Investigating the efficacy of transcranial direct current stimulation on chronic pain management in endometriosis patients: A randomized controlled trial protocol.

INTRODUCTION: Similar to chronic pain conditions, individuals with endometriosis can be affected by central sensitization syndrome (CSS), which is characterized by a loss of analgesia and central amplification of pain. Transcranial direct current stimulation (tDCS) has shown potential as an effective intervention to improve pain generated by other chronic pain conditions impacted by CSS, such as fibromyalgia and chronic pelvic issues. This study aims to evaluate the effectiveness of tDCS on pain, fatigue, and quality of life among patients affected by endometriosis. METHODS: This is a single-center, parallel, double-blinded, randomized, controlled clinical trial protocol study. We aim to recruit 40 participants affected by endometriosis (active group, n = 20; sham group, n = 20). Anodal tDCS will be delivered at an intensity of 2mA, applied over the primary motor cortex for 20 minutes per day for 10 consecutive days. There will be four assessment times: 1 week before beginning the intervention; on the 10th day following the last tDCS session; and 1 and 2 months after the last tDCS session. Pain evaluated by the algometry will be the primary outcome. Pain intensity, quality of life, fatigue, and global perception of change will be the secondary outcomes. We will calculate the effects of the active versus sham stimulation on primary and secondary outcomes by using generalized estimated equations or mixed model analysis. The effect size calculation will represent the effect measure. We expect that only the active group show reductions in pain, fatigue, and quality of life. The results of this trial will produce an important first step in providing evidence on the effectiveness of neuromodulation for the management of pain and will provide data to support new studies on tDCS. REGISTRATION: Brazilian Clinical Trials Registry (RBR-4q69573).

Pirfenidone Prevents Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-ß (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-ß inhibitor, IC50 114.3 µM), losmapimod (p38 inhibitor, IC50 17.6 µM) and SP600125 (c-Jun inhibitor, IC50 3.9 µM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients.

Influence of examiner calibration on clinical and MRI diagnosis of temporomandibular joint disc displacement: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to verify the accuracy of clinical protocols for the diagnosis of disc displacement (DD) compared with MRI, considering examiners' calibration. METHODS: PubMed, Cochrane (Central), Scopus, Web of Science, LILACS, Embase, Science Direct, Google Scholar, and DANS EASY Archive databases were searched. Two reviewers independently screened and selected the studies. A meta-analysis was conducted using the R Statistical software. Results are shown using sensitivity and specificity, and 95% confidence intervals. RESULTS: Of the 20 studies included in the systematic review, only three were classified as low risk of bias. Seventeen studies were included in the meta-analysis. Compared to MRI, clinical protocols showed overall sensitivity and specificity of 0.75 (0.63-0.83) and 0.73 (0.59-0.84) for DD diagnosis, respectively. For DD with reduction, sensitivity was 0.64 (0.48-0.77) and specificity was 0.72 (0.48-0.87). For DD without reduction, sensitivity was 0.58 (0.39-0.74) and specificity 0.93 (0.83-0.97). Only 8 studies reported examiner calibration when performing clinical and/or MRI evaluation; nevertheless, calibration showed a tendency to improve the diagnosis of DD. CONCLUSION: The sensitivity and specificity of clinical protocols in the diagnosis of DD are slightly below the recommended values, as well as the studies lack calibration of clinical and MRI examiners. Examiner calibration seems to improve the diagnosis of DD.

Renalase Levels are Decreased in Maternal Blood and Placental Tissues in Pregnancies Associated with Preterm Preeclampsia.

Preeclampsia (PEC) is a complication of pregnancy associated with hypertension and the risk of eclampsia. The pathophysiology of PEC is unknown and identifying factors associated with PEC during pregnancy is crucial for placental, fetal, and maternal health. Renalase (RNLS) is an anti-inflammatory secretory flavoprotein associated with hypertension. Recent data demonstrated a correlation between maternal serum RNLS and PEC, and work from our group identified RNLS expression in the placenta. However, it remains unknown whether RNLS levels in placenta are altered by preeclampsia. Additionally, it is unclear if there is a differential effect of preterm and term PEC on RNLS. We demonstrate that serum RNLS was reduced in preterm cases of PEC. Similarly, placental RNLS was diminished in the chorion of preterm cases of PEC. However, a reduction of RNLS in the decidua was observed with all cases of PEC, while the levels of RNLS within the placental villi were similar in all cases. Overall, we demonstrate that RNLS correlates with PEC both systemically in maternal serum and locally within the placenta, with variable effects on the different layers of the placenta and more pronounced in preterm cases.

Clinical usability study of a home-based self-administration transcranial direct current stimulation for primary dysmenorrhea: A randomized controlled trial.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.

Application of a microfluidic electronic tongue based on impedance spectroscopy for coconut water analysis.

The food industry has grown with the demands for new products and their authentication, which has not been accompanied by the area of analysis and quality control, thus requiring novel process analytical technologies for food processes. An electronic tongue (e-tongue) is a multisensor system that can characterize complex liquids in a fast and simple way. Here, we tested the efficacy of an impedimetric microfluidic e-tongue setup - comprised by four interdigitated electrodes (IDE) on a printed circuit board (PCB), with four pairs of digits each, being one bare sensor and three coated with different ultrathin nanostructured films with different electrical properties - in the analysis of fresh and industrialized coconut water. Principal Component Analysis (PCA) was applied to observe sample differences, and Partial Least Squares Regression (PLSR) was used to predict sample physicochemical parameters. Linear Discriminant Analysis (LDA) and Partial Least Square - Discriminant Analysis (PLS-DA) were compared to classify samples based on data from the e-tongue device. Results indicate the potential application of the microfluidic e-tongue in the identification of coconut water composition and determination of physicochemical attributes, allowing for classification of samples according to soluble solid content (SSC) and total titratable acidity (TTA) with over 90% accuracy. It was also demonstrated that the microfluidic setup has potential application in the food industry for quality assessment of complex liquid samples.

The dispersant Corexit 9500 and (dispersed) oil are lethal to coral endosymbionts.

Endosymbionts (Symbiodiniaceae) play a vital role in the health of corals. Seawater pollution can harm these endosymbionts and dispersants used during oil spill cleanup can be extremely toxic to these organisms. Here, we examined the impact of oil and a specific dispersant, Corexit-9500, on two representative endosymbionts - Symbiodinium and Cladocopium - from the Southwestern endemic coral Mussismilia braziliensis. The survival and photosynthetic potential of the endosymbionts decreased dramatically after exposure to the dispersant and oil by ~25 % after 2 h and ~50 % after 7 days. Low concentrations of dispersant (0.005 ml/l) and dispersed oil (Polycyclic Aromatic Hydrocarbons, 1132 µg/l; Total Petroleum Hydrocarbons, 595 µg/l) proved highly toxic to both Symbiodinium and Cladocopium. These levels triggered a reduction in growth rate, cell size, and cell wall thickness. After a few hours of exposure, cellular organelles were damaged or destroyed. These acute toxic effects underline the fragile nature of coral endosymbionts.

Are women with endometriosis more likely to experience reduced physical performance compared to women without the condition?

Background: Endometriosis is a condition of the female reproductive system associated with pelvic pain. Chronic pain can affect physical performance by limiting the functional activities, thus, it is hypothesized that women with endometriosis may also present decreased functional capacity, decreased strength, and mobility. The objective of this study is to compare physical performance in women with and without endometriosis. Methods: This is a cross-sectional study composed of 115 women equally divided into two groups: the endometriosis group (EG), composed of women with a confirmed diagnosis of the disease by magnetic resonance imaging, and the comparator group (CG), consisting of women without suspicion of the disease. Physical performance (dependent variable) was assessed using hand dynamometry, the 6-min walk test (6MWT), gait speed, and the chair stands test. CG participants performed the tests during the luteal phase of the menstrual cycle. Descriptive statistics, unpaired t-tests, and chi-square tests were used to describe and compare the groups. Multiple linear regression tested the associations adjusted for covariates (age, income, education, age at menarche, and body mass index). Results: The EG had worse gait speed (mean difference: -0.11; 95% CI: [-0.18 to -0.04]), weaker grip strength (mean difference: -3.32; 95% CI: [-5.30 to -1.33]), shorter distance covered in the 6MWT (mean difference: -83.46; 95% CI: [-121.38 to -45.53]), and a lower number of repetitions in the chair stands test (mean difference: -8.44; 95% CI: [-10.64 to -6.25]) than the CG, even after adjusting for covariates. Conclusion: Grip strength, lower limb strength, mobility, and functional capacity were worse in women diagnosed with endometriosis. Women with endometriosis should be encouraged to engage in physical exercise, adopt healthy lifestyle habits, and participate in rehabilitation activities to control pain, with the aim of reducing functional impairments.

Equivalent biodiversity area: A novel metric for No Net Loss success in Brazil's changing biomes.

This study presents a new method to incorporate the No Net Loss (NNL) principle within corporate Environmental, Social, and Governance (ESG) frameworks. This principle aims to ensure that biodiversity losses from human activities are fully offset. In this context, we tackle two main challenges: managing epistemic uncertainties in environmental modeling and accurately assessing compensatory areas needed to replace lost habitats. Focusing on Brazil's diverse biomes, which are undergoing rapid changes, we highlight the role of expert opinion surveys in addressing the uncertainties of the InVEST Habitat Quality, a model that simulates changes in landscape integrity under different land use scenarios. Our analysis across three of Brazil's regions - Caatinga Semi-arid, Cerrado Savanna, and Atlantic Forest - leverages open-source data to reveal substantial habitat losses due to activities like wind farm development, mining, and intensive agriculture, leading to a widespread decline in habitat quality. We introduce the Equivalent Biodiversity Area (EBA) metric to support NNL and Net Gain of Biodiversity efforts, measured in hectares. Findings show a reduction in EBA across all studied areas, highlighting the need for effective compensation strategies. Such strategies should merge Legal Reserves and ecological restoration into ESG policies, encourage landholder collaboration, and align with larger environmental efforts, such as watershed revitalization and Biodiversity Credits markets.

Being a woman influences the development of temporomandibular disorder: cross-sectional study / Ser mulher influencia no desenvolvimento de disfunção temporomandibular: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: Although women seem to be more susceptible to pain, there are few studies comparing the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) diagnoses between women and men. Thus, this study aimed to verify the influence of gender on Temporomandibular Disorders (TMD) and their comorbidities in a Brazilian sample. METHODS: Patients were assessed using the RDC/TMD. Diagnoses were obtained for Axis I (myofascial pain, disc displacement, and other joint conditions) and Axis II (depressive symptoms, chronic pain, somatization, and limitation of mandibular function). Logistic regression models were used to verify whether there is a difference in the prevalence and odds of developing TMD between women and men. RESULTS: The sample included 310 patients. Women had more myofascial pain and were more likely to develop it (73.04%; OR: 1.91; IC 95%: 1.08 - 3.39), as well as more joint disorders (54.78%; OR: 2.07; IC 95%: 1.08 - 3.99), in comparison to men. Furthermore, women composed the majority of the sample, more often sought treatment, and had more severe levels of depressive symptoms, somatization of pain, limitation of mandibular function, and myofascial pain. CONCLUSION: Women have more TMD and are more likely to develop it, and also show more severe levels of depressive symptoms, pain somatization, limited mandibular function, and myofascial pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: Embora as mulheres pareçam ser mais suscetíveis à dor, há poucos estudos comparando os diagnósticos obtidos por meio do Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) entre mulheres e homens. Assim, este estudo teve como objetivo verificar a influência do sexo nas disfunções temporomandibulares (DTM) e suas comorbidades em uma amostra brasileira. MÉTODOS: Os pacientes foram avaliados por meio do RDC/ TMD. Os diagnósticos foram obtidos para o Eixo I (dor miofascial, deslocamento de disco e outras condições articulares) e Eixo II (sintomas de depressão, dor crônica, somatização e limitação da função mandibular). Modelos de regressão logística foram utilizados para verificar se existe diferença na prevalência e nas chances de desenvolver DTM entre mulheres e homens. RESULTADOS: A amostra incluiu 310 pacientes. As mulheres apresentaram mais dor miofascial e foram mais propensas a desenvolvê-la (73,04%; OR: 1,91; IC 95%: 1,08 - 3,39), bem como mais distúrbios articulares (54,78%; OR: 2,07; IC 95%: 1,08 - 3,99), em comparação aos homens. Ademais, as mulheres compuseram a maioria da amostra, procuraram tratamento com maior frequência e apresentaram níveis mais graves de sintomas de depressão, somatização da dor, limitação da função mandibular e dor miofascial. CONCLUSÃO: As mulheres apresentam mais DTM e são mais propensas a desenvolvê-la, bem como apresentam níveis mais graves de sintomas de depressão, somatização da dor, limitação da função mandibular e dor miofascial.

Biological Impact of Organic Extracts from Urban-Air Particulate Matter: An In Vitro Study of Cytotoxic and Metabolic Effects in Lung Cells.

Atmospheric particulate matter (PM) with diameters below 10 µm (PM10) may enter the lungs through inhalation and are linked to various negative health consequences. Emergent evidence emphasizes the significance of cell metabolism as a sensitive target of PM exposure. However, the current understanding of the relationship between PM composition, conventional toxicity measures, and the rewiring of intracellular metabolic processes remains limited. In this work, PM10 sampled at a residential area (urban background, UB) and a traffic-impacted location (roadside, RS) of a Portuguese city was comprehensively characterized in terms of polycyclic aromatic hydrocarbons and plasticizers. Epithelial lung cells (A549) were then exposed for 72 h to PM10 organic extracts and different biological outcomes were assessed. UB and RS PM10 extracts dose-dependently decreased cell viability, induced reactive oxygen species (ROS), decreased mitochondrial membrane potential, caused cell cycle arrest at the G0/G1 phase, and modulated the intracellular metabolic profile. Interestingly, the RS sample, richer in particularly toxic PAHs and plasticizers, had a greater metabolic impact than the UB extract. Changes comprised significant increases in glutathione, reflecting activation of antioxidant defences to counterbalance ROS production, together with increases in lactate, NAD+, and ATP, which suggest stimulation of glycolytic energy production, possibly to compensate for reduced mitochondrial activity. Furthermore, a number of other metabolic variations hinted at changes in membrane turnover and TCA cycle dynamics, which represent novel clues on potential PM10 biological effects.

Relato de experiência: construção de material audiovisual como ferramenta de capacitação na Atenção Primária à Saúde durante a pandemia de Covid-19

As tecnologias educacionais podem ser utilizadas como instrumentos para disseminar informação em período de isolamento social. A pesquisa buscou descrever a experiência de produzir vídeos de avaliação cognitiva para pessoas idosas tendidas na Atenção Primária à Saúde. Método: Trata-se de um relato de experiência sobre a produção de vídeos animados contendo informações a respeito da utilização de instrumentos de avaliação cognitiva em idosos na Atenção Primária à Saúde do município de Coari-AM. Resultados: Os vídeos foram confeccionados e distribuídos para os gestores das Unidade Básicas de Saúde. Foram abordados um total de 13 gestores que tiveram acesso ao material produzido. Conclusão: A produção e divulgação dos vídeos de avaliação cognitiva em idosos possibilitou a educação continuada de maneira remota entre os gestores.

Using multilayer perceptron and similarity-weighted machine learning algorithms to reconstruct the past: A case study of the agricultural expansion on grasslands in the Uruguayan savannas.

Changes in land use and land cover (LULC) have significant implications for biodiversity, ecosystem functioning, and deforestation. Modeling LULC changes is crucial to understanding anthropogenic impacts on environmental conservation and ecosystem services. Although previous studies have focused on predicting future changes, there is a growing need to determine past scenarios using new assessment tools. This study proposes a methodology for LULC past scenario generation based on transition analysis. Aiming to hindcast LULC scenario in 1970 based on the transition analysis of the past 35 years (from 1985 to 2020), two machine learning algorithms, multilayer perceptron (MLP) and similarity weighted (SimWeight), were employed to determine the driver variables most related to conversions in LULC and to simulate the past. The study focused on the Aristida spp. grasslands in the Uruguayan savannas, where native grasslands have been extensively converted to agricultural areas. Land use and land cover data from the MapBiomas project were integrated with spatial variables such as altimetry, slope, pedology, and linear distances from rivers, roads, urban areas, agriculture, forest, forestry, and native grasslands. The accuracy of the predicted maps was assessed through stratified random sampling of reference images from the Multispectral Scanner (MSS) sensor. The results demonstrate a reduction of approximately 659 934 ha of native grasslands in the study area between 1985 and 2020, directly proportional to the increase in cultivable areas. The MLP algorithm exhibited moderate performance, with notable errors in classifying agriculture and grassland areas. In contrast, the SimWeight algorithm displayed better accuracy, particularly in distinguishing grassland and agriculture classes. The modeled map using SimWeight accurately represented the transitions between grassland and agriculture with a high level of agreement. By modeling the 1970s scenario using the SimWeight model, it was estimated that the Aristida spp. grasslands experienced a substantial reduction in grassland coverage, ranging from 9982.31 to 10 022.32 km2 between 1970 and 2020. This represents a range of 60.8%-61.07% of the total grassland area in 1970. These findings provide valuable insights into the driving factors behind land use change in the Aristida spp. grasslands and offer useful information for land management, conservation, and sustainable development in the region. The study's main contribution lies in the hindcasting of past LULC scenarios, utilizing a tool used primarily for forecasting future scenarios. Integr Environ Assess Manag 2023;00:1-16. © 2023 SETAC.

Collapse of scallop Nodipecten nodosus production in the tropical Southeast Brazil as a possible consequence of global warming and water pollution.

Mollusc rearing is a relevant global socioeconomic activity. However, this activity has faced severe problems in the last years in southeast Brazil. The mariculture scallop production dropped from 51,2 tons in 2016 to 10,2 tons in 2022 in the Baia da Ilha Grande (BIG; Rio de Janeiro). However, the possible causes of this collapse are unknown. This study aimed to analyze decadal trends of water quality in Nodipecten nodosus spat and adult production in BIG. We also performed physical-chemical and biological water quality analyses of three scallop farms and two nearby locations at BIG in 2022 to evaluate possible environmental stressors and risks. Scallop spat production dropped drastically in the last five years (2018-2022: mean ± stdev: 0.47 ± 0.45 million). Spat production was higher in colder waters and during peaks of Chlorophyll a in the last 13 years. Reduction of Chlorophyll a coincided with decreasing spat production in the last five years. Warmer periods (>27 °C) of the year may hamper scallop development. Counts of potentially pathogenic bacteria (Vibrios) and Escherichia coli were significantly higher in warmer periods which may further reduce scallop productivity. Shotgun metagenomics of seawater samples from the five studied corroborated these culture-based counts. Vibrios and fecal indicator bacteria metagenomic sequences were abundant across the entire study area throughout 2022. The results of this study suggest the collapse of scallop mariculture is the result of a synergistic negative effect of global warming and poor seawater quality.

Workaholism Scales: Some Challenges Ahead.

Although extensively used in the academic literature, workaholism as a concept has been explained in different ways, which has influenced the development and use of some measurement tools. As such, this article aims to address the subject through a systematic study review focusing on articles where the main objective was to develop, adapt, or analyze the psychometric properties of a workaholism scale. The main purpose is to describe the state of the art concerning workaholism measurement tools, highlighting trends and research perspectives for further research. In essence, this study may serve as a summary and starting point for scholars interested in measuring workaholism. It was observed that the discrepancy concerning the definition of workaholism has resulted in scales that attempt to evaluate diverging conceptualizations. Moreover, each scale has been readapted when tested in different countries. For further investigations, it is important to converge the concept of workaholism and validate the scales across differing contexts, regarding the industry, culture, and country of the sample.

Congenital Midline Cervical Cleft and Thyroglossal Duct Fibrous Cord-Like, is There a Mixed Presentation?

INTRODUCTION: Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature. CASE PRESENTATION: Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty. CONCLUSION: Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.

Impact of waitlist time on post-HSCT survival: a cohort study at a hospital in southern Brazil.

INTRODUCTION: The time elapsed from diagnosis to hematopoietic stem cell transplantation (HSCT) is influenced by numerous factors. In Brazil, patients using the public health system are also dependent on the availability of HSCT-specific beds in the hematology ward. OBJECTIVE AND METHODS: We conducted a cohort study of listed patients who underwent allogeneic HSCT at a Brazilian public hospital to investigate the impact of the waitlist time on post-HSCT survival. RESULTS: The median time from diagnosis to HSCT was 19 months (IQR, 10 - 43), of which 6 months (IQR, 3 - 9) were spent on the waitlist. The time on the waitlist for HSCT appeared to influence mainly the survival of adult patients (≥ 18 years), with an increasing risk according to this time (RR, 3.53 and 95%CI, 1.81 - 6.88 for > 3 and ≤ 6 months; RR 5.86 and 95%CI, 3.26 - 10.53 for > 6 and ≤ 12 months, and; RR 4.24 and 95%CI, 2.32 - 7.75 for > 12 months). CONCLUSION: Patients who remained on the waitlist for less than 3 months had the highest survival (median survival, 856 days; IQR, 131 - 1607). The risk of reduced survival was about 6-fold higher (95%CI, 2.8 - 11.5) in patients with malignancies.

Single-cell atlas of the human neonatal small intestine affected by necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie NEC is lacking. This study aimed at filling in this gap. We combine single-cell RNA sequencing (scRNAseq), T-cell receptor beta (TCRß) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions, and zonal changes in NEC. We find an abundance of proinflammatory macrophages, fibroblasts, endothelial cells as well as T cells that exhibit increased TCRß clonal expansion. Villus tip epithelial cells are reduced in NEC and the remaining epithelial cells up-regulate proinflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that are associated with inflammation in NEC mucosa. Our analyses highlight the cellular dysregulations of NEC-associated intestinal tissue and identify potential targets for biomarker discovery and therapeutics.

[Abdominal pain with neuropsychiatric symptoms and ventilatory failure as a presentation of acute porphyria]. / Abdomen agudo con compromiso neuropsiquiátrico y ventilatoria como presentación de porfiria agudac.

Background: Acute intermittent porphyria (AIP) is an uncommon metabolic disease, being the most common of the acute porphyrias. The most frequent symptom is acute abdominal pain, although can be accompanied by seizures, neuro-psychiatric alterations or symmetrical motor neuropathies, which in some patients can progress to respiratory musculature paralysis. Objective: To describe an atypical presentation of acute porphyria to be considered as differential diagnoses in abdominal pain. Clinical case: We present a case of a patient with AIP, presenting acute abdomen, seizures, later developed neuropsychiatric compromise and symmetrical motor neuropathy, and was admitted to mechanical ventilation. Due to the severity of the neurological involvement, he received hemin arginate, presenting with transient hypertransaminemia, an adverse event not previously reported. The evolution was favorable, with mechanical ventilation and hospital discharge withdrawn. Conclusions: The diagnosis of AIP should be considered in cases of acute abdominal pain associated with neurological and/or psychiatric symptoms, particularly young women. The administration of hemin is considered the standard of treatment, and even late could have beneficial effects.

Introducción: la porfiria aguda intermitente (PAI) es una enfermedad metabólica infrecuente, siendo la más común de las porfirias agudas. El síntoma más frecuente es el dolor abdominal agudo, aunque también pueden acompañarse de convulsiones, alteraciones neuro-psiquiátricas o neuropatías motoras simétricas, y que en algunos pacientes puede progresar a la parálisis de la musculatura respiratoria. El objetivo de este trabajo es describir una forma atípica de presentación de una porfiria aguda, a fin de considerar como diagnósticos diferenciales en dolor abdominal. Caso clínico: paciente con PAI, que presenta abdomen agudo, convulsiones, posteriormente compromiso neuro-psiquiátrico y neuropatía motora simétrica, ingresando a ventilación mecánica. Por la gravedad del compromiso neurológico recibió arginato de hemina, cursando con hipertransaminemia transitoria, evento adverso no reportado previamente. La evolución fue favorable, retirándosele la ventilación mecánica y el alta hospitalaria. Conclusiones: se debe considerar el diagnóstico de PAI en casos de dolor abdominal agudo asociado a síntomas neurológicos y/o psiquiátricos, particularmente en mujeres jóvenes. La administración de hemina es considerada el estándar de tratamiento, y aun en forma tardía podría tener efectos beneficiosos.