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OBJECTIVE: To validate the ankle-specific Pediatric Arthritis Ultrasound Scoring System (PAUSS-ankle) in children with juvenile idiopathic arthritis (JIA). METHODS: Patients with a diagnosis of JIA prospectively underwent a standard clinical assessment and musculoskeletal ultrasound (MSUS) of one or both ankles. B-mode and Power-Doppler mode MSUS images were acquired and scored according to the PAUSS-ankle protocol. A subset of patients received a contrast-enhanced MRI (ceMRI) of the affected ankle. ceMRI scoring for synovitis was performed according to the Rheumatoid Arthritis MRI System (RAMRIS). Test characteristics of the PAUSS-ankle scores were evaluated with ceMRI as reference. Associations between the findings on physical examination, PAUSS-ankle, and RAMRIS were investigated. RESULTS: Thirty-two patients with JIA contributed 63 MSUS and 15 ceMRIs of the ankles. The PAUSS-ankle total B-mode score had a moderate correlation with physical examination findings (correlation (r)=0.43, p < 0.001). The PAUSS-ankle B-mode score ≥1 exhibited a sensitivity of 79 % and specificity of 100 %, demonstrating excellent diagnostic accuracy with an area under the curve (AUC)= 0.89 (confidence intervals, CI, 0.78-1.00) while clinical assessment had a sensitivity of 57 % and AUC= 0.71 (CI: 0.58-0.85). The PAUSS-ankle B-mode score had significant strong correlations (r = 0.68-0.90, p < 0.005) with the RAMRIS for the assessment of disease severity for each joint area and the ankle joint as a whole. CONCLUSION: Our findings demonstrate excellent diagnostic accuracy of the PAUSS-ankle in detecting the presence and severity of ankle synovitis when compared to ceMRI. The PAUSS-ankle holds significant promise as an accurate measurement that may complement current clinical standards.

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Biopreservation is a powerful strategy to prolong the shelf life of food products by applying naturally occurring microorganisms and/or their metabolites. Current food trends emphasise the need to develop alternatives for chemical or thermal preservation methods. In this line, different fermentation starters from table olives present the potential to control spoilage or pathogen-occurring microorganism in table olives storage. One of the most interesting family used as biopreservative culture is Lactobacillaceae and it has also been used in combination with yeasts as olive fermentation starter. Lactic acid bacteria, from Lactobacillaceae family, are characterised by the production of bacteriocins, proteins with the potential for preserving food by changing the organisation of the membrane of spoilage microorganisms. These bacteriocins-producing bacteria can be directly inoculated, although nanosystem technology is the most promising incorporation strategy. In table olives, the most commonly used starters are Lactiplantibacillus plantarum, Lactiplantibacillus pentosus, Saccharomyces cerevisiae, Wickerhamomyces anomalus, among others. These strains with biopreservation characteristics, inoculated alone or in mixed cultures, ensure food safety by conferring the product added value and prolonging product shelf life. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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BACKGROUND: The proportion of older people living with HIV (PLWH) has increased. Non-communicable diseases occur earlier in PLWH than in the general population. OBJECTIVE: The goal of this study was to estimate the prevalence of comorbidities in PLWH and cancer in a tertiary referral center in Mexico City. MATERIAL AND METHODS: In this retrospective study, we included PLWH > 40 years with a history of cancer, coming to Instituto Nacional de Cancerologia from 2010 through 2019. All patients needed to be on antiretrovirals for at least six months. Data collected included cancer type, comorbidities, frequency of polypharmacy, FRAX score and 10-year cardiovascular risk. Patients were evaluated for depression with the Beck Inventory Depression-II Scale. Variables associated to multimorbidity (2 or more comorbidities) were evaluated. RESULTS: Of 125 patients, 69% had at least one comorbidity; 32% had ≥ 2. Common comorbidities were dyslipidemia (54%), hypertension (19%), obesity (14%) and Diabetes (12%). In patients ≥ 50 years, 29 (62%) already undergone a densitometry and 9 (31%) had osteoporosis; 56 depression questionnaires were used: 30% had mild-to-severe depression. Being ≥ 50 years was associated with multimorbidity (aOR 2.57 (1.18-5.58), p = 0.017). CONCLUSIONS: A high prevalence of multimorbidity and poor screening of bone disease and mental health is reported in patients with PLWH and cancer. A holistic approach to the PLWH in the Infectious Diseases consultation is needed to improve the detection and management of non-communicable diseases, to go beyond viral suppression and towards an improved quality of life.

INTRODUCCIÓN: La proporción de personas mayores que viven con VIH (PVVIH) va en aumento, y las enfermedades no transmisibles ocurren antes en PVVIH comparado con la población general. OBJETIVO: El objetivo de este estudio fue estimar la prevalencia de las comorbilidades en PVVIH con cáncer de un centro de tercer nivel de la Ciudad de México. MÉTODOS: Este estudio retrospectivo incluyó todas las PVVIH > 40 años con cáncer, que acudieron al Instituto Nacional de Cancerología entre 2010 y 2019). Se incluyeron datos sobre el tipo de cáncer, comorbilidades y polifarmacia. Se calcularon la puntuación FRAX, el riesgo cardiovascular a 10 años, y se aplicó un cuestionario para evaluar depresión (Beck Inventory Depression-II Scale). RESULTADOS: De 125 pacientes, 69% tenía al menos una comorbilidad; 32% tenía ≥ 2. Las comorbilidades más comunes fueron dislipidemia (54%), hipertensión (19%), obesidad (14%) y diabetes (12%). En pacientes ≥ 50 años, 29% tenía una densitometría osea; 31% tenía osteoporosis. Se aplicaron 56 cuestionarios: 30% tenía algún grado de depresión. Tener ≥ 50 años se asoció con multimorbilidad (aOR 2.57, 1.18-5.58), p = 0.017. CONCLUSIONES: Se reporta una alta prevalencia de multimorbilidad en PVVIH y cancer, con pobre escrutinio de enfermedad ósea y salud mental. Se requiere un enfoque holístico para las PVVIH en la consulta de infectología, para mejorar el manejo de las enfermedades no transmisibles, yendo más alla de la supresión virológica.

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INTRODUCTION: The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies. METHODS: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation. PRIMARY ENDPOINT: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores). RESULTS: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation. CONCLUSION: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

Severe asthma occurs when asthma symptoms remain uncontrolled despite optimised treatment. In many low-middle income countries, and in some countries in the Middle East, Asia, Latin America and the Arab Gulf, the management and treatment of patients with severe asthma remain poor, with many patients having unscheduled hospital visits or admission, and use of steroids for a prolonged period. Mepolizumab is an injectable monoclonal antibody approved as an add-on treatment for severe asthma in patients ≥ 6 years of age. In clinical trials, mepolizumab has demonstrated reductions in the risk of clinically significant exacerbations (CSE; an asthma exacerbation that requires systemic corticosteroids and/or an emergency room visit and/or hospitalisation) and the need for oral corticosteroid (OCS) treatment in patients with severe asthma by reducing inflammation caused by eosinophil (a type of white blood cell) production. The Nucala Effectiveness Study (NEST) was performed to observe the effectiveness of mepolizumab in people with severe asthma in Colombia, Chile, India, Turkey, Saudi Arabia, United Arab Emirates, Kuwait, Oman and Qatar. The frequency of CSEs and other outcomes was compared 12 months pre- and post-mepolizumab initiation. Post-initiation, the risk of CSEs was significantly reduced by 76% (p < 0.001), and 72% of patients had no CSEs. Fewer patients were dependent on OCS, with 36.1% of patients not using OCS at all, and fewer patients were hospitalised. Lung function and asthma control also improved. NEST shows that mepolizumab could benefit people with severe asthma living in countries where disease-related burden and OCS use remain high.

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Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage-induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4-fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and growth of a charismatic mega moth (Anthereae polyphemus). This work suggests that changes to the phytochemical landscape of forests, mediated by invasive outbreak insects, are likely to negatively impact native insects, with potential repercussions for community diversity and ecosystem function across expansive scales.

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An increasing number of food companies are voluntarily adopting environmental policies and sustainability initiatives to tackle climate change. The aims of this study were to analyse the presence of environmental labels on table olive products, to explore consumer perceptions of these companies' environmental commitment and initiatives, and to evaluate the influence of these messages on purchasing decisions. For this purpose, a market study was conducted in different hypermarkets and supermarkets in Spain, and an online survey was submitted to consumers (n = 227). The results show that environmental claims and/or certifications related to sustainability do not appear on table olive products, despite most of the companies that produce and/or market table olives having adopted environmental and sustainability policies and commitments (34.3% have their environmental policy published on their website). More than 85% of consumers positively value these companies' sustainability commitments and consider environmental initiatives to be very important. As a sector of consumers pays close attention to environmental commitments, it would be interesting for table olive companies to identify their sustainability policies on their products' labelling to, thus, facilitate pro-environmental consumer purchase choices. These results could help the food industry develop the best strategies to publicise their social and environmental policies and commitments.

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PURPOSE: Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia. METHODS: We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021. RESULTS: Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n = 74) and acute myeloid leukemia (n = 68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated. CONCLUSIONS: In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality.

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Establishing humane endpoints to minimize animal suffering in studies on snake venom toxicity and antivenom potency tests is crucial. Our findings reveal that Swiss mice exhibit early temperature drop following exposure to different snake venoms and combinations of venoms and antivenoms, predicting later mortality. Evaluating temperature we can identify within 3 h post-inoculation, the animals that will not survive in a period of 48 h. Implementing temperature as a criterion would significantly reduce animal suffering in these studies without compromising the outcomes.

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PURPOSE: The gastrocnemius venous system presents different anatomical variants. There have been described four locations of myofascial trigger points (MTrPs) in this muscle. However, no studies have analyzed the coincidence between vessels and MTrPs present in the gastrocnemius. Therefore, the main objective was to study the anatomical variability of the venous system by ultrasound and its coincidence with the location of the MTrPs. METHODS: A total of 100 lower limbs were studied. The gastrocnemius vessels were analyzed one by one by sector (medial, central, and lateral), quantifying the number of vessels, their distribution, and the coincidence with MTrPs. RESULTS: All muscle heads showed at least one vessel per section. A large variability was observed, from one to eight vessels per muscle head, with the most frequent number being three in the gastrocnemius medialis and two in the gastrocnemius lateralis. In all cases, the location of the vessels coincided with the MTrPs. CONCLUSIONS: The proximal gastrocnemius venous pattern is very variable between subjects in number of vessels and distribution, which has made it impossible to define a "safe" approach window for invasive procedures without ultrasound guidance. The coincidence between the clinical location of MTrPs of the gastrocnemius and the presence of vessels is total.

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Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins of the ABC transporter Ami-AliA/AliB oligopeptide permease. Exposure to these peptides alters pneumococcal phenotypes such as growth. Using a mutant in which a permease domain of the transporter was disrupted, by growth analysis and epifluorescence microscopy, we confirmed peptide uptake via the Ami permease and intracellular location in the pneumococcus. By RNA-sequencing we found that the peptides modulated expression of genes involved in metabolism, as pathways affected were mostly associated with energy or synthesis and transport of amino acids. Both peptides downregulated expression of genes involved in branched-chain amino acid metabolism and the Ami permease; and upregulated fatty acid biosynthesis genes but differed in their regulation of genes involved in purine and pyrimidine biosynthesis. The transcriptomic changes are consistent with growth suppression by peptide treatment. The peptides inhibited growth of pneumococcal isolates of serotypes 3, 8, 9N, 12F and 19A, currently prevalent in Switzerland, and caused no detectable toxic effect to primary human airway epithelial cells. We conclude that pneumococci take up K. pneumoniae peptides from the environment via binding and transport through the Ami permease. This changes gene expression resulting in altered phenotypes, particularly reduced growth.

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OBJECTIVE: Musculoskeletal ultrasound (MSUS) is widely used in adult rheumatology practice for diagnosis of arthritis and procedural guidance; however, it is not yet common practice in pediatric rheumatology. MSUS is advantageous to the pediatric population because it lacks radiation and eliminates need for sedation. This study aims to assess interest in, access to, and barriers to MSUS training in pediatric rheumatology fellowship programs in North America. METHODS: A survey was developed by pediatric rheumatology providers with experience in medical and/or MSUS education and distributed via REDCap anonymously in March 2022 (Supplementary Material). Eligible participants included current and recently graduated (<1 year) pediatric rheumatology fellows at a North American program. Descriptive statistics and bivariate analyses using design-based Pearson chi-squared tests were performed. RESULTS: Overall response rate was 78% (88/113), and 75% reported some form of MSUS training during fellowship. Only 36% indicated their program had a formal MSUS curriculum. Of those with MSUS training, 23% reported adult-only MSUS education. Eighty-four percent felt MSUS would be beneficial to their career. Major barriers to MSUS training included lack of MSUS-trained faculty, lack of time, and lack of hands-on MSUS sessions. Those who had access to MSUS training were significantly more interested in MSUS than those without (P = 0.0036). CONCLUSION: This study demonstrates that North American pediatric rheumatology fellows have a strong interest in learning MSUS, but they face significant challenges in accessing MSUS training (lack of MSUS-trained faculty, time, and access to hands-on training). MSUS should be incorporated into fellowship curriculum; however, implementation remains a challenge.

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Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic treatment, although there are cases related to failure of the deep brain stimulation system.

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INTRODUCTION: Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM and febrile neutropenia. METHODOLOGY: We included all patients with hematological malignancies (HM) who presented fever and severe neutropenia, admitted to an oncological tertiary care center in Mexico City for one year. RESULTS: Two hundred ninety-two episodes of fever and severe neutropenia were documented; 68 patients (23.2%) developed SS. Documented clinical infection was different between SS and non-SS patients (94.1% vs. 63.4%, p < 0.001); pneumonia was the most frequent infection (36.8% vs. 23.2%, p = 0.02). Also, in SS vs. non-SS, there were more positive cultures (69.1% vs. 38.4%, p < 0.001), higher frequency of Gram-negative bacteria (89.3% vs. 63.9%, p < 0.001), particularly Escherichia coli (68% vs. 44.2%) and Klebsiella spp. (23.4% vs. 15.1%). There were no differences when multidrug-resistant (MDR) microorganisms were compared. In the multivariate analysis, associated risk factors for SS were: prolonged neutropenia, a documented site of infection, and having received highly myelosuppressive chemotherapy. Risk factors for mortality at 30 days were: older patients, prolonged neutropenia, and SS. CONCLUSIONS: Severe and prolonged neutropenia was associated with SS development and mortality at 30 days. ICU management should be offered to all critically ill patients with HM if long-term survival of the underlying malignancy is expected.

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Many protein-protein interactions involve the binding of short protein segments to peptide-binding domains. Usually, such interactions require the recognition of linear motifs with variable conservation. The combination of highly conserved and more variable regions in the same ligands often contributes to the multispecificity of binding, a common property of enzymes and cell signaling proteins. Characterization of amino acid preferences of peptide-binding domains is important for the design of mediators of protein-protein interactions (PPIs). Computational methods are an efficient alternative to the often costly and cumbersome experimental techniques, enabling the design of potential mediators that can be later validated in downstream experiments. Here, we described a methodology using the Pepspec application of the Rosetta molecular modeling package to predict the amino acid preferences of peptide-binding domains. This methodology is useful when the structure of the receptor protein and the nature of the peptide ligand are both known or can be inferred. The methodology starts with a well-characterized anchor from the ligand, which is extended by randomly adding amino acid residues. The binding affinity of peptides generated this way is then evaluated by flexible-backbone peptide docking in order to select the peptides with the best predicted binding scores. These peptides are then used to calculate amino acid preferences and to optionally compute a position-weight matrix (PWM) that can be used in further studies. To illustrate the application of this methodology, we used the interaction between subunits of human interferon regulatory factor 5 (IRF5), previously known to be multispecific but globally guided by a short conserved motif called pLxIS. The estimated amino acid preferences were consistent with previous knowledge about the IRF5 binding surface. Positions occupied by phosphorylatable serine residues exhibited a high frequency of aspartate and glutamate, likely because their negatively charged side chains are similar to phosphoserine.

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Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against H2O2 oxidative stress and in rd10 mice. PIC-OCT possesses a better ADME profile than RSV. In response to H2O2, 661W cells pretreated with PIC-OCT preserved cell viability in more than 38% of cells by significantly promoting SIRT1 nuclear translocation, preserving NAD+/NADH ratio, and suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing PARP1 nuclear expression, and preventing AIF nuclear translocation. In rd10 mice, PIC-OCT inhibited PAR-polymer formation, increased SIRT1 expression, significantly reduced TUNEL-positive cells in the retinal outer nuclear layer, preserved ERGs, and enhanced light chamber activity (all p values < 0.05). Our findings corroborate that PIC-OCT protects photoreceptors by modulating the SIRT1/PARP1 axis in models of retinal degeneration.

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In the original publication [...].

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OBJECTIVE: We undertook this study to validate the Pediatric Arthritis Ultrasound Scoring System for the knee joint (PAUSS-knee) in children with juvenile idiopathic arthritis (JIA). METHODS: Children with JIA were enrolled to prospectively receive a musculoskeletal ultrasound (MSUS) examination of the knee and a physical examination to determine presence/absence of clinical arthritis. MSUS images were scored using the PAUSS-knee, a semiquantitative MSUS scoring system (0-3, normal to severe) for B-mode and power Doppler mode. In addition to MSUS, a subset of participants also received magnetic resonance imaging (MRI) of the knee, which was scored according to the combined Juvenile Arthritis MRI Scoring (JAMRIS) system. Spearman's correlations (rs ) were used to calculate associations between variables. Test characteristics of the PAUSS-knee were calculated with MRI as the reference standard. Inflammatory biomarkers were assessed in synovial fluid from involved knees. RESULTS: Eighty children with JIA contributed 112 MSUSs and 25 MRIs of the knee. Of the knees, 41% (n = 46) had clinical evidence of arthritis. The B-mode PAUSS-knee score moderately correlated with clinically determined arthritis (rs = 0.54, P < 0.001) and strongly correlated with the JAMRIS score (rs = 0.75, P < 0.001). Compared with MRI, the area under the curve for the B-mode PAUSS-knee was 0.92. For a cutoff of >1, the B-mode PAUSS-knee had a sensitivity of 83% and specificity of 82%. Biomarker analysis indicates that interleukin-2R levels correlate with PAUSS score. CONCLUSION: Our data indicate that the PAUSS-knee has excellent accuracy for the diagnosis of arthritis when compared with MRI. The PAUSS-knee has the potential to effectively inform JIA medical decision-making in real time.

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Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.

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The term “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA) describes a variety of autoimmune conditions triggered by exposure to substances with adjuvant activity. We present the case of a patient with a history of biopolymer infiltration in both glutes, who years later experienced progressive weakness and pain in the lower limbs, myalgias, cramps, and progressive functional impotence following a mild COVID-19 infection. Laboratory test results were not consistent with any autoimmune disease. Physical examination revealed diffuse bilateral subcutaneous nodules. After an extensive etiological study, a gluteal biopsy was performed, which showed findings compatible with sclerosing lipogranuloma. Our patient required treatment with high-dose glucocorticoids and showed significant improvement in symptoms during long-term follow-up. We suggest the role of COVID-19 infection as a possible trigger for ASIA, as it has already been described as a trigger for several other autoimmune diseases.(AU)

El término «síndrome autoinmune/inflamatorio inducido por adyuvantes» (ASIA) describe una variedad de condiciones autoinmunes desencadenadas por la exposición a sustancias con actividad adyuvante. Presentamos el caso de una paciente con antecedentes de infiltración de biopolímeros en ambos glúteos que años más tarde experimentó debilidad progresiva y dolor en extremidades inferiores, mialgias, calambres e impotencia funcional progresiva después de una infección leve por COVID-19. Los resultados de los análisis de laboratorio no sugerían enfermedad autoinmune. El examen físico reveló nódulos subcutáneos difusos bilaterales. Después de un extenso estudio etiológico, se realizó una biopsia glútea, la cual mostró hallazgos compatibles con lipogranuloma esclerosante. La paciente requirió tratamiento con glucocorticoides a dosis altas y mostró una mejora significativa en los síntomas durante el seguimiento a largo plazo. Sugerimos el papel de la infección por COVID-19 como posible desencadenante de ASIA, ya que se ha descrito como desencadenante de otras enfermedades autoinmunes.(AU)

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Tetrahydrocurcumin, the most abundant curcumin transformation product in biological systems, can potentially be a new alternative therapeutic agent with improved anti-inflammatory activity and higher bioavailability than curcumin. In this article, we describe the synthesis and evaluation of the anti-inflammatory activities of tetrahydrocurcumin derivatives. Eleven tetrahydrocurcumin derivatives were synthesized via Steglich esterification on both sides of the phenolic rings of tetrahydrocurcumin with the aim of improving the anti-inflammatory activity of this compound. We showed that tetrahydrocurcumin (2) inhibited TNF-α and IL-6 production but not PGE2 production. Three tetrahydrocurcumin derivatives inhibited TNF-α production, five inhibited IL-6 production, and three inhibited PGE2 production. The structure-activity relationship analysis suggested that two factors could contribute to the biological activities of these compounds: the presence or absence of planarity and their structural differences. Among the tetrahydrocurcumin derivatives, cyclic compound 13 was the most active in terms of TNF-α production, showing even better activity than tetrahydrocurcumin. Acyclic compound 11 was the most effective in terms of IL-6 production and retained the same effect as tetrahydrocurcumin. Moreover, acyclic compound 12 was the most active in terms of PGE2 production, displaying better inhibition than tetrahydrocurcumin. A 3D-QSAR analysis suggested that the anti-inflammatory activities of tetrahydrocurcumin derivatives could be increased by adding bulky groups at the ends of compounds 2, 11, and 12.

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