Divergent responses of human intestinal organoid monolayers using commercial in vitro cytotoxicity assays.

In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being used to assess therapeutics for various cancers and infectious diseases. Monitoring drug cytotoxicity in cell cultures is crucial in drug development, and several commercially available kits for cytotoxicity assessment offer distinct advantages and limitations. Given the complexity of organoid cultures, including donor-driven variability, we investigated drug-treated, tissue stem cell-derived human intestinal organoid responses with commonly used cell cytotoxicity assay kits. Using seven different compounds, we compared the cytotoxicity assay performance of two different leaky membrane-based and two metabolism-based assays. Significant variability was seen in reported viability outcomes across assays and organoid lines. High baseline activity of lactate dehydrogenase (LDH) in four human intestinal organoid lines required modification of the standard LDH assay protocol. Additionally, the LDH assay reported unique resilience to damage in a genetically-modified line contrasting results compared to other assays. This study highlights factors that can impact the measurement of cell cytotoxicity in intestinal organoid models, which are emerging as valuable new tools for research and pre-clinical drug testing and suggest the need for using multiple assay types to ensure reliable cytotoxicity assessment.

Pyogenic Granuloma in a One-Year-Old Child: A Rare Entity.

Pyogenic granuloma (PG) is a benign vascular neoplasm seen in the first and second decades of life, and it has a female predilection. It presents as a small reddish exophytic lesion, gingiva being the most common site. This article describes an unusual presentation of PG in a one-year-old female child and highlights the importance of its early diagnosis and management to avoid discomfort and distress in these patients. The diagnosis was verified by histological examination, which revealed significant markers such as endothelial growth, vascular abundance, and chronic inflammatory cell infiltration. The chosen treatment protocol was surgical excision, which led to a successful outcome with no symptoms of recurrence, as confirmed by thorough follow-up examinations.

Assessing the Impact of Neighborhood and Built Environment on Pediatric Perioperative Care: A Systematic Review of the Literature.

CONTEXT: Neighborhood and built environment encompass one key area of the Social Determinants of Health (SDOH) and is frequently assessed using area-level indices. OBJECTIVE: We sought to systematically review the pediatric surgery literature for use of commonly applied area-level indices and to compare their utility for prediction of outcomes. DATA SOURCES: A literature search was conducted using PubMed, Ovid MEDLINE, Ovid MEDLINE Epub Ahead of Print, PsycInfo, and an artificial intelligence search tool (1/2013-2/2023). STUDY SELECTION: Inclusion required pediatric surgical patients in the US, surgical intervention performed, and use of an area-level metric. DATA EXTRACTION: Extraction domains included study, patient, and procedure characteristics. RESULTS: Area Deprivation Index is the most consistent and commonly accepted index. It is also the most granular, as it uses Census Block Groups. Child Opportunity Index is less granular (Census Tract), but incorporates pediatric-specific predictors of risk. Results with Social Vulnerability Index, Neighborhood Deprivation Index, and Neighborhood Socioeconomic Status were less consistent. LIMITATIONS: All studies were retrospective and quality varied from good to fair. CONCLUSIONS: While each index has strengths and limitations, standardization on ideal metric(s) for the pediatric surgical population will help build the inferential power needed to move from understanding the role of SDOH to building meaningful interventions towards equity in care. TYPE OF STUDY: Systematic Review. LEVEL OF EVIDENCE: Level III.

Muscle-specific, liver-detargeted adeno-associated virus gene therapy rescues Pompe phenotype in adult and neonate Gaa-/- mice.

Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease.

Dietary phytate induces subclinical mechanical allodynia in mice.

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

Efficacy of a decision aid in breast cancer patients considering immediate reconstruction: results of a randomized controlled trial.

PURPOSE: Breast cancer patients face complex decisions about immediate breast reconstruction (BR) after mastectomy. We evaluated the efficacy of an online decision aid in improving the decision-making process, decision quality and health outcomes in breast cancer patients considering immediate BR. METHODS: In a multicenter randomized controlled trial, patients were allocated to either the intervention group receiving care-as-usual (CAU) with access to an online decision aid, or the control group receiving CAU with an information leaflet. The primary outcome was decisional conflict. Secondary outcomes assessed the process of decision making (e.g. preparation for decision making, satisfaction with information), decision quality (decision regret, knowledge) and health outcomes (e.g. satisfaction with BR outcomes, body image). Patients completed questionnaires at baseline (T0), 1 week after consultation with a plastic surgeon (T1), 3 months (T2), and 12 months post-surgery (T3). RESULTS: We included 250 patients. Decisional conflict decreased over time in both groups, with no between group differences. Intervention participants felt better prepared for decision making than controls (P = .002). At T2, 87% of intervention participants were (very) satisfied with the information about BR, compared to 73% of control participants (P = .011). No significant between group differences were observed in any other outcome. CONCLUSION: Our online decision aid was as effective in reducing decisional conflict as an information leaflet about immediate BR after mastectomy. However, the decision aid substantially improved the decision-making process by better preparing breast cancer patients for decisions about immediate BR.

Active surveillance versus treatment in low-risk DCIS: Women's preferences in the LORD-trial.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but most DCIS lesions remain indolent. However, guidelines recommend surgery, often supplemented by radiotherapy. This implies overtreatment of indolent DCIS. The non-randomised patient preference LORD-trial tests whether active surveillance (AS) for low-risk DCIS is safe, by giving women with low-risk DCIS a choice between AS and conventional treatment (CT). Here, we aim to describe how participants are distributed among both trial arms, identify their motives for their preference, and assess factors associated with their choice. METHODS: Data were extracted from baseline questionnaires. Descriptive statistics were used to assess the distribution and characteristics of participants; thematic analyses to extract self-reported reasons for the choice of trial arm, and multivariable logistic regression analyses to investigate associations between patient characteristics and chosen trial arm. RESULTS: Of 377 women included, 76% chose AS and 24% CT. Most frequently cited reasons for AS were "treatment is not (yet) necessary" (59%) and trust in the AS-plan (39%). Reasons for CT were cancer worry (51%) and perceived certainty (29%). Women opting for AS more often had lower educational levels (OR 0.45; 95% confidence interval [CI], 0.22-0.93) and more often reported experiencing shared decision making (OR 2.71; 95% CI, 1.37-5.37) than women choosing CT. CONCLUSION: The LORD-trial is the first to offer women with low-risk DCIS a choice between CT and AS. Most women opted for AS and reported high levels of trust in the safety of AS. Their preferences highlight the necessity to establish the safety of AS for low-risk DCIS.

Oral and Systemic Health Implications of Electronic Cigarette Usage as Compared to Conventional Tobacco Cigarettes: A review of the literature.

Purpose The health implications related to electronic cigarettes are not fully understood and has created a public health concern. The purpose of this narrative review was to highlight the oral and systemic health concerns associated with electronic cigarettes and compare these concerns to those associated with conventional tobacco cigarettes.Methods The literature was obtained from PubMed, Ovid Medline, CINAHL, and Scopus databases in June 2021 and updated in February 2023. Sources were chosen based on the following inclusion criteria: date of publication between 2011 and 2023 and written in English. Articles were excluded based on irrelevance to the topic, weak study designs, lack of outcome data, low quality randomized control trials, unavailability of the full text article, and non-empirical research designs. The Cochrane tool, ROBINS-I, was used to assess the risk of bias.Results A total of 78 studies were included in the review. E-cigarette use was associated with significant adverse effects for cardiovascular, respiratory, immunological, and periodontal health as compared to nonusers; however, impacts were worse with conventional smoked cigarettes. Long term health effects remain unknown with e-cigarettes, but associations have been identified with periodontal and peri-implant disease, oral cancer, and mental health disorders. The heterogeneity of e-cigarette use related to vaping behavior, devices, and liquids limits the ability to generalize results. There is a need for the development of a research standard for exposure methods to establish a consensus with e-cigarette use and support the validity of results among researchers.Conclusion According to current research, e-cigarettes may induce less harm than traditional tobacco products, but e-cigarettes do not remove the carcinogenic and toxic risk that has been associated with conventional cigarettes. Further research is needed to make broad conclusions on the safety of e-cigarettes compared to conventional cigarettes and to nonusers.

Dietary phytate induces subclinical mechanical allodynia in mice

Neuropathic pain is a condition with varying origins, including reduced dietary micronutrient intake. Phytate is a polyphosphate found in seeds and grains that can act as an antinutrient due to the ability of sequester essential divalent metals. Here we tested whether moderate dietary phytate intake could alter nociceptive pain. We subjected weaning mice to a chow supplemented with 1% phytate for eight weeks. Body weight gain, glycemic responses, food ingestion, water ingestion, and liver and adipose tissue weights were not altered compared to controls. We observed a decreased mechanical allodynia threshold in the intervention group, although there were no changes in heat- or cold-induced pain. Animals consuming phytate showed reduced spinal cord tumor necrosis factor (TNF), indicating altered inflammatory process. These data provide evidence for a subclinical induction of mechanical allodynia that is independent of phytate consumption in animals with otherwise normal phenotypic pattern.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Abstract Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Resumo Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts

Abstract Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Resumo Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Fibrohistiocitoma maligno / Malignant fibrohystiocytoma

RESUMEN El fibrohistiocitoma maligno es el sarcoma de partes blandas más frecuente en adultos; es poco frecuente como tumor primario cutáneo. Presenta predilección por el sexo masculino con una mayor incidencia entre la quinta y sexta década de la vida. Se localiza predominantemente en las extremidades. Presentamos a continuación el caso clínico de un paciente con diagnóstico de fibrohistiocitoma maligno localizado en hallux de pie derecho y realizaremos una revisión de la literatura.

ABSTRACT Malignant fibrohistiocytoma is the most frequent soft tissue tumor in adults; it is rare as a primary cutaneous tumor. It presents a predilection for males with the highest incidence between the fifth and sixth decade of life. It is located predominantly on the extremities. We will perform a literature review. We present below the clinical case of a patient diagnosed with malignant fibrohistiocytoma located in hallux of the right foot.

[No fear of anything: epilepsy, psychiatric comorbidity and surgery. A clinical case report]. / Sin miedo a nada: epilepsia, comorbilidad psiquiátrica y cirugía. Descripción de un caso clínico.

INTRODUCTION: Psychiatric conditions are common in patients with drug-resistant temporal lobe epilepsy. It can be extremely disabling, as it hinders the patient's integration into society. Emotional symptoms may occur during crises or can be chronic and not directly related to seizures. Some of the most common disorders are depression, followed by anxiety disorders and obsessive symptoms such as phobias. CASE REPORT: In the clinical case reported here, the patient suffers from drug-resistant focal epilepsy and psychiatric comorbidity (anxiety-depressive syndrome and phobias). In the pre-surgical evaluation, the origin of the seizures was established as the right mesial temporal region, and so surgery was performed. In check-ups, an improvement of both conditions was observed after surgery to treat her epilepsy. CONCLUSION: The activation of the amygdala and its interaction with different brain structures seem to play an important role in emotional learning and aversive stimuli, thereby conditioning (depending on its pattern of activation) the individual's ability to control their fear. There seems to be excessive activation in individuals with phobias. Surgical resection by anteromedial temporal lobectomy in patients with temporal lobe epilepsy is an effective treatment to achieve control over refractory seizures, and may also help to ease emotional symptoms, thus adding an extra benefit. A pre-surgical evaluation with a multidisciplinary approach can be used to predict post-operative neuropsychological change.

TITLE: Sin miedo a nada: epilepsia, comorbilidad psiquiátrica y cirugía. Descripción de un caso clínico.Introducción. Es común que la patología psiquiátrica se manifieste en pacientes con epilepsia farmacorresistente del lóbulo temporal. Puede llegar a ser tremendamente incapacitante, puesto que obstaculiza la integración del paciente en la sociedad. Los síntomas emocionales pueden aparecer durante las crisis o presentarse crónicamente y no directamente relacionados con ellas. Entre los trastornos más frecuentes se encuentra la depresión, seguida por los trastornos de ansiedad y los síntomas obsesivos, como pueden ser las fobias. Caso clínico. En el caso clínico presentado, la paciente padece una epilepsia focal farmacorresistente y comorbilidad psiquiátrica (síndrome ansiosodepresivo y fobias). En la evaluación prequirúrgica se establece como origen de las crisis la región temporal mesial derecha, por lo que se realiza cirugía. En revisiones se constata una mejoría de ambas patologías tras la actuación quirúrgica sobre su epilepsia. Conclusión. La activación de la amígdala y su interacción con diferentes estructuras cerebrales parecen desempeñar un papel importante en el aprendizaje emocional y en estímulos aversivos, condicionando, en función de su patrón de activación, la habilidad del individuo para controlar el miedo. Parece existir un exceso de activación en los individuos que presentan fobias. La resección quirúrgica mediante lobectomía temporal anteromedial en pacientes con epilepsia del lóbulo temporal es un tratamiento eficaz para el control de las crisis refractarias, que, además, puede ayudar a remitir los síntomas emocionales, añadiendo un beneficio adicional. Una evaluación prequirúrgica previa con un enfoque multidisciplinar puede utilizarse para predecir el cambio neuropsicológico postoperatorio.

Farnesyltransferase inhibitor LNK-754 attenuates axonal dystrophy and reduces amyloid pathology in mice.

BACKGROUND: Amyloid plaque deposition and axonal degeneration are early events in AD pathogenesis. Aß disrupts microtubules in presynaptic dystrophic neurites, resulting in the accumulation of impaired endolysosomal and autophagic organelles transporting ß-site amyloid precursor protein cleaving enzyme (BACE1). Consequently, dystrophic neurites generate Aß42 and significantly contribute to plaque deposition. Farnesyltransferase inhibitors (FTIs) have recently been investigated for repositioning toward the treatment of neurodegenerative disorders and block the action of farnesyltransferase (FTase) to catalyze farnesylation, a post-translational modification that regulates proteins involved in lysosome function and microtubule stability. In postmortem AD brains, FTase and its downstream signaling are upregulated. However, the impact of FTIs on amyloid pathology and dystrophic neurites is unknown. METHODS: We tested the effects of the FTIs LNK-754 and lonafarnib in the 5XFAD mouse model of amyloid pathology. RESULTS: In 2-month-old 5XFAD mice treated chronically for 3 months, LNK-754 reduced amyloid plaque burden, tau hyperphosphorylation, and attenuated the accumulation of BACE1 and LAMP1 in dystrophic neurites. In 5-month-old 5XFAD mice treated acutely for 3 weeks, LNK-754 reduced dystrophic neurite size and LysoTracker-Green accumulation in the absence of effects on Aß deposits. Acute treatment with LNK-754 improved memory and learning deficits in hAPP/PS1 amyloid mice. In contrast to LNK-754, lonafarnib treatment was less effective at reducing plaques, tau hyperphosphorylation and dystrophic neurites, which could have resulted from reduced potency against FTase compared to LNK-754. We investigated the effects of FTIs on axonal trafficking of endolysosomal organelles and found that lonafarnib and LNK-754 enhanced retrograde axonal transport in primary neurons, indicating FTIs could support the maturation of axonal late endosomes into lysosomes. Furthermore, FTI treatment increased levels of LAMP1 in mouse primary neurons and in the brains of 5XFAD mice, demonstrating that FTIs stimulated the biogenesis of endolysosomal organelles. CONCLUSIONS: We show new data to suggest that LNK-754 promoted the axonal trafficking and function of endolysosomal compartments, which we hypothesize decreased axonal dystrophy, reduced BACE1 accumulation and inhibited amyloid deposition in 5XFAD mice. Our results agree with previous work identifying FTase as a therapeutic target for treating proteinopathies and could have important therapeutic implications in treating AD.

Ameloblastomas mimicking apical periodontitis: a case series.

BACKGROUND: Ameloblastomas are benign odontogenic tumors that can eventually mimic the clinical and radiological features of apical periodontitis. The aim of the present study was to evaluate the clinical, radiological and histological characteristics from a series of ameloblastomas mimicking apical periodontitis diagnosed in a 14-year period. MATERIAL AND METHODS: all cases histologically diagnosed as ameloblastomas from 2005 to 2018 presenting a clinical diagnosis of periapical lesion of endodontic origin were selected for the study. Clinical, radiological and histological characteristics from all cases were tabulated and descriptively and comparatively analyzed. RESULTS: Twenty cases composed the final sample, including 18 solid and 2 unicystic ameloblastomas. Mean age of the affected patients was in the fifth decade with predilection for males (72%). The most common anatomical location was the posterior mandible (55%) and most cases presented a radiolucent unilocular (80%) well-defined (95%) image. Most cases were asymptomatic, but the presence of local swelling and bone cortical rupture were common. CONCLUSIONS: Ameloblastomas mimicking periapical lesions of endodontic origin are mostly diagnosed in adult males as well-defined radiolucent unilocular lesions producing local swelling and bone cortical rupture.

Humeral offset as a predictor of outcomes after reverse shoulder arthroplasty.

INTRODUCTION: The Grammont-style reverse shoulder arthroplasty (RSA) relies on medialization and distalization of the shoulder center of rotation. Lateralized designs have recently gained popularity. The amount of lateralization, however, remains a controversial topic. The purpose of this study was to correlate the change in humeral offset (HO) with outcomes and complications following RSA. We hypothesized that a lateralized HO following RSA would be associated with improved range of motion (ROM), better patient-reported outcomes (PROs), and fewer complications. MATERIALS AND METHODS: A consecutive series of 104 patients (109 shoulders) was retrospectively evaluated. All patients underwent primary RSA by 2 shoulder and elbow fellowship-trained orthopedic surgeons at 2 different centers. Inclusion criteria was a primary RSA with at least 1-year follow-up. All patients had the HO measured on a preoperative and a postoperative Grashey radiograph, and the change in HO was calculated (ΔHO = PostHO-PreHO). A negative value was defined as a medialized HO and a positive value as a lateralized HO. ROM and primary outcomes, including forward elevation (FE), external rotation (ER), internal rotation (IR), Subjective Shoulder Value (SSV), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, were collected. Complications and revisions were also reported. RESULTS: The mean age was 72 years with a mean follow-up of 22.3 months. The average FE (92° vs. 148°), ER (34° vs. 44°), SSV (35% vs. 87%), and ASES score (37.2 vs. 81.2) increased significantly (all P < .01) compared with preoperative values. The HO was medialized postoperatively in 63 shoulders and lateralized in 46 shoulders. No statistically significant differences in the mean values for postoperative FE (147° vs. 146°, P = .892), ER (43° vs. 45°, P = .582), IR (L3 vs. L3, P = .852), SSV (88% vs. 85%, P = .476), and ASES score (81.3 vs. 81.1, P = .961) were found between the groups. However, there was significantly more improvement in ER in the lateralized HO cohort than the medialized cohort (16° vs. 7°, P = .033). Six shoulders, 5 medialized and 1 lateralized HO, demonstrated scapular notching and remained asymptomatic. Five shoulders, 4 medialized and 1 lateralized HO, experienced at least 1 instability incident, and 2 shoulders with medialized HO had an acromion/scapular spine fracture. Overall, 2 shoulders with medialized HO underwent revision surgery because of instability. CONCLUSIONS: Although RSA provides significant improvement in ROM and PROs regardless of postoperative HO, restoring baseline HO or lateralization beyond baseline may be favorable for improving ER and decreasing complications following RSA.

Reducing Opioid-Induced Constipation Post-Cardiac Surgery: An Improvement Project in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: Pain management with opioids and underutilization of prophylaxis for constipation can prolong a patient's hospital length of stay and impede pain management efforts. PROBLEM: In pediatric postoperative cardiac patients, opioid therapy is a common approach to pain management but often places them at greater risk for constipation due to anatomy and age. METHODS: A retrospective review of 50 patients' medical records for baseline data was conducted, and a survey evaluated providers' current knowledge and practice. INTERVENTIONS: The intervention was an electronic order set that provided decision support. Additionally, prophylactic measures were supported by a validated assessment tool that created a common language to report constipation risk. RESULTS: Although not statistically significant, postintervention data demonstrated a 21.5% decrease in postoperative constipation and a 57% increase in ordered bowel regimens. CONCLUSION: More focus is needed toward prophylactic bowel regimens to reduce the risk in this already high-risk population.

Cell-free DNA analysis in current cancer clinical trials: a review.

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.

Profile of soluble factors in pleural effusions predict prognosis in mesothelioma.

BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease. OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma. METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients.Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system. RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis. CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.