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Juvenile Temporal Arteritis (JTA) is a rare non-granulomatous vasculitis affecting the superficial temporal arteries, mostly in individuals under 45 years old. It is often misdiagnosed due to its benign nature and the absence of systemic symptoms. Herein, we present a case report of a 40-year-old woman who initially presented with painless nodules in the left temporal area. Following a biopsy, the patient developed additional nodules not only in the same temple but also on the contralateral side. Remarkably, these nodules underwent spontaneous regression without further treatment, highlighting the variability in JTA's course and distinctive response to intervention. In addition, through a systematic literature review of 43 case reports - 17 with bilateral involvement - we aimed to thoroughly understand the clinical and histopathological findings, diagnostic processes, and treatment responses in JTA, with an emphasis on cases with bilateral involvement. Findings indicate that JTA typically presents as painless or painful temporal nodules, rarely accompanied by other non-specific symptoms, making histopathological examination crucial for accurate diagnosis. Collectively, our work provides the most extensive account of bilateral JTA cases to date. It emphasizes the need for clinical awareness of this condition, contributes valuable data to the limited information available on this rare condition and serves as a stepping-stone for further inquiry. The main takeaway from this review is the variable nature of JTA and the importance of histopathology in diagnosis, which helps clinicians avoid excessive testing and overtreatment and anticipate possible spontaneous resolution.
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In Long COVID, dysfunction in the pituitary-adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary-adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.
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Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1ß production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1ß production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host's innate defence against pathogens while also limiting IL-1ß-dependent inflammatory episodes through immunometabolism modulation.
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Síndromes Periódicos Asociados a Criopirina , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Interleucina-18 , Síndromes Periódicos Asociados a Criopirina/genética , Sulfonamidas/farmacología , Interleucina-1beta/metabolismoRESUMEN
OBJECTIVE: To develop and validate a method for long-term (24-h) objective quantification of absence seizures in the EEG of patients with childhood absence epilepsy (CAE) in their real home environment using a wearable device (waEEG), comparing automatic detection methods with auditory recognition after seizure sonification. METHODS: The waEEG recording was acquired with two scalp electrodes. Automatic analysis was performed using previously validated software (Persyst® 14) and then fully reviewed by an experienced clinical neurophysiologist. The EEG data were converted into an audio file in waveform format with a 60-fold time compression factor. The sonified EEG was listened to by three inexperienced observers and the number of seizures and the processing time required for each data set were recorded blind to other data. Quantification of seizures from the patient diary was also assessed. RESULTS: Eleven waEEG recordings from seven CAE patients with an average age of 8.18 ± 1.60 years were included. No differences in the number of seizures were found between the recordings using automated methods and expert audio assessment, with significant correlations between methods (ρ > .89, p < .001) and between observers (ρ > .96, p < .001). For the entire data set, the audio assessment yielded a sensitivity of .830 and a precision of .841, resulting in an F1 score of .835. SIGNIFICANCE: Auditory waEEG seizure detection by lay medical personnel provided similar accuracy to post-processed automatic detection by an experienced clinical neurophysiologist, but in a less time-consuming procedure and without the need for specialized resources. Sonification of long-term EEG recordings in CAE provides a user-friendly and cost-effective clinical workflow for quantifying seizures in clinical practice, minimizing human and technical constraints.
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Epilepsia Tipo Ausencia , Dispositivos Electrónicos Vestibles , Humanos , Niño , Electroencefalografía/métodos , Convulsiones/diagnóstico , Epilepsia Tipo Ausencia/diagnóstico , ElectrodosRESUMEN
Resumo Enquadramento: As restrições impostas pela pandemia COVID-19 dificultaram a vivência dos processos de luto, contribuindo o desenvolvimento de processos patológicos de luto. Objetivo: Determinar a prevalência de luto patológico em familiares de pessoas vítimas mortais de COVID-19; Verificar se as estratégias de coping predizem o luto. Metodologia: Estudo observacional, descritivo-correlacional e transversal. A amostra não probabilística teve 86 participantes. Os dados foram explorados através de estatística descritiva e inferencial. Resultados: Cinquenta e dois familiares (60,5%) apresentaram um processo de luto complicado. A dimensão Gestão das emoções do coping está correlacionada positivamente com o luto, no global, (p = 0,29; p = 0,01), na dimensão de Negação e revolta (p = 0,35; p < 0,001) e com a dimensão Depressiva (p = 0,28; p = 0,01). Verificou-se ainda uma correlação negativa da dimensão Focada na tarefa com a dimensão específica de Negação e revolta (p = -0,24; p = 0,03). Conclusão: Os participantes apresentam uma elevada probabilidade de desenvolver processos de luto complicado, pelo que devem ser implementadas medidas de apoio psicológico.
Abstract Background: The constraints imposed by the COVID-19 pandemic hindered the experience of grief and promoted the occurrence of complicated grief. Objective: To determine the prevalence of complicated grief in family members of people who died from COVID-19; to verify whether coping strategies can predict grief. Methodology: This is a cross-sectional observational study with descriptive-correlational analysis using a non-probability sample of 86 participants. The data were explored using descriptive and inferential statistics. Results: Fifty-two family members (60.5%) experienced complicated grief. Emotion-oriented coping correlated positively with grief in the Global dimension (p = 0.29; p = 0.01), the Denial and anger dimension (p = 0.35; p < 0.001), and the Depressive dimension (p = 0.28; p = 0.01). Task-oriented coping correlated negatively with the Denial and anger dimension (p = -0.24; p = 0.03). Conclusion: The participants present a high probability of experiencing complicated grief. Thus, the implementation of psychological support measures is recommended.
Resumen Marco contextual: Las restricciones impuestas por la pandemia de COVID-19 dificultaron la vivencia de los procesos de duelo, lo que propició el desarrollo de procesos de duelo patológico. Objetivo: Determinar la prevalencia del duelo patológico en familiares de víctimas fallecidas de COVID-19. Verificar si las estrategias de afrontamiento (coping) predicen el duelo. Metodología: Estudio observacional, descriptivo-correlacional y transversal. La muestra no probabilística contó con 86 participantes. Los datos se exploraron mediante estadística descriptiva e inferencial. Resultados: cincuenta y dos familiares (60,5%) presentaron un proceso de duelo complicado. La dimensión de gestión de las emociones del afrontamiento se correlaciona positivamente con el duelo, en general, (p = 0,29; p = 0,01), con la dimensión de la Negación y la ira (p = 0,35; p < 0,001) y con la dimensión Depresiva (p = 0,28; p = 0,01). También hubo una correlación negativa de la dimensión Centrada en la tarea con la dimensión específica de la Negación y la ira (p = -0,24; p = 0,03). Conclusión: Los participantes tienen una alta probabilidad de desarrollar procesos de duelo complicados, por lo que deben aplicarse medidas de apoyo psicológico.
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INTRODUCTION: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo. METHODS: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models. RESULTS: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish. CONCLUSION: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.
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OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.
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Conjuntivitis , Síndromes Periódicos Asociados a Criopirina , Fiebre Mediterránea Familiar , Enfermedades Autoinflamatorias Hereditarias , Uveítis , Humanos , Niño , Adulto , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genética , Estudios Retrospectivos , Adenosina Desaminasa , Péptidos y Proteínas de Señalización Intercelular , Uveítis/etiología , Uveítis/genética , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/genética , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Conjuntivitis/genéticaRESUMEN
INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.
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Síndrome Antifosfolípido , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Masculino , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/epidemiología , Placenta , Anticuerpos Antifosfolípidos , Sistema de RegistrosRESUMEN
Industrial deep-sea mining will release plumes containing metals that may disperse over long distances; however, there is no general understanding of metal effects on marine ecosystems. Thus, we conducted a systematic review in search of models of metal effects on aquatic biota with the future perspective to support Environmental Risk Assessment (ERA) of deep-sea mining. According to results, the use of models to study metal effects is strongly biased towards freshwater species (83% freshwater versus 14% marine); Cu, Hg, Al, Ni, Pb, Cd and Zn are the best-studied metals, and most studies target few species rather than entire food webs. We argue that these limitations restrain ERA on marine ecosystems. To overcome this gap of knowledge, we suggest future research directions and propose a modelling framework to predict the effects of metals on marine food webs, which in our view is relevant for ERA of deep-sea mining.
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Metales Pesados , Contaminantes Químicos del Agua , Cadena Alimentaria , Ecosistema , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Metales , Metales Pesados/análisisRESUMEN
Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7-12.8; 14.9-17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.
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COVID-19 , Insuficiencia Respiratoria , Adulto , Humanos , Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Corticoesteroides/uso terapéutico , Antivirales/uso terapéutico , Insuficiencia Respiratoria/inducido químicamenteRESUMEN
Our report shows a case of primary light-chain amyloidosis in a young patient that reflects the potential severity of bleeding diathesis associated with this plasma cell dyscrasia and the difficulty of diagnosis when only hemorrhagic manifestations are present at the onset of disease. The patient presented with recurrent and severe muscular bleeding secondary to associated acquired von Willebrand disease and fibrinolysis dysfunction. Treatment with bortezomib-cyclophosphamide and sequential hematopoietic stem cell transplantation solved coagulation alterations. On the basis of our case, we review previous reports and discuss the potential mechanism of dysfunction of coagulation in light-chain amyloidosis.
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Amiloidosis , Trastornos Hemorrágicos , Enfermedades de von Willebrand , Humanos , Fibrinólisis , Susceptibilidad a Enfermedades , Amiloidosis/complicaciones , Hemorragia/etiologíaRESUMEN
Temporal lobe epilepsy (TLE) is the most prevalent form of epilepsy, through the neuronal mechanisms of this syndrome remain elusive. In addition to the temporal lobe structures, it was found that the basal forebrain cholinergic cells are also involved in epileptogenesis. However, little is known about the involvement of the basal forebrain GABAergic neurons in epilepsy; despite this, they largely project to the temporal lobe and are crucial for the regulation of the hippocampal circuitry. In this study, we assessed epilepsy-induced changes in parvalbumin (PARV) immunoreactive neurons of the medial septum (MS) and of the magnocellular preoptic nucleus (MCPO) using the kainic acid (KA) model in rats. In addition, we estimated the respective changes in the cholinergic varicosities in the MS, where we observed a significant reduction in the PARV cell number (12849 ± 2715 vs. 9372 ± 1336, p = .029) and density (16.2 ± 2.62 vs. 10.5 ± 1.00 per .001 mm3, p =.001), and an increase in the density of cholinergic varicosities (47.9 ± 11.1 vs. 69.4 ± 17.8 per 30,000 µm2, p =.036) in KA-treated animals. In the MCPO, these animals showed a significant increase in somatic volume (827.9 ± 235.2 µm3 vs. 469.9 ± 79.6 µm3, p = .012) and total cell number (2268.6 ± 707.1 vs. 1362.4 ± 262.0, p =.028). These results show that the basal forebrain GABAergic cell populations undergo numerical and morphological changes in epileptic animals, which may contribute to an increased vulnerability of brain circuits to epilepsy and epilepsy-related functional impairments.
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Reading epilepsy recruits critical language-related areas, with synchronization and subsequent spreading of excitation in response to the epileptogenic stimulus. The mechanism by which possible generalized discharges result in the expression of bilateral or unilateral clinical symptoms remains controversial. The cortical and subcortical areas involved may constitute part of the normal reading network, such as the visual word form area (VWFA). A right-handed, 59-year-old man was diagnosed with epilepsy at the age of 15 after tonic-clonic seizures. Later, the patient described myoclonic jerks of the masticatory and perioral muscles while reading. A multimodal approach with magnetic resonance imaging and ambulatory and video-electroencephalogram was used for seizure characterization and source analysis. A left hemisphere spontaneous occipital-temporal epileptic focus, activated by reading, was observed, spreading broadly throughout frontal and temporal language networks. There was an abnormally increased cortical response to visual word presentation in comparison to pseudowords. Spatial localization of spike sources suggested a close association between the primary epileptic focus and the VWFA. This epileptiform activity seems to be selectively triggered at an early stage of lexical processing, with a functional connection between the epileptic network and the VWFA. This multimodal and functional connectivity approach could be helpful in determining the epileptic network in reading epilepsy.
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Epilepsia Refleja , Mapeo Encefálico , Electroencefalografía , Humanos , Lenguaje , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/AIM: Obesity currently affects the whole world, with greater incidence in high-income countries, with vast economic and social costs. Broccoli harvest generates many by-products equally rich in bioactive compounds with potential anti-obesity effects. This study aimed to evaluate the anti-obesity effects of broccoli by-products flour (BF) in obese mice. MATERIALS AND METHODS: A commercial high-fat diet formulation (representing a Western diet) was used to induce obesity in mice. BF (0.67% or 1.34% weight/weight) was incorporated as a chemoprevention compound into a control and a hypercholesterolemic diet, at two different concentrations, and fed for 14 weeks to C57BL/6J mice. For a therapeutic approach, two groups were fed with the hypercholesterolemic diet for 10 weeks, and then fed with BF-supplemented diets in the last 4 weeks of the study. RESULTS: BF supplementation helped to maintain a lower body weight, reduced adipose tissue accumulation, and enhanced the basal activity of superoxide dismutase and glutathione S-transferase. Although BF supplementation tended to reduce the relative liver weight increased by the Western diet, the differences were not significant. CONCLUSION: BF appears to have a beneficial effect in preventing weight gain and fat accumulation induced by hypercholesterolemic diets.
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Brassica , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/etiologíaRESUMEN
Hypocalcaemia in neonates can range from asymptomatic to a potentially life-threatening condition. We present a case of a 36 weeks gestational age boy, admitted to our neonatal intensive care unit for jitteriness, mild hypotonia and breastfeeding difficulties. By the ninth day of life, he presented with late-onset hypocalcaemia, hypomagnesaemia, low 25-OH-vitamin D and inappropriately normal parathyroid hormone. Further investigation revealed maternal hypercalcaemia with high parathyroid hormone. Maternal asymptomatic hyperparathyroidism was diagnosed and admitted as the cause of neonatal hypocalcaemia. There was a clinical improvement and calcium levels stabilisation after treatment with calcium gluconate and vitamin D3 This case highlights the importance of careful evaluation of neonatal late-onset hypocalcaemia in uncovering asymptomatic maternal hyperparathyroidism.