Automatic landmark identification in cone-beam computed tomography.

OBJECTIVE: To present and validate an open-source fully automated landmark placement (ALICBCT) tool for cone-beam computed tomography scans. MATERIALS AND METHODS: One hundred and forty-three large and medium field of view cone-beam computed tomography (CBCT) were used to train and test a novel approach, called ALICBCT that reformulates landmark detection as a classification problem through a virtual agent placed inside volumetric images. The landmark agents were trained to navigate in a multi-scale volumetric space to reach the estimated landmark position. The agent movements decision relies on a combination of DenseNet feature network and fully connected layers. For each CBCT, 32 ground truth landmark positions were identified by 2 clinician experts. After validation of the 32 landmarks, new models were trained to identify a total of 119 landmarks that are commonly used in clinical studies for the quantification of changes in bone morphology and tooth position. RESULTS: Our method achieved a high accuracy with an average of 1.54 ± 0.87 mm error for the 32 landmark positions with rare failures, taking an average of 4.2 second computation time to identify each landmark in one large 3D-CBCT scan using a conventional GPU. CONCLUSION: The ALICBCT algorithm is a robust automatic identification tool that has been deployed for clinical and research use as an extension in the 3D Slicer platform allowing continuous updates for increased precision.

Presurgical orthodontic decompensation with clear aligners.

INTRODUCTION: Orthodontists, surgeons, and patients have taken an interest in using clear aligners in combination with orthognathic surgery. This study aimed to evaluate the accuracy of tooth movements with clear aligners during presurgical orthodontics using novel 3-dimensional superimposition techniques. METHODS: The study sample consisted of 20 patients who have completed presurgical orthodontics using Invisalign clear aligners. Initial (pretreatment) digital dental models, presurgical digital dental models, and ClinCheck prediction models were obtained. Presurgical models were superimposed onto initial ones using stable anatomic landmarks; ClinCheck models were superimposed onto presurgical models using surface best-fit superimposition. Five hundred forty-five teeth were measured for 3 angular movements (buccolingual torque, mesiodistal tip, and rotation) and 4 linear movements (buccolingual, mesiodistal, vertical, and total scalar displacement). The predicted tooth movement was compared with the achieved amount for each movement and tooth, using both percentage accuracy and numerical difference. RESULTS: Average percentage accuracy (63.4% ± 11.5%) was higher than in previously reported literature. The most accurate tooth movements were buccal torque and mesial displacement compared with lingual torque and distal displacement, particularly for mandibular posterior teeth. Clinically significant inaccuracies were found for the buccal displacement of maxillary second molars, lingual displacement of all molars, intrusion of mandibular second molars, the distal tip of molars, second premolars, and mandibular first premolars, buccal torque of maxillary central and lateral incisors, and lingual torque of premolars and molars. CONCLUSIONS: Superimposition techniques used in this study lay the groundwork for future studies to analyze advanced clear aligner patients. Invisalign is a treatment modality that can be considered for presurgical orthodontics-tooth movements involved in arch leveling and decompensation are highly accurate when comparing the simulated and the clinically achieved movements.

[Cardiovascular complications in COVID-19 patients admitted to intensive care units in Chilean hospitals]. / Complicaciones cardiovasculares en pacientes COVID-19 hospitalizados en Unidades de Pacientes Críticos en Chile. Registro COVICAR.

BACKGROUND: Patients with a cardiovascular (CV) history may be at greater risk of becoming ill and die due to SARS-CoV-2. AIM: To assess the incidence of CV complications in COVID-19 patients, the type of complication, and their association with CV history. MATERIAL AND METHODS: The clinical course of 1,314 patients with COVID-19 admitted consecutively to critical care units of 10 Chilean hospitals was registered between April and August of 2020. RESULTS: The median age of patients was 59 years and 66% were men. One hundred-four (8%) had a CV history, namely heart failure (HF) in 53 (4.1%), coronary heart disease in 50 (3.8 %), and atrial fibrillation in 36 (2.7 %). There were CV complications in 359 patients (27.3%). The most common were venous thrombosis in 10.7% and arrhythmias in 10.5%, HF in 7.2%, type 2 acute myocardial infarction in 4.2%, arterial thrombosis in 2.0% and acute coronary syndrome (ACS) in 1.6%. When adjusted by age, sex and risk factors, only HF (Odds ratio (OR) = 7.16; 95% confidence intervals (CI), 3.96-12.92) and ACS (OR = 5.44; 95% CI, 1.50-19.82) were significantly associated with CV history. There was no association with arrhythmias, type 2 acute myocardial infarction, arterial or venous thrombosis. CONCLUSIONS: Patients with a history of CV disease are at greater risk of suffering HF and ACS when hospitalized due to COVID-19. Arrhythmias, type 2 AMI, and arterial or venous thrombosis occur with the same frequency in patients with or without CV history, suggesting that these complications depend on inflammatory phenomena related to the infection.

Clinical decision support systems in orthodontics: A narrative review of data science approaches.

Advancements in technology and data collection generated immense amounts of information from various sources such as health records, clinical examination, imaging, medical devices, as well as experimental and biological data. Proper management and analysis of these data via high-end computing solutions, artificial intelligence and machine learning approaches can assist in extracting meaningful information that enhances population health and well-being. Furthermore, the extracted knowledge can provide new avenues for modern healthcare delivery via clinical decision support systems. This manuscript presents a narrative review of data science approaches for clinical decision support systems in orthodontics. We describe the fundamental components of data science approaches including (a) Data collection, storage and management; (b) Data processing; (c) In-depth data analysis; and (d) Data communication. Then, we introduce a web-based data management platform, the Data Storage for Computation and Integration, for temporomandibular joint and dental clinical decision support systems.

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients. Among these studies, results derived from the use of vitamin C (Vit C) have been inconclusive so far, likely due to suboptimal study designs, misinterpretations, and the erroneous conclusions of clinical trials. Nevertheless, recent clinical trials have shown that the intravenous infusion of Vit C prior to PCI-reduced cardiac injury biomarkers, as well as inflammatory biomarkers and ROS production. In addition, improvements of functional parameters, such as left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume, showed a trend but had an inconclusive association with Vit C. Therefore, it seems reasonable that these beneficial effects could be further enhanced by the association with other antioxidant agents. Indeed, the complexity and the multifactorial nature of the mechanism of injury occurring in AMI demands multitarget agents to reach an enhancement of the expected cardioprotection, a paradigm needing to be demonstrated. The present review provides data supporting the view that an intravenous infusion containing combined safe antioxidants could be a suitable strategy to reduce cardiac injury, thus improving the clinical outcome, life quality, and life expectancy of patients subjected to PCI following AMI.

Aquaporin 4 distribution in the brain and its relevance for the radiological appearance of neuromyelitis optica spectrum disease.

BACKGROUND AND PURPOSE: To determine the precise incidence of lesions at sites of high Aquaporin-4 expression (hAQP4) and their possible association with known neuromyelitis optica spectrum disease (NMOSD) lesions patterns. MATERIALS AND METHODS: A retrospective analysis of brain and, when available, spinal cord MRI scans of 54 NMOSD patients recruited among the French NMOSD cohort was performed. Brain lesions were annotated as MS-like, non-specific, or evocative of NMOSD. The topography of hAQP4 was reassessed by human brain atlas. The incidence of lesions in hAQP4 and their association with lesions evocative of NMOSD was estimated. RESULTS: Among those included (41/54 female, mean age: 45 years) 47/54 (87%) presented brain lesions. Twenty-six/47 (55%) had lesions in hAQP4. Thirty-two/54 patients (60%) had lesions considered evocative of NMOSD. The majority of them also presented lesions in hAQP4 (65%, 21/32). Patients with lesions in hAQP4 and lesions evocative of NMOSD demonstrated more extensive myelitis compared to the other patients (7 [6-10] versus 4 [3-5] vertebral segments, P=0.009). CONCLUSION: The coexistence of lesions evocative of NMOSD and in hAQP4 is associated with significantly more extensive myelitis, and might have pathophysiological and clinical significance.

Decision Support Systems in Temporomandibular Joint Osteoarthritis: A review of Data Science and Artificial Intelligence Applications.

With the exponential growth of computational systems and increased patient data acquisition, dental research faces new challenges to manage a large quantity of information. For this reason, data science approaches are needed for the integrative diagnosis of multifactorial diseases, such as Temporomandibular joint (TMJ) Osteoarthritis (OA). The Data science spectrum includes data capture/acquisition, data processing with optimized web-based storage and management, data analytics involving in-depth statistical analysis, machine learning (ML) approaches, and data communication. Artificial intelligence (AI) plays a crucial role in this process. It consists of developing computational systems that can perform human intelligence tasks, such as disease diagnosis, using many features to help in the decision-making support. Patient's clinical parameters, imaging exams, and molecular data are used as the input in cross-validation tasks, and human annotation/diagnosis is also used as the gold standard to train computational learning models and automatic disease classifiers. This paper aims to review and describe AI and ML techniques to diagnose TMJ OA and data science approaches for imaging processing. We used a web-based system for multi-center data communication, algorithms integration, statistics deployment, and process the computational machine learning models. We successfully show AI and data-science applications using patients' data to improve the TMJ OA diagnosis decision-making towards personalized medicine.

The effect of the Covid-19 Pandemic on pediatric urology.

Medical and surgical priorities have changed dramatically at the time of this pandemic. Scientific societies around the World have provided rapid guidance, underpinned by the best knowledge available, on the adaptation of their guidelines recommendations to the current situation. There are very limited scientific evidence especially in our subspecialty of pediatric urology. We carry out a review of the little scientific evidence based mainly on the few publications available to date and on the recommendations of the main scientific societies regarding which patients should undergo surgery, when surgery should be performed and how patient visits should be organize.

Stroke in Patients With Peripheral Artery Disease.

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.

Gene dosage of DAX-1, determining in sexual differentiation: duplication of DAX-1 in two sisters with gonadal dysgenesis.

Two sisters phenotypically normal females, presenting with tumor abdominal mass with histopathological findings of teratoma and gonadoblastoma associated to 46,XY male-to-female sex reversal syndrome, secondary to a duplication in DAX-1, possibly inherited of maternal gonadal mosaicism. Copy number variation and functional effects of the duplication were done by MLPA multiplex ligation-dependent probe amplification and real time PCR. DAX-1, also known as dosage sensitive sex reversal gene (DSS), is considered the most likely candidate gene involved in XY gonadal dysgenesis when overexpressed. The excess of DAX-1 gene disturbs testicular development by down regulation of SF-1, WT1, and SOX9. This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9-SF1.

3D superimposition of craniofacial imaging-The utility of multicentre collaborations.

Clinical applications of 3D image registration and superimposition have contributed to better understanding growth changes and clinical outcomes. The use of 3D dental and craniofacial imaging in dentistry requires validate image analysis methods for improved diagnosis, treatment planning, navigation and assessment of treatment response. Volumetric 3D images, such as cone-beam computed tomography, can now be superimposed by voxels, surfaces or landmarks. Regardless of the image modality or the software tools, the concepts of regions or points of reference affect all quantitative of qualitative assessments. This study reviews current state of the art in 3D image analysis including 3D superimpositions relative to the cranial base and different regional superimpositions, the development of open source and commercial tools for 3D analysis, how this technology has increased clinical research collaborations from centres all around the globe, some insight on how to incorporate artificial intelligence for big data analysis and progress towards personalized orthodontics.

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess as primary action mechanism the inhibition of cyclooxygenases (COX-1, COX-2, and COX-3), thus producing a decreasing prostaglandin synthesis. This study was designed to evaluate whether the antinociception induced by NSAIDs could be modulated by clomipramine or risperidone using a chemical model of inflammatory acute visceral pain, the abdominal acetic acid induced a writhing test in mice. Dose-response curves, intraperitoneal, or intrathecal for the antinociceptive activity displayed by ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol were analyzed in order to obtain the ED50 of each drug. Pretreatment of mice with either clomipramine or risperidone, increased antinociceptive potency of ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol, expressed by a decrease in the values of antinociceptive ED50. The results that were obtained are in line with those where the inhibition of COXs provides a justification for most of the pharmacological actions. Nevertheless, several findings suggest other molecular mechanisms, among which may be mentioned, L-selecting shedding; inhibition of i-NOS; inhibition of NF-Kappa B; suppression metaloproteinasas; inhibition of ß2 integrin activation; activation of α2 -adrenoceptor; increase of IL-1ß; upregulation IL-6. In conclusion, the data generated in this study demonstrated that risperidone and clomipramine, separately, increase antinociceptive potency of NSAIDs in a chemical model of inflammatory acute visceral tonic pain.

Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients.

BACKGROUND: It is unclear whether fatigue is a consequence or a predictive trait of disease worsening. OBJECTIVE: To investigate the predictive value of fatigue toward conversion to confirmed moderate-severe disability in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We retrospectively selected from the Comprehensive Longitudinal Investigations in MS at the Brigham and Women's Hospital (CLIMB) study cohort RRMS patients who converted to confirmed (⩾2 years) Expanded Disability Status Scale (EDSS) score ⩾3 within a follow-up period ⩾3 years. We contrasted the Modified Fatigue Impact Scale (MFIS) score of 33 converters, obtained at least 1 year before conversion to EDSS ⩾3, with that of 33 non-converter RRMS patients matched for baseline characteristics. RESULTS: Total MFIS score was higher in converter versus non-converter MS patients (median 37 vs 13; p < 0.0001). EDSS and Center for Epidemiological Studies Depression scale (CES-D) scores were also higher in the converters (median EDSS 1.5 vs 0, p < 0.0001; median CES-D 30 vs 24, p < 0.0001) and were both associated with MFIS score (EDSS: rho = 0.42, p = 0.0005; CES-D: rho = 0.72, p < 0.0001). After adjusting for EDSS and CES-D in multivariate analysis, MFIS remained a significant predictor of subsequent conversion to confirmed EDSS ⩾3. CONCLUSION: Fatigue is a promising indicator of risk for conversion to confirmed moderate-severe disability in RRMS patients.

[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. / Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio.

BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.

BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Antinociceptive synergism of gabapentin and nortriptyline in mice with partial sciatic nerve ligation.

BACKGROUND AND METHODS: Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis. RESULTS: Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED50 of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1 ratio of their ED50, had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively. CONCLUSION: The data showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alternative that can be used for neuropathic pain management.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

BACKGROUND: Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. RESULTS: The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. CONCLUSION: These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

ShapeAXI: Shape Analysis Explainability and Interpretability.

ShapeAXI represents a cutting-edge framework for shape analysis that leverages a multi-view approach, capturing 3D objects from diverse viewpoints and subsequently analyzing them via 2D Convolutional Neural Networks (CNNs). We implement an automatic N-fold cross-validation process and aggregate the results across all folds. This ensures insightful explainability heat-maps for each class across every shape, enhancing interpretability and contributing to a more nuanced understanding of the underlying phenomena. We demonstrate the versatility of ShapeAXI through two targeted classification experiments. The first experiment categorizes condyles into healthy and degenerative states. The second, more intricate experiment, engages with shapes extracted from CBCT scans of cleft patients, efficiently classifying them into four severity classes. This innovative application not only aligns with existing medical research but also opens new avenues for specialized cleft patient analysis, holding considerable promise for both scientific exploration and clinical practice. The rich insights derived from ShapeAXI's explainability images reinforce existing knowledge and provide a platform for fresh discovery in the fields of condyle assessment and cleft patient severity classification. As a versatile and interpretative tool, ShapeAXI sets a new benchmark in 3D object interpretation and classification, and its groundbreaking approach hopes to make significant contributions to research and practical applications across various domains. ShapeAXI is available in our GitHub repository https://github.com/DCBIA-OrthoLab/ShapeAXI.

Isobolographic analysis in mice of the interaction of gabapentin and nortriptyline in relieving orofacial pain.

AIMS: To evaluate the nature of the antinociceptive interaction of systemic administration of a combination of the anticonvulsant gabapentin with the antidepressant nortriptyline, by isobolographic analysis in the formalin orofacial pain test of mice. METHODS: The study was carried out in 168 male CF-1 mice weighing 30 g, and the protocol was to test each drug (at dosages of 1, 3, 10, 30, and 100 mg/kg of gabapentin and 0.1, 1, 3, 10, and 30 mg/kg of nortriptyline; ip) alone and in combination. The isobolographic assay has two phases: phase 1 corresponds to the 5-minute period starting immediately after the formalin injection and reflects a tonic acute pain due to peripheral nociceptor sensitization; phase 2 is recorded as the 10-minute period starting 20 minutes after the formalin injection and reflects an inflammatory pain state. Results were analyzed by Student t test for independent means. RESULTS: Gabapentin was 1.61 times more potent in phase 2 than in phase 1, and nortriptyline 1.37 times more potent in phase 2 than in phase 1. The combination of both drugs was synergic, with an index of interaction of 0.134 and 0.148 for phase 1 and phase 2, respectively. Differences in the pharmacological profiles of gabapentin and nortriptyline could underlie the synergism of the two drugs. CONCLUSION: The findings of this study are important, because they are concordant with some clinical studies and also raise the possibility of potential clinical advantages of combining gabapentin and nortriptyline in pain management, since the low doses of the components may potentially have a lower incidence of adverse reactions.

Dmriprep: open-source diffusion MRI quality control framework with graphical user interface.

In the last decade, investigating white matter microstructure and connectivity via diffusion MRI (dmri) has become a crucial cornerstone in neuroimaging studies. However, even modern dmri sequences have inherently a low signal-to-noise ratio and long acquisition times, depending on the spatial resolution. Furthermore, many types of artifacts complicate the appropriate analysis of dmri, necessitating appropriate quality control (QC) procedures, including exclusion and/or correction of inappropriate/erroneous dmri data. Our group has been developing and promoting QC procedures and tools to the community to enable appropriate dmri analyses. Since its development in 2011, our DTIPrep QC tool has become a major tool due its ease of use and dmri QC performance. Over the years, novel developments in acquisition and artifact correction methods have led to a need to modernize DTIPrep. Here, we present a novel diffusion MRI analysis environment called dtiplayground with a fully redesigned and significantly enhanced QC module dmriprep, and its graphical user interface dmriprep-ui, building on in-house developed code, FSL and dipy. The user interface is designed to be a unified, user friendly tool for thorough QC of dMRI data.Artifacts addressed by dmriprep include eddy-currents, head motion, bed vibration and pulsation, venetian blind artifacts, slice-wise and gradient-wise intensity inconsistencies, and susceptibility artifacts. It further provides an user interface for visual QC of gradients and automated tractography. In summary, our work presents a novel open-source framework for modern comprehensive dmri QC.