Environmental health of water bodies from a Brazilian Amazon Metropolis based on a conventional and metagenomic approach.

AIMS: The present study aimed to use a conventional and metagenomic approach to investigate the microbiological diversity of water bodies in a network of drainage channels and rivers located in the central area of the city of Belém, northern Brazil, which is considered one of the largest cities in the Brazilian Amazon. METHODS AND RESULTS: In eight of the analyzed points, both bacterial and viral microbiological indicators of environmental contamination-physical-chemical and metals-were assessed. The bacterial resistance genes, drug resistance mechanisms, and viral viability in the environment were also assessed. A total of 473 families of bacteria and 83 families of viruses were identified. Based on the analysis of metals, the levels of three metals (Cd, Fe, and Mn) were found to be above the recommended acceptable level by local legislation. The levels of the following three physicochemical parameters were also higher than recommended: biochemical oxygen demand, dissolved oxygen, and turbidity. Sixty-three bacterial resistance genes that conferred resistance to 13 different classes of antimicrobials were identified. Further, five mechanisms of antimicrobial resistance were identified and viral viability in the environment was confirmed. CONCLUSIONS: Intense human actions combined with a lack of public policies and poor environmental education of the population cause environmental degradation, especially in water bodies. Thus, urgent interventions are warranted to restore the quality of this precious and scarce asset worldwide.

Effect of seasonality and estuarine waters on the phytoplankton of the Guamá River (Belém, Amazon, Brazil).

This study aimed to analyze the application of the Phytoplankton Community Index-PCI and Functional Groups-FG in determining the water quality of the Guamá River (Pará, Amazônia, Brazil). Samplings occurred monthly for analyses of phytoplankton and physical and chemical parameters, for two years, at the station where water was collected for human supply consumption. Seasonality influenced electrical conductivity, total suspended solids, dissolved oxygen, transparency, winds, true color, and N-ammoniacal. The ebb tide showed high turbidity and suspended solids. The density varied seasonally with the highest values occurring in September and December (61.1 ind mL-1 and 60.2 ind mL-1, respectively). Chlorophyll-a was more elevated in December (21.0 ± 4.7 µg L-1) and chlorophyll-c higher in relation to clorophyll- b indicated the dominance of diatoms. Functional Group P prevailed in the study months. Through the PCI índex the waters of Guamá River varied from reasonable to excellent and the TSI ranged from oligo to mesotrophic. The use of Functional Groups proved to be a promising tool in the determination of water quality since it covered the most abundant species in the Environment, but the PCI is not adequate to characterize Amazonian white-waters rivers, which have diatoms as the leading dominant group.

Perceptions of medical students towards the role of histology and embryology during curricular review.

BACKGROUND: The continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology. METHODS: Medical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum. RESULTS: Four hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes. CONCLUSIONS: Our study contributes to the debate about the evolution of medical curriculum. Gathering the medical students' perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.

Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication.

Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013-2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain-Barret syndrome. We previously showed that the conjugate gallic acid-Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH2)-is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.

Sacroiliac joint beyond sacroiliitis-further insights and old concepts on magnetic resonance imaging.

The sacroiliac joint (SIJ) is an amphiarthrosis composed of a posterior syndesmosis and an anterior cartilaginous portion, with limited yet present mobility. Its main function is to transmit the load from the axial skeleton to the lower limbs and vice-versa; it is susceptible to early mechanical and degenerative changes which are much more common than inflammatory sacroiliitis. Magnetic resonance imaging (MRI) has increasingly been used to evaluate these changes, and while subchondral bone marrow edema (BME) is a common finding related to both, care must be taken when applying the ASAS research MRI definition for sacroiliitis without considering lesion BME topography, size and depth, concomitant structural damage and, of course, the clinical picture. In this review, we will discuss the anatomy and biomechanics of the SIJ, the noninflammatory causes of SIJ subchondral BME, and how these concepts combined can be used to increase our diagnostic confidence.

Osteochondral lesions of the talar dome: an up-to-date approach to multimodality imaging and surgical techniques.

Osteochondral lesions (OCLs) of the talar dome consist of a multifactorial pathology of the articular cartilage and subchondral bone and can result in persistent ankle pain and osteoarthritis (OA). Along with a physical examination and clinical history, an imaging evaluation plays a pivotal role in the diagnosis of these lesions and is fundamental for making treatment decisions and determining prognosis by providing information regarding the size, location, and cartilage and subchondral bone statuses as well as associated lesions and degenerative changes. Multiple surgical techniques for OCLs of the talar dome have been developed in recent decades, including cartilage repair, regeneration, and replacement strategies, and radiologists should be acquainted with their specific expected and abnormal postoperative imaging findings to better monitor the results and predict poor outcomes. The present article proposes a thorough review of the ankle joint anatomy and biomechanics, physiopathology, diagnosis, and treatment of OCLs of the talar dome, highlighting the radiological approach and imaging findings in both pre- and postoperative scenarios.

Adaptation of ED design layout during the COVID-19 pandemic: a national cross-sectional survey.

BACKGROUND: The aim was to describe the organisational changes in French EDs in response to the COVID-19 pandemic with regard to architectural constraints and compare with the recommendations of the various bodies concerning the structural adjustments to be made in this context. METHODS: As part of this cross-sectional study, all heads of emergency services or their deputies were contacted to complete an electronic survey. This was a standardised online questionnaire consisting of four parts: characteristics of the responding centre, creation of the COVID-19 zone and activation of the hospital's emergency operations plan, flow and circulation of patients and, finally, staff management. Each centre was classified according to its workload related to COVID-19 and its size (university hospital centre, high-capacity hospital centre and low-capacity hospital centre). The main endpoint was the frequency of implementation of international guidelines for ED organisation. RESULTS: Between 11 May and 20 June 2020, 57 French EDs completed the online questionnaire and were included in the analysis. Twenty-eight EDs were able to separate patient flows into two zones: high and low viral density (n=28/57, 49.1%). Of the centres included, 52.6% set up a specific triage area for patients with suspected COVID-19 (n=30/57). Whereas, in 15 of the EDs (26.3%), the architecture made it impossible to increase the surface area of the ED. CONCLUSION: All EDs have adapted, but many of the changes recommended for the organisation of ED could not be implemented. ED architecture constrains adaptive capacities in the context of COVID-19.

Multimodality Imaging of Foreign Bodies: New Insights into Old Challenges.

Traumatic wounds and lacerations are a common reason for patients to present to emergency departments, with retained foreign bodies (FBs) accounting for 7%-15% of cases, particularly those involving the extremities. These retained materials result in a granulomatous tissue response known as an FB reaction, a pathologic attempt to isolate the FB from the host. The most common FB materials are glass, metal, and wood, but other compositions can also be found, such as plastic and animal-derived materials. Clinical history, physical examination, and wound exploration are essential in investigation of retained material but are not sufficient to exclude an FB, and additional investigation is required. Imaging evaluation is a useful tool to help depict and locate an FB, assess possible complications, and guide removal. Conventional radiography, the first-line method in this scenario, is a widely available low-cost depiction method that has good sensitivity for depicting FBs. If the retained material is not depicted at conventional radiography, US can be performed. US is highly sensitive in depicting both radiolucent and radiopaque FBs in superficial locations. For deeper objects, CT may be necessary. MRI is the best imaging modality to delineate local soft-tissue and osseous complications. Retained FBs can result in early and delayed complications, with infection being the most frequent complication. To avoid preventable morbidities related to FBs, radiologists should be familiar with imaging findings and provide essential information to help the attending physician treat each patient. Online supplemental material is available for this article. ©RSNA, 2020.

Radiologic Manifestations of Musculoskeletal Sarcoidosis.

PURPOSE OF REVIEW: The purpose of this review article is to present the spectrum of abnormalities and multi-modality imaging evaluations in patients with musculoskeletal sarcoidosis. RECENT FINDINGS: The articular manifestations of sarcoidosis are difficult to distinguish from those of the other inflammatory and degenerative arthropathies, and the muscular lesions in sarcoidosis are generally clinically silent and therefore often missed. Magnetic resonance imaging has shown these manifestations to be very common in active sarcoidosis, and should thus be included in the screening if musculoskeletal sarcoidosis is suspected. The clinician should consider magnetic resonance imaging for the evaluation of patients with sarcoidosis who have unexplained osteoarticular complaints if standard radiographs are negative. Furthermore, radiologists should include sarcoidosis in the differential diagnosis of musculoskeletal disease detected at magnetic resonance imaging in the appropriate clinical setting.

Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by primary infiltration of bone marrow and excessive production of abnormal immunoglobulin. This disease is the second most common hematologic malignancy (after lymphoma), and its spectrum of characteristic features are widely known by the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Traditionally, the diagnosis and treatment of MM have been triggered by clear end-organ damage. However, owing to recently introduced treatment options that can extend patient survival and the increasing recognition of biomarkers that can be used to identify patients at high risk of progression to active disease, the diagnostic criteria have been revised. Bone disease is one of the most prominent features of MM, and imaging has an important role in diagnosis and follow-up, with each whole-body imaging modality having different indications in distinct disease situations. Skeletal survey has been the standard imaging procedure used during the past decade, but it should no longer be used unless it is the only option. Whole-body low-dose CT is a reasonable and cost-effective initial imaging approach. Whole-body MRI is the most sensitive technique for detecting bone involvement and assessing painful complications. PET/CT is the best tool for evaluating treatment response. The importance of radiologists has increased in this scenario. Therefore, to properly assist hematologists and improve the care of patients with MM, it is essential that radiologists know the updated diagnostic criteria for MM, indications for and limitations of each imaging option, and recommendations for follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Bioacumulation of trace elements in the crab Ucides cordatus (Linnaeus, 1763) from the macrotidal mangrove coast region of the Brazilian Amazon.

In this study, trace element concentrations were measured in chelipod and gill samples of the crab U. cordatus by induced coupled plasma optical emission spectrometry (ICP OES). The element average concentrations between the structures were statistically compared. Gill concentrations of Cu and Zn were higher in female crabs, while in chelipods, Pb concentrations were higher in males. The concentration of Zn in crabs from Curuçá City were higher than the recommended by health agencies, but the provisional tolerable daily intake value (PTDI), for Zn and Cu, showed only 10 and 23% contribution, respectively. The bioaccumulation factor was higher than 1 for Cu (gills and chelipods) and Zn (only for chelipods), which suggests bioaccumulation for these elements. Further metallomic and oxidative stress analyses are suggested, in order to evaluate possible protein and/or enzymatic biomarkers of toxicity.

Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department.

Importance: An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. Objective: To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones. Design, Settings, and Participants: International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death. Exposures: Measurement of qSOFA, SOFA, and SIRS. Main Outcomes and Measures: In-hospital mortality. Results: Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P < .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis. Conclusions and Relevance: Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting. Trial Registration: clinicaltrials.gov Identifier: NCT02738164.

A conjugate of the lytic peptide Hecate and gallic acid: structure, activity against cervical cancer, and toxicity.

Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.

Caffeine inhibits hepatitis C virus replication in vitro.

Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-5'C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH-1. Caffeine efficiently inhibited HCV replication in a dose-dependent manner at non-cytotoxic concentrations and demonstrated an IC50 value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.

Evaluation of the effect of supplementing fermented milk with quinoa flour on probiotic activity.

In this work, we investigated the effect of supplementing fermented milk with quinoa flour as an option to increase probiotic activity during fermented milk production and storage. Fermented milk products were produced with increasing concentrations of quinoa flour (0, 1, 2, or 3g/100g) and submitted to the following analyses at 1, 14, and 28 d of refrigerated storage: postacidification, bacterial viability, resistance of probiotics to simulated gastrointestinal (GI) conditions, and adhesion of probiotics to Caco-2 cells in vitro. The kinetics of acidification were measured during the fermentation process. The time to reach maximum acidification rate, time to reach pH 5.0, and time to reach pH 4.6 (end of fermentation) were similar for all treatments. Adding quinoa flour had no effect on fermentation time; however, it did contribute to postacidification of the fermented milk during storage. Quinoa flour did not affect counts of Bifidobacterium animalis ssp. lactis BB-12 or Lactobacillus acidophilus La-5 during storage, it did not protect the probiotic strains during simulated GI transit, and it did not have a positive effect on the adhesion of probiotic bacteria to Caco-2 cells in vitro. Additionally, the adhesion of strains to Caco-2 cells decreased during refrigerated storage of fermented milk. Although the addition of up to 3% quinoa flour had a neutral effect on probiotic activity, its incorporation to fermented milk can be recommended because it is an ingredient with high nutritive value, which may increase the appeal of the product to consumers.

Finite element analysis of provisional structures of implant-supported complete prostheses.

The use of provisional resin implant-supported complete dentures is a fast and safe procedure to restore mastication and esthetics of patients soon after surgery and during the adaptation phase to the new denture. This study assessed stress distribution of provisional implant-supported fixed dentures and the all-on-4 concept using self-curing acrylic resin (Tempron) and bis-acrylic resin (Luxatemp) to simulate functional loads through the three-dimensional finite element method. Solidworks software was used to build three-dimensional models using acrylic resin (Tempron, model A) and bis-acrylic resin (Luxatemp, model B) for denture captions. Two loading patterns were applied on each model: (1) right unilateral axial loading of 150 N on the occlusal surfaces of posterior teeth and (2) oblique loading vector of 150 N at 45°. The results showed that higher stress was found on the bone crest below oblique load application with a maximum value of 187.57 MPa on model A and 167.45 MPa on model B. It was concluded that model B improved stress distribution on the denture compared with model A.

[Quality of hospital emergency department discharge summaries to general practitioners]. / Qualité des courriers de sortie des consultants des urgences de l'hôpital aux médecins généralistes.

INTRODUCTION: Improvement of the quality of exchanges between primary care and hospital medicine is a major challenge for continuity of care in France. The objective of this study was to evaluate the quality of communication of information to general practitioners concerning the management of patients attending a university hospital emergency department. MATERIALS AND METHODS: This retrospective study was based on the medical charts of 602 patients consulting the Angers university hospital emergency department, using an evaluation grid of discharge summaries associated with a survey of general practitioners, by postal questionnaire, concerning the time to reception, the content and the mode of transmission of these discharge summaries. RESULTS: Strong points were patient identification, the visit date, the presence of complementary imaging investigation results and the presence of a conclusion. Weak points and aspects requiring improvement were identification of the emergency physician, indicated in only 48% of discharge summaries, notification of the previous treatment absent in 93% of cases, the treatment received in the emergency department and on discharge was absent or incomplete in 78% and 92% of discharge summaries, respectively, follow-up advice was provided in 36% of cases and the information given to the patient was indicated in 16% of discharge summaries. The time to reception of discharge summaries was < or = 48 hours in 8.5% of cases and < or = one week in 99% of cases. General practitioners were satisfied with the content (90%) and the form (84%) of emergency department discharge summaries; however, they would like to receive better structured and more concise discharge summaries, preferably sent by secure e-mail for 62% of them. CONCLUSION: Standardization of discharge summaries, adapted to the general practitioner's practice, given directly to the patient and sent by secure e-mail appear to be one of the main targets for improvement of the quality of management to be introduced in hospital emergency departments.

Transcranial Magnetic Stimulation to Treat Neuropathic Pain: A Bibliometric Analysis.

Neuropathic pain is caused by a lesion or disease of the somatosensory system and is one of the most incapacitating pain types, representing a significant non-met medical need. Due to the increase in research in the field and since innovative therapeutic strategies are required, namely in intractable neuropathic pain, neurostimulation has been used. Within this approach, transcranial magnetic stimulation (TMS) that uses a transient magnetic field to produce electrical currents over the cortex emerges as a popular method in the literature. Since this is an area in expansion and due to the putative role of TMS, we performed a bibliometric analysis in Scopus with the primary objective of identifying the scientific production related to the use of TMS to manage neuropathic pain. The research had no restrictions, and the analysis focused on the characteristics of the literature retrieved, scientific collaboration and main research topics from inception to 6 July 2023. A total of 474 articles were collected. A biggest co-occurrence between the terms "neuropathic pain" and "transcranial magnetic stimulation" was obtained. The journal "Clinical Neurophysiology" leads the Top 5 most productive sources. The United States is the most productive country, with 50% of US documents being "review articles", followed by France, with 56% of French documents being "original articles". Lefaucheur, JP and Saitoh, Y are the two most influential authors. The most frequent type of document was "original article". Most of the studies (34%) that identified the neuropathic pain type focused on traumatic neuropathic pain, although a large proportion (38%) did not report the neuropathic pain type. This study allows us to provide a general overview of the field of TMS application for neuropathic pain and is useful for establishing future directions of research in this field.

Case report: First case of fungemia caused by Papiliotrema laurentii in a patient with SARS-CoV-2 infection.

Previously considered saprobe and non-pathogenic, the fungus Papiliotrema laurentii (formerly known as Cryptococcus laurentii), is rarely associated with human infection. Nevertheless, there has been an increase in reported infections by non-neoformans cryptococci. After a literature search on the Cochrane Library, LILACS, SciELO, MEDLINE, PubMed, and PMC (PubMed Central) databases, we conclude that this is the first case report of fungemia and probable meningitis caused by Papiliotrema laurentii in a previously immunocompetent host with associated COVID-19.

MRI of Pediatric Foot and Ankle Conditions.

The increase in competitive sports practice among children and lack of ionizing radiation have resulted in a higher demand for MRI examinations. MRI of the children skeleton has some particularities that can lead orthopedists, pediatricians, and radiologists to diagnostic errors. The foot and ankle have several bones with abundant radiolucent and high signal intensity cartilage in several ossification centers, apophysis and physis, that can make this interpretation even harder. The present revision aims to show, how to differentiate between normal developmental findings and anatomic variants from pathologic conditions, whether mechanical, inflammatory, infectious, or neoplastic.