Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells.

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.

Sonic hedgehog specifies flight feather positional information in avian wings.

Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Here, we show that Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities. We also reveal that Shh signalling is interpreted into specific patterns of Sim1 and Zic transcription factor expression, providing evidence of a putative gene regulatory network operating in flight feather patterning. Our data suggest that flight feather specification involved the co-option of the pre-existing digit patterning mechanism and therefore uncovers an embryonic process that played a fundamental step in the evolution of avian flight.

DNMR measurements of an asymmetric odd liquid crystal dimer: determination of the intramolecular angle and the degree of order of the two rigid cores.

In this work, we present a Deuteron Nuclear Magnetic Resonance (DNMR) study of the non-symmetric odd liquid crystal dimer α-(4-cyanobiphenyl-4'-yloxy)-ω-(1-pyrenimine-benzylidene-4'-oxy) heptane (CBO7O.Py), formed by a pro-mesogenic cyanobiphenyl unit and a bulky pyrene-containing unit, linked via alkoxy flexible chain. We have synthesized two partially deuterated samples: one with the deuterium atoms in the cyanobiphenyl moiety (dCBO7O.Py) and the other one with the deuterium atoms in the pyrenimine-benzylidene unit (CBO7O.dPy). We have performed angular distribution analysis in the SmA glassy state, obtaining the degree of order of both rigid cores and an estimation of the internal molecular angle between both structures. With the results from the angular study, we have been able to determine the degree of order of both rigid units in either the N phase and the SmA phase, far enough from the glass transition. Both rigid cores have the same degree of order close to the nematic-isotropic phase transition, but as the compound is cooled down, the degree of order of the cyanobiphenyl moiety is clearly higher than that of the pyrene-containing unit. The critical behaviour of the order parameter of the pyrene-containing moiety is consistent with the fact that, for CBO7O.Py, the N-I phase transition is tricritical, which seems to indicate that the uniaxial order parameter of the dimer is dominated by the degree of order of the pyrene-containing core.

Healthcare outcomes in patients with HIV infection at a tertiary hospital during the COVID-19 pandemic.

Background: The COVID-19 pandemic has affected the care of patients with other diseases. Difficulty in access to healthcare during these months has been especially relevant for persons with HIV infection (PWH). This study therefore sought to ascertain the clinical outcomes and effectiveness of the measures implemented among PWH in a region with one of the highest incidence rates in Europe. Methods: Retrospective, observational, pre-post intervention study to compare the outcomes of PWH attended at a high-complexity healthcare hospital from March to October 2020 and during the same months across the period 2016-2019. The intervention consisted of home drug deliveries and preferential use of non face-to-face consultations. The effectiveness of the measures implemented was determined by reference to the number of emergency visits, hospitalisations, mortality rate, and percentage of PWH with viral load >50 copies, before and after the two pandemic waves. Results: A total of 2760 PWH were attended from January 2016 to October 2020. During the pandemic, there was a monthly mean of 106.87 telephone consultations and 2075 home deliveries of medical drugs dispensed to ambulatory patients. No statistically significant differences were found between the rate of admission of patients with COVID-HIV co-infection and that of the remaining patients (1172.76 admissions/100,000 population vs. 1424.29, p = 0.401) or in mortality (11.54% vs. 12.96%, p = 0.939). The percentage of PWH with viral load >50 copies was similar before and after the pandemic (1.20% pre-pandemic vs. 0.51% in 2020, p = 0.078). Conclusion: Our results show that the strategies implemented during the first 8 months of the pandemic prevented any deterioration in the control and follow-up parameters routinely used on PWH. Furthermore, they contribute to the debate about how telemedicine and telepharmacy can fit into future healthcare models.

Introducción: La pandemia causada por el SARS-CoV-2 ha afectado a la atención de pacientes con otras enfermedades. La dificultad en el acceso a la asistencia sanitaria durante estos meses es especialmente relevante en las personas con infección por VIH (PCV). El objetivo del estudio fue conocer los resultados clínicos y la efectividad de las medidas implementadas en PCV en una de las regiones con mayor incidencia de Europa. Métodos: Estudio observacional retrospectivo, pre-postintervención, comparando los resultados de PCV atendidos en un hospital de alta complejidad entre marzo-octubre de 2020 y el mismo periodo de 2016 a 2019. La intervención consistió en el envío a domicilio de medicamentos y la realización preferente de consultas no presenciales. La efectividad de las medidas implementadas se determinó por el número de visitas a urgencias, hospitalizaciones, mortalidad y porcentaje de PCV con carga viral > 50 copias antes y después de 2 olas pandémicas. Resultados: Se atendieron 2.760 PCV entre enero de 2016 y octubre de 2020. Durante la pandemia se realizaron una media mensual de 106,87 consultas telefónicas y 2.075 envíos a domicilio de medicamentos de dispensación ambulatoria. No se encontraron diferencias estadísticamente significativas en la frecuentación de pacientes con coinfección COVID-VIH respecto al resto (1.172,76 ingresos/100.000 habitantes vs. 1.424,29, p = 0,401), ni en su mortalidad (11,54 vs. 12,96%, p = 0,939). El porcentaje de PCV con carga viral > 50 copias fue similar antes y después de la pandemia (1,20% prepandemia vs. 0,51% en 2020, p = 0,078). Conclusión: Nuestros resultados revelan que las estrategias implementadas durante los 8 primeros meses de pandemia han evitado el deterioro en parámetros de control y seguimiento empleados habitualmente en PCV. Además, contribuyen a la reflexión sobre el encaje de la telemedicina y telefarmacia en modelos asistenciales futuros.

Spectral CT as a method for identifying radiolucent gallstones.

We present the case of an 82-year-old woman with history of right colon adenocarcinoma in whom a routine control scan is performed using a dual-layer detector spectral CT scanner. Conventional CT scan images show a dilated cystic bile duct with no apparent cause of obstruction, finding also no lithiasis inside the gallbladder. Non-calcified gallstones are composed mainly of cholesterol and can have the same radiographic density as bile, making them hard or impossible to spot on conventional CT.

Acute pancreatitis secondary to migration and impaction of intragastric balloon.

Obesity represents a significant global health problem, and reducing its alarmingly high incidence is an urgent challenge. The intragastric balloon is a safe and effective device for weight loss; therefore, it is widely used. Although the frequency of serious complications resulting from its use is low, it is not exempt from them. We would like to present a case of a severe but infrequent complication secondary to this device, with the aim of highlighting the most appropriate procedure in such cases and emphasizing the importance of awareness regarding it.

[Benefits of a community physical exercise program prescribed from primary care for perimenopausal/menopausal women]. / Beneficios de un programa de ejercicio físico comunitario prescrito desde Atención Primaria en la salud de mujeres perimenopáusicas/menopaúsicas.

OBJECTIVE: To measure the benefits of a physical exercise program in a community, through the modifications in quality of life, and perimenopausal-menopausal women physical condition. SETTING: The participants were recruited in PC consultations from two health centers in Molina de Segura (Murcia). PARTICIPANTS: Women between 40 and 70 years old, or under 40 of age diagnosed with early menopause. DESIGN: Quasi-experimental study, non-randomized, controlled, open and single-center with 2 parallel branches to study. INTERVENTION: Experimental group: ACTIVA Bone Health Program for six months. CONTROL: inactive. MAIN MEASUREMENTS IN BOTH GROUPS: The SF 36 questionnaire was used to measure the Quality of life. PHYSICAL CONDITION: Aerobic condition, flexibility, balance and strength measured with the mile, flamenco, flexibility box tests, and throwing the medicine ball, respectively. Physical activity level through the GPPAQ Questionnaire. Sociodemographic variables were collected and the adherence to the program was measured. RESULTS: The quality of life improved in the intervention group compared to the control group, except «Body Pain¼ dimension (p = 0.412). As regards the intragroup level, all dimensions showed significant improvement except both «Physical Function¼ (p = 0.263) and «Body Pain¼ (p = 0.136). The physical capacities that benefited most were aerobic fitness, strength and balance. CONCLUSIONS: The Active Bone Health Physical Exercise Program piloting showed benefits on participants' physical and mental quality of life. In addition, it has been shown that performing a specific physical exercise for premenopausal-menopausal women improves their physical condition.

Intrinsic properties of limb bud cells can be differentially reset.

An intrinsic timing mechanism specifies the positional values of the zeugopod (i.e. radius/ulna) and then autopod (i.e. wrist/digits) segments during limb development. Here, we have addressed whether this timing mechanism ensures that patterning events occur only once by grafting GFP-expressing autopod progenitor cells to the earlier host signalling environment of zeugopod progenitor cells. We show by detecting Hoxa13 expression that early and late autopod progenitors fated for the wrist and phalanges, respectively, both contribute to the entire host autopod, indicating that the autopod positional value is irreversibly determined. We provide evidence that Hoxa13 provides an autopod-specific positional value that correctly allocates cells into the autopod, most likely through the control of cell-surface properties as shown by cell-cell sorting analyses. However, we demonstrate that only the earlier autopod cells can adopt the host proliferation rate to permit normal morphogenesis. Therefore, our findings reveal that the ability of embryonic cells to differentially reset their intrinsic behaviours confers robustness to limb morphogenesis. We speculate that this plasticity could be maintained beyond embryogenesis in limbs with regenerative capacity.

Comprehensive Characterization of Linalool-HP-ß-Cyclodextrin Inclusion Complexes.

The objective of the present study is to obtain linalool- cyclodextrin (CDs) solid complexes for possible applications in the food industry. For this purpose, a detailed study of linalool complexation was carried out at different pH values, to optimize the type of CDs and reaction medium that support the highest quantity of encapsulated linalool. Once demonstrated the ability of hydroxypropyl-ß-cyclodextrin (HP-ß-CDs), to form inclusion complexes with linalool (KC = 921 ± 21 L mol-1) and given their greater complexation efficacy (6.788) at neutral pH, HP-ß-CDs were selected to produce solid inclusion complexes by using two different energy sources, ultrasounds and microwave irradiation, subsequently spraying the solutions obtained in the Spray Dryer. To provide scientific solidity to the experimental results, the complexes obtained were characterized by using different instrumental techniques in order to confirm the inclusion of linalool in the HP-ß-CDs hydrophobic cavity. The linalool solid complexes obtained were characterized by using 1H nuclear magnetic resonance (1H-NMR) and 2D nuclear magnetic resonance (ROSEY), differential scanning calorimetry, thermogravimetry and Fourier transform infrared spectrometry. Moreover, the structure of the complex obtained were also characterized by molecular modeling.

Thorough characterization and stability of HP-ß-cyclodextrin thymol inclusion complexes prepared by microwave technology: A required approach to a successful application in food industry.

BACKGROUND: The aims of the present study were to obtain a stable dry powder formulation of cyclodextrins (CDs) encapsulating thymol, for successful use as an ingredient on an industrial scale, and to characterize the thymol-CDs complexes using different techniques. RESULTS: Thymol was successfully solubilized in aqueous solutions and the Kc value increased with the pH of the media until the pH was neutral, giving the highest values (2583 ± 176 L mol-1 ) for HP-ß-cyclodextrins (HP-ß-CDs). The best encapsulation efficiency of thymol in solid complexes was obtained using the microwave (MWI) encapsulation method. The different characterization techniques have demonstrated the affinity of HP-ß-CDs for thymol molecules, forming stable complexes. CONCLUSIONS: The results support the use of the MWI method in the preparation of solid HP-ß-CD-thymol complexes, due to greater encapsulation efficiency and technological and economic advantages for industrial applications. © 2018 Society of Chemical Industry.

Postmortem Cholesterol Levels in Peripheral Nerve Tissue: Preliminar Considerations on Interindividual and Intraindividual Variation.

The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times-from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.

Ectoderm-mesoderm crosstalk in the embryonic limb: The role of fibroblast growth factor signaling.

In this commentary we focus on the function of FGFs during limb development and morphogenesis. Our goal is to understand, interpret and, when possible, reconcile the interesting findings and conflicting results that remain unexplained. For example, the cell death pattern observed after surgical removal of the AER versus genetic removal of the AER-Fgfs is strikingly different and the field is at an impasse with regard to an explanation. We also discuss the idea that AER function may involve signaling components in addition to the AER-FGFs and that signaling from the non-AER ectoderm may also have a significant contribution. We hope that a re-evaluation of current studies and a discussion of outstanding questions will motivate new experiments, especially considering the availability of new technologies, that will fuel further progress toward understanding the intricate ectoderm-to-mesoderm crosstalk during limb development. Developmental Dynamics 246:208-216, 2017. © 2016 Wiley Periodicals, Inc.

Urban regeneration as population health intervention: a health impact assessment in the Bay of Pasaia (Spain).

BACKGROUND: An important health issue in urban areas is how changes arising from the regeneration of city-areas affect social determinants of health and equity. This paper examines the impacts attributable to a new fish market and to delays in the regeneration of a port area in a deteriorated region of the Bay of Pasaia (Spain). Potential differential impacts on local residents and socially vulnerable groups were evaluated to determine health inequalities. METHODS: An in-depth, prospective and concurrent Health-Impact-Assessment (HIA) focused on equity was conducted by the regional Public Health Department, following the Merseyside guidelines. Data from different sources was triangulated and impacts were identified using qualitative and quantitative methods. RESULTS: The intervention area is characterised by poor social, environmental, and health indicators. The distinctness of the two projects generates contrasting health and inequality impacts: generally positive for the new fish market and negative for the port area. The former creates recreational spaces and improves urban quality and social cohesion. By contrast, inaction and stagnation of the project in the port area perpetuates deterioration, a lack of safety, and poor health, as well as increased social frustration. CONCLUSIONS: In addition to assessing the health impacts of both projects this HIA promoted intersectoral partnerships, boosted a holistic and positive view of health and incorporated health and equity into the political discourse. Community-level participatory action enabled public health institutions to respond to new urban planning challenges and responsibilities in a more democratic manner.

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning.

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.

Citrate versus acetate-based dialysate in on-line haemodiafiltration. A prospective cross-over study.

BACKGROUND AND AIMS: A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect and improves biocompatibility. This study examines the effect of CD on dialysis efficiency, coagulation, acid-base status, electrolytes, and inflammation in patients in on-line hemodiafiltration (OL-HDF). METHODS: 35 patients in OL-HDF were enrolled in a prospective, cross-over study for a 24-week period and two phases alternating CD and acetate dialysate fluid (AD). Parameters on study were predialysis levels of bicarbonate and ionic calcium, reactive C Protein (CRP), and beta-2 microglobulin (B2MG) and postdialysis levels of activated tromboplastine time, bicarbonate, and ionized calcium. RESULTS: No significant differences in coagulation parameters, pH, and predialysis bicarbonate were found. The postdialysis bicarbonate and postdialysis calcium were lower with CD. Dialysis efficiency was greater with CD. Regarding inflammatory parameters, both CRP and B2MG were lower using CD. CONCLUSION: The use of CD is safe and effective in OL-HDF, and it improves dialysis efficacy, postdialysis alkalosis, and inflammation.

Evidence that the limb bud ectoderm is required for survival of the underlying mesoderm.

The limb forms from a bud of mesoderm encased in a hull of ectoderm that grows out from the flank of the embryo. Coordinated signaling between the limb mesoderm and ectoderm is critical for normal limb outgrowth and patterning. The apical ectodermal ridge (AER), found at the distal tip, is a rich source of signaling molecules and has been proposed to specify distal structures and maintain the survival of cells in the underlying distal mesoderm. The dorsal and ventral non-AER ectoderm is also a source of signaling molecules and is important for dorsal-ventral patterning of the limb bud. Here we determine if this ectoderm provides cell survival signals by surgically removing the dorsal or ventral ectoderm during early chicken limb bud development and assaying for programmed cell death. We find that, similar to the AER, removal of the dorsal or ventral non-AER ectoderm results in massive cell death in the underlying mesoderm. In addition, although a re-epithelialization occurs, we find perturbations in the timing of Shh expression and, for the case of the dorsal ectoderm removal, defects in soft tissue and skeletal development along the proximal-distal axis. Furthermore, ectoderm substitution experiments show that the survival signal produced by the dorsal limb ectoderm is specific. Thus, our results argue that the non-AER ectoderm, like the AER, provides a specific survival signal to the underlying mesoderm that is necessary for normal limb development and conclusions drawn from experiments in which the non-AER ectoderm is removed, need to take into consideration this observation.

Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning.

Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.

Assessment of Nutrient Levels Provided by General Hospital Patient Menus: A Cross-Sectional Study Carried Out in the Region of Murcia (Spain).

Disease-related malnutrition remains a health problem with a high prevalence that increases the risk of poor patient outcomes, in addition to an elevation of healthcare costs. The aim of this study was to evaluate the nutritional quality of the menus at Ribera Molina Hospital, including their adequacy regarding recommended daily nutrient intakes and the agreement with the theoretical nutrition information provided by catering. The mean levels of energy, macronutrients, vitamins, and minerals provided by the basal, diabetic, and soft diets were calculated through the weighing of plated food served throughout the first 14 days of February 2020. A nutritional overestimation was seen in the nutrition information provided by the catering compared to the values derived from weighing foods (p < 0.01). Despite this, the nutritional content calculated by weighing satisfied the energy and protein requirements of 203 hospitalized patients previously studied in the internal medicine area of the hospital. The mean age of these patients was 62 years, and the main causes of admission were lung, cardiovascular, renal, and digestive diseases. There seems to be an insufficient amount of vitamins E and D, as well as magnesium, on all the menus. A possible insufficient amount of calcium, potassium, zinc, and copper was observed in some of the menus studied. It is necessary to update the hospital prescription manual so the nutritional contents of the diets are accurate and based on the weighted and calculated values to improve the adequacy of diets prescribed to patients.

Phase Angle, Handgrip Strength, and Other Indicators of Nutritional Status in Cancer Patients Undergoing Different Nutritional Strategies: A Systematic Review and Meta-Analysis.

Malnutrition in cancer patients is one of the most influential factors in the evolution and mortality of such patients. To reduce the incidence of malnutrition, it is necessary to establish a correct nutritional intervention. For this purpose, precise tools and indicators must be developed to determine the patient's condition. The main objective of this systematic review and meta-analysis was to analyze the relationship between different nutritional strategies, phase angle (PA), and handgrip strength in patients with cancer, with the secondary objectives being the modification of other indicators of nutritional status, such as weight and body mass index (BMI). A systematic review of randomized clinical trials was carried out in March 2023 in the databases PubMed, Web of Science, Cochrane, and Scopus. As a risk-of-bias tool, RoB 2.0 was utilized. A total of 8 studies with a total of 606 participants were included in the analysis. A significant increase in PA was observed after the different nutritional strategies (SMD: 0.43; 95% CI: 0.10 to 0.77; p = 0.01; I2 = 65.63%), also detecting a significant increase in handgrip strength (SMD: 0.27, 95% CI: 0.08 to 0.47; p = 0.01; I2 = 30.70%). A significant increase in PA and handgrip were observed in cancer patients subjected to different nutritional strategies. These results suggest that these indicators could be used in the nutritional and functional assessment of the patients.