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1.
J Fungi (Basel) ; 10(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38786662

RESUMEN

Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics.

2.
BMJ Open ; 14(5): e081416, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802273

RESUMEN

INTRODUCTION: Fatigue is prevalent across a wide range of medical conditions and can be debilitating and distressing. It is likely that fatigue is experienced differently according to the underlying aetiology, but this is poorly understood. Digital health technologies present a promising approach to give new insights into fatigue.The aim of this study is to use digital health technologies, real-time self-reports and qualitative interview data to investigate how fatigue is experienced over time in participants with myeloma, long COVID, heart failure and in controls without problematic fatigue. Objectives are to understand which sensed parameters add value to the characterisation of fatigue and to determine whether study processes are feasible, acceptable and scalable. METHODS AND ANALYSIS: An ecological momentary assessment study will be carried out over 2 or 4 weeks (participant defined). Individuals with fatigue relating to myeloma (n=10), heart failure (n=10), long COVID (n=10) and controls without problematic fatigue or a study condition (n=10) will be recruited. ECG patches will measure heart rate variability, respiratory rate, body temperature, activity and posture. A wearable bracelet accompanied by environment beacons will measure physical activity, sleep and room location within the home. Self-reports of mental and physical fatigue will be collected via smartphone app four times daily and on-demand. Validated fatigue and affect questionnaires will be completed at baseline and at 2 weeks. End-of-study interviews will investigate experiences of fatigue and study participation. A feedback session will be offered to participants to discuss their data.Data will be analysed using multilevel modelling and machine learning. Interviews and feedback sessions will be analysed using content or thematic analyses. ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge East Research Ethics Committee (22/EE/0261). The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT05622669.


Asunto(s)
COVID-19 , Evaluación Ecológica Momentánea , Fatiga , Humanos , Fatiga/etiología , Insuficiencia Cardíaca/fisiopatología , Tecnología Digital , Mieloma Múltiple/complicaciones , SARS-CoV-2 , Autoinforme , Proyectos de Investigación , Dispositivos Electrónicos Vestibles
3.
Gynecol Oncol ; 186: 77-84, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38603955

RESUMEN

Although ovarian cancer patients typically respond to standard of care therapies, including chemotherapy and DNA repair inhibitors, the majority of tumors recur highlighting the need for alternative therapies. Ovarian cancer is an immunogenic cancer in which the accumulation of tumor infiltrating lymphocytes (TILs), particularly T cells, is associated with better patient outcome. Thus, harnessing the immune system through passive administration of T cells, a process called adoptive cell therapy (ACT), is a promising therapeutic option for the treatment of ovarian cancer. There are multiple routes by which tumor-specific T cell products can be generated. Dendritic cell cancer vaccines can be administered to the patients to induce or bolster T cell responses against tumor antigens or be utilized ex vivo to prime T cells against tumor antigens; these T cells can then be prepared for infusion. ACT protocols can also utilize naturally-occurring tumor-reactive T cells isolated from a patient tumor, known as TILs, as these cells often are heterogeneous in composition and antigen specificity with patient-specific cancer recognition. Alternatively, T cells may be sourced from the peripheral blood, including those that are genetically modified to express a tumor antigen-specific T cell receptor (TCR) or chimeric antigen receptor (CAR) to redirect their specificity and promote their activity against tumor cells expressing the target tumor antigen. Here, we review current ACT strategies for ovarian cancer and provide insights into advancing ACT therapy strategies for the treatment of ovarian cancer.

4.
bioRxiv ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38659793

RESUMEN

One of the mechanisms that can lead to the formation of new species occurs through the evolution of reproductive barriers. However, recent research has demonstrated that hybridization has been pervasive across the tree of life even in the presence of strong barriers. Swordtail fishes (genus Xiphophorus) are an emerging model system for studying the interface between these barriers and hybridization. We document overlapping mechanisms that act as barriers between closely related species, X. birchmanni and X. cortezi, by combining genomic sequencing from natural hybrid populations, artificial crosses, behavioral assays, sperm performance, and developmental studies. We show that strong assortative mating plays a key role in maintaining subpopulations with distinct ancestry in natural hybrid populations. Lab experiments demonstrate that artificial F1 crosses experience dysfunction: crosses with X. birchmanni females were largely inviable and crosses with X. cortezi females had a heavily skewed sex ratio. Using F2 hybrids we identify several genomic regions that strongly impact hybrid viability. Strikingly, two of these regions underlie genetic incompatibilities in hybrids between X. birchmanni and its sister species X. malinche. Our results demonstrate that ancient hybridization has played a role in the origin of this shared genetic incompatibility. Moreover, ancestry mismatch at these incompatible regions has remarkably similar consequences for phenotypes and hybrid survival in X. cortezi × X. birchmanni hybrids as in X. malinche × X. birchmanni hybrids. Our findings identify varied reproductive barriers that shape genetic exchange between naturally hybridizing species and highlight the complex evolutionary outcomes of hybridization.

5.
Int. j. clin. health psychol. (Internet) ; 24(1): [100425], Ene-Mar, 2024. tab, graf
Artículo en Inglés | IBECS | ID: ibc-230367

RESUMEN

Background: Executive Function (EF) is a potential mechanism linking physical activity (PA) and mental health. However, evidence regarding the association between free-living PA and EF is limited with mixed results. Across two studies, we examined associations between accelerometer-assessed moderate-to-vigorous PA (MVPA) and facets of EF in different age groups (Study 1) and at different times of day (Study 2). Method: In Study 1, we tested the association between MVPA and verbal fluency across seven days in 285 participants (children, adults, older adults). In Study 2, we tested between- and within-person associations between MVPA and working memory (afternoon, evening, next morning) across three 18-day bursts in 64 preadolescents. Results: Study 1 showed no association between MVPA and verbal fluency overall, but there was an interaction by age group: a positive association was evident in older adults only. In Study 2, we observed a positive between-person association between MVPA and subsequent afternoon and next morning working memory, but not within-person. In the evening, MVPA was not related to working memory. Conclusions: The association between free-living PA and EF differs between age groups and times of day. Future research should consider these factors when examining the association and its role for mental health.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adulto , Persona de Mediana Edad , Anciano , Cognición , Ejercicio Físico , Salud Mental , Psicología , Psicología Clínica , Neurología
7.
Gynecol Oncol ; 184: 74-82, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38290413

RESUMEN

OBJECTIVE: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC. METHODS: Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology. RESULTS: A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively). CONCLUSIONS: Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC.

8.
Nature ; 626(7997): 119-127, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38200310

RESUMEN

The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of hybrid incompatibilities, in which alleles derived from two different species no longer interact properly in hybrids1-3. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes4-6 and that incompatibilities involving multiple genes should be common7,8, but there has been sparse empirical data to evaluate these predictions. Here we describe a mitonuclear incompatibility involving three genes whose protein products are in physical contact within respiratory complex I of naturally hybridizing swordtail fish species. Individuals homozygous for mismatched protein combinations do not complete embryonic development or die as juveniles, whereas those heterozygous for the incompatibility have reduced complex I function and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the effects of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. Finally, we document the evolutionary history of the genes involved, showing signals of accelerated evolution and evidence that an incompatibility has been transferred between species via hybridization.


Asunto(s)
Núcleo Celular , Complejo I de Transporte de Electrón , Peces , Genes Letales , Especiación Genética , Hibridación Genética , Proteínas Mitocondriales , Animales , Alelos , Complejo I de Transporte de Electrón/genética , Peces/clasificación , Peces/embriología , Peces/genética , Peces/crecimiento & desarrollo , Homocigoto , Genes Letales/genética , Especificidad de la Especie , Desarrollo Embrionario/genética , Proteínas Mitocondriales/genética , Núcleo Celular/genética , Heterocigoto , Evolución Molecular
9.
Clin Cancer Res ; 30(8): 1567-1581, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-37882675

RESUMEN

PURPOSE: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: B7-H4 expression was quantified by flow cytometry and IHC. B7-H4-ADC efficacy was tested against multiple cell lines in vitro and PDX in vivo. The effect of B7-H4-ADC on cell cycle, DNA damage, and apoptosis was measured using flow cytometry. RESULTS: B7-H4 is overexpressed in 92% of HGSOC tumors at diagnosis (n = 12), persisted in recurrent matched samples after platinum treatment, and was expressed at similar levels across metastatic sites after acquired multi-drug resistance (n = 4). Treatment with B7-H4-ADC resulted in target-specific growth inhibition of multiple ovarian and breast cancer cell lines. In platinum- or PARPi-resistant ovarian cancer cells, B7-H4-ADC significantly decreased viability and colony formation while increasing cell-cycle arrest and DNA damage, ultimately leading to apoptosis. Single-dose B7-H4-ADC led to tumor regression in 65.5% of breast and ovarian PDX models (n = 29), with reduced activity in B7-H4 low or negative models. In PARPi and platinum-resistant HGSOC PDX models, scheduled B7-H4-ADC dosing led to sustained tumor regression and increased survival. CONCLUSIONS: These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population. See related commentary by Veneziani et al., p. 1434.


Asunto(s)
Inmunoconjugados , Neoplasias Ováricas , Femenino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Apoptosis , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral
10.
Int J Clin Health Psychol ; 24(1): 100425, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38089542

RESUMEN

Background: Executive Function (EF) is a potential mechanism linking physical activity (PA) and mental health. However, evidence regarding the association between free-living PA and EF is limited with mixed results. Across two studies, we examined associations between accelerometer-assessed moderate-to-vigorous PA (MVPA) and facets of EF in different age groups (Study 1) and at different times of day (Study 2). Method: In Study 1, we tested the association between MVPA and verbal fluency across seven days in 285 participants (children, adults, older adults). In Study 2, we tested between- and within-person associations between MVPA and working memory (afternoon, evening, next morning) across three 18-day bursts in 64 preadolescents. Results: Study 1 showed no association between MVPA and verbal fluency overall, but there was an interaction by age group: a positive association was evident in older adults only. In Study 2, we observed a positive between-person association between MVPA and subsequent afternoon and next morning working memory, but not within-person. In the evening, MVPA was not related to working memory. Conclusions: The association between free-living PA and EF differs between age groups and times of day. Future research should consider these factors when examining the association and its role for mental health.

11.
Stress Health ; 2023 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-38141023

RESUMEN

Our knowledge about the role of fly-in fly-out (FIFO) work-related factors on the well-being of workers across the FIFO work cycle is limited. This study examined the within-person effects of job demand and control on psychological states and health behaviours. The study employed a daily diary design, with 23 FIFO workers in the Australian mining industry completing a daily diary survey for 28 consecutive days across on-shift and off-shift periods. Multilevel analyses showed FIFO workers experienced higher positive affect and enjoyed better sleep quality, but consumed more alcohol, during off-shift days as compared to on-shift days. Within-person variability in daily demand (workload) was associated with higher anxious affect, whereas job control predicted lower anxious and depressed affects, higher positive affect, more alcohol consumption, and more physical activity. The within-person effect of demand on anxious affect was moderated by job control such that those who generally had more control over their jobs had a smaller effect of demand on anxiety than those with less control. Results suggest potentially modifiable aspects of FIFO work-particularly job control-may help alleviate the impact of workload on poorer health behaviours and mood.

12.
Front Immunol ; 14: 1256491, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022678

RESUMEN

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation.


Asunto(s)
Melanoma , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T , Antígenos CD28 , Linfocitos Infiltrantes de Tumor , Receptor 1 de Folato , Receptores Quiméricos de Antígenos/genética , Antígenos CD40 , Microambiente Tumoral
13.
Stress ; 26(1): 2283435, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37964581

RESUMEN

There is some evidence that performance-related pay (PRP) leads to higher levels of stress as it incentivizes employees to work harder for longer. However, PRP in the workplace also typically involves performance monitoring, which may introduce an additional source of stress via social-evaluative threat (SET). The current study examined the effect of PRP on stress while varying the level of performance monitoring/SET. Using an incentivized mixed design experiment, 206 participants completed a simulated work task after being randomly allocated to either a PRP contract (£0.20 per correct response, n = 110) or minimum-performance fixed payment contract (£5 for ≥10 correct responses; £0 for <10, n = 96) condition. All participants completed the task during a high SET (explicit performance monitoring) and low SET (no monitoring) condition. Subjective and objective stress were measured through self-report and salivary cortisol. High SET led to higher levels of self-reported stress but not cortisol, whereas there was no effect of the payment condition on either self-reported stress or cortisol. A statistically significant interaction revealed that high SET-fixed payment participants were significantly more stressed than those in the high SET-PRP group. Estimating the regressions separately for high- and low-performing individuals found that the effect was driven by low-performing individuals. These results suggest that fixed payment contracts that have a minimum performance threshold and which include performance monitoring and SET can be more stressful than traditional piece-rate PRP contracts. The current study suggests that incorporating performance monitoring and SET into payment contracts may affect the well-being of employees.


Asunto(s)
Hidrocortisona , Estrés Psicológico , Humanos , Saliva
14.
Curr Opin Neurobiol ; 83: 102802, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37922667

RESUMEN

All nervous systems are multiply modulated by polypeptides. However, a bulk of transmitter and modulation research has historically focused on small molecule transmitters released at synaptic sites. The stomatogastric nervous system (controls digestive movements of the foregut) and cardiac nervous system of decapod crustaceans have long been used to understand the processes that underlie neuromodulation. The circuits governing the rhythmic output from these nervous systems are comprised of a relatively small number of identified neurons, and the details of these nervous systems are well-defined. Here we discuss recent research highlighting advances in our understanding of peptidergic modulation in these systems. In particular, we focus on our ability to identify specific signaling peptide sequences and relate their expression patterns to their physiological effects, as well as on the multiple sites within a pattern generator-effector system at which modulation takes place. Recent efforts have enabled us to understand how co-modulation by two or more peptides can generate surprising effects on circuit physiology and that modulation at different receptor sites can produce supra-additive effects. Finally, we examine the protective role modulation plays in making circuits robust to perturbations, in this case, changes in temperature.


Asunto(s)
Decápodos , Neuronas , Animales , Neuronas/fisiología , Sistema Nervioso , Péptidos
15.
Disabil Rehabil ; : 1-12, 2023 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-37865851

RESUMEN

PURPOSE: Life after any amputation can be significantly altered and can have a significant impact on quality of life (QoL). However, most of the evidence base involves older aged amputees, therefore there is a lack of understanding about the impact of amputation on QoL and the factors that predict QoL in younger amputees. The aim of this review is to identify the factors that predict QoL in young amputees. METHODS: MEDLINE, CINAHL, EMBASE, PsycINFO, Web of Science were searched to identify articles that measured QoL in young amputees. Articles were independently assessed by two assessors. Data was extracted from the selected articles and a narrative synthesis performed. RESULTS: 18 articles were included in this review. QoL outcome measures varied between studies. The quality of evidence was generally low. This review identified, gender, age, cause of amputation, level of amputation, phantom pain, ability to use a prosthesis, physical function, depression, anxiety, body image, type of prosthesis as predictors of QoL. CONCLUSION: This review identified modifiable and non-modifiable predictors of QoL in young amputees. Future research needs to focus on exploring the modifiable predictors of QoL as these are the aspects that can be improved to enhance QoL.


Life after any amputation can be significantly altered and can have a significant impact on quality of life (QoL).Gender, age, cause of amputation, level of amputation, phantom pain, ability to use a prosthesis, physical function, depression and anxiety, body image and type of prosthesis were identified as predictors of QoL.The ability to use a prosthesis and access to advanced prosthetic technology are important predictors of QoL as they allow for improved mobility, which in turn increases independence and therefore QoL.

16.
Nat Cancer ; 4(10): 1410-1417, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37735588

RESUMEN

We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.


Asunto(s)
Neoplasias Ováricas , Vacunas , Humanos , Femenino , Neoplasias Ováricas/terapia , Traslado Adoptivo , Vacunación , Linfocitos T
17.
Gynecol Oncol ; 177: 86-94, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37657193

RESUMEN

OBJECTIVE: To investigate the incidence of MAPK/ERK pathway genomic alterations among patients with gynecologic malignancies. METHODS: We accessed the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange publicly available dataset (v13.0). Patients with malignant tumors of the ovary, uterus, and cervix were identified. Following stratification by tumor site and histology, we examined the prevalence of MAPK/ERK pathway gene alterations (somatic mutation, and/or structural chromosome alterations). We included the following RAS-MAPK pathway genes known to be implicated in the dysregulation of the pathway; KRAS, NRAS, BRAF, HRAS, MAP2K1, RAF1, PTPN11, NF1, and ARAF. Data from the OncoKB database, as provided by cBioPortal, were utilized to determine pathogenic gene alterations. RESULTS: We identified a total of 10,233 patients with gynecologic malignancies; 48.2% (n = 4937) with ovarian, 45.2% (n = 4621) with uterine and 6.6% (n = 675) with cervical cancer respectively. The overall incidence of MAPK pathway gene alterations was 21%; the most commonly altered gene was KRAS (13%), followed by NF1 (7%), NRAS (1.3%), and BRAF (1.2%). The highest incidence was observed among patients with mucinous ovarian (71%), low-grade serous ovarian (48%), endometrioid ovarian (37%), and endometrioid endometrial carcinoma (34%). CONCLUSIONS: Approximately 1 in 5 patients with a gynecologic tumor harbor a MAPK/ERK pathway genomic alteration. Novel treatment strategies capitalizing on these alterations are warranted.

18.
BMC Genomics ; 24(1): 427, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525141

RESUMEN

BACKGROUND: The study of the host-microbiome by the collection of non-invasive samples has the potential to become a powerful tool for conservation monitoring and surveillance of wildlife. However, multiple factors can bias the quality of data recovered from scats, particularly when field-collected samples are used given that the time of defecation is unknown. Previous studies using scats have shown that the impact of aerobic exposure on the microbial composition is species-specific, leading to different rates of change in microbial communities. However, the impact that this aging process has on the relationship between the bacterial and fungal composition has yet to be explored. In this study, we measured the effects of time post-defecation on bacterial and fungal compositions in a controlled experiment using scat samples from the endangered koala (Phascolarctos cinereus). RESULTS: We found that the bacterial composition remained stable through the scat aging process, while the fungal composition did not. The absence of an increase in facultative anaerobes and the stable population of obligate anaerobic bacteria were likely due to our sampling from the inner portion of the scat. We report a cluster of fungal taxa that colonises scats after defecation which can dilute the genetic material from the autochthonous mycoflora and inhibit recovery. CONCLUSION: We emphasize the need to preserve the integrity of scat samples collected in the wild and combat the effects of time and provide strategies for doing so.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Phascolarctidae , Animales , Heces/microbiología , Animales Salvajes
19.
J Transl Med ; 21(1): 488, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37475035

RESUMEN

The discovery and development of novel treatments that harness the patient's immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. These new approaches are focused on patients with an inadequate response to current treatments, with emerging evidence of improved responses in various cancers with new immunotherapy agents, often in combinations with existing agents. The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer.


Asunto(s)
Melanoma , Humanos , Inmunoterapia , Inmunoterapia Adoptiva , Italia , Melanoma/patología , Microambiente Tumoral
20.
J Fungi (Basel) ; 9(5)2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37233265

RESUMEN

The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few Coccidioides spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal. Approaches to understanding this range of consequences have traditionally categorized patients into a small number of groups (asymptomatic, uncomplicated self-limited, fibro-cavitary, and extra-thoracic disseminated) and then looked for immunologic differences among them. Recently, variants within genes of innate pathways have been found to account, in part, for infections that result in disseminated disease. This discovery raises the very attractive theory that, in patients without severe immunosuppression, much of the disease spectrum can be accounted for by various combinations of such deleterious variants in innate pathways. In this review, we summarize what is known about genetic determinants that are responsible for the severity of coccidioidal infections and how complex innate genetic differences among different people might account for the spectrum of disease observed clinically.

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