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1.
Sci Rep ; 14(1): 8073, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580653

RESUMEN

The fishing cat, Prionailurus viverrinus, faces a population decline, increasing the importance of maintaining healthy zoo populations. Unfortunately, zoo-managed individuals currently face a high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. To investigate the genetics of inherited diseases among captive fishing cats, we present a chromosome-scale assembly, generate the pedigree of the zoo-managed population, reaffirm the close genetic relationship with the Asian leopard cat (Prionailurus bengalensis), and identify 7.4 million single nucleotide variants (SNVs) and 23,432 structural variants (SVs) from whole genome sequencing (WGS) data of healthy and TCC cats. Only BRCA2 was found to have a high recurrent number of missense mutations in fishing cats diagnosed with TCC when compared to inherited human cancer risk variants. These new fishing cat genomic resources will aid conservation efforts to improve their genetic fitness and enhance the comparative study of feline genomes.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Gatos , Animales , Humanos , Genoma/genética , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Genómica , Células Germinativas/patología
2.
Lancet Oncol ; 25(4): e164-e172, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38547900

RESUMEN

Over the past decade, China has emerged as Africa's largest trade partner and source of foreign direct investment, with public health ranked as a top priority in China-Africa collaborations. During the same period, cancer has emerged as a leading cause of death in Africa, with more than 700 000 deaths per year and projections of more than 1 million deaths per year by 2030. In this Review, we explore the effects of increasing China-Africa collaborations on cancer control in Africa. We review the published literature on health-care assistance, research, education and training, and infrastructure and present the results of an institutional review board-approved survey of African oncology health-care professionals and institutional leaders that assessed their perception of the effects of China-Africa collaborations. From peer-reviewed articles and grey literature, we found that the number of China-Africa collaborations have grown substantially over the past decade in different areas, especially in patient care and infrastructure. Research publications have also surged in quantity in the past decade compared with previous years. However, the survey results suggest research collaborations remain infrequent and that medical professionals in African cancer centres rarely participate in direct research collaborations with Chinese institutions. The Review also highlights the challenges and benefits of increasing China-Africa collaborations. Challenges include insufficient monitoring and evaluation of the projects in Africa and poor coordination and alignment of the various initiatives. The benefits of these collaborations for Africa include improved health outcomes, strengthened health systems, and socioeconomic development. Benefits are also apparent for China, such as securing energy and resource supplies, expanded trade and investment opportunities, and improved diplomatic relations. Overall, China-Africa collaborations are increasing and having a substantial effect in both China and the African continent. Recommendations to minimise the challenges and maximise the benefits for more positive consequences on cancer control in Africa are discussed.


Asunto(s)
Atención a la Salud , Neoplasias , Humanos , África/epidemiología , Salud Pública , Internacionalidad , China/epidemiología , Neoplasias/epidemiología , Neoplasias/prevención & control
3.
Ophthalmic Physiol Opt ; 44(3): 613-625, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38404167

RESUMEN

PURPOSE: To develop criteria to predict visual hemifields with deep perimetric defects based on retinal nerve fibre layer (RNFL) reflectance, in a transparent process whose components can be assessed by independent laboratories analysing data from their own small groups. METHODS: The analysis was carried out in four stages, using three independent groups of patients-30, 33 and 62 participants-with glaucoma and age-similar controls. The first stage used Group 1 to develop a criterion for RNFL reflectance images at 24, 36 or 48 µm below the inner limiting membrane (ILM). The second stage evaluated the criterion using Group 2. The third stage developed a second criterion to improve performance for Groups 1 and 2 combined. The fourth stage evaluated the second criterion with Group 3. Confidence intervals for sensitivity and specificity were then computed by combining results from all three groups. RESULTS: The first criterion identified all hemifields with deep defects and no hemifields from controls, using a within-eye reference for healthy RNFL. For Group 2, specificity remained high but sensitivity was reduced. The second criterion improved sensitivity by using location-specific reference values. For Group 3, sensitivity remained high but reduced specificity was found. Confidence intervals showed substantial overlap for the two criteria. CONCLUSIONS: We developed two criteria to identify patients with deep perimetric defects with high specificity and sensitivity. Several improvements are warranted: automated identification of the fovea-disc angle and optic disc locations, evaluation of normal variation in patterns of RNFL thickness, improved segmentation of ILM and major vasculature, reduction of within-eye variability in RNFL reflectance of healthy eyes, assessment of effects of image quality, assessment of effects of comorbidity and effectiveness of other devices.


Asunto(s)
Presión Intraocular , Campos Visuales , Humanos , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica/métodos , Fibras Nerviosas
4.
Nat Commun ; 14(1): 3140, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280258

RESUMEN

Eighty percent of the estimated 600 million domestic cats in the world are free-roaming. These cats typically experience suboptimal welfare and inflict high levels of predation on wildlife. Additionally, euthanasia of healthy animals in overpopulated shelters raises ethical considerations. While surgical sterilization is the mainstay of pet population control, there is a need for efficient, safe, and cost-effective permanent contraception alternatives. Herein, we report evidence that a single intramuscular treatment with an adeno-associated viral vector delivering an anti-Müllerian hormone transgene produces long-term contraception in the domestic cat. Treated females are followed for over two years, during which transgene expression, anti-transgene antibodies, and reproductive hormones are monitored. Mating behavior and reproductive success are measured during two mating studies. Here we show that ectopic expression of anti-Müllerian hormone does not impair sex steroids nor estrous cycling, but prevents breeding-induced ovulation, resulting in safe and durable contraception in the female domestic cat.


Asunto(s)
Hormona Antimülleriana , Hormonas Peptídicas , Gatos , Animales , Femenino , Hormona Antimülleriana/genética , Anticoncepción/métodos , Anticoncepción/veterinaria , Esterilización Reproductiva/métodos , Esterilización Reproductiva/veterinaria , Regulación de la Población/métodos , Animales Salvajes
5.
Nanomaterials (Basel) ; 13(12)2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37368273

RESUMEN

Recent studies have highlighted the potential of smart radiotherapy biomaterials (SRBs) for combining radiotherapy and immunotherapy. These SRBs include smart fiducial markers and smart nanoparticles made with high atomic number materials that can provide requisite image contrast during radiotherapy, increase tumor immunogenicity, and provide sustained local delivery of immunotherapy. Here, we review the state-of-the-art in this area of research, the challenges and opportunities, with a focus on in situ vaccination to expand the role of radiotherapy in the treatment of both local and metastatic disease. A roadmap for clinical translation is outlined with a focus on specific cancers where such an approach is readily translatable or will have the highest impact. The potential of FLASH radiotherapy to synergize with SRBs is discussed including prospects for using SRBs in place of currently used inert radiotherapy biomaterials such as fiducial markers, or spacers. While the bulk of this review focuses on the last decade, in some cases, relevant foundational work extends as far back as the last two and half decades.

6.
POCUS J ; 8(1): 71-80, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152333

RESUMEN

Background: Point of care ultrasound (POCUS) is ubiquitous in the modern emergency department (ED). POCUS can be helpful in the management of patients with sepsis in many ways including determining the cause of sepsis, assessing fluid status, guiding resuscitation, and performing procedures. However, the frequency and manner in which POCUS is incorporated into the care of septic patients in community emergency medicine remains unclear. Objective: To evaluate POCUS frequency and exam types used in the care of patients with sepsis in two community EDs in Southern California. Methods: We performed a retrospective analysis of 5,264 ED visits with a diagnosis of sepsis at two community emergency departments between January 2014 and December 2018. Patients 18 years or older who were diagnosed with sepsis and had either lactate ≥ 4 mmol, a documented mean arterial pressure (MAP) < 65 mmHg, or a systolic blood pressure (SBP) < 90 mmHg were included. Charts were reviewed to determine if POCUS was used during the ED evaluation. Primary outcomes were frequency of POCUS use in the cohort, change in POCUS use over the study period, and the types of exams performed. Results: POCUS was used in 21% of encounters meeting inclusion criteria and was positively correlated with ED arrival year (OR = 1.09; CI 1.04, 1.15; p=0.001). The most common POCUS exam was ultrasound-guided central line placement, with the next most common exams being cardiac, followed by inferior vena cava (IVC). Only the frequency of cardiac, IVC, lung and Focused Assessment with Sonography in Trauma (FAST) exams were found to increase significantly over the study period. Conclusions: Total POCUS use increased significantly in this cohort of septic patients over the study period due to more cardiac, IVC, lung and FAST exams being performed.

7.
Ecancermedicalscience ; 17: 1508, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37113724

RESUMEN

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

8.
Sci Rep ; 13(1): 2497, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36781886

RESUMEN

Many studies have assessed structure-function relations in glaucoma, but most without topographical comparison across the central 30°. We present a method for assessing structure-function relations with en face images of retinal nerve fiber layer (RNFL) bundles allowing topographical comparison across much of this retinal area. Forty-four patients with glaucoma (median age 61 years) were recruited and tested with Optical Coherence Tomography (OCT) and perimetry. Six rectangular volume scans were gathered, and then montaged to provide en face views of the RNFL bundles. We calculated the proportion of locations showing a perimetric defect that also showed an en face RNFL defect; and the proportion of locations falling on an RNFL defect that also showed a perimetric defect. A perimetric defect for a location was defined as a total deviation (TD) value equal to or deeper than -4 dB. We found that the median (IQR) number of locations with abnormal RNFL bundle reflectance that also had abnormal TD was 78% (60%) and for locations with abnormal TD that also had abnormal RNFL bundle reflectance was 75% (44%). We demonstrated a potential approach for structure-function assessment in glaucoma by presenting a topographic reflectance map, confirming results of previous studies and including larger retinal regions.


Asunto(s)
Glaucoma , Pruebas del Campo Visual , Humanos , Persona de Mediana Edad , Pruebas del Campo Visual/métodos , Presión Intraocular , Tomografía de Coherencia Óptica/métodos , Células Ganglionares de la Retina , Fibras Nerviosas , Glaucoma/diagnóstico por imagen
9.
Theriogenology ; 197: 133-138, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36502591

RESUMEN

Threats to the Earth's biodiversity are increasing exponentially, driven by human population growth and resource consumption. As many as one million wildlife species may disappear within the next few decades due to this human-induced extinction event. This represents our current reality and has profound implications for wildlife conservation. Within this context, application of assisted reproductive technology (ART) to conservation management is unlikely to mitigate broad-scale species loss, but for select species, such as wild cats, ART may determine if populations survive or disappear. In North American and European zoos, 20 of the world's 38 wild felid species are managed within structured breeding programs, but most are not sustainable with natural breeding alone. Zoo-based breeding programs are facing tenuous futures due to triage-based responses to this growing sustainability crisis. Theoretically, ART could benefit conservation management, but only by recognizing and addressing its present challenges. The application of ART to wildlife has been rarely successful, with only 62 mammal species (including 15 cat species) ever propagated by AI, and just 35 of these species (6 cats) reproduced following frozen semen AI. Even this most basic form of ART has a minimal impact on wildlife sustainability. The drivers of this deficit include lack of species-specific reproductive knowledge and limited access to animals for study, but also is exacerbated by a science-conservation disconnect that attempts to apply advanced reproductive technologies to species in which basic ART remains unproven. For a few felid species, these scientific challenges have been overcome and AI with frozen semen is becoming feasible as a practical management tool; for other felids, further research is needed. Non-scientific issues also impair our ability to use ART to implement global management plans. Political dysfunction, regulatory barriers and societal indifference create inertia that interferes with achieving meaningful progress in applying ART to wildlife. Collectively, these challenges may seem insurmountable but human resiliency is essential if we are to resolve these issues in a systematic manner. It will require expanding collaborative efforts substantially and intensifying efforts to conserve wildlife species that are literally running out of time. Our goal is to create a new reality that includes a sustainable future for wild felids and other imperiled wildlife species.


Asunto(s)
Conservación de los Recursos Naturales , Felidae , Animales , Humanos , Reproducción/fisiología , Animales Salvajes/fisiología , Felidae/fisiología , Técnicas Reproductivas/veterinaria
10.
Ophthalmic Physiol Opt ; 42(6): 1316-1325, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35915921

RESUMEN

PURPOSE: Reflectance of retinal nerve fibre layer (RNFL) can contribute to detecting the presence of glaucomatous damage and defining its extent. As a step towards developing a normative database for RNFL reflectance, we assessed within-eye and between-subject variability for RNFL reflectance in healthy eyes. METHODS: Vertical 30° × 15° volume scans at the optic disc were gathered using SD-OCT (Spectralis OCT) from people free of eye disease. Scans were gathered for both eyes of 30 younger adults (mean ± SD = 27 ± 3 years) and for one eye of 30 older adults (68 ± 8 years). Reflectance was quantified for each voxel as the depth-resolved attenuation coefficient (AC). Values for AC were extracted for four slabs (0-52, 24-52, 24-36 and 36-60 µm) and at depths from 24 to 60 µm below the inner limiting membrane (ILM) in 4 µm steps. RESULTS: Between-subject and within-eye standard deviations (SDs) for the logarithm of AC were similar; median differences were 0.02-0.03 log unit across all four slabs and depths from 24 to 48 µm. Means for the logarithm of AC were higher for younger than older eyes by ~0.1 log unit; this age effect was not due to differences in the raw reflectance of the RNFL, but rather to age-related changes in reflectance of deeper retina affecting the calculation of AC. CONCLUSIONS: In both groups, within-eye variability in RNFL reflectance near the optic disc was similar to between-subject variability. A better understanding of within-eye variability would be useful for developing normative databases.


Asunto(s)
Disco Óptico , Estrabismo , Anciano , Humanos , Fibras Nerviosas , Retina/diagnóstico por imagen , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica
11.
Transl Vis Sci Technol ; 11(8): 3, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35917137

RESUMEN

Purpose: Test-retest variability in perimetry consists of short-term and long-term components, both of which impede assessment of progression. By minimizing and quantifying the algorithm-dependent short-term variability, we can quantify the algorithm-independent long-term variability that reflects true fluctuations in sensitivity between visits. We do this at locations with sensitivity both < 28 dB (when the stimulus is smaller than Ricco's area and complete spatial summation can be assumed) and > 28 dB (when partial summation occurs). Methods: Frequency-of-seeing curves were measured at four locations of 35 participants with glaucoma. The standard deviation of cumulative Gaussian fits to those curves was modeled for a given sensitivity and used to simulate the expected short-term variability of a 30-presentation algorithm. A separate group of 137 participants was tested twice with that algorithm, 6 months apart. Long-term variance at different sensitivities was calculated as the LOESS fit of observed test-retest variance minus the LOESS fit of simulated short-term variance. Results: Below 28 dB, short-term variability increased approximately linearly with increasing loss. Long-term variability also increased with damage below this point, attaining a maximum standard deviation of 2.4 dB at sensitivity 21 dB, before decreasing due to the floor effect of the algorithm. Above 30 dB, the observed test-retest variance was slightly smaller than the simulated short-term variance. Conclusions: Long-term and short-term variability both increase with damage for perimetric stimuli smaller than Ricco's area. Above 28 dB, long-term variability constitutes a negligible proportion of test-retest variability. Translational Relevance: Fluctuations in true sensitivity increase in glaucoma, even after accounting for increased short-term variability. This long-term variability cannot be reduced by altering testing algorithms alone.


Asunto(s)
Glaucoma , Pruebas del Campo Visual , Algoritmos , Femenino , Glaucoma/diagnóstico , Humanos , Distribución Normal , Embarazo , Convulsiones , Campos Visuales
12.
J Vis ; 22(8): 11, 2022 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-35848903

RESUMEN

The magnocellular (MC) pathway in the primate has much higher achromatic contrast sensitivity than the parvocellular (PC) pathway, and is implicated in luminance contrast detection. But MC pathway responses tend to saturate at lower achromatic contrast than do PC pathway responses. It has been proposed that the PC pathway plays a major role in discriminating suprathreshold achromatic contrast, because the MC pathway is in saturation. This has been termed the pulsed-pedestal protocol. To test this hypothesis, responses of MC and PC pathway ganglion cells have been examined under suprathreshold conditions with stimulus configurations similar to those in psychophysical tests. For MC cells, response saturation was much less for flashed or moving edges than for sinusoidal modulation, and MC cell thresholds predicted for these stimuli were similar to psychophysical discrimination (and detection) data. Results suggest the protocol is not effective in segregating MC and PC function.


Asunto(s)
Sensibilidad de Contraste , Vías Visuales , Animales , Neuronas , Estimulación Luminosa/métodos , Psicofísica , Vías Visuales/fisiología
13.
Lancet Oncol ; 23(6): e251-e312, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35550267

RESUMEN

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.


Asunto(s)
COVID-19 , Neoplasias , Enfermedades no Transmisibles , África del Sur del Sahara/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Niño , Atención a la Salud , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias
14.
Theriogenology ; 182: 26-34, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35123308

RESUMEN

Despite the invaluable role that assisted reproduction technologies (ARTs) play in conservation, pregnancy and parturition rates by embryo transfer (ET) are low for most endangered felids. Thus, efforts to expand the knowledge on pregnancy biology and ET are still required. In this context, we examined fecal sex steroid metabolites (i.e., estrogens, glucocorticoids, and progestogens) of eight ocelots submitted to natural fertilization (NF) and ET in 22 pregnancies (19 NF and 3 ET). Fecal samples were collected and assessed for each pregnancy from estrous cycle, pregnancy, and lactation, totaling 155 days. In short, progestogen levels remained high and unchanged (P < 0.05) from conception until parturition for females maintained under NF. On the other hand, females submitted to ET exhibited changes (P > 0.05) in progestogen levels from conception until parturition, with a significant decrease during pregnancy (480.72 ng/day; r2 = 0.81; P < 0.0001). Significant changes between NF and ET also were noted in estrogen levels between the first and last thirds of pregnancy (P < 0.05), in which estrogen levels exhibited a negative correlation (P < 0.01) between themselves. Regarding glucocorticoids, significant changes (P < 0.01) were observed only in the first third of pregnancy between NF and ET, which we believe may be related to the handling for ovarian synchronization and ET. Besides hormonal changes, the pregnancy was more prolonged (2.5 days) and more prone to dystocia in ET than NF. Overall, 24 embryos were transferred into eight females (3/1), with three kittens being born from three distinct deliveries (i.e., 12.5% of embryos and 37.5% of females). Our findings have supported the great potential of production and transfer of long-term frozen embryos in ocelot conservation. However, they reveal possible effects of these biotechnologies on hormonal levels during pregnancy linked with low conception and parturition rates and dystocic cases in felids.


Asunto(s)
Felidae , Animales , Gatos , Transferencia de Embrión/veterinaria , Femenino , Fertilización , Lactancia , Parto , Embarazo , Esteroides
15.
Front Oncol ; 11: 725103, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926247

RESUMEN

Among a growing body of literature in global oncology, several articles project increased cost savings and radiotherapy access by adopting hypofractionated radiotherapy (HFRT) in low- and middle-income countries (LMICs) like those in Africa. Clinical trials in Europe and the USA have demonstrated HFRT to be non-inferior to conventional radiotherapy for eligible patients with several cancers, including prostate cancer. This could be a highly recommended option to battle a severely large and growing cancer burden in resource-limited regions. However, a level of implementation research may be needed in limited resource-settings like in Africa. In this article, we present a list of evidence-based recommendations to practice HFRT on eligible prostate cancer patients. As literature on HFRT is still developing, these guidelines were compiled from review of several clinical trials and professionally accredited material with minimal resource requirements in mind. HFRT guidelines presented here include patient eligibility, prescription dose schedules, treatment planning and delivery techniques, and quality assurance procedures. The article provides recommendations for both moderately hypofractionated (2.4-3.4Gy per fraction) and ultrahypofractionated (5Gy or more per fraction) radiation therapy when administered by 3D-Conformal Radiotherapy, Intensity Modulated Radiation Therapy, or Image-Guided Radiotherapy. In each case radiation oncology health professionals must make the ultimate judgment to ensure safety as more LMIC centers adopt HFRT to combat the growing scourge of cancer.

16.
Front Oncol ; 11: 711078, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34765538

RESUMEN

Effective in situ cancer vaccines require both a means of tumor cell death and a source of adjuvant to activate local dendritic cells. Studies have shown that the use of radiotherapy (RT) to induce tumor cell death and anti-CD40 to activate dendritic cells can result in in situ vaccination in animal models. Here, investigations are carried out on potential strategies to enhance such in situ vaccination. Strategies investigated include the use of smart immunogenic biomaterials (IBM) loaded with anti-CD40 in different tumor types including immunologically cold tumors like pancreatic and prostate tumors. The use of downstream checkpoint inhibitors to further boost such in situ vaccination is also examined. Results indicate that the use of IBM to deliver the anti-CD40 significantly enhances the effectiveness of in situ vaccination with anti-CD40 compared with direct injection in pancreatic and prostate cancers (p < 0.001 and p < 0.0001, respectively). This finding is consistent with significant increase in infiltration of antigen-presenting cells in the treated tumor, and significant increase in the infiltration of CD8+ cytotoxic T lymphocyte into distant untreated tumors. Moreover, in situ vaccination with IBM is consistently observed across different tumor types. Meanwhile, the addition of downstream immune checkpoint inhibitors further enhances overall survival when using the IBM approach. Overall, the findings highlight potential avenues for enhancing in situ vaccination when combining radiotherapy with anti-CD40.

17.
Optom Vis Sci ; 98(5): 531-541, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33973913

RESUMEN

SIGNIFICANCE: Adaptive-optics scanning-laser-ophthalmoscopy (AOSLO) retinal imaging of the retinal nerve fiber layer (RNFL) helps predict the severity of perimetric damage based on absence of fibers and projection of the defects in en face images of the RNFL from spectral-domain optical coherence tomography (SD-OCT). PURPOSE: En face images of the RNFL reveal reflectance defects in patients with glaucoma and predict locations of perimetric defects. These defects could arise from either loss of retinal nerve fiber bundles or reduced bundle reflectance. This study used AOSLO to assess presence of bundles in areas with RNFL reflectance defects on SD-OCT. METHODS: Adaptive-optics scanning laser ophthalmoscopy was used to image a vertical strip of RNFL measuring approximately 30 × 3° between the optic disc and the fovea. Fifteen patients with glaucoma who had SD-OCT reflectance defects that passed through this region were chosen. Four patients had reflectance defects in both superior and inferior hemifields, so presence of bundles on AOSLO was assessed for 19 hemifields. Where bundles were present, the hemifield was scored for whether bundles seemed unusual (low contrast and/or low density). Perimetric defects were considered deep when sensitivity was below 15 dB. RESULTS: Ten hemifields had a region with no fibers present on AOSLO; all had a corresponding deep perimetric defect. The other nine hemifields had no region in the AOSLO image without fibers: four with normal fibers and five with unusual fibers. The only one of these nine hemifields with a deep perimetric defect was one with low-contrast fibers and overall thin RNFL. CONCLUSIONS: Retinal nerve fiber layer reflectance defects, which were associated with deep perimetric defects, usually had a region with absence of fibers on AOSLO images of RNFL. Ability to predict severity of perimetric damage from en face SD-OCT RNFL reflectance images could benefit from quantification that differentiated between absence of fibers and unusual fibers.


Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico por imagen , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Anciano , Interpretación Estadística de Datos , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Oftalmoscopía/métodos , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Tomografía de Coherencia Óptica/métodos , Pruebas del Campo Visual/métodos
18.
Optom Vis Sci ; 98(4): 374-383, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33828040

RESUMEN

SIGNIFICANCE: Identifying glaucomatous damage to the macula has become important for diagnosing and managing patients with glaucoma. In this study, we presented an approach that provides better perimetric sampling for the macular region, by testing four locations, with a good structure-function agreement. PURPOSE: We previously presented a basis for customizing perimetric locations within the macula. In this study, we aimed to improve perimetric sampling within the macula by presenting a stimulus at four locations, with maintaining a good structure-function agreement. METHODS: We tested one eye each of 30 patients (aged 50 to 88 years). Patients were selected based on observed structural damage to the macula, whereas perimetric defect (using 24-2) did not reflect the locations and extent of this damage. We used en face images to visualize retinal nerve fiber bundle defects. To measure perimetric sensitivities, we used a blob stimulus (standard deviation of 0.25°) at the 10-2 locations. A perimetric defect for a location was defined as any value equal to or deeper than -4, -5, and -6 dB below the mean sensitivity for 37 age-similar controls (aged 47 to 78 years). We also presented an elongated sinusoidal stimulus for 20 patients at four locations within the macula, in which we defined a perimetric defect as any value below the 2.5th percentile from controls. RESULTS: The -4, -5, and -6 dB criteria identified perimetric defects in 14, 13, and 11 patients, respectively. When testing with the elongated stimulus, 18 patients were identified with perimetric defect. The perimetric defects were consistent with the structural damage. CONCLUSIONS: The elongated stimulus showed a good structure-function agreement with only four testing locations as compared with 68 locations used with the blob stimulus. This demonstrates a clinical potential for this new stimulus in the next generation of perimetry.


Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Mácula Lútea/patología , Enfermedades de la Retina/diagnóstico , Campos Visuales/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Mácula Lútea/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/fisiopatología , Tomografía de Coherencia Óptica , Pruebas del Campo Visual/métodos
19.
Ophthalmic Physiol Opt ; 41(2): 437-446, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33492742

RESUMEN

PURPOSE: To assess continuity of perimetric defects corresponding to arcuate defects seen on optical coherence tomography (OCT) en face reflectance images of the retinal nerve fibre layer (RNFL) in patients with glaucoma. METHODS: Seven patients with glaucoma who had arcuate structural defects on OCT RNFL en face images were recruited. Static suprathreshold stimuli were presented along different meridians to localise perimetric defects in the corresponding hemifield. Then two contrasts, one 6 dB greater than the other, were used with kinetic perimetry to assess the slope of the defect. Findings with kinetic and 24-2 perimetry were compared. RESULTS: Static perimetry found that regions of perimetric abnormality spatially corresponded with the regions of en face RNFL hyporeflectivity. Kinetic perimetry found that the slopes of the edges of the defects ranged from 3-12 dB degree-1 , and that the functional abnormalities were continuous with the physiologic blind spot even when the 24-2 protocol only showed paracentral defects. CONCLUSIONS: Perimetric abnormalities and arcuate RNFL en face defects were spatially correspondent. Perimetric testing guided by OCT en face reflectance images can reveal greater functional detail of glaucomatous abnormality than 24-2 testing.


Asunto(s)
Glaucoma/fisiopatología , Presión Intraocular/fisiología , Disco Óptico/diagnóstico por imagen , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Campos Visuales/fisiología , Anciano , Femenino , Glaucoma/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Reproducibilidad de los Resultados , Pruebas del Campo Visual/métodos
20.
Theriogenology ; 159: 108-115, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33130295

RESUMEN

Felid semen has historically been frozen using an egg yolk-based cryopreservation medium. However, the use of egg introduces several potential concerns, such as variability in composition, microbial contamination, and regulatory issues. In the present study, our aim was to compare a chemically-defined, soy-based medium (SOY) to a commercial egg yolk-based medium (TEY) for the cryopreservation of sperm in four imperiled small cat species. Semen was collected from adult male cats (n = 6 black-footed cats; n = 6 sand cats; n = 4 fishing cats; and n = 7 Pallas' cats) via electroejaculation, split into two aliquots, and cryopreserved in SOY or TEY. Frozen-thawed samples were evaluated for sperm motility and rate of progressive motility (up to 24 h post-thaw) and acrosome status (0 and 6 h). No difference in post-thaw traits were observed between treatments in all four species. Heterologous IVF using oocytes collected laparoscopically from domestic cats demonstrated no difference among freezing treatments in percentage of mature oocytes that cleaved or the mean number of blastomeres at 48 h post-insemination. More spermatozoa frozen with SOY were bound to the zona pellucida in the sand cat (P = 0.018), but no treatment effect was observed in the other three species. These findings collectively demonstrate that SOY may be a preferable alternative to TEY for sperm cryopreservation in these four wild felid species.


Asunto(s)
Preservación de Semen , Animales , Gatos , Criopreservación/veterinaria , Lecitinas , Masculino , Semen , Preservación de Semen/veterinaria , Motilidad Espermática , Espermatozoides
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