Exploring the association between erythema multiforme and HIV infection: some mechanisms and implications.

Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.

Situational Awareness in the Context of Clinical Practice.

In the context of clinical practice, situational awareness refers to conscious awareness (knowledge), which is a mental model of a given clinical situation in terms of its elements and the significance of their interrelation. Situational awareness (SA) facilitates clinical reasoning, diagnostic accuracy, and appropriate goal-directed performance, and it enables clinicians to immediately adapt treatment strategies in response to changes in clinical situational actualities and to modify the course of goal-directed activities accordingly. It also helps clinicians prepare future operational plans and procedures based on the projection of situational developments. SA, therefore, is an important prerequisite for safe clinical procedures. The purpose of this narrative review is to highlight certain cognitive and external (environmental) situational factors that influence the development of situational awareness. Understanding the dynamic, adaptive, and complex interactions between these factors may assist clinicians and managers of healthcare systems in developing methods aimed at facilitating the acquisition of accurate clinical situational awareness and, in turn, may bring about a reduction in the incidence of SA, diagnostic, and operational errors.

Tumour Genetic Heterogeneity in Relation to Oral Squamous Cell Carcinoma and Anti-Cancer Treatment.

Oral squamous cell carcinoma (SCC) represents more than 90% of all oral cancers and is the most frequent SCC of the head and neck region. It may affect any oral mucosal subsite but most frequently the tongue, followed by the floor of the mouth. The use of tobacco and betel nut, either smoked or chewed, and abuse of alcohol are the main risk factors for oral SCC. Oral SCC is characterized by considerable genetic heterogeneity and diversity, which together have a significant impact on the biological behaviour, clinical course, and response to treatment and on the generally poor prognosis of this carcinoma. Characterization of spatial and temporal tumour-specific molecular profiles and of person-specific resource availability and environmental and biological selective pressures could assist in personalizing anti-cancer treatment for individual patients, with the aim of improving treatment outcomes. In this narrative review, we discuss some of the events in cancer evolution and the functional significance of driver-mutations in carcinoma-related genes in general and elaborate on mechanisms mediating resistance to anti-cancer treatment.

Incidental Pathologic Findings from Orthodontic Pretreatment Panoramic Radiographs.

Panoramic radiography is frequently performed for new patients, follow-ups and treatment in progress. This enables dental clinicians to detect pathology, view important structures, and assess developing teeth. The objective of the study was to determine prevalence of incidental pathologic findings (IPFs) from orthodontic pretreatment panoramic radiographs at a university dental hospital. A retrospective cross-sectional review was conducted of pretreatment panoramic radiographs, using data collection sheets with predefined criteria. Demographic data and abnormalities (impacted teeth, widening of periodontal ligament, pulp stones, rotated teeth, missing teeth, unerupted teeth, crowding, spacing, supernumerary teeth, and retained deciduous teeth) were reviewed. SPSS 28.0 was used to analyze data with statistical tests set at a 5% significance level. Results: One hundred panoramic radiographs were analyzed with an age range of 7 to 57 years. The prevalence of IPFs was 38%. A total of 47 IPFs were detected with altered tooth morphology predominantly (n = 17). Most IPFs occurred in males (55.3%), with 44.7% in females. A total of 49.2% were in the maxilla and 50.8% in the mandible. This difference was statistically significant (p < 0.0475). Other abnormalities were detected in 76% of panoramic radiographs; 33 with IPFs and 43 without. A total of 134 other abnormalities detected showed predominantly impacted teeth (n = 49). Most of these abnormalities were in females (n = 77). Conclusions: The prevalence of IPFs was 38%, predominated by altered tooth morphology, idiopathic osteosclerosis, and periapical inflammatory lesions. Detection of IPFs from panoramic radiographs underscored the importance for clinicians to examine them for comprehensive diagnosis and treatment planning, especially in orthodontics.

Noma staging: a review.

Noma is a bacterial, non-communicable, grossly destructive and disfiguring necrotising oro-facial disease. It is rare, but occurs most commonly in chronically malnourished children with other debilitating illnesses, in remote, poverty-stricken communities, mainly in sub-Saharan Africa, and much more rarely in central Latin America and in parts of Asia. In South Africa and in Zimbabwe, noma is observed, again rarely, in immunosuppressed HIV-seropositive subjects. The World Health Organization (WHO) has classified noma into five sequential stages: stage 1, acute necrotising ulcerative gingivitis; stage 2, oedema; stage 3, gangrene; stage 4, scarring; stage 5, sequela. In the opinion of the authors, this WHO classification requires fundamental re-appraisal. The purpose of this viewpoint article is to highlight the weaknesses of this classification, and to propose a simpler, more logical and practical evidence-based staging of noma, which if used should improve the quality and value of future epidemiological data about noma.

Is noma a neglected/overlooked tropical disease?

Noma is a debilitating orofacial necrotizing bacterial disease that disproportionately affects impoverished malnourished persons, particularly young children, the vast majority of whom live in tropical and subtropical areas in sub-Saharan Africa. It has a very high mortality rate; causes significant physical and psychological morbidity, stigmatization and social discrimination; could be prevented, controlled and indeed eliminated by common public health interventions; and is overlooked with regard to public health awareness, in-depth scientific research activities and allocation of funding for prevention, treatment and research. According to the WHO, noma comprises five sequential 'stages': (1) necrotizing gingivitis, (2) edema, (3) gangrene, (4) scarring and (5) sequelae. This WHO staging of noma is contentious, leading to diagnostic confusion with misestimation of the number of noma cases reported in epidemiological studies. We therefore suggest a simpler, more practical and scientifically valid two-stage classification comprising only (1) acute noma and (2) arrested noma. Noma meets all the WHO criteria for classification as a neglected tropical disease (NTD). Most survivors of noma live with gross physical disfigurement and disability, and with impaired psychosocial functioning, so they are very often stigmatized and unjustifiably discriminated against. Owing to the paucity of evidence-based epidemiological data on noma, the relatively low number of people affected worldwide, and its apparently limited geographic distribution, noma does not yet feature on the WHO's list of NTDs, or on any global health agenda, and thus has not become a health priority for global action. We strongly support the inclusion of noma within the WHO list of NTDs. Without doubt this will increase the awareness of noma among healthcare providers and promote the systematic international accumulation and recording of data about noma.

Judgment and decision-making in clinical dentistry.

The development of clinical judgment and decision-making skills is complex, requiring clinicians-whether students, novices, or experienced practitioners-to correlate information from their own experience; from discussions with colleagues; from attending professional meetings, conferences and congresses; and from studying the current literature. Feedback from treated cases will consolidate retention in memory of the complexities and management of past cases, and the conversion of this knowledge base into daily clinical practice. The purpose of this narrative review is to discuss factors related to clinical judgment and decision-making in clinical dentistry and how both narrative, intuitive, evidence-based data-driven information and statistical approaches contribute to the global process of gaining clinical expertise.

Interrelations between pain, stress and executive functioning.

AIM: The purpose of this narrative review is to discuss the interrelations between pain, stress and executive functions. IMPLICATIONS FOR PRACTICE: Self-regulation, through executive functioning, exerts control over cognition, emotion and behaviour. The reciprocal neural functional connectivity between the prefrontal cortex and the limbic system allows for the integration of cognitive and emotional neural pathways and then for higher-order psychological processes (reasoning, judgement etc.) to generate goal-directed adaptive behaviours and to regulate responses to psychosocial stressors and pain signals. Impairment in cognitive executive functioning may result in poor regulation of stress-, pain- and emotion-related processing of information. Conversely, adverse emotion, pain and stress impair executive functioning. The characteristic of the feedback and feedforward neural connections (quantity and quality) between the prefrontal cortex and the limbic system determine adaptive behaviour, stress response and pain experience.

Selected pathobiological features and principles of pharmacological pain management.

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury-either peripheral or central-may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling. Therefore, optimal pain management for patients with chronic neuropathic pain requires a multimodal approach that comprises pharmacological and psychological interventions. Non-opioid analgesics (e.g., paracetamol, aspirin, or other non-steroidal anti-inflammatory drugs) are first-line agents used in the treatment of mild-to-moderate acute pain, while opioids of increasing potency are indicated for the treatment of persistent, moderate-to-severe inflammatory pain. N-methyl D-aspartate receptor antagonists, antidepressants, anticonvulsants, or a combination of these should be considered for the treatment of chronic neuropathic pain. This review discusses the various neural signals that mediate acute and chronic pain, as well as the general principles of pain management.

Pain: Persistent postsurgery and bone cancer-related pain.

The generation of neuropathic pain is a complex dynamic process. Factors involved include one or more dysregulated sensory neural pathways; dysregulated activity of specific neurotransmitters, synapses, receptors and cognitive and emotional neural circuits; and the balance between degenerative and regenerative neural events. Risk factors include age, sex, cognition, emotions, genetic polymorphism, previous or ongoing chronic pain conditions and the use of certain drugs. Intense pain experienced before, during and after surgery is a risk factor for the development of central sensitization with consequent persistent postsurgery neuropathic pain. Blockade of N-methyl-D-aspartate receptors with appropriate drugs during and immediately after surgery may prevent persistent postsurgical pain. Most cancers, but particularly malignant metastases in bone, can induce persistent pain. Local factors including direct damage to sensory nerve fibres, infiltration of nerve roots by cancer cells and algogenic biological agents within the microenvironment of the tumour bring about central sensitization of dorsal horn neurons, characterized by neurochemical reorganization with persistent cancer pain. In this article, the clinical features, pathogenesis and principles of management of persistent postsurgery pain and cancer pain are briefly discussed.

Review: allergic contact stomatitis.

Allergic contact stomatitis (ACS) is an oral mucosal immunoinflammatory disorder variably characterized clinically by erythematous plaques, vesiculation, ulceration, and/or hyperkeratosis and by pain, burning sensation, or itchiness. ACS is brought about by a T cell-mediated, delayed hypersensitivity immune reaction generated by a second or subsequent contact exposure of an allergen with the oral mucosa, in a genetically susceptible, sensitized subject. Lichenoid contact reaction is a variant of ACS brought about by direct contact with the oral mucosa of certain metals in dental restorations. The features of ACS are neither clinically nor histopathologically specific, so the diagnosis is usually presumptive and can only be confirmed by resolution of the inflammation after withdrawal or removal of the suspected causative allergen. When ACS is suspected but an allergen cannot be identified, patch testing is necessary. In persistent cases, topical corticosteroids are the treatment of choice, but for severe and extensive lesions, systemic corticosteroid and systemic antihistamines may be indicated. In this short review, we highlight the clinical, immunologic, and histopathological features of ACS, and provide some guidelines for diagnosis and management.

Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.

Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.

Epstein-Barr Virus and Its Association with Oral Hairy Leukoplakia: A Short Review.

In immunocompromised subjects, Epstein-Barr virus (EBV) infection of terminally differentiated oral keratinocytes may result in subclinical productive infection of the virus in the stratum spinosum and in the stratum granulosum with shedding of infectious virions into the oral fluid in the desquamating cells. In a minority of cases this productive infection with dysregulation of the cell cycle of terminally differentiated epithelial cells may manifest as oral hairy leukoplakia. This is a white, hyperkeratotic, benign lesion of low morbidity, affecting primarily the lateral border of the tongue. Factors that determine whether productive EBV replication within the oral epithelium will cause oral hairy leukoplakia include the fitness of local immune responses, the profile of EBV gene expression, and local environmental factors.