Pain is a multidimensional experience with sensory-discriminative, affective-motivational, and cognitive-evaluative components. Pain aversiveness is one principal cause of suffering for patients with chronic pain, motivating research and drug development efforts to investigate and modulate neural activity in the brain’s circuits encoding pain unpleasantness. Here, we review progress in understanding the organization of emotion, motivation, cognition, and descending modulation circuits for pain perception. We describe the molecularly defined neuron types that collectively shape pain multidimensionality and its aversive quality. We also review how pharmacological, stimulation, neurofeedback, surgical, and cognitive-behavioral interventions alter activity in these circuits to relieve chronic pain.

Chronic pain conditions present in various forms, yet all feature symptomatic impairments in physical, mental, and social domains. Rather than assessing symptoms as manifestations of illness, we used them to develop a chronic pain classification system. A cohort of real-world treatment-seeking patients completed a multidimensional patient-reported registry as part of a routine initial evaluation in a multidisciplinary academic pain clinic. We applied hierarchical clustering on a training subset of 11,448 patients using nine pain-agnostic symptoms. We then validated a three-cluster solution reflecting a graded scale of severity across all symptoms and eight independent pain-specific measures in additional subsets of 3817 and 1273 patients. Negative affect–related factors were key determinants of cluster assignment. The smallest subset included follow-up assessments that were predicted by baseline cluster assignment. Findings provide a cost-effective classification system that promises to improve clinical care and alleviate suffering by providing putative markers for personalized diagnosis and prognosis.

Antibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4'-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.

is a common fungal pathogen in humans. Biofilm formation is an important virulence factor of infections. We investigated the ability of the plant-derived cannabidiol (CBD) to inhibit the formation and removal of fungal biofilms. Further, we evaluated its mode of action. Our findings demonstrate that CBD exerts pronounced time-dependent inhibitory effects on biofilm formation as well as disruption of mature biofilm at a concentration range below minimal inhibitory and fungicidal concentrations. CBD acts at several levels. It modifies the architecture of fungal biofilm by reducing its thickness and exopolysaccharide (EPS) production accompanied by downregulation of genes involved in EPS synthesis. It alters the fungal morphology that correlated with upregulation of yeast-associated genes and downregulation of hyphae-specific genes. Importantly, it represses the expression of virulence-associated genes. In addition, CBD increases ROS production, reduces the intracellular ATP levels, induces mitochondrial membrane hyperpolarization, modifies the cell wall, and increases the plasma membrane permeability. In conclusion, we propose that CBD exerts its activity towards biofilm through a multi-target mode of action, which differs from common antimycotic agents, and thus can be explored for further development as an alternative treatment against fungal infections.

BACKGROUND: Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals.

OBJECTIVE: To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated.

METHODS: c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.).

RESULTS: Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part.

CONCLUSION: HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep-wake cycle by engaging the hypothalamus.

A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase IIα catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.

To examine the effects of expectations for pain relief on the objective and subjective outcome of chronic orofacial pain (OFP) treatment. Sixty individuals referred to the Orofacial Pain Clinic at the Hebrew University-Hadassah School of Dental Medicine between 2015 and 2017 with OFP reported their expectation for pain relief upon initial consultation. They were also interviewed by telephone treatment and asked to recall their expectations, referred to as "recalled expectations" (RE). Correlations between RE and treatment success were calculated from pain diaries, and from subjective pain improvement rates (PIR) reported by the patients. 21 males (35.0%) and 39 females (65%), mean age of 46.90 ± 15.77 years and mean pain duration of 49.07 ± 51.95 months participated in the study. All participants rated their expectations as "10" on a 0 to 10 scale during their first visit. RE did not correlate with diary ratings, ( = 0.773) but inversely correlated (-0.3) with PIR ( = 0.020) treatment outcomes. Expectations for pain relief, reported as 10 on a 0-10 scale during the first appointment, may reflect the patient's for complete relief of their pain rather than their . Clinicians should therefore be aware of the need for clear communication and wording when examining for expectations. Inverse correlation between recalled expectations and subjective outcome may be due to the nature of recalled expectations when patients already knew their treatment outcomes, and may be explained by the concept of cognitive dissonance.

Pain is a common symptom in endodontic conditions, but differential diagnostic procedures are often needed to exclude other pain origins. Thus, general dentists and endodontists need to be aware of alternative painful orofacial conditions and be able to identify them. The new International Classification of Orofacial Pain (ICOP) is the first comprehensive classification that uniquely deals with orofacial pain. The ICOP is a hierarchical classification modeled on the International Classification of Headache Disorders and covers pain in dentoalveolar and anatomically related tissues, muscle pain, temporomandibular joint pain, neuropathic pain affecting cranial nerves, pain resembling primary headaches, and idiopathic pain in the orofacial region. A description of each condition is given, and structured diagnostic criteria for each condition are proposed based on research data when available. This narrative review aims (1) to give an overview and brief explanation of the ICOP system, (2) to describe and give examples of how it can be of use to general dentists and endodontists with special attention to differential diagnosis of tooth pain, and (3) to highlight how endodontic research can contribute to validation and improvement of the classification. A comparison to other classification and diagnostic systems is also included.

The endogenous amide -Oleoylglycine (OlGly) and its analog -Oleoylalanine (OlAla), have been shown to interfere with the affective and somatic responses to acute naloxone-precipitated MWD in male rats. Here we evaluated the potential of a single dose (5 mg/kg, ip) which alleviates withdrawal of these endogenous fatty acid amides to modify tolerance to anti-nociception, hyperthermia, and suppression of locomotion produced by morphine in male Sprague-Dawley rats. Although rats did develop tolerance to the hypolocomotor and analgesic effects of morphine, they did not develop tolerance to the hyperthermic effects of this substance. Administration of neither OlGly nor OlAla interfered with the establishment of morphine tolerance, nor did they modify behavioral responses elicited by morphine on any trial. These results suggest that the effects of OlGly and OlAla on opiate dependence may be limited to naloxone-precipitated withdrawal effects.

Nausea and vomiting are the most distressing symptoms reported by oncology patients undergoing anticancer treatment. With the currently available treatments, vomiting and especially nausea remain problematic, highlighting the need for alternative treatments. Here we review and evidence for the effectiveness of the nonpsychoactive cannabinoid cannabidiol (CBD) in managing nausea and vomiting. In addition, we also review the evidence for CBD's acidic precursor, cannabidiolic acid (CBDA), and a methylated version of CBDA (CBDA-ME) in these phenomena. Finally, we explore the potential role of CBD in the treatment of cannabinoid hyperemesis syndrome. CBD has demonstrated efficacy in reducing nausea and vomiting, with CBDA and CBDA-ME being more potent. The data suggest a need for these compounds to be evaluated in clinical trials for their ability to reduce nausea and/or vomiting.

IMPORTANCE: Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms.

OBJECTIVE: To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo, Brazil. Participants were enrolled between June 12 and November 12, 2020. A total of 214 health care professionals were recruited and assessed for eligibility, and 120 participants were randomized in a 1:1 ratio by a researcher who was not directly involved with data collection.

INTERVENTIONS: Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days.

MAIN OUTCOMES AND MEASURES: The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel.

RESULTS: A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery.

CONCLUSIONS AND RELEVANCE: In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04504877.

Interest in CBG (cannabigerol) has been growing in the past few years, due to its anti-inflammatory properties and other therapeutic benefits. Here we report the synthesis of three new CBG derivatives (HUM-223, HUM-233 and HUM-234) and show them to possess anti-inflammatory and analgesic properties. In addition, unlike CBG, HUM-234 also prevents obesity in mice fed a high-fat diet (HFD). The metabolic state of the treated mice on HFD is significantly better than that of vehicle-treated mice, and their liver slices show significantly less steatosis than untreated HFD or CBG-treated ones from HFD mice. We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.

Precise lead localization is crucial for an optimal clinical outcome of subthalamic nucleus (STN) deep brain stimulation (DBS) treatment in patients with Parkinson's disease (PD). Currently, anatomical measures, as well as invasive intraoperative electrophysiological recordings, are used to locate DBS electrodes. The objective of this study was to find an alternative electrophysiology tool for STN DBS lead localization. Sixty-one postoperative electrophysiology recording sessions were obtained from 17 DBS-treated patients with PD. An intraoperative physiological method automatically detected STN borders and subregions. Postoperative EEG cortical activity was measured, while STN low frequency stimulation (LFS) was applied to different areas inside and outside the STN. Machine learning models were used to differentiate stimulation locations, based on EEG analysis of engineered features. A machine learning algorithm identified the top 25 evoked response potentials (ERPs), engineered features that can differentiate inside and outside STN stimulation locations as well as within STN stimulation locations. Evoked responses in the medial and ipsilateral fronto-central areas were found to be most significant for predicting the location of STN stimulation. Two-class linear support vector machine (SVM) predicted the inside (dorso-lateral region, DLR, and ventro-medial region, VMR) vs. outside [zona incerta, ZI, STN stimulation classification with an accuracy of 0.98 and 0.82 for ZI vs. VMR and ZI vs. DLR, respectively, and an accuracy of 0.77 for the within STN (DLR vs. VMR)]. Multiclass linear SVM predicted all areas with an accuracy of 0.82 for the outside and within STN stimulation locations (ZI vs. DLR vs. VMR). Electroencephalogram biomarkers can use low-frequency STN stimulation to localize STN DBS electrodes to ZI, DLR, and VMR STN subregions. These models can be used for both intraoperative electrode localization and postoperative stimulation programming sessions, and have a potential to improve STN DBS clinical outcomes.

The safety of switching between generic products of antiseizure medications (ASMs) continues to be a hot topic in epilepsy management. The main reason for concern relates to the uncertainty on whether, and when, two generics found to be bioequivalent to the same brand (reference) product are bioequivalent to each other, and the risk of a switch between generics resulting in clinically significant changes in plasma ASM concentrations. This article addresses these concerns by discussing the distinction between bioequivalence and statistical testing for significant difference, the importance of intra-subject variability in interpreting bioequivalence studies, the stricter regulatory bioequivalence requirements applicable to narrow-therapeutic-index (NTI) drugs, and the extent by which currently available generic products of ASMs comply with such criteria. Data for 117 oral generic products of second-generation ASMs approved in Europe by the centralized, mutual recognition or decentralized procedure were analyzed based on a review of publicly accessible regulatory assessment reports. The analysis showed that for 99% of generic products assessed (after exclusion of gabapentin products), the 90% confidence intervals (90% CIs) of geometric mean ratios (test/reference) for AUC (area under the drug concentration vs time curve) were narrow and wholly contained within the acceptance interval (90%-111%) applied to NTI drugs. Intra-subject variability for AUC was <10% for 53 (88%) of the 60 products for which this measure was reported. Many gabapentin generics showed broader, 90% CIs for bioequivalence estimates, and greater intra-subject variability, compared with generics of other ASMs. When interpreted within the context of other available data, these results suggest that any risk of non-bioequivalence between these individual generic products is small, and that switches across these products are not likely to result in clinically relevant changes in plasma drug exposure. The potential for variability in exposure when switching across generics is likely to be greatest for gabapentin.

Neurons and satellite glial cells (SGCs) in sensory ganglia maintain bidirectional communications that are believed to be largely mediated by chemical messengers. Nerve injury leads to SGC activation, which was proposed to be mediated by nitric oxide (NO) released from active neurons, but evidence for this is lacking. Here we tested the idea that increased neuronal firing is a major factor in NO release. We activated neurons in isolated dorsal root and trigeminal ganglia from mice with capsaicin (5 µM), which acts on transient receptor potential vanilloid type 1 (TRPV1) channels in small neurons. We found that capsaicin induced SGC activation, as assayed by glial fibrillary acidic protein (GFAP) upregulation, and an NO-donor had a similar effect. Incubating the ganglia in capsaicin in the presence of the NO-synthase inhibitor L-NAME (100 µM) prevented the GFAP upregulation. We also found that capsaicin caused an increase in SGC-SGC coupling, which was shown previously to accompany SGC activation. To test the contribution of ATP to the actions of capsaicin, we incubated the ganglia with capsaicin in the presence of P2 purinergic receptor inhibitor suramin (100 µM), which prevented the capsaicin-induced GFAP upregulation. Size analysis indicated that although capsaicin acts mainly on small neurons, SGCs around neurons of all sizes were affected by capsaicin, suggesting a spread of signals from small neurons to neighboring cells. We conclude that neuronal excitation leads to NO release, which induces SGCs activation. It appears that ATP participates in NO's action, possibly by interaction with TRPV1 channels.

Astroglia are neural cells, heterogeneous in form and function, which act as supportive elements of the central nervous system; astrocytes contribute to all aspects of neural functions in health and disease. Through their highly ramified processes, astrocytes form close physical contacts with synapses and blood vessels, and are integrated into functional syncytia by gap junctions. Astrocytes interact among themselves and with other cells types (e.g., neurons, microglia, blood vessel cells) by an elaborate repertoire of chemical messengers and receptors; astrocytes also influence neural plasticity and synaptic transmission through maintaining homeostasis of neurotransmitters, K buffering, synaptic isolation and control over synaptogenesis and synaptic elimination. Satellite glial cells (SGCs) are the most abundant glial cells in sensory ganglia, and are believed to play major roles in sensory functions, but so far research into SGCs attracted relatively little attention. In this review we compare SGCs to astrocytes with the purpose of using the vast knowledge on astrocytes to explore new aspects of SGCs. We survey the main properties of these two cells types and highlight similarities and differences between them. We conclude that despite the much greater diversity in morphology and signaling mechanisms of astrocytes, there are some parallels between them and SGCs. Both types serve as boundary cells, separating different compartments in the nervous system, but much more needs to be learned on this aspect of SGCs. Astrocytes and SGCs employ chemical messengers and calcium waves for intercellular signaling, but their significance is still poorly understood for both cell types. Both types undergo major changes under pathological conditions, which have a protective function, but an also contribute to disease, and chronic pain in particular. The knowledge obtained on astrocytes is likely to benefit future research on SGCs.

No disease-modifying therapy is currently available for Parkinson's disease (PD), the second most common neurodegenerative disease. The long nonmotor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By using a mutant α-synuclein selective-overexpression mouse model of prodromal PD, we identified a cell-autonomous selective Kv4 channelopathy in dorsal motor nucleus of the vagus (DMV) neurons. This functional remodeling of intact DMV neurons leads to impaired pacemaker function in vitro and in vivo, which, in turn, reduces gastrointestinal motility, a common early symptom of prodromal PD. We identify a chain of events from α-synuclein via a biophysical dysfunction of a specific neuronal population to a clinically relevant prodromal symptom. These findings will facilitate the rational design of clinical biomarkers to identify people at risk for developing PD.

OBJECTIVES: To investigate the association of psychiatric disorders with (1) caries experience, (2) periodontal status, and (3) metabolic syndrome (MetS) components.

METHOD AND MATERIALS: This 7-year cross-sectional study retrospectively analyzed the medical records of 504 individuals aged 18 to 90 years who attended the student dental clinic. Collected data included: demographics, smoking habits, systolic and diastolic blood pressures, pulse, waist circumference, full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), maximal pocket probing depth (PPD), average and maximal radiographic bone loss (RBL), the sum of the number of decayed (D), missing (M), and filled (F) teeth (DMFT score), and presence of MetS components, consequences and related conditions including diabetes, hypertension, hyperlipidemia, ischemic heart disease, heart failure, s/p stroke, and cancer.

RESULTS: 68 (13.5%) had psychiatric disorders with an average age of 53.42 ± 15.71 years. Psychiatric disorders were positively associated with smoking (P = .008), smoking pack-years (P = .004), DMFT score (P = .005), and negatively associated with hypertension (P = .046). Psychiatric disorders had no statistically significant associations with all periodontal indices studied and with other components of MetS. Following multivariate analysis, psychiatric disorders retained a statistically significant positive association with smoking (odds ratio [OR] and 95% confidence interval [CI] = 2.24 [1.28 to 3.92]) and with DMFT (OR and 95% CI = 1.08 [1.02 to 1.14]), and a statistically significant negative association with hypertension (OR and 95% CI = 0.46 [0.25 to 0.84]).

CONCLUSIONS: Psychiatric disorders were positively associated with smoking and caries experience but not with periodontal status and metabolic morbidity. Communication between dental and medical professionals is needed to address the higher smoking consumption and caries morbidity in psychiatric patients. (Quintessence Int 2021;52:516-526; doi: 10.3290/j.qi.b1044091).

Conflicting results have been published regarding the associations between dental status and hypertension. This study aims to explore whether or not hypertension is associated with dental status among young to middle-aged adults. To that end, data from the Dental, Oral, Medical Epidemiological (DOME) study were analyzed. The DOME is a cross-sectional records-based study that combines comprehensive socio-demographic, medical, and dental databases of a nationally representative sample of military personnel. Included were 132,529 subjects aged 18-50 years who attended the military dental clinics for one year. The prevalence of hypertension in the study population was 2.5% (3363/132,529). Following multivariate analysis, the associations between hypertension and dental parameters were lost and hypertension retained a positive association with obesity (Odds ratio (OR) = 4.2 (3.7-4.9)), diabetes mellitus (OR = 4.0 (2.9-5.7)), birth country of Western Europe vs. Israeli birth country (OR = 1.9 (1.6-2.2)), male sex (OR = 1.9 (1.6-2.2)), cardiovascular disease (OR = 1.9 (1.6-2.3)), presence of fatty liver (OR = 1.8 (1.5-2.3)), the birth country Asia vs. Israeli birth country (OR = 1.6 (1.1-2.3)), smoking (OR = 1.2 (1.05-1.4)), and older age (OR = 1.05 (1.04-1.06)). Further analysis among an age-, smoking- and sex matched sub-population ( = 13,452) also revealed that the dental parameters lost their statistically significant association with hypertension following multivariate analysis, and hypertension retained a positive association with diabetes (OR = 4.08 (2.6-6.1)), obesity (OR = 2.7 (2.4-3.2)), birth country of Western Europe vs. Israel (OR = 1.9 (1.6-2.3)), cardiovascular disease (OR = 1.8 (1.5-2.2)), fatty liver (OR = 1.7 (1.3-2.3)), high school education vs. academic (OR = 1.5 (1.3-1.8)), and low socio-economic status (SES) vs. high (OR = 1.4 (1.03-1.8)). We analyzed the associations between C-reactive protein (CRP) and dental parameters and combined the statistically significant variables to create a dental inflammation score (DIS). This crated a final model with the appropriate weights written as follows: DIS = (periodontal disease × 14) + (the number of teeth that required crowns × 11) + (missing teeth × 75). The mean DIS was 10.106 ± 25.184, and it exhibited a weak positive association with hypertension in the univariate analysis (OR = 1.011 (1.010-1.012)). Receiver operating characteristic (ROC) analysis of the DIS against hypertension produced a failed area under the curve (AUC) result (0.57 (0.56-0.58)). Moreover, the DIS also lost its statistical significance association with hypertension following multivariate analysis. We conclude that hypertension had no statistically significant nor clinically significant association with dental status. The study established a profile of the "patient vulnerable to hypertension", which retained well-known risk factors for hypertension such as older age, male sex, smoking, diabetes, obesity, and fatty liver but not dental parameters.

Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are classified as autoimmune diseases, where the body's own immune response causes it to attack the host tissues, as if the latter were antigens. RA is the most common autoimmune disease that affects joints. The clinical diagnosis of RA is based on the history and examination, integrated with laboratory tests including blood tests on inflammatory markers, serology, and imaging. There are no diagnostic criteria, but there are classification criteria. SLE affects most major organ systems in the body. The diagnosis of SLE relies on the constellation of characteristic symptoms, signs, and laboratory findings in the appropriate clinical context and after excluding other reasonable diagnoses. Epidemiologically, both conditions show a definitive female predilection. The focus of this review article is epidemiology, and the major clinical features with an emphasis on the orofacial manifestations. The relevant clinical points for the dental practitioner area summarized.