Aceite esencial de hojas de Minthostachys mollis [HBK] Griseb. del Ecuador: extracción, composición química, capacidad antioxidante y actividad antimicrobiana / Essential oil of Minthostachys mollis [HBK] Griseb. leaves from Ecuador: extraction, chemical composition, antioxidant capacity and antimicrobial activity

The aim of this study was to optimize by response surface design, the extraction of the leaf essential oil (EO) from Minthostachys mollis [HBK] Griseb., grown in Ecuador, using steam distillation. The factors used were extraction time (XTIE) of 60, 105 and 150 min and plant material/water ratio (XRMA) of 1:3, 1:4 and 1:5. The optimal combination was reached with XRMA 1:5 and XTIE 150 min, obtaining a process yield of 0.67%. The chemical composition of the EO analyzed by GC - MS was determined, where the main compounds were carvacryl acetate (44.01%), carvacrol (16.51%) and menthone (8.20%). The anti oxidant capacity of EO was evaluated using the FRAP and ABTS methodologies, with an IC 50 243.21 µmol Fe 2+ /g and 0.12 mg/mL, respectively. In addition, the antimicrobial activity of EO was found against Pseudomonas aeruginosa , Salmonella enterica , Escherich ia coli and Staphylococcus aureus .

El objetivo del estudio fue optimizar, mediante un diseño de superficie respuesta, la extracción d el aceite esencial (AE) de hojas de Minthostachys mollis [HBK] Griseb. del Ecuador, mediante destilación por arrastre de vapor. Los factores fueron el tiempo de extracción (XTIE) de 60, 105 y 150 min, y relación de material vegetal/ agua destilada (XRMA) d e 1:3, 1:4 y 1:5. La combinación óptima se logró con XTIE 150 min y XRMA 1:5 para un rendimiento de 0,67%. Se determinó la composición química del AE por GC - MS donde los compuestos mayoritarios fueron acetato de carvacrilo (44,01%), carvacrol (16,51%) y me ntona (8,20%). Se evaluó la capacidad antioxidante del AE por las metodologías FRAP y ABTS, con CI 50 de 243,21 µmol Fe 2+ /g y 0,12 mg/mL, respectivamente. Además, se demostró la actividad antimicrobiana contra Pseudomonas aeruginosa , Salmonella enterica , Es cherichia coli y Staphylococcus aureus .

Dietary xylo-oligosaccharides and arabinoxylans improved growth efficiency by reducing gut epithelial cell turnover in broiler chickens.

BACKGROUND: One of the main roles of the intestinal mucosa is to protect against environmental hazards. Supplementation of xylo-oligosaccharides (XOS) is known to selectively stimulate the growth of beneficial intestinal bacteria and improve gut health and function in chickens. XOS may have an impact on the integrity of the intestinal epithelia where cell turnover is critical to maintain the compatibility between the digestive and barrier functions. The aim of the study was to evaluate the effect of XOS and an arabinoxylan-rich fraction (AXRF) supplementation on gut function and epithelial integrity in broiler chickens. METHODS: A total of 128 broiler chickens (Ross 308) were assigned into one of two different dietary treatments for a period of 42 d: 1) control diet consisting of a corn/soybean meal-based diet; or 2) a control diet supplemented with 0.5% XOS and 1% AXRF. Each treatment was randomly distributed across 8 pens (n = 8) with 8 chickens each. Feed intake and body weight were recorded weekly. On d 42, one male chicken per pen was selected based on average weight and euthanized, jejunum samples were collected for proteomics analysis. RESULTS: Dietary XOS/AXRF supplementation improved feed efficiency (P < 0.05) from d 1 to 42 compared to the control group. Proteomic analysis was used to understand the mechanism of improved efficiency uncovering 346 differentially abundant proteins (DAP) (Padj < 0.00001) in supplemented chickens compared to the non-supplemented group. In the jejunum, the DAP translated into decreased ATP production indicating lower energy expenditure by the tissue (e.g., inhibition of glycolysis and tricarboxylic acid cycle pathways). In addition, DAP were associated with decreased epithelial cell differentiation, and migration by reducing the actin polymerization pathway. Putting the two main pathways together, XOS/AXRF supplementation may decrease around 19% the energy required for the maintenance of the gastrointestinal tract. CONCLUSIONS: Dietary XOS/AXRF supplementation improved growth efficiency by reducing epithelial cell migration and differentiation (hence, turnover), actin polymerization, and consequently energy requirement for maintenance of the jejunum of broiler chickens.

Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Neuropathological and sociodemographic factors associated with the cortical amyloid load in aging and Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive abilities. A pathological hallmark of AD is a region-specific accumulation of the amyloid-beta protein (Aß). Here, we explored the association between regional Aß deposition, sociodemographic, and local biochemical factors. We quantified the Aß burden in postmortem cortical samples from parietal (PCx) and temporal (TCx) regions of 27 cognitively unimpaired (CU) and 15 AD donors, aged 78-100 + years. Histological images of Aß immunohistochemistry and local concentrations of pathological and inflammatory proteins were obtained at the "Aging, Dementia and TBI Study" open database. We used the area fraction fractionator stereological methodology to quantify the Aß burden in the gray and white matter within each cortical region. We found higher Aß burdens in the TCx of AD octogenarians compared to CU ones. We also found higher Aß loads in the PCx of AD nonagenarians than in AD octogenarians. Moreover, AD women exhibited increased Aß deposition compared to CU women. Interestingly, we observed a negative correlation between education years and Aß burden in the white matter of both cortices in CU samples. In AD brains, the Aß40, Aß42, and pTau181 isoforms of Aß and Tau proteins were positively correlated with the Aß burden. Additionally, in the TCx of AD donors, the proinflammatory cytokine TNFα showed a positive correlation with the Aß load. These novel findings contribute to understanding the interplay between sociodemographic characteristics, local inflammatory signaling, and the development of AD-related pathology in the cerebral cortex.

Abnormal biomarkers predict complex FAS or FADD defects missed by exome sequencing.

BACKGROUND: Elevated TCRαß+CD4-CD8- double-negative T cells (DNT) and serum biomarkers help identify FAS mutant patients with autoimmune lymphoproliferative syndrome (ALPS). However, in some patients with clinical features and biomarkers consistent with ALPS, germline or somatic FAS mutations cannot be identified on standard exon sequencing (ALPS-undetermined: ALPS-U). OBJECTIVE: We sought to explore whether complex genetic alterations in the FAS gene escaping standard sequencing or mutations in other FAS pathway-related genes could explain these cases. METHODS: Genetic analysis included whole FAS gene sequencing, copy number variation analysis, and sequencing of FAS cDNA and other FAS pathway-related genes. It was guided by FAS expression analysis on CD57+DNT, which can predict somatic loss of heterozygosity (sLOH). RESULTS: Nine of 16 patients with ALPS-U lacked FAS expression on CD57+DNT predicting heterozygous "loss-of-expression" FAS mutations plus acquired somatic second hits in the FAS gene, enriched in DNT. Indeed, 7 of 9 analyzed patients carried deep intronic mutations or large deletions in the FAS gene combined with sLOH detectable in DNT; 1 patient showed a FAS exon duplication. Three patients had reduced FAS expression, and 2 of them harbored mutations in the FAS promoter, which reduced FAS expression in reporter assays. Three of the 4 ALPS-U patients with normal FAS expression carried heterozygous FADD mutations with sLOH. CONCLUSION: A combination of serum biomarkers and DNT phenotyping is an accurate means to identify patients with ALPS who are missed by routine exome sequencing.

Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse.

Hippocampal GluN2B subunit-containing NMDAR (GluN2B-NMDAR) activation during recall destabilizes fear extinction memory, which must undergo brain-derived neurotrophic factor (BDNF)-dependent reconsolidation to persist. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr protein kinase essential for hippocampus-dependent memory processing that acts downstream GluN2B-NMDAR and controls BDNF expression, but its participation in fear extinction memory reconsolidation has not yet been studied. Using a combination of pharmacological and behavioral tools, we found that in adult male Wistar rats, intra dorsal-CA1 administration of the CaMKII inhibitors autocamtide-2-related inhibitory peptide (AIP) and KN-93, but not of their inactive analogs scrambled AIP and KN-92, after fear extinction memory recall impaired extinction and caused GluN2B-NMDAR-dependent recovery of fear. Our results indicate that hippocampal CaMKII is necessary for fear extinction reconsolidation, and suggest that modulation of its activity around the time of recall controls the inhibition that extinction exerts on learned fear.

[Recommendations for psoriasis treatment in Pediatrics]. / Recomendaciones para el tratamiento de la psoriasis en Pediatría.

Introduction: in one third of patients with psoriasis, symptoms start during childhood and adolescence, with a strong emotional and psychosocial impact. Objective: to develop a guideline for the systemic treatment of psoriasis in pediatric patients by means of recommendations based on the best available evidence. Materials and methods: Sources: articles indexed in PubMed, Epistemonikos, Google Scholar, Cochrane Library and Scielo, published between January 2010 and May 2022, in English, Spanish and Portuguese. Study selection: evidence-based clinical practice guidelines, systematic reviews, meta-analyses, randomized controlled studies, observational studies (case-control, cohort studies, real-life registries) and evaluations of biosimilar drugs in patients up to and including 17 years of age were considered. The keywords "psoriasis" and "treatment" were used in all three languages. Data extraction: the literature was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) recommendations. Data synthesis: evidence tables were developed and analyzed by the expert committee. The questions for the development of recommendations were based on the PICO system (population, intervention, comparison, outcome). Results: A total of 8 recommendations and 7 points of good practice were developed. The direction and strength of the recommendations were expressed according to the GRADE system. Conclusions: the final decision on a specific therapy should be based on the best opinion of the treating physician, the individual characteristics, and the values and preferences of the patients and their caregivers.

Introducción: un tercio de los pacientes con psoriasis comienzan con sus síntomas en la niñez y la adolescencia, con fuerte impacto emocional y psicosocial. Objetivo: elaborar una guía de tratamiento sistémico de la psoriasis en pacientes pediátricos mediante recomendaciones fundamentadas en la mejor evidencia disponible. Materiales y métodos: Fuentes: artículos indexados en PubMed, Epistemonikos, Google Académico, Cochrane Library y Scielo, publicados entre enero de 2010 y mayo de 2022, en inglés, castellano y portugués. Selección de estudios: se consideraron guías de práctica clínica basadas en la evidencia, revisiones sistemáticas, metanálisis, estudios controlados y aleatorizados, estudios observacionales (casos y controles, estudios de cohortes, registros de la vida real) y evaluaciones de medicamentos biosimilares en pacientes de hasta 17 años de edad inclusive. Se utilizaron las palabras clave "psoriasis" y "tratamiento" en los tres idiomas. Extracción de datos: la bibliografía fue evaluada mediante las recomendaciones del sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Síntesis de datos: elaboración de tablas de evidencia que fueron analizadas por el comité de expertos. Las preguntas para el desarrollo de recomendaciones se fundamentaron en el sistema PICO (población, intervención, comparación, outcome [desenlace]). Resultados: se elaboraron un total de 8 recomendaciones y 7 puntos de buena práctica. La dirección y fuerza de las recomendaciones se expresaron de acuerdo con lo sugerido por el sistema GRADE. Conclusiones: la decisión final de una terapia específica se fundamentará en la mejor opinión del médico tratante, las características individuales, y los valores y preferencias de los pacientes y sus cuidadores.

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative.

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Mordedura humana em dorso nasal: relato de caso / Human bite on nasal dorsum: case report / Mordida humana en espalda nasal: reporte de caso

As lesões na face decorrentes de mordedura humana estão entre os tipos de trauma causados por violência interpessoal. Injúrias causadas nesta região podem gerar uma série de morbidades como perdas teciduais importantes, infecções, além de cicatrizes irreversíveis quando a ferida é passível de reparo, portanto, os cuidados pós-trauma devem visar à minimização de cura, além da funcionalidade, buscando o máximo de estética possível. Este trabalho tem como objetivo relatar um caso clínico de mordida humana em região de dorso nasal, com avulsão da ponta nasal, atendida no Hospital da Restauração Governador Paulo Guerra, Recife-PE, pelo serviço de Cirurgia Buco-Maxilo-Facial. Procedeu-se com reparo primário e antibioticoterapia profilática, no qual o resultado do tratamento foi considerado satisfatório, boa cicatrização tecidual e sem queixas funcionais e estéticas... (AU)

Injuries to the face resulting from human bite are among the types of trauma caused by interpersonal violence. The injuries caused in this region, can generate a series of morbidities such as major tissue loss, infection, and irreversible scarring when the wound is repairable, therefore, posttrauma care should aim to minimize healing, in addition to functionality, seeking maximum aesthetics as possible. This paper aims to report a clinical case of human bite in the nasal dorsum region, with avulsion of the nasal tip, attended at the Hospital da Restauração Governador Paulo Guerra, Recife-PE, by the service of Oral and Maxillofacial Surgery. It was proceeded with primary repair and prophylactic antibiotic therapy, in which the result of the treatment was considered satisfactory, good tissue healing and without functional and aesthetic complaints... (AU)

Las lesiones faciales producidas por mordeduras humanas se encuentran entre los tipos de traumatismos causados por la violencia interpersonal. Las lesiones causadas en esta región pueden generar una serie de morbilidades como la pérdida de tejidos importantes, la infección y la cicatrización irreversible cuando la herida es reparable, por lo tanto, los cuidados posttrauma deben tener como objetivo minimizar la cicatrización, además de la funcionalidad, buscando la máxima estética posible. Este trabajo tiene como objetivo reportar un caso clínico de mordedura humana en la región del dorso nasal, con avulsión de la punta nasal, atendido en el Hospital da Restauração Governador Paulo Guerra, Recife-PE, por el servicio de Cirugía Oral y Maxilofacial. Se procedió a la reparación primaria y a la terapia antibiótica profiláctica, en la que el resultado del tratamiento se consideró satisfactorio, con buena cicatrización de los tejidos y sin quejas funcionales y estéticas... (AU)

CAD-CAM natural restorations-Reproducing nature using a digital workflow.

OBJECTIVES: Natural restorations combine digital workflow and shell technique to create CAD/CAM restorations with the form and texture of natural teeth. This case report describes an interdisciplinary digital workflow combined with CAD/CAM natural restorations to achieve the naturalness of an anterior rehabilitation. CLINICAL CONSIDERATIONS: A 38-year-old patient attended to the office with esthetic issues. An interdisciplinary treatment plan was conducted, which included periodontal surgery to recreate the gingival contour, associated with bleaching and manufacturing CAD/CAM ceramic veneers to return an optimal teeth surface texture and shape. CONCLUSIONS: The design and manufacturing of CAD/CAM natural restorations using a digital workflow allowed a predictable result and overcame the limitations of conventional shell technique. CLINICAL SIGNIFICANCE: Conventional shell technique is used to create restorations with the form and texture of natural teeth. This article presents a combination of the conventional shell technique with a digital workflow, facilitating the design and manufacturing of CAD/CAM natural restorations.

The landscape of vitiligo in Latin America: a call to action.

Vitiligo is a chronic pigmentary condition and severely impacts patient quality of life (QoL). It is an underrecognized burden for patients, healthcare systems, and society in Latin America (LA). This paper examines the journey of a vitiligo patient in LA and assesses the disease landscape. Americas Health Foundation (AHF) assembled a panel of six Argentine, Brazilian, Colombian, and Mexican vitiligo experts. On 10-12 May 2022, they met in a virtual meeting. Each panelist wrote a short paper on barriers to vitiligo diagnosis and treatment in LA before the meeting. AHF staff moderated as the panel reviewed and modified each paper over three days. The panel approved the recommendations based on research, professional opinion, and personal experience. The panel agreed that lack of disease awareness and research, social ostracization, and limited therapeutic options hinder patients in their quest for diagnosis and treatment. In addition to the medical and psychological difficulties associated with vitiligo, problems connected to the Latin American healthcare system may negatively impact diagnosis, prognosis, and treatment. Access to timely diagnosis and treatment is crucial for improving outcomes. Governments, medical societies, academics, patient organizations, industry, and the public must unite to eliminate these challenges.

Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism.

Autism spectrum disorder (ASD) is manifested by abnormal cell numbers and patches of gene expression disruption in higher-order brain regions. Here, we investigated whether layer-specific changes in glia/neuron ratios (GNR) characterize patches in the dorsolateral prefrontal cortex (DL-PFC) of children with ASD. We analyzed high-resolution digital images of postmortem human brains from 11 ASD and 11 non-ASD children obtained from the Autism Study of the Allen Human Brain Atlas. We found the GNR is overall reduced in the ASD DL-PFC. Moreover, layers II-III belonging to patches presented a lower GNR in comparison with layers V-VI. We here provide a new insight into how brain cells are arranged within patches that contributes to elucidate how neurodevelopmental programs are altered in ASD.

Clinical acute presentation of lumbar facet joint ganglia with bilateral sciatica / Apresentação clínica aguda de quistos facetários lombares com ciatalgia bilateral / Presentación clinica aguda de quistes facetarios lumbares con dolor ciático bilateral

ABSTRACT Facet joint ganglia are benign cystic lesions located adjacent to a facet joint. The majority is asymptomatic. However, can cause important low-back pain and radiculopathy. Neurogenic deficit, claudication, and cauda equina syndrome have also been reported. The authors report two cases of acute low back pain with bilateral sciatica, dorsal foot dysesthesia, and hallux dorsiflexion/extension deficit, due to the presence of encapsulated cysts adjacent to the facet joints causing a significant reduction of the spinal canal. Urgent surgical decompression was performed in both patients with an uneventful recovery. Symptomatic facet joint ganglia is a highly unusual cause of back pain, although it can present with acute onset of bilateral sciatica and canal stenosis requiring urgent surgical decompression. This paper highlights facet joint synovial as a differential diagnosis of lumbar pain and describes two different surgical approaches with good outcomes. Level of Evidence IV; Case Series.

RESUMO: Os quistos facetários são lesões císticas benignas localizadas adjacentes a uma articulação facetária. A maioria é assintomática. No entanto, podem ser causa de importante dor lombar e radiculopatia. Estão ainda relatados casos de déficit neurogénico, claudicação e síndrome de cauda equina. Os autores apresentam dois casos de dor lombar aguda com ciatalgia bilateral, disestesia do dorso do pé e défice na dorsiflexão/extensão do hálux, causados por uma redução significativa do canal medular devido à presença de quistos encapsulados adjacentes às articulações facetarias. Os doentes foram submetidos a descompressão cirúrgica urgente com uma excelente recuperação. Os quistos facetários sintomáticas são uma causa rara de lombalgia, porém podem apresentar-se inicialmente com um quadro agudo de ciatalgia bilateral e estenose canalar com necessidade de descompressão cirúrgica urgente. Este artigo realça os quistos facetários como diagnóstico diferencial de lombalgia e descreve duas abordagens cirúrgicas diferentes com bons resultados. Nível de Evidência IV; Série de Casos.

RESUMEN: Los quistes facetarios son lesiones quísticas benignas situadas junto a una articulación facetaria. La mayoría es asintomática. Pero pueden causar dolor lumbar y radiculopatía importantes. También se han descrito déficit neurogénico, claudicación y síndrome de cauda equina. Los autores presentan dos casos de lumbalgia aguda con dolor ciático bilateral, disestesia del dorso del pie y déficit en la dorsiflexión/extensión del hallux, causados por una reducción significativa del canal medular debido a la presencia de quistes encapsulados adyacentes a las articulaciones facetarias. Los pacientes fueron sometidos a descompresión quirúrgica urgente con una excelente recuperación. Los quistes facetarios sintomáticos son una causa poco frecuente de lumbalgia, aunque pueden presentarse inicialmente con un cuadro agudo de dolor ciático bilateral y estenosis del canal que requiere descompresión quirúrgica urgente. Este artículo destaca los quistes facetarios como diagnóstico diferencial de la lumbalgia y describe dos abordajes quirúrgicos diferentes con buenos resultados. Nivel de Evidencia IV; Serie de Casos.

Age, Education Years, and Biochemical Factors Are Associated with Selective Neuronal Changes in the Elderly Hippocampus.

Brain aging involves regional alterations of specific cellular subpopulations in the human hippocampus: a network hub for memory consolidation. The present study investigates whether age, sex, education years, and the concentration of neuropathological and inflammatory proteins influence neuronal-type marker expression in the elderly hippocampus. We analyzed the digital images (1 µm/pixel) of postmortem hippocampal sections from 19 non-demented individuals (from 78 to 99 years). This material was obtained from the "Aging Dementia and TBI Study" open database. Brain samples were processed through in situ hybridization (ISH) for the immunodetection of VGLUT1 (glutamatergic transporter) and GAT1 (GABAergic transporter) and mRNAs and Luminex protein quantifications. After image acquisition, we delineated the dentate gyrus, CA 3/2, and CA1 hippocampal subdivisions. Then, we estimated the area fraction in which the ISH markers were expressed. Increased VGLUT1 was observed in multiple hippocampal subfields at late ages. This glutamatergic marker is positively correlated with beta-amyloid and tau proteins and negatively correlated with interleukin-7 levels. Additionally, education years are positively correlated with GAT1 in the hippocampus of elderly women. This GABAergic marker expression is associated with interferon-gamma and brain-derived neurotrophic factor levels. These associations can help to explain how hippocampal sub-regions and neurotransmitter systems undergo distinct physiological changes during normal aging.

Odontoma composto extenso em paciente pediátrico: relato de caso / Extended compound odontoma in a pediatric patient: case report / Odontoma compuesta ampliada en paciente pediátrico: reporte de caso

Introdução: Odontomas são tumores odontogênicos, considerados hamartomas de desenvolvimento que frequentemente interferem na erupção dentária. O presente estudo tem como objetivo relatar o caso clínico de odontoma composto em região posterior da mandíbula, desde o achado radiográfico até o momento cirúrgico e confirmação diagnóstica com exame histopatológico. Relato do caso: trata-se de paciente do sexo feminino, 7 anos, branca, encaminhada da Unidade de Saúde da Família (USF) ao ambulatório do Serviço de Cirurgia e Traumatologia Buco-Maxilo-Facial do Hospital Universitário Oswaldo Cruz (UHOC), devido a um achado radiográfico radiopaco, de limites bem definidos, com halo radiolúcido circundante, no corpo da mandíbula do lado esquerdo, entre as raízes dos dentes 74 e 75. O tratamento proposto foi a excisão cirúrgica conservadora sob anestesia geral. Após a retirada da lesão, foram identificadas calcificações múltiplas diferentes tamanhos e formas, de assemelhando-se a dentículos, encaminhadas para exame histopatológico e confirmando o diagnóstico de odontoma composto. Após 7 dias, observou-se um processo de cicatrização satisfatório. Ela será acompanhada para analisar a progressão do reparo e movimentação da bolsa óssea na dentição permanente na região. Considerações finais: Portanto, recomenda-se o tratamento cirúrgico conservador, através da remoção completa da lesão e preservação máxima dos dentes retidos. Para isso, a identificação na fase inicial e o tratamento adequado são essenciais... (AU)

Introduction: Odontomas are odontogenic tumors, considered developmental hamartomas that often interfere with tooth eruption. The present study aims to report the clinical case of compound odontoma in the posterior region of the jaw, from the radiographic finding to the surgical moment and diagnostic confirmation with histopathological examination. Case report: this is a female patient, 7 years old, white, referred from the Family Health Unit (FHU) to the outpatient clinic of the Oral and Maxillofacial Surgery and Traumatology Service of the Oswaldo Cruz University Hospital (OCUH), due to a radiopaque radiographic finding, with well-defined limits and a surrounding radiolucent halo, in the body of the jaw on the left side, between the roots of teeth 74 and 75. The proposed treatment was conservative surgical excision under general anesthesia. After removal of the lesion, multiple calcifications of different sizes and shapes were identified, resembling denticles, referred for histopathological examination and confirming the diagnosis of compound odontoma. After 7 days, a satisfactory healing process was observed. She will be followed up to analyze the progression of bone pocket repair and movement in permanent dentition in the region. Final considerations: Therefore, conservative surgical treatment is recommended, through the complete removal of the lesion and maximum preservation of retained teeth. For this identification at an early stage and proper treatment are essential... (AU)

Use of multisensory stimulation in institutionalized older adults with moderate or severe dementia.

The Multisensory Stimulation Program can help manage behavioral and psychological symptoms of dementia. Objective: The objective of this study was to investigate the effects of the Multisensory Stimulation Program on behavioral, mood, and biomedical parameters of older adults with moderate and severe dementia compared to a control group not submitted to this program. Methods: This study is an interventional, parallel, open-label, quasi-experimental clinical trial, which is quantitative and qualitative in nature and is also an exploratory type. The sample was divided for convenience into intervention group (IG) and control group (GC) that did not participate in the Multisensory Stimulation Program. Data analysis included descriptive statistics, nonparametric tests (two-tailed alpha value of 0.1 was applied), and thematic content analysis. Results: The sample consisted of 20 older adults (IG=10 and GC=10), with a mean age of 83 years, an average of 3 years of education, and moderate or severe dementia. Reduction in intervention group behavioral changes (p=0.059) and numerical improvement in intervention group cognition were observed. A decrease in heart rate (p<0.05) and diastolic blood pressure (p<0.05) was observed before and immediately after the session in the intervention group. The caregivers described engaged behavior in intervention group, while they reported apathetic behavior in control group. Session records described verbal and nonverbal communication and sustained attention for more than 3 min regarding the sensory resource explored. Conclusions: The Multisensory Stimulation Program could be a new look at the health care practices performed in the nursing homes that consider the older adults' sensory preferences and may help with dementia behavior management.

Um programa de estimulação multissensorial pode auxiliar no manejo dos sintomas comportamentais e psicológicos da demência. Objetivo: Investigar os efeitos do programa de estimulação multissensorial sobre o comportamento, o humor e parâmetros biomédicos de idosos com demência moderada e grave, quando comparados a um grupo controle não submetido a esse programa. Métodos: Estudo de intervenção quase experimental, paralelo, mascaramento aberto, de natureza quantitativa e qualitativa, do tipo exploratório. Amostra foi dividida igualmente por conveniência entre grupo de intervenção (GI) e grupo controle (GC), que não participou do programa de estimulação multissensorial. estatística descritiva, testes não paramétricos (valor alfa bicaudal de 10% aplicado) e análise temática de conteúdo. Resultados: Amostra composta de 20 idosos (GI=10 e GC=10), com média de idade de 83 anos, média de três anos de escolaridade e demência moderada ou grave. Houve redução de alterações comportamentais (p=0.059) e melhora numérica no desempenho da cognição de Grupo de Intervenção. Observou-se diminuição da frequência cardíaca (p<0.05) e da pressão arterial diastólica (p<0.05) antes e imediatamente depois da sessão no grupo de intervenção. Os cuidadores descreveram comportamento engajado no grupo de intervenção, enquanto relataram comportamento apático no grupo controle. Os registros da sessão descreveram ações de interação verbal e não verbal e atenção sustentada por mais de três min diante do recurso sensorial explorado. Conclusões: O programa de estimulação multissensorial poderia ser um novo olhar sobre as práticas de saúde realizadas em instituições de longa permanência de idosos que considerem as preferências sensoriais do idoso, e pode auxiliar no manejo do comportamento demencial.

Use of multisensory stimulation in institutionalized older adults with moderate or severe dementia / Uso da estimulação multissensorial em idosos institucionalizados com demência moderada ou grave

ABSTRACT. The Multisensory Stimulation Program can help manage behavioral and psychological symptoms of dementia. Objective: The objective of this study was to investigate the effects of the Multisensory Stimulation Program on behavioral, mood, and biomedical parameters of older adults with moderate and severe dementia compared to a control group not submitted to this program. Methods: This study is an interventional, parallel, open-label, quasi-experimental clinical trial, which is quantitative and qualitative in nature and is also an exploratory type. The sample was divided for convenience into intervention group (IG) and control group (GC) that did not participate in the Multisensory Stimulation Program. Data analysis included descriptive statistics, nonparametric tests (two-tailed alpha value of 0.1 was applied), and thematic content analysis. Results: The sample consisted of 20 older adults (IG=10 and GC=10), with a mean age of 83 years, an average of 3 years of education, and moderate or severe dementia. Reduction in intervention group behavioral changes (p=0.059) and numerical improvement in intervention group cognition were observed. A decrease in heart rate (p<0.05) and diastolic blood pressure (p<0.05) was observed before and immediately after the session in the intervention group. The caregivers described engaged behavior in intervention group, while they reported apathetic behavior in control group. Session records described verbal and nonverbal communication and sustained attention for more than 3 min regarding the sensory resource explored. Conclusions: The Multisensory Stimulation Program could be a new look at the health care practices performed in the nursing homes that consider the older adults' sensory preferences and may help with dementia behavior management.

RESUMO. Um programa de estimulação multissensorial pode auxiliar no manejo dos sintomas comportamentais e psicológicos da demência. Objetivo: Investigar os efeitos do programa de estimulação multissensorial sobre o comportamento, o humor e parâmetros biomédicos de idosos com demência moderada e grave, quando comparados a um grupo controle não submetido a esse programa. Métodos: Estudo de intervenção quase experimental, paralelo, mascaramento aberto, de natureza quantitativa e qualitativa, do tipo exploratório. Amostra foi dividida igualmente por conveniência entre grupo de intervenção (GI) e grupo controle (GC), que não participou do programa de estimulação multissensorial. estatística descritiva, testes não paramétricos (valor alfa bicaudal de 10% aplicado) e análise temática de conteúdo. Resultados: Amostra composta de 20 idosos (GI=10 e GC=10), com média de idade de 83 anos, média de três anos de escolaridade e demência moderada ou grave. Houve redução de alterações comportamentais (p=0.059) e melhora numérica no desempenho da cognição de Grupo de Intervenção. Observou-se diminuição da frequência cardíaca (p<0.05) e da pressão arterial diastólica (p<0.05) antes e imediatamente depois da sessão no grupo de intervenção. Os cuidadores descreveram comportamento engajado no grupo de intervenção, enquanto relataram comportamento apático no grupo controle. Os registros da sessão descreveram ações de interação verbal e não verbal e atenção sustentada por mais de três min diante do recurso sensorial explorado. Conclusões: O programa de estimulação multissensorial poderia ser um novo olhar sobre as práticas de saúde realizadas em instituições de longa permanência de idosos que considerem as preferências sensoriais do idoso, e pode auxiliar no manejo do comportamento demencial.

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Neoantigens as potential vaccines in hepatocellular carcinoma.

BACKGROUND: Neoantigens, new immunogenic sequences arising from tumor mutations, have been associated with response to immunotherapy and are considered potential targets for vaccination. Hepatocellular carcinoma (HCC) is a moderately mutated tumor, where the neoantigen repertoire has not been investigated. Our aim was to analyze whether tumors in HCC patients contain immunogenic neoantigens suitable for future use in therapeutic vaccination. METHODS: Whole-exome sequencing and RNAseq were performed in a cohort of fourteen HCC patients submitted to surgery or liver transplant. To identify mutations, single-nucleotide variants (SNV) originating non-synonymous changes that were confirmed at the RNA level were analyzed. Immunogenicity of putative neoAgs predicted by HLA binding algorithms was confirmed by using in vitro HLA binding assays and T-cell stimulation experiments, the latter in vivo, by immunizing HLA-A*02.01/HLA-DRB1*01 (HHD-DR1) transgenic mice, and in in vitro, using human lymphocytes. RESULTS: Sequencing led to the identification of a median of 1217 missense somatic SNV per patient, narrowed to 30 when filtering by using RNAseq data. A median of 13 and 5 peptides per patient were predicted as potential binders to HLA class I and class II molecules, respectively. Considering only HLA-A*02.01- and HLA-DRB1*01-predicted binders, 70% demonstrated HLA-binding capacity and about 50% were immunogenic when tested in HHD-DR1 mice. These peptides induced polyfunctional T cells that specifically recognized the mutated but not the wild-type sequence as well as neoantigen-expressing cells. Moreover, coimmunization experiments combining CD8 and CD4 neoantigen epitopes resulted in stronger CD8 T cell responses. Finally, responses against neoantigens were also induced in vitro using human cells. CONCLUSION: These results show that mutations in HCC tumors may generate immunogenic neoantigens with potential applicability for future combinatorial therapeutic strategies.