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1.
J Phys Condens Matter ; 37(2)2024 Oct 23.
Article in English | MEDLINE | ID: mdl-39406259

ABSTRACT

All-inorganic perovskite quantum dots with the usual cubic shape have emerged as a successful and low-cost alternative to electronically functional nanomaterials motivating various fields of applications, including high-efficiency photovoltaics. Here, we present an efficient and almost analytic approach for optical absorption coefficient calculation on self-assembled perovskite quantum dot films with type-II band alignment. The approach takes advantage of the special point technique for integration over the two-dimensional Brillouin zone, which minimizes the computational cost. The set of special wave-vector points is generated using the Monkhorst and Pack method. The optical absorption spectrum for phenyl-C60-butyric acid methyl ester (PCBM)/CsPbI3quantum dot films is computed, in good agreement with the experiment assuming a homogeneous linewidth of 50 meV and considering a ten special-point set. We show that light absorption in these systems is a cooperative optoelectronic property resulting from the quantum-mechanical coupling between perovskite nanocubes, leading to extended system states. The generality of this approach makes it suitable for calculating the optical absorption coefficient in a broad class of perovskite quantum dot systems.

2.
Heliyon ; 10(13): e33724, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39040238

ABSTRACT

This work assessed the psychosocial risks of 124 workers from the plywood industry in Ecuador's Amazon region. Two psychosocial risk assessment (PRA) methods were selected due to their widespread use in Ecuadorian organisations: FPSICO from the Spanish National Institute for Occupational Safety and Health and the "Psychosocial Risk Assessment Questionnaire" (PRAQ) from the Ecuadorian Labour Ministry. Therefore, two surveys of 89 and 58 items were applied to evaluate nine scales and eight risk dimensions for FPSICO and PRAQ, respectively. Results show that according to FPSICO, the main psychosocial risks were detected in the scales of working time (WT), variety and content (VC), and workload (WL), with a prevalence of 34.8 % and 41.7 %. For PRAQ, the margin of action and control (D4), load and work rate (D1), and leadership (D3) were the most affected dimensions, with a risk prevalence between 29.1 % and 43.6 %. Although there is a lower risk prevalence in the rest of the scales and dimensions assessed, improvement actions are needed in the short term. Furthermore, the findings suggest an association between gender and risk prevalence, especially in the dimensions of Leadership (D3), Skills development (D2), and Self-perceived health (D8.8), where being a woman increases the likelihood of suffering from these conditions by up to three times. In addition, a brief comparative analysis was conducted, looking for coincidences in the scales that each PRA instrument assesses and the prevalence of the psychosocial risks detected.

3.
Front Genet ; 15: 1356786, 2024.
Article in English | MEDLINE | ID: mdl-38711916

ABSTRACT

Introduction: The combination of gene content on the marker chromosome, chromosomal origin, level of mosaicism, origin mechanism (chromothripsis), and uniparental disomy can influence the final characterization of sSMCs. Several chromosomal aberrations, including sSMCs, have been observed in 30%-60% of patients with pigmentary mosaicism, and in more than 80%, chromosomal abnormalities are present in the mosaic state. In patients with pigmentary mosaicism the most representative chromosomes involved in sSMCs are 3, 5, 6, 9, 10, 13, 15, 18, 20, and X. In this study, we included the complete clinical, cytogenetic, and molecular characterization of seven patients with pigmentary mosaicism associated with the presence of SMCs of different chromosomal origins. Methods: The patients were diagnosed by the Genetics and Dermatology Department of three different hospitals. Cytogenetic and FISH analyses were performed on peripheral blood, light skin, and dark skin. FISH analysis was performed using different probes, depending on the marker chromosome description. Different array analysis was performed. Results: To date, of the seven cases studied, the chromosomal origins of six were successfully identified by FISH or array analysis. The chromosomes involved in SMCs were 6, 9, 15, and 18, X. The most frequently found was the centric minute structure. Discussion: To date, this group of seven patients constitutes the largest clinical and cytogenetically finely described study of cases with pigmentary mosaicism associated with sSMCs. Undoubtedly, analysis of the two skin types is a fundamental part of our study, as numerical differences may occur in the cell lines found in each skin type. The knowledge generated in this study will help delineate a very heterogeneous entity more accurately, and in the future, analyzing more patients with PM will likely establish a more definite association with the presence of this genetic alteration.

4.
Cell Rep ; 43(5): 114144, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38656874

ABSTRACT

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.


Subject(s)
Pilocarpine , Proto-Oncogene Proteins c-abl , Seizures , Animals , Male , Mice , Apoptosis/drug effects , Mice, Inbred C57BL , Neurons/drug effects , Neurons/pathology , Neurons/metabolism , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-abl/metabolism , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Seizures/pathology , Status Epilepticus/chemically induced , Status Epilepticus/drug therapy , Status Epilepticus/pathology
5.
J Phys Condens Matter ; 36(32)2024 May 16.
Article in English | MEDLINE | ID: mdl-38478995

ABSTRACT

We present a theoretical investigation of the Goös-Hanchen shift (GHS) experienced by acoustic and optical vibrational modes reflected and transmitted from the surfaces of a semiconductor thin film sandwiched between two semi-infinite media. Our study focuses on the impact of the incident angle on the GHS, considering the coupling between longitudinal and transverse modes. For acoustic vibrations, our findings reveal that the GHS can reach magnitudes up to seven times larger than the thickness of the thin film and up to 20 times larger than the incident wavelength. Besides, it is shown that this significant amplification of the GHS highlights the strong influence of the incident angle and the frequency of the modes involved. In the case of optical vibrations, we observe even more pronounced GHS values, exceeding 30 times the incident wavelength. This demonstrates the potential of GHS in acoustical systems, which opens up possibilities for applications in the design of acoustic devices.

6.
PhytoKeys ; 229: 21-46, 2023.
Article in English | MEDLINE | ID: mdl-37457384

ABSTRACT

A checklist of Orchidaceae from Caquetá, Colombia is presented here. We recorded 98 genera and 418 species, exceeding a previous inventory by 276 species. The checklist is conservative in the number of genera and species by including only taxa that were fully and reliably identified and that are either linked to a corresponding herbarium voucher, a living collection specimen or a photo taken in the field and published in iNaturalist by one of the authors or a collaborator. The documented species diversity in the region could dramatically increase in the next few years with additional collecting efforts in the eastern slopes of the Andes nested in Caquetá. About 9% (418/4600) of all Orchidaceae species recorded for Colombia are reported for this area, showing the important contribution to orchid diversity of Andean-Amazonian foothills of Caquetá.

7.
J Phys Condens Matter ; 35(39)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37336206

ABSTRACT

The transfer matrix method is considered to obtain the fundamental properties of 1D Dirac-like problems. The case of 1D problems in monolayer graphene is addressed. The main characteristics of the transfer matrix are analyzed, contrasting them with the ones corresponding to 1D Schrödinger-like problems. Analytic expressions for the transmission coefficient and bound states are obtained. The continuity between bound states and states of perfect transmission is demonstrated in general, and in particular showed for the case of single electrostatic barriers. These findings in principle can be extended to 2D materials with Hamiltonian similar to monolayer graphene such as silicene and transition metal dichalcogenides.

8.
Data Brief ; 48: 109096, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37101778

ABSTRACT

An increasing share of dispatchable renewable generation is required to achieve energy decarbonisation goals and ensure a reliable supply to power grids. Concentrating solar power (CSP) plants hybridised with biomass boilers are promising alternatives to replace part of the peaking and baseload power generated from fossil fuel-based systems. This paper includes data related to the design variables, equations, valuation parameters and detailed results that support the research article "Market profitability of CSP-Biomass hybrid power plants: Towards a firm supply of renewable energy." The profitability assessment is based on integrating the hourly variation of electricity prices in the Iberian day-ahead market (MIBEL) to the results of the techno-economic model through a novel economic metric named Profitability Factor. In addition, stochastic simulations were conducted to capture the uncertainty of relevant input variables on the profitability of the proposed hybrid plants. The resulting datasets presented in this paper will provide insights for researchers looking to address the economic performance of renewable generation concepts from a market profitability approach. Furthermore, the data can be used by investors and policymakers to better understand the risks and implications associated with the profitability potential of these systems.

9.
Rev. otorrinolaringol. cir. cabeza cuello ; 82(1): 65-69, mar. 2022. ilus, tab
Article in Spanish | LILACS | ID: biblio-1389832

ABSTRACT

Resumen El tiroides ectópico es una alteración congénita infrecuente que presenta una prevalencia entre 1/100.000-1/300.000. En el 90% de los casos se encuentra en la línea media cervical, siendo los casos de tiroides ectópico cervical lateral muy infrecuentes. Presentamos el caso de una paciente de 44 años que consultó por presentar una tumoración submandibular izquierda de más de seis meses de evolución. Las pruebas de imagen (ecografía, tomografía computarizada y gammagrafía) sugirieron un bocio ectópico multinodular; la punción aspiración con aguja fina (PAAF) informó de tejido tiroideo sin atipias (Bethesda II) y el estudio sanguíneo de hormonas tiroideas fue normal, orientando finalmente el caso como un bocio multinodular ectópico submandibular eutiroideo. Ante la ausencia de síntomas y signos sugerentes de malignidad, en conjunto con una PAAF con características de benignidad, se decidió realizar seguimiento. En el momento que presentó clínica por efecto masa se decidió realizar la exéresis de la lesión, que confirmó el diagnóstico de bocio multinodular ectópico. Los casos descritos en la literatura de bocio multinodular ectópico submandibular como único tejido tiroideo funcionante son excepcionales. El tiroides ectópico se debe considerar en el diagnóstico diferencial de una masa submandibular. Aunque actualmente no existe un consenso en relación con el manejo de dicha patología, el crecimiento de la masa puede contribuir a la decisión de una exéresis completa del tiroides ectópico, aun tratándose del único tejido tiroideo funcionante.


Abstract Ectopic thyroid is an uncommon congenital disorder with a prevalence between 1/100,000-1/300,000. In 90% of cases, it is placed in cervical midline, being the cases of lateral cervical ectopic thyroid very infrequent. We present the case of a 44-year-old female patient who had a left submandibular mass during more than six months. Imaging tests (ultrasound, computed tomography and scintigraphy) suggested a multinodular ectopic goiter; fine needle aspiration (FNA) reported thyroid tissue without atypia (Bethesda II) and the thyroid hormone blood tests were normal, finally orienting the case as a euthyroid submandibular ectopic multinodular goiter. In the absence of symptoms and signs suggestive of malignancy, together with an FNA with benign characteristics, it was decided to follow up. When the patient presented clinical symptoms due to mass effect, it was decided to perform excision of the lesion, which confirmed the diagnosis of ectopic multinodular goiter. There are very few cases described in the literature of submandibular ectopic multinodular goiter as the only functioning thyroid tissue. Ectopic thyroid should be considered in the differential diagnosis of a submandibular mass. Although there is currently no consensus on the management of this pathology, the growth of the mass may contribute to the decision of a complete excision of the ectopic thyroid, even if it is the only functioning thyroid tissue.


Subject(s)
Humans , Female , Adult , Choristoma/diagnostic imaging , Goiter, Nodular/diagnostic imaging , Thyroidectomy/methods , Tomography, X-Ray Computed/methods , Choristoma/surgery , Goiter, Nodular/surgery
10.
Sci Rep ; 11(1): 13872, 2021 Jul 06.
Article in English | MEDLINE | ID: mdl-34230518

ABSTRACT

Fano resonances of bilayer graphene could be attractive for thermoelectric devices. The special profile presented by such resonances could significantly enhance the thermoelectric properties. In this work, we study the thermoelectric properties of bilayer graphene single and double barrier structures. The barrier structures are typically supported by a substrate and encapsulated by protecting layers, reducing considerably the phonon thermal transport. So, we will focus on the electronic contribution to the thermal transport. The charge carriers are described as massive chiral particles through an effective Dirac-like Hamiltonian. The Hybrid matrix method and the Landauer-Büttiker formalism are implemented to obtain the transmission, transport and thermoelectric properties. The temperature dependence of the Seebeck coefficient, the power factor, the figure of merit and the efficiency is analyzed for gapless single and double barriers. We find that the charge neutrality point and the system resonances shape the thermoelectric response. In the case of single barriers, the low-temperature thermoelectric response is dominated by the charge neutrality point, while the high-temperature response is determined by the Fano resonances. In the case of double barriers, Breit-Wigner resonances dominate the thermoelectric properties at low temperatures, while Fano and hybrid resonances become preponderant as the temperature rises. The values for the figure of merit are close to two for single barriers and above three for double barriers. The system resonances also allows us to optimize the output power and the efficiency at low and high temperatures. By computing the density of states, we also corroborate that the improvement of the thermoelectric properties is related to the accumulation of electron states. Our findings indicate that bilayer graphene barrier structures can be used to improve the response of thermoelectric devices.

11.
Biomater Sci ; 9(11): 4178-4190, 2021 Jun 07.
Article in English | MEDLINE | ID: mdl-33982040

ABSTRACT

The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the Aß peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Moreover, after a recurrent treatment for one month with GNRs-D1/Ang2, we observed a diminution of amyloid load and inflammatory markers in the brain. Thus, this new designed nanosystem exhibits promising properties for neurotheranostics of AD.


Subject(s)
Alzheimer Disease , Nanotubes , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Animals , Brain/metabolism , Disease Models, Animal , Gold , Mice , Mice, Transgenic , X-Ray Microtomography
12.
Clin Transl Oncol ; 23(8): 1529-1541, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33620682

ABSTRACT

The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System.


Subject(s)
Consensus , Membrane Glycoproteins/genetics , Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Receptor, trkA/genetics , Receptor, trkB/genetics , Receptor, trkC/genetics , Adult , Age Factors , Benzamides/therapeutic use , Child , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Indazoles/therapeutic use , Molecular Targeted Therapy , Neoplasms/diagnosis , Neoplasms/therapy , Oncogene Proteins, Fusion/analysis , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Reverse Transcriptase Polymerase Chain Reaction , Societies, Medical , Spain
13.
Clin Transl Oncol ; 23(5): 922-930, 2021 May.
Article in English | MEDLINE | ID: mdl-33405052

ABSTRACT

Soft-tissue sarcomas constitute an uncommon and heterogeneous group of tumors of mesenchymal origin. Diagnosis, treatment, and management should be performed by an expert multidisciplinary team. MRI/CT of the primary tumor and biopsy is mandatory before any treatment. Wide surgical resection with tumor-free tissue margin is the mainstay for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not suitable for re-excision. Perioperative chemotherapy should be discussed for high-risk sarcomas of the extremities and trunk-wall. In the case of oligometastatic disease, patients should be considered for local therapies. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. Other drugs have shown activity in second-line therapy and in specific histological subtypes but options are limited and thus, a clinical trial should always be discussed.


Subject(s)
Sarcoma/diagnosis , Sarcoma/therapy , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/therapy , Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , Checklist , Chemotherapy, Adjuvant/methods , Dermatofibrosarcoma/therapy , Female , Fibromatosis, Aggressive/genetics , Fibromatosis, Aggressive/therapy , Humans , Magnetic Resonance Imaging , Male , Medical Oncology , Neoadjuvant Therapy/methods , Radiotherapy/methods , Retroperitoneal Neoplasms/therapy , Sarcoma/diagnostic imaging , Sarcoma/pathology , Societies, Medical , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/pathology , Solitary Fibrous Tumors/drug therapy , Spain , Tomography, X-Ray Computed , Uterine Neoplasms/therapy
14.
Microbiol Res ; 239: 126539, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32622285

ABSTRACT

Clostridioides difficile is a nosocomial, Gram-positive, strictly anaerobic, spore-forming pathogen capable of colonizing and proliferating in the human intestine. In bacteria, it has been shown that the Toxin-Antitoxin systems mediate the cellular response to external stress by initiating processes such as biofilm formation and programmed cell death. This work aims to evaluate the functionality of four type II TA modules of Clostridioides difficile R20291. We performed bioinformatic analysis to search for putative TA systems using the TADB platform. Then we performed a heterologous expression assay to evaluate the functionality of these systems. Our results showed that the MazEF and RelBE systems were functional, suggesting that their corresponding toxins possess an endoribonuclease activity. In conclusion, MazEF and RelBE systems of C. difficile R20291 are functional in a heterologous expression system.


Subject(s)
Clostridioides difficile/genetics , Clostridioides difficile/physiology , Toxin-Antitoxin Systems , Bacterial Proteins/metabolism , Bacterial Toxins/metabolism , Computational Biology
15.
Clin Transl Oncol ; 22(9): 1499-1505, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31974820

ABSTRACT

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.


Subject(s)
Pancreatectomy/methods , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Prospective Studies , Survival Rate , Treatment Outcome
16.
Clin Transl Oncol ; 22(2): 213-222, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31993963

ABSTRACT

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Clinical Trials as Topic/standards , Drug-Related Side Effects and Adverse Reactions/prevention & control , Immunotherapy/adverse effects , Neoplasms/drug therapy , Practice Guidelines as Topic/standards , Disease Management , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/pathology , Humans , Medical Oncology , Neoplasms/immunology , Societies, Medical
17.
Clin Transl Oncol ; 22(4): 555-562, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31256362

ABSTRACT

PURPOSE: There is limited evidence on the efficacy and safety of anti-programmed cell death protein 1 (PD-1)-/anti-programmed death-ligand 1 (PD-L1)-based immunotherapy in the elderly, particularly those aged over 75 years. METHODS/PATIENTS: The clinical response and toxicity profile of anti-PD-1-/anti-PD-L1-based immunotherapy in patients aged over 75 years were assessed in this retrospective observational study conducted in the Medical Oncology Service of a tertiary level hospital. The associations among clinical responses, adverse events, and geriatric syndromes were evaluated. RESULTS: In total, 20 patients aged between 75 and 94 years were evaluated. Pembrolizumab and nivolumab were the most commonly used drugs. A clinical benefit (stable disease, partial response or complete response) was documented in 13 patients (65%). This proportion was 80% in patients aged between 75 and 79 years, and 50% in those aged over 79 years (p = 0.236). The adverse events were similar to those reported in younger patients. At least one clinical adverse event (cAE) and one laboratory adverse event (lAE) was reported in 75% and 55% of patients, respectively. Polypharmacy was observed for all patients and multi-morbidity in 95%. Patients without gait disorders showed more responses to immunotherapy. The number of lAEs was significantly associated with the number of commonly prescribed drugs (slope = 0.218, p = 0.010), the Eastern Cooperative Oncology Group score, and the number of cAEs. CONCLUSIONS: The elderly can obtain benefits from anti-PD-1-/anti-PD-L1-based immunotherapy. The toxicity profile was similar to that reported in younger counterparts.


Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Aged , Aged, 80 and over , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Male , Neoplasms/mortality , Retrospective Studies
18.
Clin Transl Oncol ; 21(8): 961-976, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30637710

ABSTRACT

Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients. In fact, atezolizumab when combined with chemotherapy has achieved the milestone of being the first drug to improve survival in patients with newly diagnosed extensive-stage SCLC. Other immunotherapeutic approaches evaluated in clinical trials for SCLC include the use of cytokines, cancer vaccines, antiganglioside therapies, TLR9 inhibition, anti-Notch signaling, and anti-CD47. This review discusses the rationale and clinical evidence of immunotherapy in SCLC, the conflictive clinical results of novel immunotherapeutic agents and combinatorial therapies under evaluation in SCLC patients.


Subject(s)
Immunotherapy/methods , Lung Neoplasms/therapy , Small Cell Lung Carcinoma/therapy , Animals , Humans , Lung Neoplasms/immunology , Small Cell Lung Carcinoma/immunology
19.
B. Indústr. Anim. ; 762019. ilus, tab
Article in Portuguese | VETINDEX | ID: vti-21182

ABSTRACT

O presente estudo teve como objetivo avaliar o uso de dispositivos intravaginais contendo doses altas ou baixas de progesterona (P4) na taxa de prenhez de novilhas zebuínas submetidas à inseminação artificial em tempo fixo (IATF). Novilhas Bos indicus (Nelore) receberam, no dia 0, uma injeção via intramuscular (im) de 2 mg de benzoato de estradiol (BE) e, em seguida, foram divididas aleatoriamente em três grupos. Nos grupos 1 (n = 80) e 2 (n = 79) foi colocado um dispositivo intravaginal contendo 1,9 g (grupo 1) e 0,75 g (grupo 2) de P4, enquanto que o grupo 3 (n = 76) não recebeu dispositivo. Os dispositivos intravaginais foram removidos no dia 8, juntamente com a aplicação im de uma dose luteolíticade cloprostenol. Metade dos animais de cada grupo recebeu, adicionalmente, uma injeção im de 300 UI de eCG. Vinte e quatro horas depois, todos animais receberam uma segunda aplicação im de 1 mg de BE e foram inseminados 54-56 horas após a aplicação de cloprostenol. O diagnóstico de prenhez foi realizado 40 dias após a IATF, por meio de ultrassonografia transretal. Os dados foram analisados por regressão logística. As taxas de prenhez foram de 27,5%, 30,4% e 28,9% para os grupos 1, 2 e 3, respectivamente (P>0,05). A injeção de eCG, bem como outras variáveis tais como escore corporal, fazenda e presença de CL no início dos tratamentos não influenciaram esse resultado. Em conclusão, o uso de dispositivos intravaginas contendo alto (1,9 g) ou baixo (0,75 g) teor de P4 resultou em semelhantes taxas de prenhez após IATF de novilhas Nelore púberes.(AU)


This study aimed to evaluate the use of low- or high-dose intravaginal progesterone (P4)-releasing devices on pregnancy rates of Zebu heifers submitted to fixed-timed artificial insemination (TAI). Pubertal Bos indicus Nellore heifers were injected at day 0 with 2 mg estradiol benzoate (EB) and assigned randomly to three groups. An intravaginal device containing 1.9 or 0.75 g P4 was inserted in animals of groups 1 (n=80) and 2 (n=79), while group 3 (n=76) received no device. The intravaginal devices were removed on day 8 and one luteolytic dose (125 μg) of d-cloprostenol was administered. Half of the animals in each group additionally received 300 IU of eCG. Twenty-four hours later, the heifers received a second injection of 1 mg EB and TAI was performed 54 hours after the injection of cloprostenol. Pregnancy was diagnosed 40 days after TAI by transrectal ultrasonography. Data were analyzed by logistic regression. Pregnancy rates were 27.5%, 30.4% and 28.9% in groups 1, 2 and 3, respectively (P>0.05). This result was not influenced by body score, farm, eCG, or presence of CL at the beginning of the treatments. In conclusion, the use of intravaginal devices containing either a high (1.9 g) or low (0.75 g) dose of P4 resulted in similar pregnancy rates after TAI in pubertal Nellore heifers.(AU)


Subject(s)
Animals , Female , Pregnancy , Cattle , Progesterone/administration & dosage , Progesterone/adverse effects , Insemination, Artificial/veterinary , Pregnancy Rate , Administration, Intravaginal
20.
Bol. ind. anim. (Impr.) ; 762019. ilus, tab
Article in Portuguese | VETINDEX | ID: biblio-1466960

ABSTRACT

O presente estudo teve como objetivo avaliar o uso de dispositivos intravaginais contendo doses altas ou baixas de progesterona (P4) na taxa de prenhez de novilhas zebuínas submetidas à inseminação artificial em tempo fixo (IATF). Novilhas Bos indicus (Nelore) receberam, no dia 0, uma injeção via intramuscular (im) de 2 mg de benzoato de estradiol (BE) e, em seguida, foram divididas aleatoriamente em três grupos. Nos grupos 1 (n = 80) e 2 (n = 79) foi colocado um dispositivo intravaginal contendo 1,9 g (grupo 1) e 0,75 g (grupo 2) de P4, enquanto que o grupo 3 (n = 76) não recebeu dispositivo. Os dispositivos intravaginais foram removidos no dia 8, juntamente com a aplicação im de uma dose luteolíticade cloprostenol. Metade dos animais de cada grupo recebeu, adicionalmente, uma injeção im de 300 UI de eCG. Vinte e quatro horas depois, todos animais receberam uma segunda aplicação im de 1 mg de BE e foram inseminados 54-56 horas após a aplicação de cloprostenol. O diagnóstico de prenhez foi realizado 40 dias após a IATF, por meio de ultrassonografia transretal. Os dados foram analisados por regressão logística. As taxas de prenhez foram de 27,5%, 30,4% e 28,9% para os grupos 1, 2 e 3, respectivamente (P>0,05). A injeção de eCG, bem como outras variáveis tais como escore corporal, fazenda e presença de CL no início dos tratamentos não influenciaram esse resultado. Em conclusão, o uso de dispositivos intravaginas contendo alto (1,9 g) ou baixo (0,75 g) teor de P4 resultou em semelhantes taxas de prenhez após IATF de novilhas Nelore púberes.


This study aimed to evaluate the use of low- or high-dose intravaginal progesterone (P4)-releasing devices on pregnancy rates of Zebu heifers submitted to fixed-timed artificial insemination (TAI). Pubertal Bos indicus Nellore heifers were injected at day 0 with 2 mg estradiol benzoate (EB) and assigned randomly to three groups. An intravaginal device containing 1.9 or 0.75 g P4 was inserted in animals of groups 1 (n=80) and 2 (n=79), while group 3 (n=76) received no device. The intravaginal devices were removed on day 8 and one luteolytic dose (125 μg) of d-cloprostenol was administered. Half of the animals in each group additionally received 300 IU of eCG. Twenty-four hours later, the heifers received a second injection of 1 mg EB and TAI was performed 54 hours after the injection of cloprostenol. Pregnancy was diagnosed 40 days after TAI by transrectal ultrasonography. Data were analyzed by logistic regression. Pregnancy rates were 27.5%, 30.4% and 28.9% in groups 1, 2 and 3, respectively (P>0.05). This result was not influenced by body score, farm, eCG, or presence of CL at the beginning of the treatments. In conclusion, the use of intravaginal devices containing either a high (1.9 g) or low (0.75 g) dose of P4 resulted in similar pregnancy rates after TAI in pubertal Nellore heifers.


Subject(s)
Female , Animals , Pregnancy , Cattle , Insemination, Artificial/veterinary , Progesterone/administration & dosage , Progesterone/adverse effects , Pregnancy Rate , Administration, Intravaginal
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