Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma.

BACKGROUND: There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. METHODS: We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. RESULTS: Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models evaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. CONCLUSIONS: Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.

Effect of different calcium sources on the bioactive compounds stability of extruded and nixtamalized blue maize flours.

The stability of antioxidants in extruded and nixtamalized blue maize flours with calcium hydroxide [Ca(OH)2] and calcium lactate [C6H10O6Ca] were evaluated. Extruded blue maize flours batches were obtained by mixing blue maize flours separately with different Ca(OH)2 (0.1, 0.2 and 0.3 %) and C6H10O6Ca (0.3, 0.6 and 0.9 %) concentrations respectively and extruded to obtain the extruded flours. For nixtamalized flours, the maize grains were cooked at 1 % Ca(OH)2 and 2.95 % C6H10O6Ca concentrations respectively. Color, antioxidant activity, total phenolics, total anthocyanins and individual anthocyanins, contents were analyzed. Color, antioxidant activity, anthocyanins contents and total phenolics decreased as the calcium hydroxide concentration increased. In contrast, increasing the calcium lactate concentration on the extruded flours had the opposite effect. The extrusion process retained 57-47 %, 72-62 % and 79-65 % of the anthocyanins content, total phenolic content and antioxidant activity, respectively. These retention rates were higher than those of the nixtamalized flours using the same calcium sources. Cyanidin-3-glucoside and pelargonidin-3-glucoside were identified in the maize kernel and flours. Cyanidin-3-glucoside concentration was increased by both extrusion and nixtamalization processed with either of the two calcium sources. In contrast, pelargonidin-3-glucoside concentration decreased by both processes. Other anthocyanins were observed, but they were not identified.

Models Used by Nurse Case Managers in Different Autonomous Communities in Spain: A Scoping Review.

(1) Background: The role of the nurse case manager is unknown to the population. The main objective is to analyze the existing differences within the national territory in order to make known the situation in Spain with a view to the recognition of its functions and the creation of the professional profile in an equal manner. (2) Methods: A scoping review was conducted in order to achieve the main aim. Selected articles were subjected to a critical reading, and the levels of evidence and grades of recommendation of the Joanna Briggs Institute were verified. The search field was limited to the last ten years. (3) Results: Case management models are heterogeneous in different autonomous communities in Spain. Case nurse management is qualified for high-complexity patients, follow up on chronic patients, and coordinate health assistance. (4) Conclusions: It concludes that nursing's role is crucial in the field of case management, being required in the follow-up of chronic patients of high complexity. Despite the proven health benefits, efficacy, and efficiency of case management, there are many heterogeneous models that coexist in Spain. This involves a restriction in the development of a nursing career because of the lack of a definition of its functions and competences.

Potential benefits of structured lipids in bulk compound chocolate: Insights on bioavailability and effect on serum lipids.

The bioavailability impact of serum lipids in compound chocolate products based on structured lipids was studied. Compound chocolate products containing fat with and without structured lipids were digested in vitro under simulated gastrointestinal lipolysis conditions and were studied in vivo in healthy C57BL/6J mice. The in vitro digestion results show that products containing structured lipids, milk compound chocolate filling and white compound coating, significantly reduced the release rate of Free Fatty Acids (FFA) and improved the caloric reduction between 12.49% and 13.71% compared to products without structured lipids, suggesting that FFA were not absorbed. Animal feeding studies revealed no adverse effects on the compound products intake; in fact, these products reduced total cholesterol, LDL-c, VLDL-c and triacylglycerols. The present work shows the relevance of developing functional compound chocolate as providing a potential healthy initiative through the biological effect of the bioactive ingredients incorporated.

Nurse Intervention: Attitudes and Knowledge About Organ Donation and Transplantation in Adolescents.

BACKGROUND: The problems involved in obtaining authorization in favor of organ donation have led us to evaluate the level of knowledge and attitudes of a group of Spanish adolescents (14-16 years) regarding organ donation, transplantation, and brain death. The evaluation was carried out before and after a health education intervention by nursing personnel. METHODS: Experimental, prospective and quantitative study. The educational intervention was carried out at Las Salinas high school (Laguna de Duero, Spain). We collected 86 preworkshop questionnaires and 88 post-workshop questionnaires. RESULTS: The composition of the groups did not differ significantly in sex (P = .653), age (P = .266), or in the desire to be a donor (P = .099). We found significant postworkshop improvements in knowledge about brain death (P < .001) and which organs can be donated (P < .001), as well as in the total score (18.29 ± 2.45 before vs 21.47 ± 2.70 after) (P < .001). We discovered a vast lack of knowledge about the organs that cannot be transplanted, which included the penis (38.4%), uterus (31.4%), prostate (41.9%), or bladder (37.2%); these beliefs decreased significantly after the intervention (P < .01). The increase in knowledge of the organs that can be donated, including eye (P = .024), lung (P = .025), stomach (P < .001), intestine (P = .001), and skin (P < .001), was also significant. CONCLUSIONS: The good results reflected the importance of conducting educational programs taught by health personnel on donation and organ transplantation in adolescents.

TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma.

Interleukin-8 (IL-8/CXCL8) is a pro-angiogenic and pro-inflammatory chemokine that plays a role in cancer development. Non-small cell lung carcinoma (NSCLC) produces high amounts of IL-8, which is associated with poor prognosis and resistance to chemo-radio and immunotherapy. However, the signaling pathways that lead to IL-8 production in NSCLC are unresolved. Here, we show that expression and release of IL-8 are regulated autonomously by TRAIL death receptors in several squamous and adenocarcinoma NSCLC cell lines. NSCLC constitutively secrete IL-8, which could be further enhanced by glucose withdrawal or by treatment with TRAIL or TNFα. In A549 cells, constitutive and inducible IL-8 production was dependent on NF-κB and MEK/ERK MAP Kinases. DR4 and DR5, known regulators of these signaling pathways, participated in constitutive and glucose deprivation-induced IL-8 secretion. These receptors were mainly located intracellularly. While DR4 signaled through the NF-κB pathway, DR4 and DR5 both regulated the ERK-MAPK and Akt pathways. FADD, caspase-8, RIPK1, and TRADD also regulated IL-8. Analysis of mRNA expression data from patients indicated that IL-8 transcripts correlated with TRAIL, DR4, and DR5 expression levels. Furthermore, TRAIL receptor expression levels also correlated with markers of angiogenesis and neutrophil infiltration in lung squamous carcinoma and adenocarcinoma. Collectively, these data suggest that TRAIL receptor signaling contributes to a pro-tumorigenic inflammatory signature associated with NSCLC.

Optimisation of the ultrasound-assisted extraction of betalains and polyphenols from Amaranthus hypochondriacus var. Nutrisol.

The present study optimised the ultrasound-assisted extraction (UAE) of bioactive compounds from Amaranthus hypochondriacus var. Nutrisol. Influence of temperature (25.86-54.14 °C) and ultrasonic power densities (UPD) (76.01-273.99 mW/mL) on total betalains (BT), betacyanins (BC), betaxanthins (BX), total polyphenols (TP), antioxidant activity (AA), colour parameters (L*, a*, and b*), amaranthine (A), and isoamaranthine (IA) were evaluated using response surface methodology. Moreover, betalain extraction kinetics and mass transfer coefficients (KLa) were determined for each experimental condition. BT, BC, BX, TP, AA, b*, KLa, and A were significantly affected (p < 0.05) by temperature extraction and UPD, whereas L*, a*, and IA were only affected (p < 0.05) by temperature. All response models were significantly validated with regression coefficients (R2) ranging from 87.46 to 99.29%. BT, A, IA, and KLa in UAE were 1.38, 1.65, 1.50, and 29.93 times higher than determined using conventional extraction, respectively. Optimal UAE conditions were obtained at 41.80 °C and 188.84 mW/mL using the desired function methodology. Under these conditions, the experimental values for BC, BX, BT, TP, AA, L*, a*, b*, KLa, A, and IA were closely related to the predicted values, indicating the suitability of the developed quadratic models. This study proposes a simple and efficient UAE method to obtain betalains and polyphenols with high antioxidant activity, which can be used in several applications within the food industry.

Security and Violence Perception of Medical Interns during Social Service Practice in Mexico.

The increase of insecurity levels in Mexico, as well as the fact that violence is a frequent experience among health personnel, motivated this study whose purpose was to evaluate the perception of security and violence that social service medical interns (SSMI) had on the institutions and localities where they carried out their social work and make visible the main types of violence to which they were exposed. This was a cross-sectional study, based on a perception survey self-administered to 157 SSMI from Zacatecas, in Mexico. A high proportion of the participants (75.8%) stated that they were victims of violence, describing 134 incidents; however, only 33.6% of SSMI made an official report. The reported incidents were related to organized crime (31.9%), verbal violence (20.6%), violence by the authorities (14.7%) and sexual harassment (11.8%). One hundred percent of the victims of sexual harassment were women (p = 0.039). According to the above, it is a priority to generate strategies to prevent and reduce the risk of exposure to the violence generated in the medical units and communities where SSMI carry out their activities as medical graduates, as well as, to efficiently process formal violence reports to promote a safe environment that favors the fulfillment of the practice of SSMIs in Mexico.

Type 1 Diabetes Mellitus in Pediatric Patients and Its Impact on Relationships in the Family Environment.

PURPOSE: The aim of this study is to assess the impact of type 1 diabetes mellitus on family environment relationships, as well as the management and approach to this disease. PATIENTS AND METHODS: One hundred one children, 52.47% male and 47.52% female, with an average age of 8.55 ± 4.01 years, diagnosis of type 1 diabetes mellitus. Quantitative cross-sectional descriptive study was conducted using the validated questionnaires "Modified Diabetes Quality of Life" and "Questionnaire for the assessment of psychological impact in parents/guardians of diabetic children". RESULTS: Most of the children (70.3% versus 29.7%) identified diabetes as unpleasant or not fun. The ≤5-year-olds expressed that they felt concerned about the consequences of being diabetic (8.1% by age group), as opposed to the 10-year-olds who did not feel concerned (85.1% by age group), P <0.001. The family environment was affected in 98.1% (n=99) of the cases. CONCLUSION: Self-care of type 1 diabetes mellitus in pediatric patients is a complex process that impacts the family environment and their relationship with their peers, especially for children under the age of 5. Fear, concern and insecurity were prevalent feelings in children suffering type 1 diabetes mellitus.

Continuous Flow UV-C Irradiation Effects on the Physicochemical Properties of Aloe vera Gel and Pitaya (Stenocereus spp.) Blend.

Physicochemical properties of a blend of 10% Aloe vera gel with 5% pitaya juice subjected to UV-C doses of 16.5, 27.7, and 40 mJ/cm2 were evaluated at pH 3.5 and 5.5. Unprocessed treatments were used as the control. The a* color parameter decreased and luminosity increased at pH 3.5. The decrease in the reddish color was consistent with the decrease in total betalains content and stabilized at pH 5.5. The NMR analyses of UV-C treatments showed changes in betalains signal patterns. Polyphenolics content was significantly reduced in the UV-C treatments at pH 5.5. UV-C processing decreased the antioxidant activity 1.25 times compared to unprocessed treatments. Total sugar content was reduced as the UV-C dose increased. Doses above 16.5 mJ/cm2 resulted in a higher simple sugar content at a pH 3.5. The UV-C continuous flow technology can be applied to stabilize betalains in Aloe vera-pitaya blends at a UV-C dose of 16.5 mJ/cm2 and pH 5.5.

Effect of Agave Fructans as Carrier on the Encapsulation of Blue Corn Anthocyanins by Spray Drying.

Effects of agave fructans as carrier agents on the encapsulation of blue corn anthocyanins using spray-drying were evaluated. Blue corn extract was mixed with 6%, 8%, 10%, and 12% (w/v) of agave fructans in duplicate and dried at 150 °C. The extract showed good contents of anthocyanins, polyphenols, and antioxidant activity. The increase of agave fructans in the encapsulated powders caused a significant increase (p < 0.05) in the humidity, water activity (aw), pH, bulk density, water solubility index (WSI), and color L* values. On the contrary, the agave fructan addition decreased the hygroscopicity, water absorption index (WAI), antioxidant activity, total anthocyanin, total polyphenol, and individual anthocyanin contents. The encapsulation of blue corn extract with 6% agave fructans (w/v) resulted in good physical, thermal, morphological, and high antioxidant properties. The results suggest that the use of agave fructans as wall material represents advantages in the conservation of anthocyanins and other bioactive compounds from blue corn extract during their encapsulation. The application of blue corn anthocyanin encapsulated powders as a food ingredient is promising for food pigmentation, representing additional advantages for their contribution as a soluble fiber that can benefit the health of consumers.

Effects of UV-C irradiation and traditional thermal processing on acemannan contained in Aloe vera gel blends.

The effects of pH (3.5, 4.5, and 5.5) and UV-C irradiation dose (12.8, 24.2, 35.8, and 54.6 mJ/cm2) on the physicochemical properties changes in 10% Aloe vera gel blends; in addition, the acemannan concentration and structural changes in the precipitated polysaccharides were evaluated. A thermal treatment (TT; 45 s at 90 °C) was used for comparison. In contrast to TT, a dose of 24.2 mJ/cm2 did not induce significant changes of free sugar content. Moreover, TT and UV-C irradiation did not significantly affect the content of mannose but increased those of galactose, fructose, and glucose. 1H NMR analysis revealed minimal changes in the isolated fractions of acemannan, indicating that compared to the unprocessed control sample, the acemannan deacetylation was more pronounced by TT (27%) than by UV-C irradiation (11% at 54.6 mJ/cm2), without any significant difference between the two. UV-C irradiation of Aloe vera gel blends at pH 3.5 and 24.2 mJ/cm2 was an alternative to TT and efficiently preserve the characteristics of acemannan.

Adenoma trabecular hialinizante de tiroides. Presentación de un caso / Thyroid hysterin trabecular adenoma. Case presentation

El adenoma trabecular hialinizante es una neoplasia infrecuente de la glándula tiroides. Es un tumor de origen folicular encapsulado, relativamente pequeño con un comportamiento clínico benigno o de bajo potencial maligno. Se presenta el caso de una paciente de 45 años de edad, que acudió a consulta multidisciplinaria de nódulo de tiroides del Hospital General Universitario Dr. Gustavo Aldereguía, de Cienfuegos, con nódulo tiroideo en lóbulo izquierdo de la glándula, de 1 cm de diámetro. Se le realizó TSH, T4, ultrasonido de tiroides, citología con aguja fina que informó atipia de significado indeterminado. Fue sometida a intervención quirúrgica y se le realizó lobectomía izquierda. El diagnóstico histopatológico arrojó:tiroiditis crónica de Hashimoto sobre la que se insertaron dos afecciones neoplásicas, adenoma macro y micro folicular del tiroides, tumor tiroideo trabecular hialinizado, inferior a un campo de 4 x no encapsulado. La técnica de inmunohistoquímica Ki.67 (MIB.1) resultó positiva. La importancia de su diagnóstico radica en el hecho que son interpretados por sus similitudes histológicas, inmunohistoquímica y moleculares con otras entidades, como cáncer papilar y medular de tiroides, de ahí que se haya decidido la presentación de este caso.

Thyroid hysterin trabecular adenoma is an infrequent neoplasia of the thyroid gland. It is a Tumor of encapsulated follicular origin, relatively small with a benign clinical behavior or of low malignant potential. The case of a 45 year old female patient, is presented, who attended a multidisciplinary thyroid nodule visit at the General University Hospital Dr. Gustavo Aldereguía, from Cienfuegos, with 1 cm in diameter thyroid nodule in the gland left lobe. It underwent a TSH, T4, thyroid ultrasound, fine needle cytology that reported atypia of undetermined significance (according to Bethesda III). Left lobectomy was performed. The histopathological diagnosis was chronic Hashimoto's thyroiditis, on which two neoplastic diseases, macro adenoma and micro follicular thyroid, a hyalinized trabecular thyroid tumor, were inserted, inferior to a non-encapsulated 4x field. The Ki.67 immunohistochemistry technique (MIB.1) was positive. The importance of their diagnosis lies in the fact that they are interpreted by their histological, immunohistochemical and molecular similarities with other entities, such as papillary and medullary thyroid cancer.