RESUMO
[Figure: see text].
Assuntos
Netrina-1/metabolismo , Placa Aterosclerótica/metabolismo , Animais , Aorta/citologia , Aorta/metabolismo , Aorta/patologia , Movimento Celular , Inativação Gênica , Interleucina-10/metabolismo , Macrófagos/metabolismo , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Netrina-1/genética , Fagocitose , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Receptores CCR7/metabolismoRESUMO
OBJECTIVES: Our study aims to describe the association between SLE and sexual function, analysing demographic variables, comorbidities and other disease-related factors. As an exploratory objective, the impact of asking about sexual function during outpatient consultation was evaluated. METHODS: From 2018 to 2019, we invited sexually active men diagnosed with SLE to complete questionnaires that evaluated their sexual function and quality of life. Additionally, patients were asked if they believed they had sexual dysfunction, whether they would be interested in receiving specialized sexual care, and if they considered SLE to be detrimental to their sexual function. Epidemiological and disease-related data were retrieved from the patients' clinical records. RESULTS: We included 124 men with SLE. Twenty-two (18%) patients answered positively when asked if they believed they had sexual dysfunction. These patients had lower overall erectile function scores and lower physical function scores than those who did not consider they had sexual dysfunction. In the multivariable analysis, factors that were associated with better sexual function were high physical function (B = 0.126, p = .031), lower BMI (B = 0.53, p = .010) and the patient's perception of normal sexual function (B = 13.0, p < .001). Comorbidities associated with worse sexual function were type 2 diabetes (B = -8.1, p = .017) and a history of thrombosis (B = -5.12, p = .019). CONCLUSION: Sexual function of male patients with SLE is impaired, independently of disease activity, chronic disease damage or pharmacological treatment. A simple question about perception of sexual function in the outpatient clinic can be used to help determine which patients could benefit from a multidisciplinary intervention to improve sexual health.
Assuntos
Diabetes Mellitus Tipo 2 , Lúpus Eritematoso Sistêmico , Disfunções Sexuais Fisiológicas , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologiaRESUMO
The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.
RAD VACCINE MIBC is a phase II clinical trial that aims to determine the safety and effectiveness of a study drug called sasanlimab (an immune checkpoint inhibitor), combined with radiation therapy (stereotactic body radiation therapy) prior to surgery to remove the bladder (known as radical cystectomy [RC]) in muscle-invasive bladder cancer patients. For this type of cancer, patients typically receive chemotherapy followed by RC as the standard of care. However, many patients who have pre-existing medical conditions such as poor kidney function are unable to receive chemotherapy. These patients undergo RC alone at the risk of less optimal cancer control. Bladder cancer is known to inhibit the immune cells (T cells) from attacking it, which is an important way in which the body controls cancer cells. Sasanlimab allows T cells that are specific to the cancer to potentially reactivate. Ongoing studies have shown that drugs similar to sasanlimab can be used to achieve improvement in cancer control in the bladder (as measured by shrinking the cancer or eradicating it) before surgery. The authors are studying the use of the study drug with the addition of stereotactic body radiotherapy (SBRT) as a combined therapy. The role of SBRT as a combined therapy to immune checkpoint inhibition has been well studied to help improve the process of how immune cells recognize cancer cells. By giving both the study drug and SBRT together before RC, the authors aim to demonstrate the safety of this technique and its effectiveness in eradicating all cancer in the bladder. Clinical Trial Registration: NCT05241340 (ClinicalTrials.gov).
Assuntos
Terapia Neoadjuvante , Radiocirurgia , Neoplasias da Bexiga Urinária , Vacinas , Anticorpos Monoclonais Humanizados/uso terapêutico , Cisplatino , Ensaios Clínicos Fase II como Assunto , Terapia Combinada/efeitos adversos , Cistectomia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Vacinas/uso terapêuticoRESUMO
An optimal response to immune checkpoint blockade requires the presence of effector cells in the tumor microenvironment. We designed a PD-L1-targeted delivery strategy for chemokines, key molecules that drive leukocyte trafficking, to the tumor microenvironment, as a means of attracting the relevant leukocyte populations. This strategy combines a PD-L1-blocking single-domain antibody fragment (nanobody or VHH), a charge-engineered chemokine CCL21, and its subsequent characterization in a microfluidic device that resembles the tumor microenvironment. We show that the PD-L1-blocking VHH is a reliable fusion partner for the preparation of a functional chemokine fusion. Engineering the surface charge of CCL21 reduced its nonspecific binding to glycosaminoglycans, a property of chemokines that complicates their targeted delivery. Using a microfluidic assay, we show that it is possible to deliver a chemokine-VHH fusion to a PD-L1-positive environment and recruit effector cells.
Assuntos
Quimiocinas/metabolismo , Microambiente Tumoral/fisiologia , Animais , Anticorpos Monoclonais/metabolismo , Quimiocina CCL21/metabolismo , Matriz Extracelular/metabolismo , Humanos , Dispositivos Lab-On-A-ChipRESUMO
BACKGROUND: Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are few randomized controlled trials comparing the efficacy of dexmedetomidine to other commonly used sedatives. AIM: To compare the efficacy of sedation with intranasal dexmedetomidine to oral chloral hydrate for auditory brainstem response (ABR) testing. METHODS: In this double-blind, double-dummy study, children undergoing ABR testing were randomized to receive intranasal dexmedetomidine 3 mcg · kg(-1) plus oral placebo (Group IN DEX) or oral chloral hydrate 50 mg · kg(-1) plus intranasal saline placebo (Group CH). We recorded demographic data, times from sedative administration to start and completion of testing, quality of sedation, occurrence of predefined adverse events, discharge times, and return to baseline activity on the day of testing. RESULTS: Testing completion rates with a single dose of medication were higher in the IN DEX group (89% vs 66% for CH, odds ratio with 95% confidence intervals 4.04 [1.3-12.6], P = 0.018). The median [95% CI)] time to successful testing start was shorter (25 [20-29] min vs 30 [20-49] min for IN DEX and CH, respectively, log rank test P = 0.02) and the proportion of children whose parents reported a return to baseline activity on the day of testing was greater for the IN DEX than the CH group (89% vs 64%, OR [95% CI] 4.71 [1.34-16.6], P = 0.02). There were no major adverse events in either group and no significant differences in the incidence of minor events. CONCLUSION: Intranasal dexmedetomidine is an effective alternative to oral chloral hydrate sedation for ABR testing, with the advantages of a higher incidence of testing completion with a single dose, shorter time to desired sedation level, and with significantly more patients reported to return to baseline activity on the same day.
Assuntos
Hidrato de Cloral/farmacologia , Dexmedetomidina/farmacologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Administração Intranasal , Administração Oral , Pré-Escolar , Hidrato de Cloral/administração & dosagem , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lactente , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Antibody-drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but further advances are constrained by the complex structures of full-sized antibodies. Camelid-derived single-domain antibody fragments (VHHs or nanobodies) offer a possible solution to this challenge by providing expedited target screening and validation through switching between imaging and therapeutic activities. We used a nanobody (VHH7) specific for murine MHC-II and rendered "sortase-ready" for the introduction of oligoglycine-modified cytotoxic payloads or NIR fluorophores. The VHH7 conjugates outcompeted commercial monoclonal antibodies (mAbs) for internalization and exhibited high specificity and cytotoxicity against A20 murine B-cell lymphoma. Non-invasive NIR imaging with a VHH7-fluorophore conjugate showed rapid tumor targeting on both localized and metastatic lymphoma models. Subsequent treatment with the nanobody-drug conjugate efficiently controlled tumor growth and metastasis without obvious systemic toxicity.
Assuntos
Antineoplásicos/uso terapêutico , Antígenos de Histocompatibilidade Classe II/química , Linfoma de Células B/terapia , Anticorpos de Domínio Único , Animais , Linhagem Celular Tumoral , Humanos , Linfoma de Células B/patologia , CamundongosRESUMO
INTRODUCTION: Most cancer patients are never enrolled in clinical trials, resulting in missed potential therapeutic benefits to patients and barriers to drug development and approval. With a focus on urologic oncology clinical trials, we reviewed the current literature on barriers to accrual and present effective interventions to overcome these barriers. METHODS: PubMed was searched for articles regarding physician referral and patient accrual to clinical trials in urologic oncology from January 2000 through June 2021. Studies were included if they were in English, related to clinical trial utilization or patient accrual in urologic oncology, peer-reviewed, primary research, survey, or systematic review, and pertained to clinical trials in the U.S. Major overlapping themes related to barriers to accrual and effective interventions were identified. RESULTS: Thirty-six studies met our inclusion criteria. Barriers fall into three categories: 1) provider; 2) patient; or 3) structural. Provider barriers include issues such as poor funding, logistical challenges, and time constraints. Patient barriers include cost, distrust of medical institutions, and lack of knowledge regarding ongoing studies. Structural barriers include lack of time and resources in community settings and difficulty with physician referrals. Effective strategies identified include increasing provider referrals through continuing education and referral pathways, increasing patient education through patient-centered marketing material, and decreasing structural barriers through patient navigation programs and community partnerships. CONCLUSIONS: We identified barriers and potential multipronged strategies targeted at patients, providers, and practices to increase clinical trial enrollment. We hope these strategies will benefit patients and providers and facilitate research development.
RESUMO
PURPOSE: The current standard of care for muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy with lymph node dissection. Although this treatment provides therapeutic benefit, it is associated with notable morbidity. Bladder sparing techniques, such as concurrent chemo-radiation, are less invasive and prioritize organ preservation in individuals with invasive bladder cancer and offer comparable disease control. High-dose-rate brachytherapy is an emerging paradigm in the management of muscle-invasive bladder cancer. During high-dose-rate brachytherapy, radioactive sources are introduced to the area of the primary tumor through specialized catheters. The specific placement of brachytherapy catheters results in heightened effectiveness of the radiation treatment with less radiation damage to surrounding structures. For bladder-sparing therapies such as brachytherapy to rival radical cystectomy, these techniques need to be refined further by radiation oncologists. PROCEDURE: One such modality for developing and practicing these techniques is the use of cadaveric models in innovation-focused clinical training facilities, which provide a simulated sterile surgical environment without the concern for extending intraoperative time. FINDINGS AND CONCLUSIONS: The objective of this technical note is to demonstrate how clinical training facilities such as the Houston Methodist Institute for Technology, Innovation & Education are ideal for the development, testing, and training of novel brachytherapy techniques using cadaveric models. By utilizing a network of similarly innovative training centers, research and development of brachytherapy techniques can be expedited, and novel bladder-sparing treatment methods can be implemented as the standard of care for bladder cancer.
Assuntos
Braquiterapia , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Humanos , Braquiterapia/métodos , Estudos de Viabilidade , Neoplasias da Bexiga Urinária/radioterapia , Cistectomia/métodos , Terapia Combinada , Cadáver , Invasividade NeoplásicaRESUMO
BACKGROUND: Surgical resection of oligometastatic disease has been shown to be associated with an improved survival in other malignancies, though its role is not established in metastatic urothelial carcinoma (mUC). We sought to examine utilization trends of metastasectomy in mUC and associated outcomes using the NCDB database. METHODS: We queried the NCDB from 2004 to 2016 for patients with metastatic urothelial carcinoma who had undergone metastasectomy. The annual utilization trend of metastasectomy was evaluated by linear regression. We compared overall survival (OS) between propensity score matched patients who had undergone metastasectomy and those who had not using two-sided log-rank and Cox regression models. We also performed sensitivity analyses on subcohorts of mUC. RESULTS: The utilization rate of metastasectomy in mUC was 7% and did not change significantly over time. Patients who received metastasectomy on average were younger, had >cT3 disease, had radical surgery to the primary tumor, and received systemic therapy. After propensity score matching, metastasectomy was not associated with an OS benefit for mUC patients (HR, 0.94; 95% CI, 0.83 to 1.07; P=0.38). Stratified subgroup analysis based on systemic therapy, radical surgery to primary tumor, clinical N stage, and primary location of disease did not show an OS benefit of metastasectomy. CONCLUSION: Metastasectomy is uncommonly used, though utilization has persisted over more than a decade. Despite selection biases and residual confounding favoring patients undergoing metastasectomy, we found similar OS among these individuals and those who did not undergo metastasectomy.
Assuntos
Metastasectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Immune checkpoint-inhibitor (ICI)-based therapy is the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC). It is unclear whether prior removal of the primary tumor influences the efficacy of these treatments. We performed a systematic review and meta-analysis of studies of first-line ICI in mRCC to determine whether the efficacy of ICI-therapy, compared to sunitinib, is altered based on receipt of prior nephrectomy. METHODS: We systematically reviewed studies indexed in MEDLINE (PubMed), Embase, and Scopus and conference abstracts from relevant medical societies as of August 2020 to identify randomized clinical trials assessing first-line immunotherapy-based regimes in mRCC. Studies were included if overall survival (OS) and progression-free survival (PFS) outcomes were reported with data stratified by nephrectomy status. We pooled hazard ratios (HRs) stratified by nephrectomy status and performed random effects meta-analysis to assess the null hypothesis of no difference in the survival advantage of immunotherapy-based regimes based on nephrectomy status, while accounting for study level correlations. RESULTS: Among 6 randomized clinical trials involving 5,121 patients, 3,968 (77%) had undergone prior nephrectomy. We found an overall survival benefit for immunotherapy-based regimes, compared to sunitinib, among both patients who had undergone nephrectomy (HR 0.75, 95% CI 0.63 -0.88) and those who had not (HR 0.74, 95% CI 0.59 -0.92), without evidence of difference based on nephrectomy history (Pâ¯=â¯0.70; I2â¯=â¯36%). Results assessing PFS were similar (Pâ¯=â¯0.45, I2â¯=â¯0%). CONCLUSIONS: These clinical data suggest that prior nephrectomy does not affect the efficacy of ICI-based regimens in mRCC relative to sunitinib.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Metástase NeoplásicaRESUMO
Importance: Surgeon sex is associated with differential postoperative outcomes, though the mechanism remains unclear. Sex concordance of surgeons and patients may represent a potential mechanism, given prior associations with physician-patient relationships. Objective: To examine the association between surgeon-patient sex discordance and postoperative outcomes. Design, Setting, and Participants: In this population-based, retrospective cohort study, adult patients 18 years and older undergoing one of 21 common elective or emergent surgical procedures in Ontario, Canada, from 2007 to 2019 were analyzed. Data were analyzed from November 2020 to March 2021. Exposures: Surgeon-patient sex concordance (male surgeon with male patient, female surgeon with female patient) or discordance (male surgeon with female patient, female surgeon with male patient), operationalized as a binary (discordant vs concordant) and 4-level categorical variable. Main Outcomes and Measures: Adverse postoperative outcome, defined as death, readmission, or complication within 30-day following surgery. Secondary outcomes assessed each of these metrics individually. Generalized estimating equations with clustering at the level of the surgical procedure were used to account for differences between procedures, and subgroup analyses were performed according to procedure, patient, surgeon, and hospital characteristics. Results: Among 1â¯320â¯108 patients treated by 2937 surgeons, 602â¯560 patients were sex concordant with their surgeon (male surgeon with male patient, 509â¯634; female surgeon with female patient, 92â¯926) while 717â¯548 were sex discordant (male surgeon with female patient, 667â¯279; female surgeon with male patient, 50â¯269). A total of 189â¯390 patients (14.9%) experienced 1 or more adverse postoperative outcomes. Sex discordance between surgeon and patient was associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio [aOR], 1.07; 95% CI, 1.04-1.09), as well as death (aOR, 1.07; 95% CI, 1.02-1.13), and complications (aOR, 1.09; 95% CI, 1.07-1.11) but not readmission (aOR, 1.02; 95% CI, 0.98-1.07). While associations were consistent across most subgroups, patient sex significantly modified this association, with worse outcomes for female patients treated by male surgeons (compared with female patients treated by female surgeons: aOR, 1.15; 95% CI, 1.10-1.20) but not male patients treated by female surgeons (compared with male patients treated by male surgeons: aOR, 0.99; 95% CI, 0.95-1.03) (P for interaction = .004). Conclusions and Relevance: In this study, sex discordance between surgeons and patients negatively affected outcomes following common procedures. Subgroup analyses demonstrate that this is driven by worse outcomes among female patients treated by male surgeons. Further work should seek to understand the underlying mechanism.
Assuntos
Relações Médico-Paciente , Complicações Pós-Operatórias , Cirurgiões , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Médicas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores SexuaisRESUMO
We studied the geographic variation of skulls of Lycalopex culpaeus using qualitative and quantative analyses. The sampling area covered Chile, from its northern portion, to Tierra del Fuego and the neighbouring Hoste Island, as well as part of Argentina. Five subespecies are currently recognized from this large area. We found two morphotypes that are segregated geographically. Both groups mostly differ by morphometric attributes, followed by qualitative features. Specimens from northern Chile (Tarapacá and Antofagasta) have small skulls, short rostrum, a liriform sagital zone, and lack the interparietal crest. The second group is formed by specimens from north-western and central Argentina, central-south Chile, Patagonia, and the austral islands of Tierra del Fuego and Hoste. This group presents a strong sagital crest, large rostrum, and a large skull. Our results agree with observed patterns of mitochondrial DNA variation. We propose to retain the name L. c. andinus for the populations of northern Chile and to synonymize L. c. magellanicus, L. c. lycoides, and L. c. smithersi under L. c. culpaeus.
Assuntos
Raposas/classificação , Crânio/anatomia & histologia , Animais , Argentina , Cefalometria , Chile , DNA Mitocondrial/genética , Raposas/anatomia & histologia , Raposas/genética , GeografiaRESUMO
INTRODUCTION: It is well documented in literature that most prostate carcinomas (PCa) arise in the peripheral zone (PZ). Additionally, an inverse relationship between prostate size and the incidence of PCa has been demonstrated in recent studies. However, little is known about gland distribution in the peripheral zone of larger prostates compared to smaller prostates. In this study, we examined the histo-anatomical gland distribution within the peripheral zone in small and large prostates and discuss possible clinical implications. METHODS: A semi-quantitative analysis of gland density and capsule thickness was performed using light microscopy on 10 large (≥80 g) prostate specimens and 10 small (<30 g) prostate specimens from patients who underwent radical prostatectomy at Texas Tech University Health Sciences Center between the years 2010 and 2016. Samples from radical prostatectomies were used to ensure a whole, preserved prostate with an intact surgical capsule. Gland counts were performed on five random fields under 100 × magnification, while capsule thickness was measured on three random fields per case; thus, a total 50 fields and 30 fields were analyzed for each of the two groups for gland counts and capsule thickness measurements, respectively. Microscopy was standardized to the posterior aspect of the prostate, between 4 o'clock and 6 o'clock along the equatorial region between the apex and base. RESULTS: Large prostates possessed a significantly lower mean gland count per field compared to small prostates (10.34±4.15, n=50 vs 18.00±5.41, n=50; t=8.16, df=49, P<0.001). Additionally, large prostates showed a significantly higher average capsule thickness in millimeters compared to small prostates (1.80 mm, ±1.12 mm, n=30 vs 0.90 mm, ±0.56, n=30; t=8.16, df=49, P<0.001). CONCLUSION: The results demonstrate that prostate hypertrophy leads to both decreased gland density in the peripheral zone and increased capsule thickness, suggesting that growth-induced expansion of the prostate against its capsule leads to compression-induced atrophy and fibrosis of glandular tissue within the peripheral zone (PZ). A decrease in gland density within the PZ may have clinical implications shedding light, for instance, on the reduction in PCa incidence in patients with large prostates as compared to smaller prostates, a phenomenon well documented in the literature.
RESUMO
OBJECTIVE: The aim of this study was to describe the prevalence of erectile dysfunction (ED), as well as associated demographic and clinical features, in men with systemic lupus erythematosus (SLE), by means of a systematic, standardized evaluation. METHODS: We performed a transversal study in 8 tertiary care centers in Latin America. We included male patients ≥ 16 years who fulfilled ≥ 4 American College of Rheumatology criteria for SLE and had regular sexual activity, and evaluated them with the International Index of Erectile Function-5 questionnaire. Relevant demographic, clinical, and serological characteristics were recorded. We included 2 control groups: the first was made up of healthy men and the second of men with autoimmune diseases other than SLE (non-SLE group). RESULTS: We included 590 subjects (174 SLE, 55 non-SLE, and 361 healthy controls). The prevalence of ED in the SLE group was 69%. Mean age in that group was 36.3 ± 1.03 years. Among SLE patients with and without ED, these factors were significantly different: the presence of persistent lymphopenia (p = 0.006), prednisone dose (9.3 ± 1.2 vs 5.3 ± 1.3 mg, p = 0.026), and the Systemic Lupus International Collaborating Clinics damage score (1.25 ± 0.14 vs 0.8 ± 0.16 points, p = 0.042). Independent risk factors for ED in patients with SLE were persistent lymphopenia (OR 2.79, 95% CI 1.37-5.70, p = 0.001) and corticosteroid use in the previous year (OR 2.15, 95% CI 1.37-3.37, p = 0.001). CONCLUSION: Regardless of comorbidities, treatment (excluding steroids), and type of disease activity, patients with SLE have a high prevalence of ED, especially considering that most patients are young. Recent corticosteroid use and persistent lymphopenia, which could be related to endothelial dysfunction, are risk factors for this complication in men with SLE.
Assuntos
Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Lúpus Eritematoso Sistêmico/complicações , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Humanos , América Latina/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfopenia/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Comportamento Sexual , Centros de Atenção TerciáriaRESUMO
Introduction: Coral reefs worldwide decline has prompted coral restoration as a viable strategy to rewild vulnerable, foundational coral species. Stony corals are now propagated by thousands in both in-water and ex situ (land-based) coral nurseries, the latter being unexplored in Costa Rica, despite their potential benefits as a reef management tool. Objective: To analyze the viability of ex situ culturing of the Pacific reef-building corals Porites lobata and Pocillopora damicornis at Parque Marino del Pacífico (PMP), Puntarenas, Costa Rica, aquaculture facilities. Methods: From May to October 2018 a total of 180 coral fragments were kept in an aquaculture recirculated system. Survival, growth, and fragment yield in relation to culture medium (physicochemical parameters) were recorded. Results: Survival and growth rate varied between species and culture tanks. On average, surviving P. lobata fragments (68.89 %) placed in Tank 1 (T1) grew 216 %, while fragments placed in Tank 2 (T2) had a survival rate of 71.11 % and an increase of 277 % in live tissue area. P. damicornis fragments survival, basal and crown area percentage increase were: 71.11 %, 980 % and 366 % in T1, and 100 %, 976 % and 287 % in T2. Although fragments survival and growth were net positive, the yield in terms of culture was low, due to culture conditions in the tanks not meeting coral culture optimal requirements. Conclusions: Survival and growth of both species varied depending on the tank in which they were placed. Survival was similar to that found in other ex situ studies and growth was similar to those reported in the wild, however culture performance in terms of yield was low. Aquaculture systems at PMP constitute a good base for the cultivation of corals, however for the culture effort to achieve maximum yield, current systems must be optimized according to the requirements of the target coral species.
Introducción: El declive mundial de los arrecifes de coral, ha impulsado a la restauración coralina como una estrategia viable para recuperar especies de coral fundacionales, en estado vulnerable. Los corales pétreos se propagan por miles, tanto en viveros subacuáticos como ex situ (en tierra). Siendo el segundo método poco explorado en Costa Rica, a pesar de sus potenciales beneficios como medida como herramienta de manejo arrecifal. Objetivo: Analizar la viabilidad del cultivo ex situ de las especies de coral constructoras de arrecifes Porites lobata y Pocillopora damicornis en el módulo de acuicultura del Parque Marino del Pacífico (PMP), Puntarenas, Costa Rica. Métodos: Desde el 17 de mayo hasta el 17 de octubre de 2018, se mantuvieron un total de 180 fragmentos de coral en un sistema de recirculación de acuicultura. Se registraron la supervivencia, el crecimiento y el rendimiento de los fragmentos en relación con el medio de cultivo (parámetros fisicoquímicos). Resultados: La tasa de supervivencia y crecimiento varió entre especies y tanques de cultivo. En promedio, los fragmentos de P. lobata supervivientes (68.89 %) colocados en el tanque 1 (T1) crecieron un 216 %. En contraste con los fragmentos colocados en el tanque 2 (T2) que mostraron una tasa de supervivencia del 71.11 % y un aumento del 277 % en el área de tejido vivo. En el caso de P. damicornis, los porcentajes de supervivencia, de aumento del área basal y del área de la corona fueron: 71.11 %, 980 %, y 366 %, y 100 %, 976 %, y 287 % para los fragmentos colocados en T1 y T2, respectivamente. Aunque la supervivencia y el crecimiento de los fragmentos fueron positivos, el rendimiento en términos de cultivo fue bajo, debido a que las condiciones en los tanques no cumplían con las condiciones ideales para el cultivo de corales. Conclusiones: La supervivencia y el crecimiento de ambas especies variaron en función del tanque en el que se colocaron. La supervivencia fue similar a la observada en otros estudios ex situ y el crecimiento fue similar al reportado en la naturaleza, pero el rendimiento del cultivo fue bajo. Los sistemas de acuicultura del PMP constituyen una buena base para el cultivo de corales, sin embargo, para que el esfuerzo de cultivo alcance un máximo de rendimiento, los sistemas actuales deben optimizarse en función de los requisitos de las especies de coral objetivo.
RESUMO
Unusual patterns of glycosylation on the surface of transformed cells contribute to immune modulation and metastasis of malignant tumors. Active immunization against them requires effective antigen presentation, which is complicated by a lack of access to tumor-specific posttranslational modifications through standard genetic approaches and by the low efficiency of passive antigen sampling. We found that antigen targeted to antigen presenting cells via class II MHC products can elicit a robust immune response against MUC1(Tn) bearing a defined tumor-associated glycoform, Tn. The two-component vaccine construct was prepared by sortase-mediated protein ligation of a synthetic MUC1(Tn) fragment to a class II MHC-binding single-domain antibody fragment (VHH7) as targeting moiety. We show that VHH7 targets antigen presenting cells in vivo, and when conjugated to MUC1(Tn) can elicit a strong αMUC1(Tn) immune response in mice. The resulting sera preferentially recognized the MUC1 epitope with the tumor-associated carbohydrate antigen Tn and were capable of killing cancer cells in a complement-mediated cytotoxicity assay. Immunoglobulin isotype analysis and cytokine release assays suggested a favorable Th1 response. A single boost 12 months after primary immunization triggered a recall response of the same quality, suggesting that long-term αMUC1(Tn) memory had been achieved.
RESUMO
Geographic variation of the fox Lycalopex culpaeus (Mammalia, Canidae) in Chile: taxonomic implications. We studied the geographic variation of skulls of Lycalopex culpaeus using qualitative and quantative analyses. The sampling area covered Chile, from its northern portion, to Tierra del Fuego and the neighbouring Hoste island, as well as part of Argentina. Five subespecies are currently recognized from this large area. We found two morphotypes that are segregated geographically. Both groups mostly differ by morphometric attributes, followed by qualitative features. Specimens from northern Chile (Tarapacá and Antofagasta) have small skulls, short rostrum, a liriform sagital zone, and lack the interparietal crest. The second group is formed by specimens from north-western and central Argentina, central-south Chile, Patagonia, and the austral islands of Tierra del Fuego and Hoste. This group presents a strong sagital crest, large rostrum, and a large skull. Our results agree with observed patterns of mitochondrial DNA variation. We propose to retain the name L. c. andinus for the populations of northern Chile and to synonymize L. c. magellanicus, L. c. lycoides, and L. c. smithersi under L. c. culpaeus. Rev. Biol. Trop. 57 (1-2): 421-432. Epub 2009 June 30.
Mediante análisis cualitativos y cuantitativos, se estudió la variación geográfica del cráneo de Lycalopex culpaeus en Chile (desde Tarapacá a la islas australes), y de algunas poblaciones argentinas. En dicha distribución se reconocen cinco de las seis subespecies del culpeo. Los resultados muestran dos grupos morfológicos geográficamente segregados; los mismos se diferencian principalmente por atributos morfométricos, y secundariamente por caracteres cualitativos. individuos del norte chileno (Tarapacá y Antofagasta) presentan cráneos pequeños, poco desarrollados, hocico levemente corto, ausencia de cresta interparietal y una tenue zona sagital "liriforme". Por otra parte, los individuos del noroeste y centro argentino, centro sur chileno, Patagonia e islas australes (islas de Tierra del Fuego y Hoste) (grupo B), no muestran diferencias significativas en su morfometría dento-craneal. En el grupo B destacó una fuerte cresta interparietal y zona sagital, hocicos prolongados y cráneos de mayor tamaño que los del norte chileno. Nuestros resultados coinciden con estudios de patrones de variación en el ADN mitocondrial de cánidos de Chile. Por lo tanto, se propone mantener el nombre L. c. andinus para las poblaciones del norte de Chile y sinonimizar los taxones L. c. magellanicus, L. c. lycoides y L. c. smithersi bajo la forma L. c. culpaeus.