Long-term association between water intake and kidney function in a population at high cardiovascular risk.

OBJECTIVES: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). METHODS: Three-year prospective analysis conducted in 1986 older adults (aged 55-75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. RESULTS: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: ß: 1.4 ml/min/1.73 m2; 95%CI: 0.5-2.3, ß: 1.0; 95%CI: 0.1-2.0, respectively). CONCLUSIONS: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. TRIAL REGISTRATION: ISRCTN89898870. Retrospectively registered on 24 July 2014.

Poorly Controlled New-Onset Diabetes Mellitus and Other Atypical Signs as an Early Sign of Pancreatic Adenocarcinoma.

A 50-year-old man presented with poorly controlled new-onset diabetes mellitus. Six months after diagnosis, episodes of intense abdominal pain with vomiting appeared. Abdominal CT revealed signs of acute pancreatitis with structural changes in the pseudocysts. In the absence of biliary lithiasis or a toxic etiology of acute pancreatitis, the patient progressed unfavorably with increased abdominal pain and fever. Control imaging tests (two and 10 months later) showed the evolution of phlegmonous/necrotic collections, together with portal vein thrombosis and splenomegaly. Given the suggestive signs of possible occult malignancy, such as portal thrombosis, histological analysis of the ascitic fluid revealed a pancreatic adenocarcinoma. Despite the initiation of chemotherapy, the patient died 12 months after diagnosis.

An Acute Infection due to Hepatitis E in the Context of a Patient with Rituximab and Methotrexate Therapy.

Background: This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an anti-synthetase syndrome and treatment with methotrexate and rituximab. Case description: The patient arrived at the Emergency Department with epigastric pain, vomiting and dark urine. Initial examination revealed signs of inflammation and hepatic dysfunction. Subsequent laboratory tests and imaging confirmed acute hepatitis E infection in the context of recent initiation of rituximab therapy. Despite initial suspicion of pancreatitis, subsequent investigations ruled out pancreatic involvement. Treatment with ribavirin, along with supportive measures, led to significant clinical improvement with resolution of jaundice, ascites, and oedema. Conclusions: This case underscores the importance of considering hepatitis E in patients with autoimmune conditions, especially when initiating immunosuppressive therapies, a situation that is not well described in scientific literature and is increasingly common, necessitating proper recognition. LEARNING POINTS: Suspect hepatitis E virus infection in the presence of persistent liver failure of unknown cause.Recognise immunosuppression as a cause of increased risk of hepatitis E infection.Take into account the repercussions of immunosuppressive therapy such as rituximab regarding hepatitis E infections in immunocompromised patients.

A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells.

Cellular senescence is implicated in the occurrence and progression of multiple age-related disorders. In this context, the selective elimination of senescent cells, senolysis, has emerged as an effective therapeutic strategy. However, the heterogeneous senescent phenotype hinders the discovery of a universal and robust senescence biomarker that limits the effective of senolytic with off-target toxic effects. Therefore, the development of more selective strategies represents a promising approach to increase the specificity of senolytic therapy. In this study, we have developed an innovative nanodevice for the selective elimination of senescent cells (SCs) based on the specific enzymatic activity of the senescent secretome. The results revealed that when senescence is induced in proliferating WI-38 by ionizing radiation (IR), the cells secrete high levels of matrix metalloproteinase-3 (MMP-3). Based on this result, mesoporous silica nanoparticles (MSNs) were loaded with the senolytic navitoclax (Nav) and coated with a specific peptide which is substrate of MMP-3 (NPs(Nav)@MMP-3). Studies in cells confirmed the preferential release of cargo in IR-induced senescent cells compared to proliferating cells, depending on MMP-3 levels. Moreover, treatment with NPs(Nav)@MMP-3 induced a selective decrease in the viability of SCs as well as a protective effect on non-proliferating cells. These results demonstrate the potential use of NPs to develop enhanced senolytic therapies based on specific enzymatic activity in the senescent microenvironment, with potential clinical relevance. STATEMENT OF SIGNIFICANCE: The common ß-galactosidase activity has been exploited to develop nanoparticles for the selective elimination of senescent cells. However, the identification of new senescent biomarkers is a key factor for the development of improved strategies. In this scenario, we report for the first time the development of NPs targeting senescent cells based on specific enzymatic activity of the senescent secretome. We report a navitoclax-loaded nanodevice responsive to the matrix metalloproteinase-3 (MMP-3) associated with the senescent phenotype. Our nanosystem achieves the selective release of navitoclax in an MMP-3-dependent manner while limiting off-target effects on non-senescent cells. This opens the possibility of using nanoparticles able to detect an altered senescent environment and selectively release its content, thus enhancing the efficacy of senolytic therapies.

Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project.

This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.

Targeted Delivery of the Pan-Inflammasome Inhibitor MM01 as an Alternative Approach to Acute Lung Injury Therapy.

Acute lung injury (ALI) is a severe pulmonary disorder responsible for high percentage of mortality and morbidity in intensive care unit patients. Current treatments are ineffective, so the development of efficient and specific therapies is an unmet medical need. The activation of NLPR3 inflammasome during ALI produces the release of proinflammatory factors and pyroptosis, a proinflammatory form of cell death that contributes to lung damage spreading. Herein, it is demonstrated that modulating inflammasome activation through inhibition of ASC oligomerization by the recently described MM01 compound can be an alternative pharmacotherapy against ALI. Besides, the added efficacy of using a drug delivery nanosystem designed to target the inflamed lungs is determined. The MM01 drug is incorporated into mesoporous silica nanoparticles capped with a peptide (TNFR-MM01-MSNs) to target tumor necrosis factor receptor-1 (TNFR-1) to proinflammatory macrophages. The prepared nanoparticles can deliver the cargo in a controlled manner after the preferential uptake by proinflammatory macrophages and exhibit anti-inflammatory activity. Finally, the therapeutic effect of MM01 free or nanoparticulated to inhibit inflammatory response and lung injury is successfully demonstrated in lipopolysaccharide-mouse model of ALI. The results suggest the potential of pan-inflammasome inhibitors as candidates for ALI therapy and the use of nanoparticles for targeted lung delivery.

Increased ultra-processed food consumption is associated with worsening of cardiometabolic risk factors in adults with metabolic syndrome: Longitudinal analysis from a randomized trial.

BACKGROUND AND AIMS: The association between changes in ultra-processed food (UPF) consumption and cardiometabolic risk (CMR) factors remains understudied. We evaluated the association between changes in UPF consumption over 12 months of follow-up and changes in CMR factors in adults diagnosed with metabolic syndrome. METHODS: We analysed data from 5373 adults (aged 55-75 years) participating in the PREDIMED-Plus trial. Diet was evaluated at baseline, 6- and 12-month visits using a validated food frequency questionnaire, and UPF consumption (in grams/day and percentage of total daily dietary intake in grams) was categorized based on NOVA classification. We used mixed-effects linear models with repeated measurements at baseline, 6 and 12 months of follow-up to assess the associations between changes in UPF consumption and changes in CMR factors adjusting for sociodemographic and lifestyles variables. RESULTS: In multivariable-adjusted models, when comparing the highest versus the lowest quartile of UPF consumption, positive associations were found for several CMR factors: weight (kg, ß = 1.09; 95% confidence interval 0.91 to 1.26); BMI (kg/m2, ß = 0.39; 0.33 to 0.46); waist circumference (cm, ß = 1.03; 0.81 to 1.26); diastolic blood pressure (mm Hg, ß = 0.67; 0.29 to 1.06); fasting blood glucose (mg/dl, ß = 1.66; 0.61 to 2.70); HbA1c (%, ß = 0.04; 0.01 to 0.07); triglycerides (mg/dl, ß = 6.79; 3.66 to 9.91) and triglycerides and glucose index (ß = 0.06; 0.04 to 0.08). CONCLUSIONS: Higher UPF consumption was associated with adverse evolution in objectively measured CMR factors after 12 months of follow-up in adults with metabolic syndrome. Further research is needed to explore whether these changes persist for longer periods.

Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome.

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, ß: -0.64 ml/min/1.73 m2; 95% CI: -1.21 to -0.08 and NEAP, ß: -0.56 ml/min/1.73 m2; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome.

Dualplex lateral flow assay for simultaneous scopolamine and "cannibal drug" detection based on receptor-gated mesoporous nanoparticles.

We report herein the design of a strip-based rapid test utilizing bio-inspired hybrid nanomaterials for the in situ and at site detection of the drug scopolamine (SCP) using a smartphone for readout, allowing SCP identification in diluted saliva down to 40 nM in less than 15 min. For this purpose, we prepared a nanosensor based on mesoporous silica nanoparticles loaded with a fluorescent reporter (rhodamine B) and functionalized with bethanechol, a potent agonist of recombinant human muscarinic acetylcholine receptor M2 (M2-AChR). M2-AChR interaction with the anchored bethanechol derivative leads to capping of the pores. The sensing mechanism relies on binding of SCP to M2-AChR resulting in pore opening and delivery of the entrapped rhodamine B reporter. Moreover, the material was incorporated into strips for lateral-flow assays coupled to smartphone readout, giving fast response time, good selectivity, and exceptional sensitivity. In an attempt to a mobile analytical test system for law enforcement services, we have also developed a dualplex lateral flow assay for SCP and 3,4-methylenedioxypyrovalerone (MDPV) also known as the so-called "cannibal drug".

Impact of COVID-19 pandemic on the PREDIMED-Plus randomized clinical trial: Effects on the interventions, participants follow-up, and adiposity.

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity. Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown. Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04]). Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity. Clinical trial registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870.

A Sensitive Nanosensor for the In Situ Detection of the Cannibal Drug.

A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4-methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B), and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently, causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM, and it is able to detect the MDPV drug both in saliva and blood plasma samples.

Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I-NBOMe.

This work reports the synthesis, characterization, and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I-NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5-HT2A receptor antibody. In the presence of 25I-NBOMe the capping antibody is displaced, leading to pore opening and rhodamine B release. This delivery was ascribed to 5-HT2A receptor antibody detachment from the surface due to its stronger coordination with 25I-NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 µm) and selective recognition of the 25I-NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA, and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I-NBOMe illicit drug in artificial saliva and in sweets.

A clinical trial comparing propofol versus propofol plus midazolam in diagnostic endoscopy of patients with a low anesthetic risk.

BACKGROUND AND OBJECTIVES: propofol and midazolam are two of the most commonly used sedatives in upper gastrointestinal endoscopy (UGE). The objective of this study was to evaluate these two sedation regimens administered to patients who underwent an UGE with regard to security, efficiency, quality of exploration and patient response. PATIENTS AND METHODS: a prospective, randomized and double-blind study was performed which included 83 patients between 18 and 80 years of age of a low anesthetic risk (ASA - American Society of Anesthesiologists- I-II) who underwent a diagnostic UGE. Patients were randomized to receive sedation with either placebo plus propofol (group A) or midazolam plus propofol (group B). RESULTS: in group A, 42 patients received a placebo bolus (saline solution) and on average up to 115 mg of propofol in boluses of 20 mg. In group B, 41 patients received 3 mg of midazolam and an average of up to 83 mg of propofol in boluses of 20 mg. There were no significant differences in the adverse effects observed in either group and all adverse events were treated conservatively. The patients in group B (midazolam plus propofol) entered the desired sedated state more quickly with no variation in the overall time of the exploration. The quality of the endoscopic evaluation was similar in both groups and the patients were equally satisfied regardless of the sedatives they received. CONCLUSIONS: the use of midazolam plus propofol as a sedative does not affect the overall exploration time, a lower dose of propofol can be used and it is as safe as administering propofol as a monotherapy while providing the same level of both exploration quality and patient approval.

Chromogenic and Fluorogenic Probes for the Detection of Illicit Drugs.

The consumption of illicit drugs has increased exponentially in recent years and has become a problem that worries both governments and international institutions. The rapid emergence of new compounds, their easy access, the low levels at which these substances are able to produce an effect, and their short time of permanence in the organism make it necessary to develop highly rapid, easy, sensitive, and selective methods for their detection. Currently, the most widely used methods for drug detection are based on techniques that require large measurement times, the use of sophisticated equipment, and qualified personnel. Chromo- and fluorogenic methods are an alternative to those classical procedures.

An OFF-ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo.

A naphthalimide-based two-photon probe (AHGa) for the detection of cell senescence is designed. The probe contains a naphthalimide core, an l-histidine methyl ester linker, and an acetylated galactose bonded to one of the aromatic nitrogen atoms of the l-histidine through a hydrolyzable N-glycosidic bond. Probe AHGa is transformed into AH in senescent cells resulting in an enhanced fluorescent emission intensity. In vivo detection of senescence is validated in mice bearing tumor xenografts treated with senescence-inducing chemotherapy.

Monitoring of emerging pollutants in Guadiamar River basin (South of Spain): analytical method, spatial distribution and environmental risk assessment.

Guadiamar River is located in the southwest of the Iberian Peninsula and connects two protected areas in the South of Spain: Sierra Morena and Doñana National Park. It is sited in an area affected by urban, industrial and agriculture sewage pollution and with tradition on intensive mining activities. Most of the studies performed in this area have been mainly focused on the presence of heavy metals and, until now, little is known about the occurrence of other contaminants such as emerging organic pollutants (EOPs). In this work, an analytical method has been optimized and validated for monitoring of forty-seven EOPs in surface water. The analytical method has been applied to study the distribution and environmental risk of these pollutants in Guadiamar River basin. The analytical method was based on solid-phase extraction and determination by liquid chromatography-triple quadrupole-tandem mass spectrometry. The 60 % of the target compounds were found in the analyzed samples. The highest concentrations were found for two plasticizers (bisphenol A and di(2-ethyhexyl)phthalate, mean concentration up to 930 ng/L) and two pharmaceutical compounds (caffeine (up to 623 ng/L) and salicylic acid (up to 318 ng/L)). This study allowed to evaluate the potential sources (industrial or urban) of the studied compounds and the spatial distribution of their concentrations along the river. Environmental risk assessment showed a major risk on the south of the river, mainly due to discharges of wastewater effluents.

ANALYSIS OF HOUSEHOLD MEDICINE CHESTS: A SIGNIFICANT LEARNING EXPERIENCE FOR NURSING STUDENTS / ANÁLISE DAS CAIXAS DE PRIMEIROS SOCORROS: ESTUDO REALIZADO EM ESTUDANTES DE ENFERMAGEM / ANALISIS DE LOS BOTIQUINES DOMÉSTICOS: UNA EXPERIENCIA DE APRENDIZAJE SIGNIFICATIVA PARA LOS ESTUDIANTES DE ENFERMERÍA

This is an observational, descriptive, cross-sectional study in which 214 nursing students from the University of Barcelona participated, in order to examine and assess the state and management of their household medicine chests. A semi-structured questionnaire specifically prepared for the study was used to collect data. The results showed that only 18.2% of the medicine chests examined contained all the recommended dressing materials and medicines. Inspection frequency was less than 12 months in 66.4% of the cases. A high percentage of the nursing students' homes stored medications in unsuitable locations and held on to them beyond their expiration dates or without their package. In contrast, knowledge about the use of the medications and the habit of recycling was better. Carrying out an analysis of their own medicine chest can help nursing students improve their competences in this area.

Estudo descritivo e transversal, no qual participaram 214 estudantes de enfermagem da Universidade de Barcelona com o objetivo de analisar e avaliar o estado e a gestão das caixas de primeiros socorros de suas casas. Um questionário semi-estruturado foi utilizado para coleta de dados. Os resultados mostram que apenas 18,2% dos kits examinados tinham todos os materiais de curativos e medicamentos recomendados. A frequência de revisão é inferior a doze meses em 66,4 % dos casos. Uma elevada porcentagem de residências familiares de estudantes de enfermagem continuvam mantendo os medicamentos armazenados em locais inadequados e vencidos, e fora de sua embalagem. Entretanto, se observou melhor conhecimento do uso dos medicamentos e do hábito de reciclagem. Realizar esta análise em sua própia caixa de primeiros socorros pode ajudar estudantes de enfermagem a melhorar suas habilidades sobre o tema.

Estudio observacional descriptivo y transversal en el que participaron 214 estudiantes de Enfermería de la Universidad de Barcelona con el objetivo de analizar y valorar el estado y la gestión de sus propios botiquines domésticos. Para la recogida de datos se utilizó un cuestionario semiestructurado de elaboración propia. Los resultados mostraron que solo el 18,2% de los botiquines examinados tenían todos los materiales de curas y medicamentos recomendados. La periodicidad de revisión fue inferior a 12 meses en un 66,4% de los casos. Un elevado porcentaje de los hogares de los estudiantes de enfermería seguían guardando los medicamentos en lugares inadecuados y los almacenan caducados y fuera de su envase. En contraste, el conocimiento del uso de los medicamentos y el hábito de reciclaje fue mejor. Realizar un análisis sobre su propio botiquín podría ayudar a los estudiantes de enfermería a mejorar sus competencias sobre el tema.

[Tuberculous arthritis of the temporomandibular joint caused by Mycobacterium bovis. A diagnostic conundrum]. / Artritis temporomandibular por Mycobacterium bovis. Un problema diagnóstico.

Infrequent variants of extrapulmonary tuberculosis pose a challenging public health problem because of the delay in their diagnosis and treatment. Joint involvement is usually encountered in major joints (hip, elbow, knee and ankle). Tuberculous involvement of the temporomandibular joint is extremely uncommon but must be considered in patients with pain, inflammation or joint stiffness not resolved with conventional treatment.