Advances in screening hyperthermic nanomedicines in 3D tumor models.

Hyperthermic nanomedicines are particularly relevant for tackling human cancer, providing a valuable alternative to conventional therapeutics. The early-stage preclinical performance evaluation of such anti-cancer treatments is conventionally performed in flat 2D cell cultures that do not mimic the volumetric heat transfer occurring in human tumors. Recently, improvements in bioengineered 3D in vitro models have unlocked the opportunity to recapitulate major tumor microenvironment hallmarks and generate highly informative readouts that can contribute to accelerating the discovery and validation of efficient hyperthermic treatments. Leveraging on this, herein we aim to showcase the potential of engineered physiomimetic 3D tumor models for evaluating the preclinical efficacy of hyperthermic nanomedicines, featuring the main advantages and design considerations under diverse testing scenarios. The most recent applications of 3D tumor models for screening photo- and/or magnetic nanomedicines will be discussed, either as standalone systems or in combinatorial approaches with other anti-cancer therapeutics. We envision that breakthroughs toward developing multi-functional 3D platforms for hyperthermia onset and follow-up will contribute to a more expedited discovery of top-performing hyperthermic therapies in a preclinical setting before their in vivo screening.

Public-Private Partnerships Model Applied to Hospitals-A Critical Review.

In this paper, a conceptual framework for investigating the PPP model as it relates to hospitals is proposed. When the PPP model is applied to healthcare (hospitals), it is possible to discover the path to success by developing a critical assessment and deriving a clear model. It is concluded that most PPP model implementations in hospitals around the world have produced favorable outcomes, both in terms of the performance of healthcare units and in terms of cost-effectiveness. Additionally, a path-to-success model that applies to hospitals is offered, taking into account six PPP model dimensions: (i) Environment; (ii) Potentiate Benefits; (iii) Constant Measure; (iv) Evaluation; (v) Management; and (vi) Enhance Strengths. The PPP model only applies case by case and under specific requirements that should be met cumulatively to provide additional value to healthcare's quality of service. The right conditions are created, the right benefits are amplified, public concerns are frequently assessed, private contributions are carefully considered, and all pressing challenges are managed by enhancing both public and private strengths. Leading decision- and action-making processes in corporate, governmental, and social sectors is the goal of managing PPP models.

Diaphragmatic hernia after radiofrequency ablation of liver metastases: a case report and review of the literature.

A diaphragmatic hernia is the protrusion of abdominal tissues into the thoracic cavity secondary to a defect in the diaphragm. Reviewing the literature, we found only 44 references to diaphragmatic hernia secondary to percutaneous radiofrequency treatment. The vast majority of these cases were secondary to the treatment of hepatocellular carcinoma in segments V and VIII. Nevertheless, to date, this is the first reported case of diaphragmatic hernia after radiofrequency ablation of a liver metastasis from colorectal cancer. Complications secondary to diaphragmatic hernias are very diverse. The principal risk factor for complications is the contents of the hernia; when small bowel or colon segments protrude in the thoracic cavity, they can become incarcerated. Asymptomatic cases have also been reported in which the diaphragmatic hernia was discovered during follow-up. The pathophysiological mechanism is not totally clear, but it is thought that these diaphragmatic hernias might be caused by locoregional thermal damage. Given that most communications correspond to asymptomatic and/or treated cases, it is likely that the incidence is underestimated. However, due to the advent of percutaneous treatments, this complication might be reported more often in the future. Most cases are treated with primary herniorrhaphy, done with a laparoscopic or open approach at the surgeon's discretion; no evidence supports the use of one approach over the other. Nevertheless, it seems clear that surgery is the only definitive treatment, as well as the treatment of choice if complications develop. However, in asymptomatic patients in whom a diaphragmatic hernia is discovered in follow-up imaging studies, management should probably be guided by the patient's overall condition, taking into account the potential risks of complications (contents, diameter of the opening into the thoracic cavity …).

Hernia diafragmática tras radiofrecuencia de metástasis hepática. Reporte de caso clínico y revisión de la literatura / Diaphragmatic hernia after radiofrequency ablation of liver metastases: a case report and review of the literature

La hernia diafragmática (HD) es la protrusión de los tejidos abdominales a la cavidad torácica secundaria a un defecto en el diafragma. Tras una revisión de la bibliografía, únicamente se han identificado 44 referencias al respecto, donde se describen 35 casos de HD secundarias a tratamientos percutáneos con radiofrecuencia (RF). En su gran mayoría son secundarias a lesiones por carcinoma hepatocelular en los segmentos V y VIII. No obstante, hasta la fecha, este es el primer caso comunicado de HD tras RF para el tratamiento de una metástasis hepática por carcinoma colorrectal. Las complicaciones secundarias a las HD son muy diversas. El principal factor de riesgo para ello es su contenido; así se describen casos incarceración de colon e intestino delgado. Igualmente, se describen casos asintomáticos en los que la HD ha sido un hallazgo en el seguimiento de los pacientes. El mecanismo fisiopatológico no está del todo esclarecido, pero se especula con la posibilidad de un daño térmico locorregional. Dado que la mayoría de las comunicaciones corresponden a casos sintomáticos y/o tratados, probablemente la incidencia esté infraestimada. No obstante, debido al advenimiento de los tratamientos percutáneos, esta complicación podría verse comunicada en mayor número en los próximos años. Respecto a los tratamientos descritos, en la mayoría de los casos se ha optado por una herniorrafia primaria, con una vía de abordaje abierta o laparoscópica a discreción del cirujano. No se dispone de evidencia que apoye ninguna actitud al respecto, si bien parece claro que el tratamiento quirúrgico es el único definitivo y el de elección en caso de complicación. Sin embargo, en pacientes asintomáticos en quienes la HD sea un hallazgo radiológico de control, el manejo quizá deba guiarse por el estado general del paciente, así como los riesgos potenciales de complicación (contenido, diámetro del orificio herniario…). (AU)

A diaphragmatic hernia is the protrusion of abdominal tissues into the thoracic cavity secondary to a defect in the diaphragm. Reviewing the literature, we found only 44 references to diaphragmatic hernia secondary to percutaneous radiofrequency treatment. The vast majority of these cases were secondary to the treatment of hepatocellular carcinoma in segments V and VIII. Nevertheless, to date, this is the first reported case of diaphragmatic hernia after radiofrequency ablation of a liver metastasis from colorectal cancer. Complications secondary to diaphragmatic hernias are very diverse. The principal risk factor for complications is the contents of the hernia; when small bowel or colon segments protrude in the thoracic cavity, they can become incarcerated. Asymptomatic cases have also been reported in which the diaphragmatic hernia was discovered during follow-up. The pathophysiological mechanism is not totally clear, but it is thought that these diaphragmatic hernias might be caused by locoregional thermal damage. Given that most communications correspond to asymptomatic and/or treated cases, it is likely that the incidence is underestimated. However, due to the advent of percutaneous treatments, this complication might be reported more often in the future. Most cases are treated with primary herniorrhaphy, done with a laparoscopic or open approach at the surgeon's discretion; no evidence supports the use of one approach over the other. Nevertheless, it seems clear that surgery is the only definitive treatment, as well as the treatment of choice if complications develop. However, in asymptomatic patients in whom a diaphragmatic hernia is discovered in follow-up imaging studies, management should probably be guided by the patient's overall condition, taking into account the potential risks of complications (contents, diameter of the opening into the thoracic cavity …). (AU)

Ex-situ magnetic activated carbon for the adsorption of three pharmaceuticals with distinct physicochemical properties from real wastewater.

Pharmaceuticals are able to evade conventional wastewater treatments and therefore, are recurrently found in the environment with proven potential to cause harm to human and wildlife. Adsorption onto activated carbon (AC) is a promising complement. However, AC production from non-renewable resources and its difficult after-use recuperation are prohibitive. Hence, a waste-based magnetic activated carbon (MAC) was produced from paper mill sludge, via an ex-situ synthesis, for the adsorptive removal of carbamazepine (CBZ), sulfamethoxazole (SMX) and ibuprofen (IBU) from ultrapure water and wastewater. The MAC was obtained through the promotion of electrostatic interactions between magnetic and activated carbon particles in a water suspension at controlled pH between the points of zero charge of both surfaces. The optimized condition (MACX3) presented remarkable properties regarding specific surface area (SBET=795 m2 g-1) and saturation magnetization (MS=19 emu g-1). Kinetic and equilibrium adsorption studies were performed under batch conditions. Adsorption equilibrium was reached in up to 30 min for all pharmaceuticals in both matrices, proving the low dependence on the adsorbate and the broad applicability of MACX3 in pharmaceutical adsorption. Regarding equilibrium experiments, high Langmuir maximum adsorption capacities (qm) were achieved in ultrapure water (up to 711 ± 40 µmol g-1). Equilibrium studies in wastewater revealed a decay in qm when compared to ultrapure water: 28% for CBZ (468 ± 20 µmol g-1 (111 ± 5 mg g-1)), 78% for SMX (145 ± 10 µmol g-1 (37 ± 3 mg g-1)) and 62% for IBU (273 ± 8 µmol g-1 (56 ± 2 mg g-1)), attributed to the wastewater pH, which dictates the speciation of the pharmaceuticals and controls electrostatic interactions between pharmaceuticals and MAC, and to competition effects by organic matter. It was demonstrated the promising applicability of a waste-based ex-situ MAC, rapidly retrievable from water, as an alternative tertiary wastewater treatment for pharmaceuticals removal.

Development of a warning score for early detection of colorectal anastomotic leakage: Hype or hope?

BACKGROUND: Colorectal anastomotic leakage (CAL), a severe postoperative complication, is associated with high morbidity, hospital readmission, and overall healthcare costs. Early detection of CAL remains a challenge in clinical practice. However, some decision models have been developed to increase the diagnostic accuracy of this event. AIM: To develop a score based on easily accessible variables to detect CAL early. METHODS: Based on the least absolute shrinkage and selection operator method, a predictive classification system was developed [Early ColoRectAL Leakage (E-CRALL) score] from a prospective observational, single center cohort, carried out in a colorectal division from a non-academic hospital. The score performance and CAL threshold from postoperative day (POD) 3 to POD5 were estimated. Based on a precise analytical decision model, the standard clinical practice was compared with the E-CRALL adoption on POD3, POD4, or POD5. A cost-minimization analysis was conducted, on the assumption that all alternatives delivered similar health-related effects. RESULTS: In this study, 396 patients who underwent colorectal resection surgery with anastomosis, and 6.3% (n = 25) developed CAL. Most of the patients who developed CAL (n = 23; 92%) were diagnosed during the first hospital admission, with a median time of diagnosis of 9.0 ± 6.8 d. From POD3 to POD5, the area under the receiver operating characteristic curve of the E-CRALL score was 0.82, 0.84, and 0.95, respectively. On POD5, if a threshold of 8.29 was chosen, 87.4% of anastomotic failures were identified with E-CRALL adoption. Additionally, score usage could anticipate CAL diagnosis in an average of 5.2 d and 4.1 d, if used on POD3 and POD5, respectively. Regardless of score adoption, episode comprehensive costs were markedly greater (up to four times) in patients who developed CAL in comparison with patients who did not develop CAL. Nonetheless, the use of the E-CRALL warning score was associated with cost savings of €421442.20, with most (92.9%) of the savings from patients who did not develop CAL. CONCLUSION: The E-CRALL score is an accessible tool to predict CAL at an early timepoint. Additionally, E-CRALL can reduce overall healthcare costs, mainly in the reduction of hospital costs, independent of whether a patient developed CAL.

Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage: A prospective observational study.

BACKGROUND: Colorectal anastomotic leakage (CAL) is one of the most dreaded complications after colorectal surgery, with an incidence that can be as high as 27%. This event is associated with increased morbidity and mortality; therefore, its early diagnosis is crucial to reduce clinical consequences and costs. Some biomarkers have been suggested as laboratory tools for the diagnosis of CAL. AIM: To assess the usefulness of plasma C-reactive protein (CRP) and calprotectin (CLP) as early predictors of CAL. METHODS: A prospective monocentric observational study was conducted including patients who underwent colorectal resection with anastomosis, from March 2017 to August 2019. Patients were divided into three groups: G1 - no complications; G2 - complications not related to CAL; and G3 - CAL. Five biomarkers were measured and analyzed in the first 5 postoperative days (PODs), namely white blood cell (WBC) count, eosinophil cell count (ECC), CRP, CLP, and procalcitonin (PCT). Clinical criteria, such as abdominal pain and clinical condition, were also assessed. The correlation between biomarkers and CAL was evaluated. Receiver operating characteristic (ROC) curve analysis was used to compare the accuracy of these biomarkers as predictors of CAL, and the area under the ROC curve (AUROC), specificity, sensitivity, positive predictive value, and negative predictive value (NPV) during this period were estimated. RESULTS: In total, 25 of 396 patients developed CAL (6.3%), and the mean time for this diagnosis was 9.0 ± 6.8 d. Some operative characteristics, such as surgical approach, blood loss, intraoperative complications, and duration of the procedure, were notably related to the development of CAL. The length of hospital stay was markedly higher in the group that developed CAL compared with the group with complications other than CAL and the group with no complications (median of 21 d vs 13 d and 7 d respectively; P < 0.001). For abdominal pain, the best predictive performance was on POD4 and POD5, with the largest AUROC of 0.84 on POD4. Worsening of the clinical condition was associated with the diagnosis of CAL, presenting a higher predictive effect on POD5, with an AUROC of 0.9. WBC and ECC showed better predictive effects on POD5 (AUROC = 0.62 and 0.7, respectively). Those markers also presented a high NPV (94%-98%). PCT had the best predictive effect on POD5 (AUROC = 0.61), although it presented low accuracy. However, this biomarker revealed a high NPV on POD3, POD4, and POD5 (96%, 95%, and 96%, respectively). The mean CRP value on POD5 was significantly higher in the group that developed CAL compared with the group without complications (195.5 ± 139.9 mg/L vs 59.5 ± 43.4 mg/L; P < 0.00001). On POD5, CRP had a NPV of 98%. The mean CLP value on POD3 was significantly higher in G3 compared with G1 (5.26 ± 3.58 µg/mL vs 11.52 ± 6.81 µg/mL; P < 0.00005). On POD3, the combination of CLP and CRP values showed a high diagnostic accuracy (AUROC = 0.82), providing a 5.2 d reduction in the time to CAL diagnosis. CONCLUSION: CRP and CLP are moderate predictors of CAL. However, the combination of these biomarkers presents an increased diagnostic accuracy, potentially decreasing the time to CAL diagnosis.

Evaluación de la parálisis diafragmática con ultrasonido y espirometría: comparación del bloqueo supraclavicular vs bloqueo interescalénico en cirugía de hombro / Evaluation of diaphragmatic paralysis with ultrasound and spirometry: comparison of supraclavicular vs interscalene block in shoulder surgery

Resumen: Introducción: la cirugía artroscópica de hombro ha ganado popularidad recientemente; sin embargo, el dolor postquirúrgico se reporta de moderado a severo. La anestesia regional es útil para el control del dolor postquirúrgico. El bloqueo interescalénico y supraclavicular produce parálisis diafragmática en diferente proporción. Se busca encontrar cuál es el porcentaje y duración de la parálisis hemidiafragmática mediante mediciones ultrasonográficas, correlacionadas con espirometría comparando el abordaje supraclavicular con interescalénico. Material y métodos: ensayo clínico, controlado y aleatorizado. Se incluyeron 52 pacientes entre 18 y 90 años, programados para cirugía artroscópica de hombro, divididos en dos grupos (bloqueo interescalénico y supraclavicular). Se midió la excursión diafragmática y se realizó una espirometría previo al ingreso al quirófano y a las 24 horas de instalación del bloqueo, el estudio concluyó a las 24 horas del evento anestésico. Resultados: la capacidad vital se redujo en 0.7% en el grupo del bloqueo supraclavicular y 7.7% en el grupo interescalénico, el VEF1 se redujo en 0.2% en el supraclavicular y 9.5% en el interescalénico con una diferencia estadísticamente significativa (p = 0.001). La parálisis diafragmática en ventilación espontánea se presentó en ambos abordajes a los 30 minutos, sin diferencia significativa. A las seis y ocho horas continuó la parálisis en el grupo interescalénico, mientras que en el abordaje supraclavicular se mantuvo en comparación con la basal. Conclusiones: el bloqueo supraclavicular resulta tan efectivo como el bloqueo interescalénico en la cirugía artroscópica de hombro, con menor bloqueo diafragmático (1.5 veces más parálisis diafragmática en el interescalénico).

Abstract: Introduction: arthroscopic shoulder surgery has recently gained popularity, however, postoperative pain is reported as moderate to severe. Regional anesthesia is useful for the control of postoperative pain. Interscalene and supraclavicular blocks produce diaphragmatic paralysis in different proportions. The aim of this study is to find the percentage and duration of hemidiaphragmatic paralysis, by means of ultrasonographic measurements, correlated with spirometry, comparing the supraclavicular approach with interscalene. Material and methods: clinical, controlled and randomized trial. Fifty-two patients, between 18 and 90 years of age, scheduled for arthroscopic shoulder surgery were included, divided into 2 groups (interscalene or supraclavicular block). Diaphragmatic excursion was measured and spirometry was performed prior to admission to the operating room and 24 hours after installation of the block, the study concluded 24 hours after the anesthetic event. Results: vital capacity was reduced by 0.7% in the supraclavicular block and 7.7% for the interscalene, FEV1 was reduced by 0.2% for the supraclavicular and 9.5% in the interscalene with a statistically significant difference (p = 0.001). Diaphragmatic paralysis in spontaneous ventilation appeared in both approaches at 30 minutes, without significant difference. At 6 and 8 hours, paralysis continued in the interscalene group, while in the supraclavicular approach it remained preserved compared to the baseline. Conclusions: supraclavicular block is as effective as interscalene block in arthroscopic shoulder surgery, with less diaphragmatic block (1.5 times more diaphragmatic paralysis in interscalene).

Antineuroinflammatory Effect of Amburana cearensis and Its Molecules Coumarin and Amburoside A by Inhibiting the MAPK Signaling Pathway in LPS-Activated BV-2 Microglial Cells.

Microglia plays an important role in the neuroinflammatory response, identified as one of the major factors in the development and progression of neurodegenerative diseases. Amburana cearensis and its bioactive compounds, including coumarin (CM), vanillic acid (VA), and amburoside A (AMB), exert antioxidant, anti-inflammatory, and neuroprotective activities, on 6-OHDA-induced neurotoxicity in rat mesencephalic cells determined by our group. The present study investigated the anti-inflammatory effect of the dry extract from A. cearensis (DEAC), CM, AMB, and VA on lipopolysaccharide- (LPS-) stimulated microglial cells and elucidated the possible molecular mechanism of action. The DEAC was characterized by HPLC-PDA (chemical markers: CM, AMB, and VA). The BV-2 microglial cell line was pretreated with increasing concentrations of DEAC, CM, AMB, or VA in the presence or absence of LPS to evaluate the toxicity and anti-inflammatory activity. The cytotoxicity of DEAC, CM, AMB, or VA on BV-2 cells was evaluated by the MTT test, the free radical scavenging activity of test drugs was investigated, and the nitric oxide (NO) production was determined using the Griess reagent, while cytokine levels were measured by ELISA. The expressions of toll-like receptor 4 (TLR-4), nuclear factor kappa B (NF-κB), MAPK members (JNK and ERK1/2), and iNOS were determined through Western blot analysis. DEAC, CM, AMB, or VA (5-100 µg/mL) did not induce any detectable cytotoxicity in BV-2 cells. All test drugs (100 µg/mL) showed free radical scavenging activity (hydroxyl and superoxide radicals); however, only DEAC, CM, and AMB (5-100 µg/mL) significantly reduced NO production. DEAC (100 µg/mL), as well as CM (50 and 100 µg/mL) and AMB (25 µg/mL), reduced at least 50% of NO produced and markedly decrease the production of TNF-α and IL-6 but they did not significantly affect IL-10 levels. Only DEAC (100 µg/mL) and AMB (25 µg/mL) reduced the expression of iNOS, and they did not affect arginase activity. DEAC (100 µg/mL) suppressed the activation of the MAPKs JNK and ERK1/2 in LPS-activated BV-2 cells but it did not suppress the expression of TLR-4 nor the phosphorylation of NF-κB. In conclusion, DEAC, CM, and AMB exerted anti-inflammatory activity in LPS-activated microglial cells as observed by the reduction in the production of inflammatory mediators and the expression of iNOS. We identified the MAPK signaling pathway as a probable mechanism of action to the anti-inflammatory effects observed.

Butyrate administration strengthens the intestinal epithelium and improves intestinal dysbiosis in a cholestasis fibrosis model.

AIM: Intestinal dysfunction in cirrhosis patients is linked to death by bacterial infections. Currently, there is no effective therapy for this complication. This study aims to evaluate butyrate, a novel postbiotic, on the intestinal inflammatory response, tight junction proteins and the microbiota in the cholestasis model. METHODS AND RESULTS: Wistar rats underwent 15 days of bile duct ligation (BDL). We administered butyrate at a concentration of 1%. The BDL group did not receive treatment. The results showed that butyrate could significantly reduce pro-inflammatory cytokines (IL-17A, IFN-γ, TNF-α) in the ileum and colon while promoting IL-10 expression in the colon. Moreover, it significantly promotes tight junction protein (cld-1, occludin and ZO-1) expression in the ileum. A similar effect was observed in the colon except for ZO-1. Additionally, butyrate limited taxa diversity loss and promoted probiotic genera expansion such as Lachnospira, Prevotella and Lactobacillus. The increase in Turicibacter and Clostridiaceae distinguished the BDL group. CONCLUSIONS: Butyrate is effective in regulating the inflammatory response, tight junction proteins and limits bacterial diversity loss. SIGNIFICANCE AND IMPACT OF THE STUDY: This research reveals that butyrate could represent an interesting postbiotic metabolomic intervention for intestinal epithelium dysfunction in liver disease.

[Evaluation of diaphragmatic paralysis with ultrasound and spirometry: comparison of supraclavicular vs interscalene block in shoulder surgery]. / Evaluación de la parálisis diafragmática con ultrasonido y espirometría: comparación del bloqueo supraclavicular vs bloqueo interescalénico en cirugía de hombro.

INTRODUCTION: arthroscopic shoulder surgery has recently gained popularity, however, postoperative pain is reported as moderate to severe. Regional anesthesia is useful for the control of postoperative pain. Interscalene and supraclavicular blocks produce diaphragmatic paralysis in different proportions. The aim of this study is to find the percentage and duration of hemidiaphragmatic paralysis, by means of ultrasonographic measurements, correlated with spirometry, comparing the supraclavicular approach with interscalene. MATERIAL AND METHODS: clinical, controlled and randomized trial. Fifty-two patients, between 18 and 90 years of age, scheduled for arthroscopic shoulder surgery were included, divided into 2 groups (interscalene or supraclavicular block). Diaphragmatic excursion was measured and spirometry was performed prior to admission to the operating room and 24 hours after installation of the block, the study concluded 24 hours after the anesthetic event. RESULTS: vital capacity was reduced by 0.7% in the supraclavicular block and 7.7% for the interscalene, FEV1 was reduced by 0.2% for the supraclavicular and 9.5% in the interscalene with a statistically significant difference (p = 0.001). Diaphragmatic paralysis in spontaneous ventilation appeared in both approaches at 30 minutes, without significant difference. At 6 and 8 hours, paralysis continued in the interscalene group, while in the supraclavicular approach it remained preserved compared to the baseline. CONCLUSIONS: supraclavicular block is as effective as interscalene block in arthroscopic shoulder surgery, with less diaphragmatic block (1.5 times more diaphragmatic paralysis in interscalene).

INTRODUCCIÓN: la cirugía artroscópica de hombro ha ganado popularidad recientemente; sin embargo, el dolor postquirúrgico se reporta de moderado a severo. La anestesia regional es útil para el control del dolor postquirúrgico. El bloqueo interescalénico y supraclavicular produce parálisis diafragmática en diferente proporción. Se busca encontrar cuál es el porcentaje y duración de la parálisis hemidiafragmática mediante mediciones ultrasonográficas, correlacionadas con espirometría comparando el abordaje supraclavicular con interescalénico. MATERIAL Y MÉTODOS: ensayo clínico, controlado y aleatorizado. Se incluyeron 52 pacientes entre 18 y 90 años, programados para cirugía artroscópica de hombro, divididos en dos grupos (bloqueo interescalénico y supraclavicular). Se midió la excursión diafragmática y se realizó una espirometría previo al ingreso al quirófano y a las 24 horas de instalación del bloqueo, el estudio concluyó a las 24 horas del evento anestésico. RESULTADOS: la capacidad vital se redujo en 0.7% en el grupo del bloqueo supraclavicular y 7.7% en el grupo interescalénico, el VEF1 se redujo en 0.2% en el supraclavicular y 9.5% en el interescalénico con una diferencia estadísticamente significativa (p = 0.001). La parálisis diafragmática en ventilación espontánea se presentó en ambos abordajes a los 30 minutos, sin diferencia significativa. A las seis y ocho horas continuó la parálisis en el grupo interescalénico, mientras que en el abordaje supraclavicular se mantuvo en comparación con la basal. CONCLUSIONES: el bloqueo supraclavicular resulta tan efectivo como el bloqueo interescalénico en la cirugía artroscópica de hombro, con menor bloqueo diafragmático (1.5 veces más parálisis diafragmática en el interescalénico).

Pylephlebitis - a rare complication of a fish bone migration mimicking metastatic pancreatic cancer: A case report.

BACKGROUND: Pylephlebitis is a rare condition, poorly recognized by clinicians and with few references. In this case, the clinical appearance resembled the clinical course of a pancreatic cancer and was originated by the ingestion of a fish bone, making the case more interesting and rare. CASE SUMMARY: A 79-year-old female presented to the emergency department with fever, loss of appetite and jaundice. Tenderness in the right upper quadrant was present. Inflammation marker were high. A computed tomography (CT) scan revealed gallstones and aspects compatible with acute pancreatitis. The patient was admitted to surgery ward and has her condition aggravated. A magnetic resonance revealed multifocal liver lesions. Later, a cholangiopancreatography and an endoscopic ultrasound (US) were able to diagnose the condition. Specific treatment was implemented and the patient made a complete recovery. CONCLUSION: In conclusion, this case report demonstrates for the first time the diagnosis of an unusual case of pylephlebitis complicated by the migration of a fish bone, mimicking metastatic pancreatic cancer. Clinical presentation and traditional imaging studies, such as transabdominal US and CT, remain the standard for diagnosing this condition.

Crosstalk Between ATP-P2X7 and Adenosine A2A Receptors Controlling Neuroinflammation in Rats Subject to Repeated Restraint Stress.

Depressive conditions precipitated by repeated stress are a major socio-economical burden in Western countries. Previous studies showed that ATP-P2X7 receptors (P2X7R) and adenosine A2A receptors (A2AR) antagonists attenuate behavioral modifications upon exposure to repeated stress. Since it is unknown if these two purinergic modulation systems work independently, we now investigated a putative interplay between P2X7R and A2AR. Adult rats exposed to restraint stress for 14 days displayed an anxious (thigmotaxis, elevated plus maze), depressive (anhedonia, increased immobility), and amnesic (modified Y maze, object displacement) profile, together with increased expression of Iba-1 (a marker of microglia "activation") and interleukin-1ß (IL1ß) and tumor necrosis factor α (TNFα; proinflammatory cytokines) and an up-regulation of P2X7R (mRNA) and A2AR (receptor binding) in the hippocampus and prefrontal cortex. All these features were attenuated by the P2X7R-preferring antagonist brilliant blue G (BBG, 45 mg/kg, i.p.) or by caffeine (0.3 g/L, p.o.), which affords neuroprotection through A2AR blockade. Notably, BBG attenuated A2AR upregulation and caffeine attenuated P2X7R upregulation. In microglial N9 cells, the P2X7R agonist BzATP (100 µM) or the A2AR agonist CGS26180 (100 nM) increased calcium levels, which was abrogated by the P2X7R antagonist JNJ47965567 (1 µM) and by the A2AR antagonist SCH58261 (50 nM), respectively; notably JNJ47965567 prevented the effect of CGS21680 and the effect of BzATP was attenuated by SCH58261 and increased by CGS21680. These results provide the first demonstration of a functional interaction between P2X7R and A2AR controlling microglia reactivity likely involved in behavioral adaptive responses to stress and are illustrative of a cooperation between the two arms of the purinergic system in the control of brain function.

BWDAT: A research tool for analyzing the consumption of VOD content at home.

INTRODUCTION: New approaches to the study of the binge-watching phenomenon require new technology, leading to the development of a non-intrusive and low-cost analytical research software that facilitates a holistic understanding of binge-watching in an uncontrolled environment remotely (e.g., the home). BWDAT was developed to allow the collection of three types of data: users' physiological data gathered from a smartwatch, users' interactions from video-on-demand interfaces, and self-reported data. This tool offers the possibility to generate automatic data analysis reports, facilitating researchers' data analysis tasks. METHODS: Two trial studies and a long-term study were used to evaluate the design and the technical implementation of the BWDAT tool. The metrics used were the BWDAT smartwatch's App data coverage of the viewing sessions, and the data's reliability of the viewer's interactions with the Netflix interface, collected by the BWDAT Chrome Extension. RESULTS: High percentages of data coverage and content coverage were verified in the sessions collecting the smartwatch's data. The reporting system developed proved to be useful in the collection and synchronization of physiological and users' interaction data with Netflix interface, both generated in uncontrolled environments. Furthermore, the BWDAT tool facilitated the analysis of a large amount of nuanced data. CONCLUSION: The results obtained confirm the reliability, accuracy, and usability of BWDAT. This tool has the potential to help researchers shed new light on the field of media and audience studies, and in particular on binge-watching.

Efficient Brownian oscillators and nanoheaters based on gallium-doped ε-Fe2O3.

Wireless actuation at the nanoscale is vital in many contexts, and magnetic fields acting on nanoparticles (NPs) are among the most effective tools when actuation concerns linear forces. However, effective tools to apply torques at the nanoscale are still missing, because NPs where the magnetic moment is strongly coupled to the lattice agglomerate due to their high magnetic moment. Here, we show that gallium-doped ε-iron oxide NPs have small interparticle magnetic interactions and huge lattice-coupling for efficiently applying torques at the nanoscale. In this view, they are expected to be useful tools to efficiently apply mechanical forces to induce cellular apoptosis and to discern between mechanical and thermal contributions to cellular apoptosis currently under debate.

Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids.

Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies. Breast cancer monotypic and heterotypic models comprising cancer cells and cancer associated fibroblasts (CAFs) were self-assembled under controlled conditions using the liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology and necrotic regions, similarly to native solid tumors. For evaluating tumoritropic therapies in organotypic tumor-stroma 3D models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) were synthesized and administered to human bone-marrow derived MSCs (hBM-MSCs). The dual-loaded PDA nano-platforms were efficiently internalized, exhibited highly efficient NIR-light responsivity and assured MSCs viability up to 3 days. The administration of PDA-ICG-DOX nano-in-MSC tumoritropic units to microtumor models was performed in ultra-low adhesion surfaces for simulating in vitro the stem cell-tumor interactions observed in the in vivo scenario. Bioimaging analysis revealed hBM-MSCs adhesion to 3D cancer cells mass and MSCs-chemo-photothermal nanotherapeutics exhibited higher anti-tumor potential when compared to their standalone chemotherapy treated 3D tumor counterparts. Overall, the proposed methodology is suitable for evaluating MSCs-microtumors individualized interactions and enables a rapid high-throughput screening of tumoritropic therapies bioperformance.

Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer's Disease.

The lack of effective disease-modifying therapeutics to tackle Alzheimer's disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-ß (Aß) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

In situ functionalization of a cellulosic-based activated carbon with magnetic iron oxides for the removal of carbamazepine from wastewater.

The main goal of this work was to produce an easily recoverable waste-based magnetic activated carbon (MAC) for an efficient removal of the antiepileptic pharmaceutical carbamazepine (CBZ) from wastewater. For this purpose, the synthesis procedure was optimized and a material (MAC4) providing immediate recuperation from solution, remarkable adsorptive performance and relevant properties (specific surface area of 551 m2 g-1 and saturation magnetization of 39.84 emu g-1) was selected for further CBZ kinetic and equilibrium adsorption studies. MAC4 presented fast CBZ adsorption rates and short equilibrium times (< 30-45 min) in both ultrapure water and wastewater. Equilibrium studies showed that MAC4 attained maximum adsorption capacities (qm) of 68 ± 4 mg g-1 in ultrapure water and 60 ± 3 mg g-1 in wastewater, suggesting no significant interference of the aqueous matrix in the adsorption process. Overall, this work provides evidence of potential application of a waste-based MAC in the tertiary treatment of wastewaters. Graphical abstract.

Anomalous relative intensity noise transfer in ultralong random fiber lasers.

We present, for the first time, an experimental demonstration of RIN noise transfer dampening at low frequencies in random distributed feedback ultralong Raman fibre lasers based on conventional telecommunication fibres. Furthermore, we present a thorough theoretical description of the phenomenon and demonstrate how our model can be used to predict the observed behaviour, identifying the general requirements for system improvement through RIN transfer reduction.

Monitoring Proteolytic Activity in Real Time: A New World of Opportunities for Biosensors.

Proteases play a pivotal role in several biological processes, from digestion, cell proliferation, and differentiation to fertility. Deregulation of protease metabolism can result in several pathological conditions (i.e., cancer, neurodegenerative disorders, and others). Therefore, monitoring proteolytic activity in real time could have a fundamental role in the early diagnosis of these diseases. Herein, the main approaches used to develop biosensors for monitoring proteolytic activity are reviewed. A comparison of the advantages and disadvantages of each approach is provided along with a discussion of their importance and promising opportunities for the early diagnosis of severe diseases. This new era of biosensors can be characterized by the ability to control and monitor biological processes, ultimately improving the potential of personalized medicine.