions A web-based exercise programming system improved home exercise adherence and confidence in ability to undertake exercise, although the clinical relevance of the results needs to be established. Corresponding author: Dr Kim Bennell, Department of Physiotherapy, The University of Melbourne, Parkville, Victoria, 3010. ph: + 61 3 83444135, email: k.bennell@unimelb.edu.au Authors Disclosures: This trial was funded by the National Health and Medical Research Council (NHMRC, Program Grant #631717). Physitrack® provided use of the program as well as iPads for the physical therapists. Neither the funder nor Physitrack® had any role in the collection or analysis of the data nor in the interpretation of the findings. KLB is funded by a NHMRC Principal Research Fellowship (#1058440). RSH is funded by an Australian Research Council Future Fellowship (FTFT0991413). KB previously received funds as a consultant for Physitrack®. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Biceps femoris and semitendinosus conjoint tendon avulsion in a dancer No abstract available

One Year of Knee Pain in a 21-year-old Male Frisbee Player A 21-year-old male ultimate Frisbee player presented with one year of anterolateral right knee pain that was worse with activity. There was a remote history of trauma. Physical exam was unremarkable except for tenderness at the superolateral patella. X-ray revealed a bipartite patella. MRI revealed mild cystic change, sclerosis and bone marrow edema around the synchondrosis of the bipartite patella. Bipartite patella is an uncommon anatomic variant that is often asymptomatic and discovered incidentally; however, it rarely can be a primary cause of knee pain, can be diagnosed with MRI, and is amenable to conservative and surgical interventions. Treatment options are varied and include conservative management, injections, and various surgical approaches. Corresponding Author: Perry Zelinger, MD, 515 E. 82nd St. Apt 1C, New York, NY 10028, Perryzelinger@gmail.com, 516-317-0063 All authors have nothing to disclose No funding was received for this study. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Evidence-Based Physiatry: Relative Energy Deficiency in Sport (RED-S) No abstract available

Fwd: Pollution

Pollution

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Your mycotoxins in water paper

Subject: Reply to letter to the Editor (ESPR-D-18-05279) about our manuscript

Biochemical impacts in adult and juvenile farmed European seabass and gilthead seabream from semi-intensive aquaculture of southern European estuarine systems Abstract The nutritional value and developmental variations of cultured fish were assessed for European seabass and gilthead seabream specimens reared in semi-intensive aquaculture systems in two Portuguese estuaries. Quantification of total protein and of carbohydrate and fatty acid profiles was carried out to determine differences between the composition of the same species in two development stages reared in four distinct farms. A significant influence of the rearing site on the nutritional composition of the same species was found for adult European seabass regarding saturated, monounsaturated and highly unsaturated fatty acids contents, both between estuaries and within each estuary. In gilthead seabream, saturated, monounsaturated, polyunsaturated and highly unsaturated fatty acids content were also influenced by the rearing site. Carbohydrate analysis showed a significant influence of the rearing site on free sugar and polysaccharide content in fish of both species, and there was no influence on the species' protein content. Differences in fatty acid and carbohydrate content among juvenile and adult stages were found for all the groups studied. The present study supported the existing evidence that semi-intensive rearing systems are subjected to the variability of extrinsic factors in the rearing sites, influencing the nutritional value of the same species, namely regarding lipid and carbohydrate profiles, depending on the production site. From a consumer's perspective, such differences may come as a disadvantage of the rearing method, as it is expected for a product to provide equal nutritional properties and benefits regardless its origin, especially within the same country.

Lower cadmium accumulation and higher antioxidative capacity in edible parts of Brassica campestris L . seedlings applied with glutathione under cadmium toxicity Abstract Glutathione (GSH) is involved in not only plant developmental processes but also plant responses to abiotic stresses. A hydroponic experiment was performed to explore the protective roles of exogenous GSH in mitigating cadmium (Cd) stress in Brassica campestris L. seedlings by analyzing the morphological and physiological parameters. Results showed that Cd caused severe growth inhibition and Cd accumulation. However, application of GSH significantly mitigated toxic symptoms induced by Cd, including the improvement of the photosynthesis-, plant growth-, and root morphology-related parameters in seedlings under Cd stress. These responses were associated with a striking increase in activities of representative antioxidative enzymes and contents of corresponding non-enzymatic antioxidants. In vivo imaging of O2.- and H2O2, and the detection of lipid peroxidation further demonstrated that increased ability by GSH for Brassica campestris L. seedlings to endure Cd stress was consistent with a striking elevation of ratios of reduced to oxidized glutathione (GSH/GSSG) and ascorbic acid to dehydroascorbic acid (AsA/DHA). Additionally, GSH application increased Cd retained in roots, thus significantly decreased its translocation from root to shoot, ultimately decreased Cd accumulation in shoots. Taken together, our results proved evidence for GSH in ameliorating Cd toxicity via reducing Cd accumulation in shoots and increasing oxidation resistance. Accordingly, application of GSH could be a high-efficiency and promising strategy to decrease Cd concentration in edible parts of Brassica campestris L. in agricultural production.

Highly efficient removal of Cr(VI) and Cu(II) by biochar derived from Artemisia argyi stem Abstract In this work, a novel biochar was prepared from the Artemisia argyi stem at 300 °C (AS300), 450 °C (AS450), and 600 °C (AS600). The structural properties of these biochars were characterized with various tools. The sorption kinetic processes of Cr(VI) and Cu(II) onto these biochars were better described by the pseudo-second order. The sorption isotherm processes of Cr(VI) onto these biochars were better described by the Freundlich model while the adsorption processes of Cu(II) were consistent with the Langmuir model. Batch sorption experiments showed that AS600 had the maximum adsorption capacity to Cr(VI) and Cu(II) with 161.92 and 155.96 mg/g, respectively. AS600 was selected for the follow-up batch and dynamic adsorption experiments. Results showed that AS600 had larger adsorption capacity for Cr(VI) at lower pH while the larger adsorption capacity for Cu(II) was found at higher pH. The effect of ionic strength on the adsorption of Cu(II) by AS600 was greater than that on the adsorption of Cr(VI). Dynamic adsorption experiments showed that Cu(II) had a higher affinity for the adsorption sites on the AS600 compared with Cr(VI). The adsorption mechanisms mainly involved electrostatic attraction, ion exchange, pore filling, and chemical bonding effect. Graphical abstract

Modulation of photosynthetic parameters, sugar metabolism, polyamine and ion contents by silicon amendments in wheat ( Triticum aestivum L.) seedlings exposed to arsenic Abstract The objective of the present investigation was to consider the effectiveness of exogenous silicate supplementation in reviving the arsenate imposed alterations on pigment content, Hill activity, photosynthetic parameters, sugar metabolism, polyamine, and ion contents in wheat (Triticum aestivum L. cv. PBW-343) seedlings. Experiments were conducted under different levels of arsenate (0, 25 μM, 50 μM, and 100 μM) in combination with silicate (0, 5 mM) in a hydroponic environment with modified Hoagland's solution for 21 days to determine the ameliorative role of silicon (Si). Arsenate exposure led to a decline in chlorophyll content by 28% and Hill activity by 30% on an average along with photosynthetic parameters. Activity of starch phosphorylase increased causing a subsequent decrease in starch contents by 26%. Degradation of starch enhanced sugar contents by 61% in the test cultivar. Dose-dependant increments in the activities of carbohydrate metabolizing enzymes viz., sucrose synthase, sucrose phosphate synthase, and acid invertase were also noted. Putrescine content was significantly enhanced along with a consequent decline in spermidine and spermine contents. The macro- and micronutrient contents declined proportionally with arsenate imposition. Conversely, silicate amendments irrespective of all arsenate concentrations brought about considerable alterations in all parameters tested with respect to arsenate treatment alone. Marked improvement in pigment content and Hill activity also improved the gas exchange parameters. Soluble sugar contents decreased and starch contents were enhanced. Increase in polyamine contents improved the ionic balance in the test cultivar as well. This study highlights the potentiality of silicon in ameliorating the ecotoxicological risks associated with arsenic pollution and the probable ability of silicon to offer an approach in mitigating arsenate-induced stress leading to restoration of growth and metabolism in wheat seedlings.

Study on the purification effect of aeration-enhanced horizontal subsurface-flow constructed wetland on polluted urban river water Abstract The issue of urban river pollution has attracted great attention due to high concentrations of ammonia nitrogen (NH4+-N) and low concentrations of dissolved oxygen (DO) in polluted water bodies. In order to investigate the effects of aeration-enhanced horizontal subsurface-flow constructed wetlands on polluted river water, unaerated aeration (NA), continuous aeration (CA), and intermittent aeration (IA) constructed wetlands were established. The purification effects of the wetland on various pollutants and the form of effluent nitrogen, influences of temperature on the removal rates of pollutants, the change of redox potential—oxidation reduction potential (ORP)—and the difference of dissolved oxygen (DO) between influent and effluent were investigated. The results indicated that aeration enhancement can improve the purification efficiencies of chemical oxygen demand (COD) and NH4+-N in constructed wetlands. The purification efficiencies of TN in IA and CA constructed wetlands were 91.9% and 53.7%, respectively, indicating that IA is the optimized aeration method for removal of various pollutants in wetlands. Changes of DO and ORP in effluent under IA and CA suggested improvement of aeration on the water environment. Meanwhile, DO was more sensitive to temperature compared with ORP. Additionally, a study of the nitrogen content in effluent suggested that the aeration method had a significant influence on the nitrogen content in effluent. The removal rates of both NH4+-N and TN degraded as the temperature dropped. The results also demonstrated that the removal rate of NH4+-N under aeration condition was more sensitive to temperature than that under NA condition and the effect of temperature on the removal rate of NH4+-N was greater than that of TN.

Nutritional and toxicity constraints of phytoplankton from a Brazilian reservoir to the fitness of cladoceran species Abstract Camorim is a small, eutrophic reservoir in Rio de Janeiro, Brazil, with a phytoplankton community dominated most of the year by the filamentous diatom Aulacoseira spp. and the toxic cyanobacterium Cylindrospermopsis raciborskii. As filamentous species can be a poor food for grazers, we hypothesize that phytoplankton from this reservoir would constrain cladoceran fitness due to nutritional limitation and/or toxicity when animals fed mixtures of cultured green algae and natural seston. Clones of different cladoceran species were exposed either to seston from Camorim reservoir sampled in different seasons or to a C. raciborskii strain (CYLCAM-2) isolated from the reservoir. In short-term assays, cladocerans were exposed to either 100% seston or mixtures of 50% seston added to green algae (200 μg C L−1), and their survivorship and somatic growth were measured for 4 days. In life table assays, neonates were exposed to the same seston treatments over 14 days and age at first reproduction, survivorship, fecundity, total offspring, and the intrinsic rate of natural increase (r) were assessed. In general, seston negatively affected cladoceran survivorship and fitness (r), but this response was seasonally and species specific. Stronger effects of CYLCAM-2 than those caused by seston on survivorship, somatic growth, and r were found for all cladoceran species, especially when the proportion of CYLCAM-2 was higher than 50% in relation to green algae in a fixed total food concentration. Our results suggest that both nutritional (C/P and morphology) and toxicity factors can act to impair cladoceran fitness and help explain the absence of cladocerans in Camorim reservoir.

Environmental improvement in the printing industry: the case study of self-adhesive labels Abstract Labels are used for marketing, technical information, local of production and environmental declarations of products. The aim of the study was to evaluate the life cycle of two sets of front and back adhesive labels made with different liners: polyethylene terephthalate (PET) and glassine paper. The study is a pioneering initiative in the labelling industry using life cycle assessment, especially in Brazil. The attributional life cycle assessment method was based on the ISO 14044 standard and covered the entire life cycle, cradle to grave. Primary data for key suppliers, printing facility and label use composed the foreground data, while the ecoinvent database composed the background data. The material efficiency was assessed through mass balance. The impact assessment methods were cumulative energy demand for non-renewable energy and ILCD 2011 midpoint for the environmental categories. The glassine liner is heavier than the PET which resulted in larger environmental indicator values for production, transportation and waste treatment. On the other hand, energy demand of label set with glassine liner was lower than the PET. Furthermore, the hotspot analysis of each impact category was presented per process and substance. The label set made with glassine liner tended to present larger environmental indicator values in most categories, 13 of the 16 assessed, compared to the label set made with PET liner, despite the uncertainties. Contribution analysis identified that the pre-manufacturing step presented larger environmental indicator values than manufacturing, use and post-use steps along the label set life cycle. Therefore, environmental improvement opportunities were evaluated through scenarios of end of life, recycled inputs, domestic suppliers, waste prevention and product redesign. Moreover, the life cycle assessment was useful for diagnosing the energy and environmental profiles of self-adhesive labels and planning cleaner production measures that avoid environmental tradeoffs.

Adsorption of pharmaceuticals from biologically treated municipal wastewater using paper mill sludge-based activated carbon Abstract A waste-based alternative activated carbon (AAC) was produced from paper mill sludge under optimized conditions. Aiming its application in tertiary wastewater treatment, AAC was used for the removal of carbamazepine, sulfamethoxazole, and paroxetine from biologically treated municipal wastewater. Kinetic and equilibrium adsorption experiments were run under batch operation conditions. For comparison purposes, they were also performed in ultrapure water and using a high-performance commercial AC (CAC). Adsorption kinetics was fast for the three pharmaceuticals and similar onto AAC and CAC in either wastewater or ultrapure water. However, matrix effects were observed in the equilibrium results, being more remarkable for AAC. These effects were evidenced by Langmuir maximum adsorption capacities (qm, mg g−1): for AAC, the lowest and highest qm were 194 ± 10 (SMX) and 287 ± 9 (PAR), in ultrapure water, and 47 ± 1 (SMX) and 407 ± 14 (PAR), in wastewater, while for CAC, the lowest and highest qm were 118 ± 7 (SMX) and 190 ± 16 (PAR) in ultrapure water and 123 ± 5 (SMX) and 160 ± 7 (CBZ) in wastewater. It was found that the matrix pH played a key role in these differences by controlling the surface electrostatic interactions between pharmaceutical and AC. Overall, it was evidenced the need of adsorption results in real matrices and demonstrated that AAC is a promising option to be implemented in tertiary wastewater treatments for pharmaceuticals' removal. Graphical abstract Production of an alternative activated carbon (AC) comparing favourably with a commercial AC in the removal of neutral and positive pharmaceuticals from wastewater

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Cancer Nanotechnology

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Use of a lipid nanoparticle system as a Trojan horse in delivery of gold nanoparticles to human breast cancer cells for improved outcomes in radiation therapy Abstract Background Radiotherapy is commonly used for treating cancer. Novel sensitizers, such as gold nanoparticles (GNPs), are being used to enhance the local radiation dose. It is not known how the uptake and radiation dose enhancement of GNPs vary in synchronized vs unsynchronized (control) tumor cell populations. Successful application of GNPs in radiation therapy requires NPs to be accumulated within individual tumor cells at clinically feasible NP concentrations. Use of small GNPs as a radiation dose enhancer in the past required very high NP concentration, since the driving force for the uptake of smaller GNPs is low. We used a novel lipid-based NP of 50 nm diameter system as a Trojan horse to deliver smaller GNPs of size 5 nm (LNP–GNP) at 0.2 nM concentration. We investigated the changes in GNP uptake and survival fraction with the LNP delivery at different cell stages using human breast cancer as our tumor model and choosing the triple-negative MDA-MB-231 cell line. Results Using the LNP–GNP system resulted in a 39- and 73-fold enhancement in uptake of 5 nm GNPs in unsynchronized and synchronized tumor cell populations, respectively. The NP uptake per cell increased from 800 to 1200 and from 30,841 to 88,477 for individual 5 nm GNPs and 5 nm GNPs incorporated in LNPs, respectively. After a radiation dose of 2 Gy with 6 MeV photons, synchronized tumor cell populations incorporated with LNP–GNPs produced a 27% enhancement in tumor cell death compared to the control (unsynchronized; no GNPs; 2 Gy). The findings of our experimental results were supported by modeling predictions based on Monte Carlo calculations. Conclusions This study clearly shows that the cell cycle, GNPs, and radiation therapy can be combined to improve outcome of cancer therapy. Using the experimental data, we estimated the predicted improvement for a clinical treatment plan where 30 fractions of 2 Gy radiation dose were given over a period of time. Enhanced uptake and radiation sensitivity of a synchronous tumor cell population would produce a significant improvement in cell killing. For example, synchronizing cells and the addition of LNP–GNPs into tumor cells produced a 1000-fold enhancement in cell killing. Because the agents used for cell synchronization are in clinical practice, this approach may be a simple and cost-effective way to further enhance local radiation dose. Finally, this study provides a novel lipid-based NP platform to further improve GNP-mediated radiation therapy through synchronization of breast cancer cell population.

Comb-like PEG-containing polymeric composition as low toxic drug nanocarrier Abstract Background Development of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create "smart" drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone. Results We have demonstrated that the synthesized PNC possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116) and breast (MCF-7) tumor cell lines. Additionally, after a long period (20 days) of intraperitoneal administration, the PNC had no significant toxic effects in laboratory white mice (470 mg/kg body mass in 1 ml) and Wistar rats (440 mg/kg body mass in 10 ml). Conclusion The developed PNC we studied can be qualified as a compound of grade 4 toxicity (low toxicity substance). The reduced toxicity of this PNC in combination with its improved bioavailability and previously detected capability to enhance cytotoxicity toward tumor cells in vitro and potential tumor treatment effects in vivo suggests its potential as a safe drug delivery platform for treating various diseases, especially cancer.

Enhanced nanoparticle delivery exploiting tumour-responsive formulations Abstract Nanoparticles can be used as drug carriers, contrast agents and radiosensitisers for the treatment of cancer. Nanoparticles can either passively accumulate within tumour sites, or be conjugated with targeting ligands to actively enable tumour deposition. With respect to passive accumulation, particles < 150 nm accumulate with higher efficiency within the tumour microenvironment, a consequence of the enhanced permeability and retention effect. Despite these favourable properties, clinical translation of nano-therapeutics is inhibited due to poor in vivo stability, biodistribution and target cell internalisation. Nano-therapeutics can be modified to exploit features of the tumour microenvironment such as elevated hypoxia, increased pH and a compromised extracellular matrix. This is in contrast to cytotoxic chemotherapies which generally do not exploit the characteristic pathological features of the tumour microenvironment, and as such are prone to debilitating systemic toxicities. This review examines strategies for tumour microenvironment targeting to improve nanoparticle delivery, with particular focus on the delivery of nucleic acids and gold nanoparticles. Evidence for key research areas and future technologies are presented and critically evaluated. Among the most promising technologies are the development of next-generation cell penetrating peptides and the incorporation of micro-environment responsive stealth molecules.

Towards photon radiotherapy treatment planning with high Z nanoparticle radiosensitisation agents: the Relative Biological Effective Dose (RBED) framework Abstract A novel treatment planning framework, the Relative Biological Effective Dose (RBED), for high Z nanoparticle (NP)-enhanced photon radiotherapy is developed and tested in silico for the medical exemplar of neoadjuvant (preoperative) breast cancer MV photon radiotherapy. Two different treatment scenarios, conventional and high Z NP enhanced, were explored with a custom Geant4 application that was developed to emulate the administration of a single 2 Gy fraction as part of a 50 Gy radiotherapy treatment plan. It was illustrated that there was less than a 1% difference in the dose deposition throughout the standard and high Z NP-doped adult female phantom. Application of the RBED framework found that the extent of possible biological response with high Z NP doping was great than expected via the dose deposition alone. It is anticipated that this framework will assist the scientific community in future high Z NP-enhanced in-silico, pre-clinical and clinical trials.

C 60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes Abstract Background C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro. Methods Analysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation. Results Cytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties. Conclusions The antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles Abstract Background Recently, some studies have focused on dendrimer nanopolymers as a magnetic resonance imaging (MRI) contrast agent or a vehicle for gene and drug delivery. Considering the suitable properties of these materials, they are appropriate candidates for coating iron-oxide nanoparticles which are applied in magnetic hyperthermia. To the best of our knowledge, the novelty of this study is the investigation of fourth-generation dendrimer-coated iron-oxide nanoparticles (G4@IONPs) in magnetic hyperthermia and MRI. Methods IONPs were synthesized via co-precipitation and coated with the fourth generation (G4) of polyamidoamine dendrimer. The cytotoxicity of G4@IONPs with different concentrations was assessed in a human breast cancer cell line (MCF7) and human fibroblast cell line (HDF1). Hemolysis and stability of G4@IONPs were investigated, and in addition, the interaction of these particles with MCF7 cells was assessed by Prussian blue staining. Heat generation and specific absorption rate (SAR) were calculated from measurement and simulation results at 200 and 300 kHz. MCF7 and HDF1 cells were incubated with G4@IONPs for 2 h and then put into the magnetic coil for 120 min. Relaxometry experiments were performed with different concentrations of G4@IONPs with T1- and T2-weighted MR images. Results The TEM results showed that G4@IONPs were 10 ± 4 nm. The in vitro toxicity assessments showed that synthesized nanoparticles had low toxicity. The viability of MCF7 cells incubated with G4@IONPs decreased significantly after magnetic hyperthermia. In addition, MR imaging revealed that G4@IONPs improved transverse relaxivity (r2) significantly. Conclusions Our results encouraged the future application of G4@IONPs in magnetic hyperthermia and MR imaging.

Cisplatin-loaded hollow gold nanoparticles for laser-triggered release Abstract Background Hollow gold nanoparticles (HGNPs) exposed to near-infrared (NIR) light yield photothermal effects that can trigger a variety of biological effects for potential biomedical applications. However, the mechanism of laser-triggered drug release has not been studied before. Methods A tripeptide Ac-Glu-Glu-Cys-NH2 (Ac-EEC) was directly linked to the surface of HGNPs. The EEC-HGNPs conjugate was then complexed with cisplatin Pt(II) to give Ac-EEC(Pt)-HGNPs. Folic acid was introduced to the gold surface of Ac-EEC-HGNPs through a thioctic acid-terminated polyethylene glycol linker (F-PEG-TA) followed by complexation with Pt(II) to give F-Ac-EEC(Pt)-HGNPs. Laser treatment was instituted with a 15-ns pulsed laser at a repetition rate of 10 Hz. The released Pt(II) was quantified by inductively coupled plasma mass spectroscopy, and the nature of the released Pt-containing species was characterized by liquid chromatography–mass spectroscopy. The cytotoxicity was studied using the MTT assay. Results Pt(II) was released from Ac-EEC(Pt)-HGNPs via two modes: (1) sustained release through an inverse ligand exchange reaction with chloride ions and (2) rapid release through cleavage of the Au–S bond between the tripeptide linker and Au surface upon NIR laser irradiation. The folate (F) conjugate of the nanoconstruct, F-Ac-EEC(Pt)-HGNPs, in combination with laser treatment showed a significantly greater effect on cell mortality against folate-overexpressing human epidermoid carcinoma KB cells than F-Ac-ECC(Pt)-HGNPs alone after 24 h of incubation. Conclusions These results demonstrate that the photothermal property of HGNPs can be used for dual-modality photothermal therapy and NIR laser-triggered platinum-based chemotherapy.

Gene therapy with RALA/iNOS composite nanoparticles significantly enhances survival in a model of metastatic prostate cancer Abstract Background Recent approvals of gene therapies by the FDA and the EMA for treatment of inherited disorders have further opened the door for assessment of nucleic acid pharmaceuticals for clinical usage. Arising from the presence of damaged or inappropriate DNA, cancer is a condition particularly suitable for genetic intervention. The RALA peptide has been shown to be a potent non-viral delivery platform for nucleic acids. This study examines the use of RALA to deliver a plasmid encoding inducible nitric oxide synthase (iNOS) as an anti-cancer treatment. Methods The physiochemical properties of the RALA/DNA nanoparticles were characterized via dynamic light scattering and transmission electron microscopy. The nanoparticles were labelled with fluorophores and tracked over time using confocal microscopy with orthogonal sections to determine cellular location. In vitro studies were employed to determine functionality of the nanoparticles both for pEGFP-N1 and CMV-iNOS. Nanoparticles were injected intravenously into C57/BL6 mice with blood and serum samples analysed for immune response. PC3-luc2M cells were injected into the left ventricle of SCID mice followed by treatment with RALA/CMV-iNOS nanoparticles to evaluate the tumour response in a metastatic model of prostate cancer. Results Functional cationic nanoparticles were produced with gene expression in PC-3 prostate cancer cells. Furthermore, repeated administrations of RALA/DNA nanoparticles into immunocompetent mice did not produce any immunological response: neutralization of the vector or release of inflammatory mediators. RALA/CMV-iNOS reduced the clonogenicity of PC-3 cells in vitro, and in an in vivo model of prostate cancer metastasis, systemically delivered RALA/CMV-iNOS significantly improved the survival of mice. Conclusion These studies further validate RALA as a genetic cargo delivery vehicle and iNOS as a potent therapy for the treatment of cancer.

Gold nanoparticle mediated combined cancer therapy Abstract Background The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold–thiol bond. Methods Gold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKKKKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNP–drug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay. Results Cancer cells internalized with the GNP–drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons. Conclusions The experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.

Antiangiogenic and antiapoptotic effects of green-synthesized zinc oxide nanoparticles using Sargassum muticum algae extraction Abstract Background Algae are one of the natural materials used to green synthesis of nanoparticles. This method leads to minimize the toxicity of the chemical materials used to nanoparticle synthesis. Methods In this study, zinc oxide nanoparticles (ZnO NPs) synthesized by Sargassum muticum algae extraction used to evaluate its cytotoxicity and apoptotic properties on human liver cancer cell line (HepG2). Results Trypan blue assay results demonstrate a concentration-dependent decrease in cell viability and MTT assay shows increased growth inhibition in time and dose-dependent manner. In addition, CAM assay confirmed the ability of ZnO NPs to inhibit angiogenesis, but chick morphology (both the CR and weight) was not changed. Apoptotic tests (annexin V/PI and AO/PI) show that green-synthesized ZnO NPs induce apoptosis in all three time points (24, 48 and 72h). Conclusions Our results confirm the beneficial cytotoxic effects of green-synthesized ZnO NPs on Human liver cancer cell. This nanoparticle decreased angiogenesis and induces apoptosis, so we conclude that these nanoparticles can be used as a supplemental drug in cancer treatments.

Fwd: Craniofacial Surgery

Surgical Treatment of Polyostotic Craniomaxillofacial Fibrous Dysplasia Associated With Acromegalia: The McCune: –: Albright Syndrome Introduction: The McCune–Albright syndrome (MAS) is a complex congenital disorder caused by the embryonic post-zygotic somatic activating mutations in the GNAS1 gene. In such syndrome, phenotypes are heterogeneous and comprised polyostotic/monostotic fibrous dysplasia, café au lait macules, and hyperfunctioning endocrinopathies as the excess growth hormone. Likewise, acromegaly, as a manifestation of the endocrine hyperfunction, is unusual and affects about 20% of patients with MAS. Case Presentation: This research study describes a case of a 31-year-old female subject presenting polyostotic fibrous dysplasia with severe facial involvement, along with acromegaly and the MAS. The case was satisfactorily managed by surgical re-alignment and presented no clinical signs of relapse in a 12-year follow-up period. Finally, a literature review was conducted to discuss the standard protocols and the controversies when treating such cases. Conclusion: Patients with craniomaxillofacial fibrous dysplasia associated with acromegaly may present significant facial deformities that can be satisfactorily treated by cosmetic treatment, especially in patients with psychological problems and severe social acceptance. Address correspondence and reprint requests to Jéferson Martins Pereira Lucena Franco, DDS, Department of Oral and Maxillofacial Surgery, Hospital Geral de Fortaleza—HGF, Rua Paulo Morais, 321, Papicu, Fortaleza, Ceará, Zip Code: 60175-175, Brazil; E-mail: jefersonlucenaodonto@hotmail.com Received 26 June, 2018 Accepted 21 February, 2019 The authors state that they have no conflict of interest. © 2019 by Mutaz B. Habal, MD.

Cranial Base Superimposition of Cone-Beam Computed Tomography Images: A Voxel-Based Protocol Validation Objectives: The primary objective of the present study was to find the gold-standard accuracy of voxel-based superimposition of cone-beam computed tomography (CBCT) datasets with a protocol developed for the Dolphin Imaging 3D software. The secondary objectives were to analyze reproducibility and efficiency of this protocol. Study Design: Twenty-five CBCT datasets of patients with dental implants present were selected. Each Base Volume dataset was duplicated to create a second volume. Subsequently, both volumes were superimposed with a voxel-based protocol consisting of 3 successive steps "Side-by-side Superimposition"; "Overlay Superimposition"; and "Export Orientation to 2nd Volume". The protocol's accuracy was evaluated by measuring the mean distance between the apex of each dental implant on the Base Volume and second volume datasets. Efficiency was given by the mean time needed to complete all superimposition steps. Reproducibility was analyzed by calculating the intraclass correlation coefficients. Results: Mean time needed to complete the protocol was 198 seconds. The protocol had a rotational accuracy of 0.10° to 019° and a translational accuracy of 0.20 to 0.24 mm. Intra-observer and inter-observer reproducibility were 1 and 0.921 to 1, respectively. Conclusions: The protocol is accurate, precise, reproducible, and efficient. The validation of this method enables unbiased analysis of surgical outcomes based on a single, user-friendly software product that is widely available in academic and clinical settings. Address correspondence and reprint requests to Orion Luiz Haas Junior, DDS, MSc, PhD, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Av. Ipiranga, n.6681, Building 6, Porto Alegre, RS 91530-001, Brazil; E-mail: olhj@hotmail.com Received 31 July, 2018 Accepted 24 February, 2019 Orion Luiz Haas Junior and Raquel Guijarro-Martínez Both co-authors contributed equally to this work. All patients provided written informed consent for the use of their CBCT scans and the Teknon Medical Center ethical committee approved the study (CIR-ECL-2012-03). Brazilian Ministry of Education, Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES), Programa de Doutorado Sanduíche no Exterior (PDSE), grant no. 99999.006660/2015-00 awarded to Orion Luiz Haas Junior. The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Intra- and Postoperative Blood Loss and Transfusion Requirements in Children Undergoing Craniofacial Surgery Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14–33 mL/kg) and postoperatively 27 mL/kg (18–37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10–24 mL/kg) and postoperative 14 mL/kg (9–21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0–6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60–300 minutes). Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight. Address correspondence and reprint requests to Alexander Lindholm D'Amore, MD, Department of Anaesthesiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard, DK-8200 Aarhus N, Denmark; E-mail: alexanderdamore@gmail.com Received 3 October, 2018 Accepted 18 February, 2019 Source of funding: The study from Novo Nordisk Fonden (NNF14OC0011787). The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Comprehensive Treatment of Facial Deformity Due to Radiotherapy in Rhabdomyosarcoma Patients: Distraction Osteogenesis and Free Flaps Surgical Technique Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry. Several studies have shown that the management of irradiated bones still remains challenging. The possibility of obtaining functional and aesthetic results when managing facial deformities due to radiation therapy with distraction osteogenesis combined with free flaps reconstruction is not common and not well documented in recent literature. In this report, we present the long-term results of distraction osteogenesis and soft tissue reconstruction via microvascular free flap to correct the facial hypoplasia of a young patient who underwent radiation therapy for rhabdomyosarcoma. This is the first presentation of 26 years long-term results in a patient who also underwent free flaps reconstruction as ancillary surgery for esthetic good results. Address correspondence and reprint requests to Marco Cicciù, DDS, PhD, Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, Messina University, School of Dentistry University of Messina, Policlinico G. Martino, Via Consolare Valeria, Messina, 98100, ME, Italy; E-mail: acromarco@yahoo.it Received 5 November, 2018 Accepted 18 December, 2018 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Evaluation of the Facial Soft-Tissue Thickness in Patients With Cleft Lip and Palate Aim: In this study the authors aimed to evaluate craniofacial morphology and facial soft tissue thickness of the patients with cleft lip and palate.(CLP), and to compare the results with a sex and age-matched noncleft healthy control group. Methods: Craniofacial and soft tissue thickness measurements of 20 patients with unilateral cleft lip palate (UCLP) and 20 patients with bilateral cleft lip palate (BCLP) were compared with 20 noncleft control subjects. Angles between Sella-Nasion-A point, Sella-Nasion-B point, Nasion-A and Nasion-B line, Sella-Nasion line and Gonion-Gnation line, and linear (glabella, rhinion, subnasale, labrale superius, stomion, labrale inferius, labiomentale, pogonion, and gnathion) measurements were assessed on lateral cephalometric radiographs. Group differences were evaluated with 1-way analysis of variance and post hoc Tukey test. Results: Unilateral cleft lip palate and BCLP groups demonstrated lower values of skeletal measurements than control group except for Sella-Nasion line and Gonion-Gnation line value (P < 0.01). Maxillary incisors were retruded in BCLP group compared with the other groups (P < 0.001). Thickness of the rhinion, subnasale, and stomion demonstrated no significant difference between UCLP and BCLP groups (P > 0.05). Thickness of rhinion and stomion was found significantly higher in both groups, and thickness of the subnasale was found significantly lower than the healthy group (P < 0.05). Conclusion: Findings of the study suggested that patients with CLP showed differences on craniofacial morphology and facial soft tissue thickness. Before planning orthodontic treatment and esthetic surgeries, soft tissue thickness should be taken into consideration in addition to skeletal measurements in CLP patients. Address correspondence and reprint requests to Emire Aybuke Erdur, PhD, Emire Aybuke Erdur Department of Orthodontics, Faculty of Dentistry, Necmettin Erbakan University, 42050 Konya, Turkey; E-mail: dtaybuke@gmail.com Received 24 October, 2018 Accepted 24 February, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

"Three Subunit" Classification of Lesser-Form Cleft Lip and Muscle Analysis and Reconstruction of These Subunits Based on the Microanatomic Structures of Muscles in the Normal Upper Lip Background: The main phenotypic features of lesser-form cleft lip include nasal, philtrum, and vermilion deformities. The manifestations of lesser-form cleft lip vary greatly, and it is difficult to rebuild these subunits during the operation. Methods: "Three subunits" classification of lesser-form cleft lip was identified as nasal deformity (N), philtrum deformity (P), or vermilion deformity (V); and slight deformity (0) or obvious deformity (1). A total of 200 patients with lesser-form cleft lip were classified into one of the following 8 types: N1P1V1, N1P1V0, N0P1V1, N1P0V1, N0P0V1, N1P0V0, N0P1V0, or N0P0V0. Then the authors discussed the deformities of the lesser-form cleft lip and the reconstruction of the muscles in these subunits based on the microanatomic structure of the nasolabial muscle. Results: This retrospective review included 200 patients with a lesser-form cleft lip, who were seen at our center from 2015 to 2017. There were 149 (74.5%) N1P1V1, 11 (5.5%) N1P1V0, 13 (6.5%) N0P1V1, 4 (2.0%) N1P0V1, 8 (4.0%) N0P0V1, 10 (5.0%) N1P0V0, 1 (0.5%) N0P1V0, and 4 (2%) N0P0V0 clefts. The various deformities of nasal floor, philtrum ridge, and vermilion may suggest that the muscle bundles in these subunits are abnormal and the operation should be performed to simulate the running directions and tension lines of these local muscles. Conclusions: The microanatomic structure and the tension lines of the nasolabial muscles can provide new perspectives for better understanding and repairing the lesser-form cleft lip in subunits. Address correspondence and reprint requests to Tao Song, MD, Department of Cleft Lip and Palate, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, PR China; E-mail address: songtao2059@163.com Received 21 November, 2018 Accepted 15 February, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

The Right to Heresy: Letters to the Editor No abstract available

Statistical Shape Analysis of Cerebellum in Patients With Chiari Malformation I The surgical procedure is viewed as a typical treatment choice for patients with Chiari malformation (CM). Decompression is the preferred method for surgery, but it is not always possible to understand whether decompression has been successful especially in an early period. The present study focuses on investigating the shape differences in the cerebellums of Chiari patients compared with healthy controls, and to assess the clinical application of this situation whether if present. The MRI scans were reviewed retrospectively. Cerebellar data were obtained from the digital images and 9 anthropometric landmarks were marked on each image. Shape difference was assessed by performing Generalized Procrustes analysis. The cerebellar shape deformation from control to the patient was evaluated performing the Thin Plate Spline approach. There is a statistically significant cerebellar shape difference between groups. Highest deformation was determined at the cerebellar tonsillar inferior area, posterior of the uvula, and anterior of inferior medullary velum. The present study demonstrated cerebellar shape differences in CM I patients using a landmark-based geometric morphometric approach, considering the topographic distribution of cerebellum for the first time. Address correspondence and reprint requests to Gokhan Ocakoglu, PhD, Uludag University Medical School, Department of Biostatistics, 16059 Bursa, Turkey; E-mail: gocakoglu@gmail.com Received 4 December, 2018 Accepted 13 February, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

A Craniometric Analysis of the Posterior Cranial Base After Posterior Vault Distraction Background: Posterior vault distraction osteogenesis (PVDO) has been demonstrated to effectively increase intracranial volume, treat increased intracranial pressure, and improve head shape in syndromic patients. The purpose of this study is to compare changes along the posterior cranial base before and after distraction. Methods: A retrospective review was completed of subjects who underwent PVDO with computed tomography scans at 2 time-points: within 3 months preoperatively and 1 to 6 months postoperatively. Using Mimics software, craniometric landmarks were identified and surface area of the foramen magnum was calculated. A comparison of pre- to postoperative measurements was completed using Wilcoxon matched-paired signed rank tests and linear regression. Results: A total of 65 PVDO subjects were identified, 12 subjects met inclusion criteria. Mean operative age was 3.0 ± 4.0 years. The cranial vault was distracted on average 25.0 ± 6.0 mm, with those < 12 months of age distracted 29.5 ± 4.9 mm and >12 months of age distracted 22.0 ± 4.9 mm (P = 0.0543). There was a significant increase in pre- to postoperative foramen magnum surface area (52.1 ± 63.2 mm2, P = 0.002), length (0.9 ± 1.4 mm, P = 0.050), and width (0.6 ± 1.0 mm, P = 0.050). Similarly, linear distances between nasion and posterior cranial base landmarks such as foramen magnum (3.4 ± 4.2 mm, P = 0.010), and occipital protuberance (9.1 ± 9.6 mm, P = 0.003) were increased. Subjects under 12 months had a greater percentage increases in posterior vault length than those over 12 months. Conclusion: Posterior vault distraction osteogenesis is associated with an increase in size of the foramen magnum, and lengthening of the posterior cranial base, both of which may be beneficial in patients with turribrachycephaly. Address correspondence and reprint requests to Jesse A. Taylor, MD, Division of Plastic and Reconstructive Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Colket Translational Research Building, 3501 Civic Center Blvd, 9th floor, Philadelphia, PA 19104; E-mail: taylorj5@email.chop.edu Received 8 February, 2018 Accepted 20 February, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Comparison Between Intermaxillary Fixation With Screws and an Arch Bar for Mandibular Fracture Purpose: Intermaxillary fixation (IMF) using the arch bar has been the standard technique for a long time in the management of mandibular fracture. But because of several complications, intermaxillary fixation with screws has been introduced and adopted to use. This investigation compared the outcomes and complications between the traditional IMF and modified intermaxillary fixation with screws techniques in terms of the malocclusion, surgical time, root injury, and screw or arch bar failure. Methods: This retrospective review included 66 patients who underwent reconstruction of mandibular fractures that uses traditional arch bar or IMF screws as IMF. Preoperative and postoperative facial bone computed tomography, panoramic x-ray were used to evaluate the patients. The complaints and complications were recorded in electric medical record based on patients' consultation during follow-up. Results: The total complication rate was no higher using anchoring screw as an IMF than using arch bar fixation as an IMF. Mean surgical time was significantly shorter in the anchoring screw group than arch bar fixation (111 versus 157 min; P < .05). After compensation of the number of fracture sites, there was a significant difference in operation time (linear regression model, P = .009). Conclusion: This investigation revealed that the IMF using IMF screw systems could be a good alternative for the management of mandibular fracture. It could minimize the whole operation time with the similar complication ratio. Address correspondence and reprint requests to Jong-Woo Choi, MD, PhD, Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea; E-mail: pschoi@amc.seoul.kr Received 4 March, 2018 Accepted 14 February, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.