Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model.

Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure. Here, we developed a nano-in-micro device combining lipid vesicles (LVs) and dissolving microneedle array patches (DMAPs) for targeted skin delivery. CsA-LVs allowed the effective incorporation of CsA in the hydrophilic DMAP matrix despite the hydrophobicity of the drug. Polymeric matrix composed of poly (vinyl alcohol) (5% w/v), poly (vinyl pyrrolidine) (15% w/v) and CsA-LV dispersion (10% v/v) led to the formation of CsA-LVs@DMAPs with adequate mechanical properties to penetrate the stratum corneum barrier. The safety and biocompatibility were ensured in an in vitro viability test using HaCaT keratinocytes and L929 fibroblast cell lines. Ex vivo permeability studies in a Franz-diffusion cell setup showed effective drug retention in the skin structure. Finally, CsA-LVs@DMAPs were challenged in an in vivo murine model of delayed-type hypersensitivity to corroborate their potential to ameliorate skin inflammatory conditions. Different findings like photon emission reduction in bioluminescence study, normalisation of histological damage and decrease of inflammatory cytokines point out the effectivity of CsA-LVs@DMAPs to treat these conditions. Overall, our study demonstrates that CsA-LVs@DMAPs can downregulate the skin inflammatory environment which paves the way for their clinical translation and their use as an alternative to corticosteroid-based therapies.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1ß maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1ß and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.

Adipose Tissue Protects against Hepatic Steatosis in Male Rats Fed a High-Fat Diet plus Liquid Fructose: Sex-Related Differences.

Non-alcoholic fatty liver disease is a sexual dimorphic disease, with adipose tissue playing an essential role. Our previous work showed that female rats fed a high-fat high-fructose diet devoid of cholesterol (HFHFr) developed simple hepatic steatosis dissociated from obesity. This study assessed the impact of the HFHFr diet on the male rat metabolism compared with data obtained for female rats. A total of 16 Sprague Dawley (SD) male rats were fed either a control (standard rodent chow and water) or HFHFr (high-fat diet devoid of cholesterol, plus 10% fructose in drinking water) diet for 3 months. Unlike female rats, and despite similar increases in energy consumption, HFHFr males showed increased adiposity and hyperleptinemia. The expression of hormone-sensitive lipase in the subcutaneous white adipose tissue was enhanced, leading to high free fatty acid and glycerol serum levels. HFHFr males presented hypertriglyceridemia, but not hepatic steatosis, partially due to enhanced liver PPARα-related fatty acid ß-oxidation and the VLDL-promoting effect of leptin. In conclusion, the SD rats showed a sex-related dimorphic response to the HFHFr diet. Contrary to previous results for HFHFr female rats, the male rats were able to expand the adipose tissue, increase fatty acid catabolism, or export it as VLDL, avoiding liver lipid deposition.

Validation of a Nursing Workload Measurement Scale, Based on the Classification of Nursing Interventions, for Adult Hospitalization Units.

We conducted validation of a scale to measure nursing workloads, previously designed using NIC interventions within the four nursing functions (patient care, teaching, management, and research). METHODS: This is an analytical, descriptive, prospective, and observational study using qualitative methodology (focus groups and in-depth interviews) with a quantitative and qualitative section (committee of experts and real application of the scale through a validation pilot and with multicentric application, including hospitalization units of internal medicine and surgery of four hospitals). Qualitative analysis was performed with Atlas.ti8 and quantitative analysis with R. RESULTS: Qualitatively, all the participants agreed on the need to measure workloads in all nursing functions with standardized terminology. The expert committee found greater relevance (91.67%) in "prevention" and "health education" as well as consistency with the construct and adequate wording in 99% of the selected items. In the pilot test and multicenter application, the nurses spent more time on the caring dimension, in the morning shift, and on the items "self-care", "medication", "health education", "care of invasive procedures", "wounds care", "comfort", and "fluid therapy". Cronbach's alpha 0.727, composite reliability 0.685, AVE 0.099, and omega coefficient 0.704 were all acceptable. Construct validity: KMO 0.5 and Bartlett's test were significant. CONCLUSIONS: The scale can be considered valid to measure nursing workloads, both qualitatively in obtaining the consensus of experts and health personnel and quantitatively, with acceptable reliability and validity superior to other similar scales.

Proteomic characterization of spinal cord synaptoneurosomes from Tg-SOD1/G93A mice supports a role for MNK1 and local translation in the early stages of amyotrophic lateral sclerosis.

The isolation of synaptoneurosomes (SNs) represents a useful means to study synaptic events. However, the size and density of synapses varies in different regions of the central nervous system (CNS), and this also depends on the experimental species studied, making it difficult to define a generic protocol for SNs preparation. To characterize synaptic failure in the spinal cord (SC) in the Tg-SOD1/G93A mouse model of amyotrophic lateral sclerosis (ALS), we applied a method we originally designed to isolate cortical and hippocampal SNs to SC tissue. Interestingly, we found that the SC SNs were isolated in a different gradient fraction to the cortical/hippocampal SNs. We compared the relative levels of synaptoneurosomal proteins in wild type (WT) animals, with control (Tg-SOD1) or Tg-SOD1/G93A mice at onset and those that were symptomatic using iTRAQ proteomics. The results obtained suggest that an important regulator of local synaptic translation, MNK1 (MAP kinase interacting serine/threonine kinase 1), might well influence the early stages of ALS.

Multicenter application of a nursing workload measurement scale in adult hospitalization units.

Objectives: The study aimed to the multicenter application of a nursing workload measurement scale in the internal medicine and surgery adults hospitalization units. Methods: The study design was a multicenter, observational, and descriptive study. A multicenter application of the MIDENF® nursing workload measurement scale was carried out, which consists of 21 items, and covers the four nursing functions (patient care items, teaching, manager, and researcher), in units of hospitalization of adults of internal medicine and surgery of four different hospitals. Each item contains one or more of the nursing interventions of Nursing Interventions Classification (NIC) and has an assigned time, after comparing the real time it takes to perform each intervention with the North American Nursing Diagnosis Association (NANDA) standardized time. The study was carried out during nine months of the year 2020, measuring two days each month in the three work shifts (morning, evening, and night) to all patients admitted on the days of measurement in the indicated units. Results: The descriptive and inferential analysis of 11,756 completed scales, 5,695 in general surgery and 6,061 in internal medicine, showed a greater care load for the two units during the morning shift (227,034 min in general surgery, 261,835 min in internal medicine), especially in the items of "self-care", "medication", "common invasive procedures", "fluid therapy", and "patient and family support", while the managerial function was similar during the three work shifts in the two units studied, getting values between 57,348 and 62,901 min. In the analysis by shift and unit, statistical significance was obtained both for the total workload and the four nursing functions(P < 0.001). Conclusions: It is shown that the use of validated scales with the standardized language of nursing functions, adapted to the units, provides objective information to adjust the nursing staff to the real situation of care in any hospital and unit where it is applied, improving quality and patient safety.

Relationship between Job Satisfaction and Workload of Nurses in Adult Inpatient Units.

Among Nursing and Psychology professionals, the job satisfaction of those in Adult Inpatient Units is analyzed, with a new scale to measure nursing workloads validated. Objective: The objective of this study was to relate nursing workloads to professional job satisfaction. Methods: This is an observational, analytical, descriptive, concurrent and quantitative study, which used the Overall Job Satisfaction scale and subscales therein, to identify global satisfaction-intrinsic or related to motivational factors and extrinsic or associated with hygienic factors-in nursing professionals (n = 104) from eight Inpatient Units of Internal Medicine and Surgery, in four hospital centers, to describe job satisfaction in the professionals studied and to find statistically significant associations between job satisfaction and workload (measured with the scale MIDENF®) in the inpatient units where they work. Results: There were higher levels of satisfaction in the variables "relationship with immediate boss" and "relationship with fellow workers", and lower levels in "relationship with senior management" and "organizational system of the unit". In the inferential analysis, the scores were 75.63 for overall satisfaction, 35.28 for intrinsic satisfaction, and 40.36 for extrinsic satisfaction. Conclusions: There is a close relationship between workload and job satisfaction, showing more dissatisfaction regarding organizational aspects and professional recognition.

Triiodothyronine-stimulated dendritic cell vaccination boosts antitumor immunity against murine colon cancer.

Given the ability of dendritic cells (DCs) to modulate other immune players, their manipulation holds great potential for inducing efficient antitumor immunity. However, DC vaccine manufacturing deserve optimization since tumor cell cargo and DC functional state induced by maturation signals influence their in vivo immunogenic potential. We reported that triiodothyronine (T3) stimulates mice DCs' maturation and their ability to promote pro-inflammatory and cytotoxic T-cell responses. This study aimed to evaluate the efficacy of T3-conditioned DC vaccination in a murine model of colon carcinoma, deciphering the molecular players involved; and to examine the effects of T3 on the maturation and activation of human DCs (huDCs). Bone marrow-derived DCs were exposed to T3 and MC38 cancer cells that underwent cell death (MC38-Apo/Nec) by UVB irradiation. Our results showed that MC38-Apo/Nec cells are efficiently uptaken by DCs and that T3 upregulates CD86 expression with increased production of the pro-inflammatory cytokines IL-12, IL-6 and TGF-ß. In a colon cancer model, vaccination with T3-stimulated and tumor antigen-loaded DCs inhibited tumor growth in wild type mice, an effect that was eliminated in IL-17-deficient animals. Notably, secretion of high levels of IFN-γ and IL-17, induction of Th1, Th17 and tumor-specific cytotoxic T lymphocytes characterized the antitumor response upon vaccination. Moreover, our initial findings demonstrated a significant increase in CD86 expression and IL-12 production by huDCs induced by T3. Overall, these results reinforce the adjuvant properties of T3-conditioned DCs to potentiate T-cell-mediated antitumor immunity and support promising advances in the translation process to human oncotherapy.

Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling.

Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.

Proteína C reactiva y su relación con las complicaciones posoperatorias en cirugía colorrectal electiva / Association between C-reactive protein and postoperative complications in elective colorectal surgery

RESUMEN Antecedentes: el uso de la proteína C reactiva (PCR) ha adquirido relevancia como identificador de complicaciones posoperatorias La morbilidad en cirugía colorrectal se estima en un 30% de los pacientes operados, lo que demanda medidas para su temprana identificación y terapéutica. Objetivo: describir las curvas de mediciones sucesivas de PCR y su relación con el desarrollo de complicaciones posoperatorias y niveles de glóbulos blancos en una serie de pacientes operados de cirugía colorrectal. Materiales y métodos: se realizó una revisión retrospectiva sobre un registro prospectivo de 2205 pacientes operados por la División de Cirugía Gastroenterológica del Hospital de Clínicas, entre enero de 2019 y julio de 2020. Se incluyeron 69 pacientes que cumplieron con los criterios de selección. Se consignaron datos del seguimiento clínico y dosaje de PCR, recuento de glóbulos blancos, vía de abordaje y desarrollo de complicaciones. Resultados: el promedio de edad fue de 59 años (DS 13,6; rango 33-85), 31 fueron hombres (43%). La tasa de complicaciones fue del 13,04%; más frecuente fue la fístula anastomótica (fístula, colección), seguida por complicaciones de la herida (hematoma, evisceración). Todos los pacientes mostraron un ascenso inicial del valor de PCR entre el 2° y 3er día, en relación con la lesión quirúrgica, los no complicados presentaron una cinética de descenso y los complicados. curvas de segundo ascenso o no descenso en las mediciones seriadas de PCR, y exhibían valores superiores de PCR cada día Se advirtieron diferencias estadísticamente significativas entre los valores de proteína C reactiva al 5° día posoperatorio en el subgrupo de pacientes complicados con respecto a aquellos con un curso indolente (28 mg/dL vs. 6,1 mg/dL, p < 0,001; IC: 11,24-39,61). hubo diferencia significativa al 5o día entre complicados y no complicados, independientemente de la vía de abordaje. con un valor de corte de PCR de 10,92 mg/dL obtuvimos una sensibilidad del 87,50% y una especificidad del 100% para excluir complicaciones. Conclusiones: la medición de la proteína C reactiva de forma seriada en los posoperatorios de cirugía colorrectal mostró un correlato con la identificación temprana de las complicaciones en nuestra serie, tanto en sus valores absolutos diarios como en la cinética de su comportamiento. se formula el uso de valores de corte para el alta segura.

ABSTRACT Background: The use of C-reactive protein (CRP) has gained relevance as a marker of marker of postoperative complications. As the incidence of complications of colorectal surgery is estimated to be of 30%, measures should for their early identification and treatment. Objective: To describe the performance of consecutive CRP determinations and their relationship with the development of postoperative complications and with white blood cell count in a series of patients undergoing colorectal surgery. Materials and methods: A retrospective review was performed using a prospective registry of 2205 patients operated on at the Department of Digestive Surgery of Hospital de Clínicas, between January 2019 and July 2020. A total of 69 patients fulfilling the selection criteria were included. Clinical follow-up data, CRP levels, white blood cell count, type of approach and development of complications were recorded. Results: Mean age was 59 years (SD 13.6; range 33-85) and 31 were men (43%). The complication rate was 13.04%. Anastomotic leak (fistula, fluid collection) was the most common complication, followed by surgical site complications (hematoma, evisceration). All patients showed an initial increase in CRP values between days 2 and 3, in relation with the surgical lesion, and then decreased in those without complications. Patients with complications had second rise or lack of decrease in serial CRP measurements, and higher CRP values each day. There were statistically significant differences between the CRP levels on postoperative day 5 in the subgroup of patients with complications compared with those with an indolent course (28 mg/dL vs. 6.1 mg/dL, p < 0.001; CI: 11.24-39.61). There was a significant difference on day 5 between patients with and without complications, irrespective of the approach. With a cut-off value of CRP of 10.92 mg/dL on postoperative day 5 we obtained a sensitivity of 87.50% and specificity of 100% to rule out complications. Conclusions: Serial determination of CRP in the postoperative period after colorectal surgery was associated with early identification of complications in our series, both in daily absolute values and in the kinetics of its performance. The use of cut-off values for safe discharge is proposed.

Validação qualitativa de uma escala para medir a carga de trabalho de enfermagem em unidades de internação / Validación cualitativa de una escala para medir la carga de trabajo de enfermería en unidades de internación / Qualitative validation of a scale for nursing workloads in hospitalization units

Resumo Objetivo Projetar e validar uma escala para medir a carga de trabalho de enfermagem em Unidades de Internação de Adultos com base na Classificação de Intervenções de Enfermagem (NIC). Métodos Estudo analítico, descritivo, observacional, prospectivo, utilizando principalmente metodologia de pesquisa qualitativa, por meio de grupos focais, comitê de especialistas e entrevistas individuais, para validar uma Escala de Medição da Carga de Trabalho em Unidades de Internação de Adultos, a partir das intervenções selecionadas (NIC), com base nas características inerentes a tais unidades. Foi utilizada seleção aleatória para determinar os participantes (enfermeiros e especialistas) e é representativa das unidades de hospitalização em estudo. O estudo foi realizado de outubro de 2018 a abril de 2019. Resultados Não apenas os grupos focais, mas também as entrevistas individuais e o comitê de especialistas demonstraram concordância sobre a importância de se obter um instrumento para medir a carga de trabalho validado pelos próprios profissionais e representativo de seu trabalho, com linguagem padronizada e adaptada à saúde real. A análise quantitativa conduzida pelo comitê de especialistas mostra uma maior relevância (91,67%) nos itens: "Prevenção" e "Educação para a saúde", bem como a consistência com a construto e a redação apropriada em 99% dos itens selecionados. Os avaliadores mantiveram a ação em todos os itens com uma taxa de aceitação de 75% a 100%. Conclusão O estudo qualitativo realizado fornece os dados necessários para a concepção e validação de uma escala para medir as cargas de trabalho de enfermagem, identificadas a partir das intervenções de enfermagem (NIC), como indicadores da gestão de recursos humanos.

Resumen Objetivo Proyectar y validar una escala para medir la carga de trabajo de enfermería en unidades de internación de adultos con base en la Clasificación de Intervenciones de Enfermería (NIC). Métodos Estudio analítico, descriptivo, observacional, prospectivo, que utilizó principalmente metodología de investigación cualitativa, por medio de grupos focales, comité de especialistas y entrevistas individuales, para validar una Escala de Medición de Carga de Trabajo en Unidades de Internación de Adultos, a partir de las intervenciones seleccionadas (NIC), con base en las características inherentes a tales unidades. Se utilizó selección aleatoria para definir los participantes (enfermeros y especialistas), que es representativa de las unidades de hospitalización en estudio. El estudio fue realizado de octubre de 2018 a abril de 2019. Resultados No solo los grupos focales, como también las entrevistas individuales y el comité de especialistas demostraron concordancia sobre la importancia de obtener un instrumento para medir la carga de trabajo, validado por los propios profesionales y representativo de su trabajo, con un lenguaje estandarizado y adaptado a la salud real. El análisis cuantitativo conducido por el comité de especialistas muestra una mayor relevancia (91,67 %) en los ítems: "Prevención" y "Educación para la salud", así como una consistencia respecto a la elaboración y redacción apropiada en el 99 % de los ítems seleccionados. Los evaluadores mantuvieron la acción en todos los ítems con un índice de aceptación de 75 % a 100 %. Conclusión El estudio cualitativo realizado proporciona los datos necesarios para la elaboración y validación de una escala para medir la carga de trabajo en enfermería, identificada a partir de las intervenciones de enfermería (NIC), como indicadores de la gestión de recursos humanos.

Abstract Objective To design and validate a scale to measure nursing workloads in Adult Hospitalization Units based on Nursing Interventions (NIC). Methods Analytical, descriptive, observational, prospective study, using mainly qualitative research methodology, by means of focus groups, committee of experts and individual interviews, to validate a Workload Measurement Scale in Adult Hospitalization Units, from the selected interventions (NIC) on a basis of the inherent characteristics of such units. A random selection was used to determine the participants (nurses and experts) and it is representative of the hospitalization units under study. It was carried out from October 2018 to April 2019. Results Not only the focus groups but also the individual interviews and the committee of experts conducted agree on the importance of obtaining an instrument to measure workloads validated by the professionals themselves and representative of their work, with standardized language and adapted to actual healthcare. The quantitative analysis conducted by the committee of experts shows a highest relevance (91,67%) in the items: "Prevention" and "Health education", as well as consistency with the construct and appropriate wording in 99% of the items selected. Evaluators maintained the action on all items with a 75% to 100% acceptance rate. Conclusion The qualitative study carried out provides the necessary data for the design and validation of a scale to measure nursing workloads, identified from the nursing interventions (NIC), as indicators of human resources management.

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium.

Leukocyte cell recruitment into the vascular subendothelium constitutes an early event in the atherogenic process. As the effect of the constitutive androstane receptor (CAR) on leukocyte recruitment and endothelial dysfunction is poorly understood, this study investigated whether the role of CAR activation can affect this response and the underlying mechanisms involved. Under physiological flow conditions, TNFα-induced endothelial adhesion of human leukocyte cells was concentration-dependently inhibited by preincubation of human umbilical arterial endothelial cells with the selective human CAR ligand CITCO. CAR agonism also prevented TNFα induced VCAM-1 expression, as well as MCP-1/CCL-2 and RANTES/CCL-5 release in endothelial cells. Suppression of CAR expression with a small interfering RNA abrogated the inhibitory effects of CITCO on these responses. Furthermore, CITCO increased interaction of CAR with Retinoid X Receptor (RXR) and reduced TNFα-induced p38-MAPK/NF-κB activation. In vivo, using intravital microscopy in the mouse cremasteric microcirculation treatment with the selective mouse CAR ligand TCPOBOP inhibited TNFα-induced leukocyte rolling flux, adhesion, and emigration and decreased VCAM-1 in endothelium. These results reveal that CAR agonists can inhibit the initial inflammatory response that precedes the atherogenic process by targeting different steps in the leukocyte recruitment cascade. Therefore, CAR agonists may constitute a new therapeutic tool in controlling cardiovascular disease-associated inflammatory processes.

[Value of the intraoperative pathology in thyroid surgery. Comparison with preoperative aspiration puncture and deferred pathology]. / Valor del estudio patológico intraoperatorio de tiroides. Comparación con la punción aspiración preoperatoria y la patología diferida.

To evaluate the usefulness of intraoperative pathology (IP) in thyroid surgery, a retrospective review of its results in 350 patients was performed in comparison with the results of the preoperative fine-needle biopsy (FNB) and the surgical pathology report (SPR). The FNB was reported according to the Bethesda system as type II in 91 cases (26.0%), type III in 21 (6.0%), type IV in 73 (21.9%), type V in 54 (15.4%), and type VI in 111 (31.7%). The IP showed benign lesions in 137 cases (39.1%), malignancy in 169 (48.2%), and inconclusive results in 44 (12.6%). The SPR results were benign pathology in 161 cases (46%) and carcinoma in 189 (54%); carcinoma was found in 8 patients (5.8%) in whom the IP had reported benignity, and in 12 (27.2%) with IP inconclusive results; 13 of those 20 cases were incidental microcarcinomas. The IP did not report any false positive result (specificity 100 %, sensitivity 89.4%, positive predictive value 100%, negative predictive value 90.0%, and accuracy 94.2%). When discriminated by Bethesda types, the malignant lesions detected by IP and SPR were, respectively: II 3 (3.3%) and 7 (7.70%); III 8 (38.1%) and 10 (47.6%); IV 3 (4.1%) and 10 (13.7%); V 47 (87.0%) and 52 (96.3%); VI 108 (97.3%) and 110 (99.1%). In most cases, the IP did not provide additional information to the FNB report nor did it detect microcarcinomas in others, so it does not seem justified to perform it routinely.

Para evaluar la utilidad diagnóstica del estudio patológico intraoperatorio (EPI) en cirugía tiroidea se realizó una revisión retrospectiva de sus resultados en 350 pacientes en comparación con la biopsia preoperatoria por punción con aguja fina (PAAF) y el estudio patológico diferido (EPD). Los resultados de la PAAF se clasificaron según el sistema de Bethesda en categoría II (91 casos, 26.0%), III (21 casos, 6.0%), IV (73 casos, 21.9%), V (54 casos, 15.4%) y VI (111 casos, 31.7%). El EPI mostró lesiones benignas en 137 casos (39.1%), malignas en 169 (48.2%), y resultados no definitivos en 44 (12.6 %). El EPD informó patología benigna en 161 casos (46%) y carcinoma en 189 (54%); se encontró carcinoma en 8 pacientes (5.8%) en quienes el EPI había informado lesión benigna y en 12 (27.2%) en quienes había informado no definitivo; 13 de estos 20 casos fueron microcarcinomas incidentales. El EPI no informó ningún falso positivo (especificidad 100%, sensibilidad 89.4%, valor predictivo positivo 100%, valor predictivo negativo 90.0%, exactitud 94.2%). Los resultados de malignidad con EPI y EPD, según categorías de Bethesda fueron respectivamente: II 3 (3.3%) y 7 (7.7%); III 8 (38.1%) y 10 (47.6%); IV 3 (4.1%) y 10 (13.7%); V 47 (87.0%) y 52 (96.3%); VI 108 (97.3%) y 110 (99.1%). El EPI no dio información adicional a la biopsia por PAAF en la mayoría de los casos ni detectó microcarcinomas en otros, por lo que no parece justificado indicarlo rutinariamente.

Valor del estudio patológico intraoperatorio de tiroides. Comparación con la punción aspiración preoperatoria y la patología diferida / Value of the intraoperative pathology in thyroid surgery: comparison with preoperative aspiration puncture and deferred pathology

Resumen Para evaluar la utilidad diagnóstica del estudio patológico intraoperatorio (EPI) en cirugía tiroidea se realizó una revisión retrospectiva de sus resultados en 350 pacientes en comparación con la biopsia preoperatoria por punción con aguja fina (PAAF) y el est udio patológico diferido (EPD). Los resultados de la PAAF se clasificaron según el sistema de Bethesda en categoría II (91 casos, 26.0%), III (21 casos, 6.0%), IV (73 casos, 21.9%), V (54 casos, 15.4%) y VI (111 casos, 31.7%). El EPI mostró lesiones benignas en 137 casos (39.1%), malignas en 169 (48.2%), y resultados no definitivos en 44 (12.6 %). El EPD informó patología benigna en 161 casos (46%) y carcinoma en 189 (54%); se encontró carcinoma en 8 pacientes (5.8%) en quienes el EPI había informado lesión benigna y en 12 (27.2%) en quienes había informado no definitivo; 13 de estos 20 casos fueron microcarcinomas incidentales. El EPI no informó ningún falso positivo (especificidad 100%, sensibilidad 89.4%, valor predictivo positivo 100%, valor predictivo negativo 90.0%, exactitud 94.2%). Los resultados de malignidad con EPI y EPD, según categorías de Bethesda fueron respectivamente: II 3 (3.3%) y 7 (7.7%); III 8 (38.1%) y 10 (47.6%); IV 3 (4.1%) y 10 (13.7%); V 47 (87.0%) y 52 (96.3%); VI 108 (97.3%) y 110 (99.1%). El EPI no dio información adicional a la biopsia por PAAF en la mayoría de los casos ni detectó microcarcinomas en otros, por lo que no parece justificado indicarlo rutinariamente.

Abstract To evaluate the usefulness of intraoperative pathology (IP) in thyroid surgery, a retrospective review of its results in 350 patients was performed in comparison with the results of the preoperative fine-needle biopsy (FNB) and the surgical pathology report (SPR). The FNB was reported according to the Bethesda system as type II in 91 cases (26.0%), type III in 21 (6.0%), type IV in 73 (21.9%), type V in 54 (15.4%), and type VI in 111 (31.7%). The IP showed benign lesions in 137 cases (39.1%), malignancy in 169 (48.2%), and inconclusive results in 44 (12.6%). The SPR results were benign pathology in 161 cases (46%) and carcinoma in 189 (54%); carcinoma was found in 8 patients (5.8%) in whom the IP had reported benignity, and in 12 (27.2%) with IP inconclusive results; 13 of those 20 cases were incidental microcarcinomas. The IP did not report any false positive result (specificity 100 %, sensitivity 89.4%, positive predictive value 100%, negative predictive value 90.0%, and accuracy 94.2%). When discriminated by Bethesda types, the malignant lesions detected by IP and SPR were, respectively: II 3 (3.3%) and 7 (7.70%); III 8 (38.1%) and 10 (47.6%); IV 3 (4.1%) and 10 (13.7%); V 47 (87.0%) and 52 (96.3%); VI 108 (97.3%) and 110 (99.1%). In most cases, the IP did not provide additional information to the FNB report nor did it detect microcarcinomas in others, so it does not seem justified to perform it routinely.

Smart material based on boron crosslinked polymers with potential applications in cancer radiation therapy.

Organoboron compounds have been playing an increasingly important role in analytical chemistry, material science, health applications, and particularly as functional polymers like boron carriers for cancer therapy. There are two main applications of boron isotopes in radiation cancer therapy, Boron Neutron Capture Therapy and Proton Boron Fusion Therapy. In this study, a novel and original material consisting of a three-dimensional polymer network crosslinked with [Formula: see text]B enriched boric acid molecules is proposed and synthesized. The effects of the exposition to thermal neutrons were studied analyzing changes in the mechanical properties of the proposed material. Dedicated Monte Carlo simulations, based on MCNP and FLUKA main codes, were performed to characterize interactions of the proposed material with neutrons, photons, and charged particles typically present in mixed fields in nuclear reactor irradiations. Experimental results and Monte Carlo simulations were in agreement, thus justifying further studies of this promising material.

Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

Linfomas extranodales de cabeza y cuello / Extranodal lymphomas of the head and neck

RESUMEN Antecedentes: los linfomas extranodales de cabeza y cuello (LECC) son neoplasias infrecuentes. El papel diagnóstico de la cirugía justifica considerar estas entidades entre los diagnósticos diferenciales de la patología quirúrgica de la región. Objetivo: describir las características clínico-patológicas, la localización y la asociación con enfermeda des sistémicas de una serie de pacientes operados con LECC. Material y métodos: se realizó una revisión retrospectiva de las historias clínicas de 5489 pacientes operados entre junio de 2009 y junio de 2019. Diecinueve de ellos (0,35%) presentaron LECC. Resultados: el promedio de edad fue de 56 años (rango 17- 84, DS 19,3), 16 fueron mujeres (84%). La localización de los LECC fue: glándula parótida en 12 casos (63%), glándula submaxilar en 3 casos (16%), glándula salival menor en 2 casos (11%), glándula lagrimal en 1 caso (5%), glándula tiroides en 1 caso (5%). Todos fueron linfomas no Hodgkin. Los tipos citológicos fueron: linfoma de tejido linfoideo asociado a mucosas (MALT) 9 (48%), linfoma folicular 4 (21%), linfoma de células B grandes 3 (16%), linfoma de células pequeñas 1 (5%), linfoma del manto 1 (5%), linfoma anaplásico 1 (5%). Cuatro pa cientes (21%) presentaron síndrome de Sjögren en el momento del diagnóstico, tres linfomas MALT y uno linfoma folicular. Diferentes procedimientos quirúrgicos permitieron llegar al diagnóstico. Conclusión: los LECC constituyen una forma singular de presentación de neoplasias oncohematológica. En la presente serie se manifestaron en un amplio rango de edad, con mayor frecuencia de mujeres y en la glándula parótida. Su diagnóstico pudo alcanzarse con la biopsia o resección de la zona afectada.

ABSTRACT Background: Extranodal lymphomas of the head and neck (ELHN) are rare neoplasms. The role of surgery for the diagnosis justifies thinking of these neoplasms among the differential diagnoses of the surgical disorders of the region. Objective: The aim of this study was to describe the clinical and pathological characteristics of ELHN, their location and association with systemic diseases in a series of patients undergoing surgery. Material and methods: The clinical records of 5489 patients undergoing surgery between June 2009 and June 2019 were retrospectively reviewed. Nineteen patients (0.35%) presented ELHN. Results: Mean age was 56 years (range: 17-84; SD 19.3) and 84% (n = 16) were women. The location of ELHN were the parotid gland (n =12, 63%), submaxillary gland (n = 3, 16%), salivary gland (n = 1, 5%), lacrimal gland (n = 1, 5%) and thyroid gland (n =1, 5%). All the tumors were non-Hodgkin lymphomas with the following subtypes: mucosa associated lymphoid tissue (MALT) lymphoma (n = 9, 48%), follicular lymphoma (n = 4, 21%), large B-cell lymphoma (n = 3, 16%), small B-cell lymphoma (n = 1, 5%), mantle cell lymphoma (n = 1, 5%), and anaplastic lymphoma (n =1, 5%). Four patients (21%) presented Sjögren syndrome at the moment of the diagnosis; three were MALT lymphomas and one patient had follicular lymphoma. The diagnosis was made with different surgical procedures. Conclusion: ELHN constitute a singular presentation of onco-hematology neoplasms. In our series, these tumors occurred within a wide age range and were more common in women. The parotid gland was more commonly affected. The diagnosis was made by surgical biopsy or resection of the area affected.

Antiviral Properties of Alginate-Based Biomaterials: Promising Antiviral Agents against SARS-CoV-2.

The COVID-19 pandemic has made it essential to explore alternative antiviral materials. Alginate is a biodegradable, renewable, biocompatible, water-soluble and antiviral biopolymer with many potential biomedical applications. In this regard, this review shows 17 types of viruses that have been tested in contact with alginate and its related biomaterials. Most of these studies show that alginate-based materials possess little or no toxicity and are able to inhibit a wide variety of viruses affecting different organisms: in humans by the human immunodeficiency virus type 1, the hepatitis A, B, and C viruses, Sindbis virus, herpes simplex virus type 1 and 2, poliovirus type 1, rabies virus, rubella virus, and the influenza virus; in mice by the murine norovirus; in bacteria by the T4 coliphage, and in plants by the tobacco mosaic virus and the potato virus X. Many of these are enveloped positive-sense single-stranded RNA viruses, like SARS-CoV-2, which render alginate-based materials highly promising in the COVID-19 pandemic.