Reproducibility of three-dimensional posterior cranial base angles using low-dose computed tomography.

OBJECTIVES: One of the key aspects of three-dimensional (3D) craniofacial cephalometry is the measurement of posterior cranial base angle as this area is deeply involved in craniofacial development. The purpose of our retrospective study was to define the best reproducible 3D posterior cranial base angles among five 3D angles transposed from 2D cephalometry (Cousin, BL1 of Ross and Ravosa, Bjork, Delaire, CBA4 of Liberman) and seven 3D angles based on physical anthropology studies and on new concepts (R1 to R7). The null hypothesis was that all 3D posterior cranial base angles were equally reproducible. MATERIAL AND METHODS: We used a preoperative low-dose computed tomography (CT) data from 20 adult patients undergoing orthognathic surgery after approval by local ethical committee. Two independent observers performed two series of 23 3D landmark identifications on 3D CT surface rendering of each patient using Maxilim software. Then, the same observers performed twice 3D cephalometric analyses (23 landmarks, 4 midpoints, 19 planes) that provided the automatic measurement of 12 posterior cranial base angles. RESULTS: Inter-observer correlation coefficient varied from 0.545 (Cousin) to 0.695 (CBA4 of Liberman) and from -0.177 (R2) to 0.827 (R4). CONCLUSIONS: The null hypothesis was rejected. The most reproducible angle was 3D angle R4 based on "basion," "superior optic" (right, left), and "crista galli inferior" landmarks. CLINICAL RELEVANCE: R4 angle might be used as reference 3D posterior cranial base angle in further clinical studies involving 3D cephalometry as a diagnostic tool for orthodontics and for orthognathic surgery.

Preoperative, intraoperative, and postoperative complications in orthognathic surgery: a systematic review.

OBJECTIVES: The aim of this study was to determine whether orthognathic surgery is associated with any complications, and what type of complications may occur. MATERIALS AND METHODS: Data were obtained using PubMed (MEDLINE), ISI Web of Knowledge, Ovid, Cochrane Library, Embase Library, and an additional manual search. The titles and abstracts of the electronic search results were screened and evaluated by two observers for eligibility according to the inclusion and exclusion criteria. RESULTS: A total of 1924 articles were identified, and we retained 44 articles for the final analysis. The Prisma diagram flowchart demonstrates our selection scheme. For the purpose of this study, the Cochrane data extraction form was modified. One review author extracted data from the included studies, and the second author checked all of the forms. The hierarchy of evidence classification from the UK NHS Centre for Reviews and Dissemination was used to assess the level of evidence for the retrieved studies. CONCLUSIONS: An evaluation of the obtained studies revealed the existence of a large number of varied complications associated with orthognathic surgery procedures. CLINICAL RELEVANCE: Oral and maxillofacial surgeons, orthodontists, and the surgical team need to prevent such complications during preoperative, intraoperative, and postoperative periods to increase the safety of orthognathic surgery procedures. This review was registered on http://www.crd.york.ac.uk/PROSPERO as CRD42013004711.

Shape and volume of craniofacial cavities in intentional skull deformations.

Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.

Reproducibility of three-dimensional cephalometric landmarks in cone-beam and low-dose computed tomography.

OBJECTIVES: The purpose of this study is to compare the reproducibility of three-dimensional cephalometric landmarks on three-dimensional computed tomography (3D-CT) surface rendering using clinical protocols based on low-dose (35-mAs) spiral CT and cone-beam CT (I-CAT). The absorbed dose levels for radiosensitive organs in the maxillofacial region during exposure in both 3D-CT protocols were also assessed. MATERIALS AND METHODS: The study population consisted of ten human dry skulls examined with low-dose CT and cone-beam CT. Two independent observers identified 24 cephalometric anatomic landmarks at 13 sites on the 3D-CT surface renderings using both protocols, with each observer repeating the identification 1 month later. A total of 1,920 imaging measurements were performed. Thermoluminescent dosimeters were placed at six sites around the thyroid gland, the submandibular glands, and the eyes in an Alderson phantom to measure the absorbed dose levels. RESULTS: When comparing low-dose CT and cone-beam CT protocols, the cone-beam CT protocol proved to be significantly more reproducible for four of the 13 anatomical sites. There was no significant difference between the protocols for the other nine anatomical sites. Both low-dose and cone-beam CT protocols were equivalent in dose absorption to the eyes and submandibular glands. However, thyroid glands were more irradiated with low-dose CT. CONCLUSIONS: Cone-beam CT was more reproducible and procured less irradiation to the thyroid gland than low-dose CT. CLINICAL RELEVANCE: Cone-beam CT should be preferred over low-dose CT for developing three-dimensional bony cephalometric analyses.

A simple, no-cost method for 3D printed model identification.

3D printed models are often very similar in shape and can be inadvertently switched if the related patient is not identified correctly. Here, we present a free and simple method to imprint letters and numbers in a 3D model. CT scan data were used to create an STL file of a patient's mandible. We then used Blender software to modify it with numbers and letters. We chose to imprint a series of four letters and numbers on our 3D models. We chose representative letters and numbers of the Latin alphabet. Six models were printed with an Up plus 2 - easy 120 3D printer with different character sizes and shape to evaluate the readability. All models were printed without any failures. Regarding readability, 2 mistakes were made among ten readers. The favourite extrusion depth was 3 mm, and the largest model was preferred. Identification can be done at different times and by different means, but identifying the 3D model during its creation is safer. Moreover these identified 3D models could be saved in the digital patient medical file. The identification location should take into consideration the future indication of the 3D printed medical model. We recommend that 3D identification should be done using at least 7.5mm high, with a depth of 3mm. Our method allows easy, fast and free 3D text. This 3D text identification printing method may be a first step towards the legal use of 3D printed models made within the hospital.

Communicating a clinical problem to the engineers: towards a common methodology.

The purpose of this article is to present a method for communicating a clinical problem to a group of engineers. The seven-step design process described has been used for this type of communication and audience. A research project focusing on improvement of orthognathic surgery planning, including transfer of information to the operating room, is used as an example. The adoption of the seven-step design process, positioned within the symmetrical problem/solution model, could be the first step in facilitating communication between clinicians and engineers in translational research, and assisting in group focus on the development of a device (system) intended to solve a specific clinical problem.

Three-dimensional computed tomography cephalometric craniofacial analysis: experimental validation in vitro.

The development of three-dimensional (3D) cephalometric analysis is essential for the computer-assisted planning of orthognathic surgery. The aim of this study was to transform and adapt Delaire's two-dimensional cephalometric analysis into the third dimension; this transposition was then validated. The comparative advantage of using 3D computed tomography (CT) surface renderings over profile X-rays was analysed. Comparison was made of inter- and intra-observer reproducibility of the cephalometric measurements done on profile X-rays and on 3D CT surface renderings on the same 26 dry skulls. The accuracy was also tested of the measurements done on 3D CT surface renderings (ACRO 3D) in relation to those directly taken on dry skulls with the help of a 3D measuring instrument. Inter- and intra-observer reproducibility proved significantly superior (p<0.0001) following the 3D CT method. There were no significant differences in the accuracy of measurements between the ACRO 3D software and the 3D measuring instrument. The ACRO 3D software was confirmed as being a reliable tool for developing 3D CT cephalometric analyses. Further research may entail clinical validation of the 3D CT craniofacial cephalometric method of analysis.

[Evaluation of some selected structural and functional parameters of red blood cells as oxidative stress markers in elderly people]. / Ocena wybranych parametrów strukturalnych i czynnosciowych krwinek czerwonych jako markerów stresu oksydacyjnego u osób w wieku podeszlym.

UNLABELLED: The ageing process induces age-related involutionary changes and leads to increased occurrence of many diseases. One of the most important theories of ageing and development of many pathologies is the free radical theory, which assumes that ageing process leads to lost of oxidative balance. THE AIM: of the research was to evaluate the degree of membrane lipid peroxidation, internal microviscosity, activity of membrane ATPase, both total and Na(+)K(+)-dependent, and markers of oxidative damage in erythrocyte membrane protein in elderly people. MATERIAL: The examination was performed on 35 people. The examined group (15 persons, mean age 71,3) consisted of healthy elderly people. The reference group was formed with younger healthy people (20 persons, mean age 55). RESULTS: Erythrocyte membrane lipid peroxidation was found stronger in the group of elderly people. Erythrocyte internal microviscosity was significantly higher in the elderly. The activity of ATPase, both total and Na(+)K(+)-dependent, appeared remarkably greater in the group of younger people. Stronger membrane lipid damage was observed in older age group, which may be implied by lower--SH group concentration, and higher W/S parameter value. CONCLUSION: The obtained results reveal that in elderly people the intensification of oxidative stress in the entire body occurs, which may be confirmed by structural and functional oxidative erythrocyte damage. This conclusion may be significant for pathogenesis of many diseases in this period of life.

Recommendations for Lung Ultrasound in Internal Medicine

A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with the application of QUADAS, QUADAS-2 and GRADE criteria) and expert evaluation carried out consistently with the modified Delphi method (three rounds of on-line discussions, followed by a secret ballot by the panel of experts after each completed discussion). Publications to be analyzed were selected from the following databases: Pubmed, Medline, OVID, and Embase. New reports published as of October 2019 were added to the existing POLLUS-IM database used for the original publication of 2018. Altogether, 528 publications were systematically reviewed, including 253 new reports published between September 2017 and October 2019. The new recommendations concern the following conditions and issues: pneumonia, heart failure, monitoring dialyzed patients' hydration status, assessment of pleural effusion, pulmonary embolism and diaphragm function assessment. POLLUS-IM 2020 recommendations were established primarily for clinicians who utilize lung ultrasound in their everyday clinical work.

Stimulation of neutrophil activation during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegia.

BACKGROUND: During myocardial ischemia, activation of polymorphonuclear neutrophils (PMNs) results in the production of free oxygen radicals, which increase myocardial injury. It has been shown that PMNs also produce nitric oxide. It is not clear whether PMNs become activated as a result of their direct contact with ischemic/reperfused myocardium or if PMN activation and free oxygen radical production are effects of specific stimuli released during coronary artery bypass grafting (CABG). The aim of the current study was to evaluate plasma-mediated neutrophil stimulation and production of superoxide anion (O2) and nitric oxide in patients undergoing CABG, and to verify whether crystalloid and blood cardioplegia can modify such stimulation. METHODS: Coronary sinus, peripheral arterial, and venous plasma samples were collected from 50 patients who underwent CABG and were divided into 2 equal groups which received either crystalloid or blood cardioplegia: directly before myocardial ischemia and aortic cross-clamping; at the beginning of reperfusion after aortic clamp release; and 30 minutes after reperfusion. O2 and nitric oxide production by PMN was evaluated by standard methods. RESULTS: There was a significant (p < 0.05) increase in O2 production by PMN incubated with plasma obtained from the coronary sinus immediately after reperfusion in patients receiving crystalloid cardioplegia compared to blood cardioplegia. No difference was observed in plasma stimulation of nitric oxide production by PMN in the 2 groups of patients at different times during the procedure. CONCLUSIONS: Cardioplegia may affect release of neutrophil-oriented stimuli from ischemic myocardium and modify neutrophil activation during coronary artery bypass grafting.

Endothelin-1 is involved in plasma mediated stimulation of neutrophil adherence during coronary artery bypass grafting.

OBJECTIVE: Myocardial ischaemia followed by reperfusion during coronary artery bypass grafting (CABG) is known to result in the activation of polymorphonuclear neutrophils (PMN). The activation of PMN during ischaemia/reperfusion may be a result of their direct contact with activated endothelial cells and/or an effect of stimuli released from ischaemic myocardium. Increased expression of adhesion molecules on the PMN surface, after activation, leads to coronary capillary plugging with a subsequent decrease in blood flow. The purpose of the study was to evaluate plasma-mediated stimulation of PMN adhesion during CABG and to verify if endothelin-1 (ET-1), known to be a potent stimulus for PMN, is involved in stimulation of neutrophils adhesion mediated by integrins. METHODS: Coronary sinus, peripheral artery and peripheral venous plasma samples were taken from 11 patients undergoing coronary surgery before aortal cross-clamping, at the beginning of reperfusion and 30 min thereafter. PMN isolated from five healthy volunteers were incubated with the plasma (20 samples per patient) in the presence of saline or a specific ET-1 receptor blocker, and PMN adherence to a microtiter plate covered with a monoclonal antibody against CD 18 antigen (beta-subunit of the integrin family of adhesion molecules) was evaluated. RESULTS: We have observed a significant increase in adhesion of PMN incubated in the presence of saline with the plasma taken from coronary sinus at the beginning of reperfusion (7.79+/-1.64% of adhering cells) as compared with plasma obtained before aortal cross-clamping from the same place (6.78+/-1.3%, P = 0.04) and from peripheral artery at the beginning of reperfusion (6.64+/-1.1%, P = 0.04, means +/- SEM). ET-1 receptor blocker, significantly decreased stimulation of PMN adhesion by coronary sinus plasma obtained at the beginning of reperfusion (6.7+/-1.51%, P = 0.02). Plasma levels of ET-1 (ELISA) in the samples taken from coronary sinus at the beginning of reperfusion, were higher than in samples obtained before myocardial ischaemia or 30 min after reperfusion. CONCLUSIONS: We conclude, that soluble stimuli capable of stimulation of PMN adhesion are released following myocardial ischaemia during CABG and ET-1 may be involved in PMN stimulation.

Soluble adhesion molecules in reperfusion during coronary bypass grafting.

OBJECTIVE: Adhesion of activated leukocytes to the endothelial cells as a result of myocardial ischaemia/reperfusion during open chest coronary artery surgery has been shown to be involved in the development of tissue damage. Activated leukocytes adhere to endothelium via adhesion molecules expressed by both cell types, resulting in the impairment of coronary capillary flow. Upon cell activation, adhesion proteins may be released in the soluble form to circulating blood. The purpose of our study was to verify whether myocardial ischaemia/reperfusion occurring during coronary artery bypass grafting results in release of the soluble adhesion molecules VCAM-1, ICAM-1, E-selectin and L-selectin into the circulation. METHODS: Plasma levels of the soluble adhesion molecules were measured in vein, arterial and coronary sinus blood samples taken from 15 patients undergoing coronary artery bypass grafting (CABG). Blood samples for estimations were collected during the procedure: before aorta cross-clamping, at the beginning of reperfusion and 30 min after reperfusion. Soluble adhesion molecules levels were measured by standard ELISA assays. RESULTS: Mean plasma levels of soluble VCAM-1 in arterial samples increased significantly at the beginning of reperfusion and 30 min after reperfusion. In contrast, soluble L-selectin plasma levels in arterial samples remained unchanged. In coronary sinus samples, levels of soluble ICAM-1 significantly increased 30 min after reperfusion. Moreover, in coronary sinus samples collected 30 min after reperfusion, soluble ICAM-1 levels were significantly higher than in arterial samples obtained at the same time. The mean concentration of soluble E-selectin in samples obtained from coronary sinus decreased significantly 30 min after reperfusion. Moreover, plasma levels of soluble E-selectin in coronary sinus samples obtained 30 min after reperfusion were significantly decreased compared with these observed in arterial samples collected at the same time. CONCLUSIONS: The reperfusion of ischaemic myocardium during CABG results in a significant increase in plasma levels of the soluble endothelial adhesion molecules VCAM-1 and ICAM-1 and significant decrease in soluble E-selectin plasma levels. L-selectin plasma levels during CABG procedure remain unchanged. We propose that the increased plasma concentrations of soluble VCAM-1 and ICAM-1 are a result of endothelial cell activation during ischaemia/reperfusion following bypass surgery.

Assessment of wall velocity gradient imaging using a test phantom.

A new phantom has been designed to gain a better understanding of tissue Doppler imaging (TDI). Specifically, the phantom can easily be used to determine myocardial velocity gradients. The phantom mimics the left ventricle and is made of fine-grade sponge material whose ultrasound image closely resembles the gray scale image obtained from heart walls. Theoretical analysis of phantom wall movements offers a plausible explanation for the velocity gradients developing across the heart walls. The results of computer analysis were found to be in very good agreement with TDI M-mode recordings of phantom wall displacement.

Doppler myocardial imaging vs. B-mode grey-scale imaging: a comparative in vitro and in vivo study into their relative efficacy in endocardial boundary detection.

Doppler myocardial imaging (DMI) is a new ultrasound imaging modality in which colour Doppler algorithms are adapted to visualise the myocardium. It allows measurement of regional intramyocardial velocities and quantification of intramural left ventricular function. However promising the technique is, to date the accuracy of endocardial boundary detection by DMI has not been validated. As Doppler velocity estimation is based on measurement of phase shift rather than signal strength, the technique is relatively independent of chest wall attenuation. In the current study, a series of in vitro and in vivo studies was performed to compare standard B-mode grey-scale imaging (GSI) and DMI techniques in endocardial boundary detection. In vitro, the minimum and maximum volumes of a single-chamber tissue-mimicking phantom were calculated using both imaging techniques. In vivo, left ventricular end-diastolic (ED) volume and end-systolic (ES) volume indices were measured from GSI and DMI images in a group of 40 volunteers. All images were obtained in the freeze-frame mode with the Doppler display turned on and off so that simultaneous DMI and GSI information was obtained. In vitro, the limits of agreement between the minimum volume of the phantom and the minimum volume measured by GSI and DMI was 4% and 3%, respectively. For maximum volumes, limits of agreement were 3% for GSI and 2% for DMI. In vivo, the limits of agreement between the two imaging techniques in volume measurements were 6 mL (9%) for ED and 4 mL (11%) for ES. The comparison of the endocardial boundary detection by GSI vs. DMI showed DMI to be significantly superior: ED (72 +/- 16% vs. 85 +/- 8%, respectively; p < 0.05) and ES (71 +/- 13% vs. 88 +/- 7%, respectively; p < 0.05). The results of the study show that: (1) in vitro, based on two-dimensional algorithms, DMI provides as accurate volume measurements as GSI; and (2) in vivo, there is a very good agreement of left ventricular volume measurements between GSI and DMI. However, the endocardial boundary is more reliably displayed and visually easier to detect using DMI than GSI.

[Maxillo-facial surgery in the future, interdisciplinary innovation for medicine]. / Chirurgie maxillo-faciale du futur, l'innovation interdisciplinaire au service de la médecine.

The computer assisted craniomaxillofacial surgery (CAS-CMFS) is an emergent scientific domain in interaction between maxillofacial surgery, three dimensional CT imaging and remote signal engineering. The different stages to develop a synergy between these scientific areas are presented on example of the HEROL project (2002-2006, Region Wallonne grant). The 3D cephalometric analysis is made first with an original ACRO 3D software. Then, the craniomaxillofacial surgery preoperative planning, using 3D informations from ACRO 3D, is performed with ACROSIM 3D software. The major information concerning craniomaxillofacial surgery (incisions, nerve visualization, osteotomy lines visualization, ostheosynthesis position visualization) are transmitted from the virtual word (ACRO 3D & ACROSIM 3D), through the augmented reality (AR) head-mounted display, to the operating theatre. This study describes the HEROL project real advancement and future potential applications of AR in surgery.

[Contrast agents in echocardiography]. / Srodki cieniujace w echokardiografii.

Contrast echocardiography is new imaging modality dynamically entering to clinical practice. The efficient application of the contrast agents needs some knowledge of microbubbles physics. In this paper the basic principles of echo-contrast effects are presented and ultrasound microbubble fluid dynamics in the ultrasonic pressure field is addressed briefly. The recent developments in harmonic imaging end the transient and non-linear acoustic phenomena allow ultrasound to detect of blood flow in the microcirculation. In the second part of the paper it was demonstrated a potential for myocardial opacification by contrast echocardiography and the more recent application such as myocardial perfusion. The authors also reported intracardiac shunts imaging, enhancing endocardial border definition and bringing out of weak Doppler signals. The review of new contrast agents coming to the clinical practice is presented.

[Fibrinogen serum levels in patients with stable coronary artery disease and acute coronary syndrome]. / Stezenie fibrynogenu w surowicy chorych ze stabilna choroba wiencowa i ostrym zespolem wiencowym.

Increased plasma fibrinogen level is an important prognostic factor of recurrent unstable angina and myocardial infarction in patients with acute coronary syndrome (ACS). The aim of our study was to assess the plasma fibrinogen level at baseline condition in patients admitted to hospital due to coronary artery disease (CAD). Plasma fibrinogen was measured in 51 consecutive patients presenting with ACS within the last 24 hours and in 50 patients with angiographically proven CAD that was stable for the past 30 days. For statistical analysis Mann-Whitney U test, Student t-test, chi-square test and Pearson correlation was used, p < 0.05 being considered statistically significant. There was significant correlation between fibrinogen level and diagnosis of ACS or CAD (r = 0.29, p = 0.002). In our population plasma fibrinogen levels (g/L +/- SD) were significantly different in patients with ACS when compared to CAD subjects (3.87 +/- 1.2 vs. 3.26 +/- 0.65, p = 0.002). There was difference between ACS and CAD subjects in male:female ratio (40/11 vs. 47/4, p < 0.001) and age (63.4 +/- 10.1 vs. 58.4 +/- 10.0, p = 0.014). Our results confirm the role of fibrinogen in pathogenesis of CAD. In our opinion plasma fibrinogen level may be an important diagnostic tool in assessment of patients with chest pain.

[The improvement of echocardiographic assessment of the left ventricle by the use of perflenapent and harmonic imaging]. / Poprawa echokardiograficznej oceny lewej komory przy zastosowaniu perflenapentu i obrazowania harmonicznego.

Contrast echocardiography and harmonic imaging (HI) are promising new modalities applied in order to obtain improved visualisation of the left ventricle. Perflenapent (EchoGen, Abbott) is a new generation echocardiographic contrast agent that crosses the pulmonary capillary bed and produces long-term ventricle opacification. Our aim was to assess the left ventricle endocardial visualisation after perflenapent infusion and HI technique. We studied a pilot group of 10 patients (mean age 52.5 +/- 7.6, mean weight 76.9 +/- 10.1 kg, one female) with previously obtained sub-optimal non-contrast echocardiograms. Perflenapent was injected intravenously at dosis 0.05 ml/kg. Echocardiography was performed before perflenapent injection and during the time between injection and LV image disappearance. Images were assessed using four-point scale, 0 standing for the poorest and 3 for excellent visualisation. Perflenapent produced full chamber opacification in all pts. Contrast effect was observed for 550-15824 sec and myocardial enhancement was seen for 176-2116 sec after i.v. administration. After perflenapent administration, endocardial border was significantly better visible than before (1.9 +/- 0.57 vs. 2.9 +/- 0.31, p < 0.001). No hemodynamic effects were noted, as assessed by oxygen saturation, blood pleasure and heart rate. A mild, transient somnolence was seen in one pt. Perflenapent improved left ventricular function diagnostic capabilities, and provided enhanced visualisation of the myocardium.

Experimental and clinical assessment of three-dimensional cephalometry: a systematic review.

OBJECTIVES: This study provides a systematic review of the current scientific literature on three-dimensional (3D) cephalometry. The null hypothesis was that 3D cephalometry is an accurate and reproducible diagnostic technique. To examine this hypothesis, the following three research questions were proposed: 1) What is the accuracy of 3D cephalometric measurements compared to in vitro measurements? 2) What is the intra- and inter-observer reliability of the selection of 3D cephalometric landmarks? 3) What is the reproducibility of the linear and angular measurements? METHODS: A comprehensive database search was performed, using Medline, the Cochrane Central Register of Controlled Trials, Web of Science and Google Scholar. The titles and abstracts obtained from the search were screened and evaluated by two observers according to the inclusion and exclusion criteria. RESULTS: The evaluation process yielded 21 articles. A high level of agreement (<1 mm) between the in vitro measurements and those obtained from 3D cephalometry was observed and some landmarks provided highly reproducible results. However, the linear (0.04-7.49 mm) and angular (0.99-9.30°) measurements differed greatly. CONCLUSIONS: The null hypothesis was rejected. This study indicates critical points regarding 3D cephalometry and provides guidance for future research in this field.

NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia.

The most widely validated animal models of the positive, negative and cognitive symptoms of schizophrenia involve administration of d-amphetamine or the open channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII), an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate (NAAG) and reduces positive and negative behaviors induced by PCP in several of these models. NAAG is an agonist at the metabotropic glutamate receptor 3 (mGluR3). Polymorphisms in this receptor have been associated with expression of schizophrenia. This study aimed to determine whether two different NAAG peptidase inhibitors are effective in dopamine models, whether their efficacy was eliminated in GCPII knockout mice and whether the efficacy of these inhibitors extended to MK-801-induced cognitive deficits as assessed using the novel object recognition test. ZJ43 blocked motor activation when given before or after d-amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA), another potent NAAG peptidase inhibitor, also reduced motor activation induced by PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2-PMPA also blocked MK-801-induced deficits in novel object recognition when given before, but not after, the acquisition trial. The group II mGluR antagonist LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2-PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By bridging the dopamine and glutamate theories of schizophrenia with two structurally different NAAG peptidase inhibitors and demonstrating their efficacy in blocking MK-801-induced memory deficits, these data advance the concept that NAAG peptidase inhibition represents a potentially novel antipsychotic therapy.