Lights and Shadows in Immuno-Oncology Drug Development

The rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials. We have identified at least five areas in the development of promising IO treatments that should be redefined for more efficient designs and accelerated approvals. Here we review those critical aspects of IO drug development that could be optimized for more successful outcome rates in all cancer types. It is important to focus our efforts on the mechanisms of action, types of response and adverse events of these novel agents. The use of appropriate clinical trial designs with robust biomarkers of response and surrogate endpoints will undoubtedly facilitate the development and subsequent approval of these drugs. Further research is also needed to establish biomarker-driven strategies to select which patients may benefit from immunotherapy and identify potential mechanisms of resistance

Case 170: Pericardial fat necrosis

History: A 30-year-old man presented to our emergency department with acute pleuritic chest pain. He had no fever, dyspnea, or other symptoms, nor did he have a history of chest trauma. A physical examination yielded normal findings. Laboratory test results and electrocardiographic findings were normal. Axial chest computed tomography (CT) was performed

Verifique sus conocimientos sobre radiología de urgencias (3)

La presente entrega de la serie de Nursing sobre las pruebas complementarias es la tercera parte que complementa a las dos anteriores dedicadas a la radiología de urgencias, que trata de las situaciones clínicas y de las imágenes radiológicas más habituales obtenidas del estudio de alteraciones musculoesqueléticas. En la presente entrega se estudian las imágenes radiológicas relacionadas con alteraciones abdominales y torácicas habituales en el servicio de urgencias. Además, se presentan imágenes de tomografía computarizada correspondientes a situaciones clínicas que, por su prevalencia, se pueden producir en urgencias. Las tres entregas de Nursing dedicadas a las pruebas diagnósticas..

Mesenchymal stromal cells for articular cartilage repair: preclinical studies

Rheumatic diseases such as osteoarthritis (OA) are a major social and economic burden because of the population aging and the lack of curative solutions. An effective cell therapy may be the best treatment option for OA and other cartilage diseases. However, the main cellular strategy used to repair articular cartilage, the transplantation of autologous chondrocytes, is limited to a small number of patients with traumatic lesions. The use of joint replacement after years of disease progression proves the great medical need in current practice. Mesenchymal stromal/stem cells (MSCs) provide an alternative cell source for cartilage regeneration due to numerous advantages, comprising relative ease to isolate and culture, chondrogenic capacity, and anti-inflammatory effects. Initial clinical trials with MSCs have led to encouraging results, but many variables have to be considered to attain true amelioration of disease or repair (type and status of cartilage disease, source and conditions of cells, administration regime, combinatorial approaches). Particularly, allogeneic MSCs are an advantageous cellular product. The animal models chosen for preclinical evaluation are also relevant for successful translation into clinical practice. Considering the limitations in the field, rigorous comparative and validating studies in well-established animal models (including large animals) are still needed to set up the bases for additional clinical trials. The present review of studies performed in small and large animal models should help clarify the applicability of MSC-based therapies for articular cartilage repair

Mesenchymal Stromal Cells for Articular Cartilage Repair: Preclinical Studies

[Abstract] Rheumatic diseases such as osteoarthritis (OA) are a major social and economic burden because of the population aging and the lack of curative solutions. An effective cell therapy may be the best treatment option for OA and other cartilage diseases. However, the main cellular strategy used to repair articular cartilage, the transplantation of autologous chondrocytes, is limited to a small number of patients with traumatic lesions. The use of joint replacement after years of disease progression proves the great medical need in current practice. Mesenchymal stromal/stem cells (MSCs) provide an alternative cell source for cartilage regeneration due to numerous advantages, comprising relative ease to isolate and culture, chondrogenic capacity, and antiinflammatory effects. Initial clinical trials with MSCs have led to encouraging results, but many variables have to be considered to attain true amelioration of disease or repair (type and status of cartilage disease, source and conditions of cells, administration regime, combinatorial approaches). Particularly, allogeneic MSCs are an advantageous cellular product. The animal models chosen for preclinical evaluation are also relevant for successful translation into clinical practice. Considering the limitations in the field, rigorous comparative and validating studies in well-established animal models (including large animals) are still needed to set up the bases for additional clinical trials. The present review of studies performed in small and large animal models should help clarify the applicability of MSC-based therapies for articular cartilage repair

Flexible thermoelectric energy harvesting system based on polymer composites

[Abstract] Flexible and easy processing lightweight thermoelectric materials for energy harvesting applications have shown an increasing interest. Thermoplastic polyvinylidene fluoride (PVDF) and elastomer styrene-ethylene/butylene- styrene (SEBS) polymers reinforced with thermoelectric ceramics, including bismuth sulfide (Bi2S3), bismuth telluride (Bi2Te3) and antimony telluride (Sb2Te3), and electrically conductive carbon nanotubes (CNT) have been developed, tailoring their thermal and electrical properties for thermoelectric device applications. The Seebeck coefficient of the composites increases with thermoelectric ceramic filler content for semicrystalline PVDF composites, slightly decreasing for amorphous SEBS composite. Thermoelectric power factor and figure-of- merit in the polymer composites increases up to 9 orders of magnitude with respect to the pristine polymer, up to a maximum value of 10 3 µW/(m⋅K2) and 10 6, respectively, for the PVDF/CNT/Bi2Te3 composite. A device composed by 2 printable p-n thermocouples based on PVDF/50Bi2S3 and PVDF/50Bi2Te3 can generate power in the order of the nW and charge a capacitor with 5 V. Theoretical modeling allows to evaluate different thermoelectric configurations, the effect of the number of thermocouples and the influence of the temperature gradient on device performance

Caracterización epidemiológica, clínica y virológica de los nuevos diagnósticos de infección por VHC en Galicia (2014-2015)

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Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

ab initio modeling of open systems: charge transfer, electron conduction, and molecular switching of a C_{60} device

We present an {\it ab initio} analysis of electron conduction through a $C_{60}$ molecular device. Charge transfer from the device electrodes to the molecular region is found to play a crucial role in aligning the lowest unoccupied molecular orbital (LUMO) of the $C_{60}$ to the Fermi level of the electrodes. This alignment induces a substantial device conductance of $\sim 2.2 \times (2e^2/h)$. A gate potential can inhibit charge transfer and introduce a conductance gap near $E_F$, changing the current-voltage characteristics from metallic to semi-conducting, thereby producing a field effect molecular current switch

Rotura esplénica poscolonoscopia

Con la sospecha de perforación colónica, se realiza TC abdominal que muestra la presencia de hematoma subcapsular y periesplénico, así como moderado hemoperitoneo secundario a un punto de sangrado activo en la periferia esplénica. Dada la imposibilidad de realizar una embolización arterial selectiva..