RESUMO
BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (Pâ <â .001; CCIâ =â 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (Pâ <â .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (Pâ =â .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (Pâ =â .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (Pâ =â .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.
RESUMO
Maternal separation with early weaning (MSEW) is a popular early life stress (ELS) model in rodents, which emulates childhood neglect through scheduled mother-offspring separation. Although variations of ELS models, including maternal separation and MSEW, have been published for the mouse species, the reported results are inconsistent. Corticosterone is considered the main stress hormone involved in regulating stress responses in rodents-yet generating a robust and reproducible corticosterone response in mouse models of ELS has been elusive. Considering the current lack of standardization for MSEW protocols, these inconsistent results may be attributed to variations in model methodologies. Here, we compared the effects of select early wean diet sources-which are the non-milk diets used to complete early weaning in MSEW pups-on the immediate stress phenotype of C57BL/6J mice at postnatal day 21. Non-aversive handling was an integral component of our modified MSEW model. The evaluation of body weight and serum corticosterone revealed the early wean diet to be a key variable in the resulting stress phenotype. Interestingly, select non-milk diets facilitated a stress phenotype in which low body weight was accompanied by significant corticosterone elevation. Our data indicate that dietary considerations are critical in MSEW-based studies and provide insight into improving the reproducibility of key stress-associated outcomes as a function of this widely used ELS paradigm.
RESUMO
Introduction: Intravenous thrombolysis and mechanical thrombectomy are effective time-sensitive treatments for selected cases of acute ischaemic stroke. While thrombolysis is widely available, thrombectomy can only be provided at facilities with the necessary equipment and interventionists. Suitable patients admitted to other hospitals require secondary transfer, causing delays to treatment. Pre-hospital ambulance redirection to thrombectomy facilities may improve access but treatment eligibility cannot be confirmed pre-hospital. Some redirected patients would travel further and be displaced without receiving thrombectomy. This study aimed to elicit stroke survivor and carer/relative views about the possible consequences of introducing a conceptual, idealised ambulance redirection pathway. Methods: Focus groups were undertaken using a topic guide describing four hypothetical ambulance redirection scenarios and their possible consequences: earlier treatment with thrombectomy; delayed diagnosis of non-stroke 'mimic' conditions; delayed thrombolysis treatment; and delayed diagnosis of haemorrhagic stroke. Meetings were audio recorded, transcribed verbatim and data analysed thematically using emergent coding. Results: Fifteen stroke survivors and carers/relatives participated in three focus groups. There was wide acceptance of possible low-risk consequences of ambulance redirection, including extended travel time, being further from home and experiencing longer hospital stays. Participants were more uncertain about higher-risk consequences, including delays in diagnosis/treatment for patients unsuitable for thrombectomy, but remained positive about ambulance redirection overall. Participants rationalised acceptance of higher-risk consequences by recognising that redirected patients would still access appropriate treatment, even if delayed. In addition, acceptance of ambulance redirection would be increased if there were robust clinical evidence showing net benefit over secondary transfer pathways. Conclusions: Participant views were generally supportive of ambulance redirection to facilitate access to thrombectomy. Further research is needed to demonstrate overall benefit in an NHS context.
RESUMO
Background: Single-legged hop tests have been widely used to assess performance-based outcomes after anterior cruciate ligament (ACL) reconstruction. Traditional single, triple, or 6-meter (6m) timed hop tests only measure distance or time as the principal variables, neglecting other variables, such as individual hop distances within a series of hops, flight time, and stance time. The development of portable instrumented pressure walkways has made it possible to collect parameters such as hop velocity, flight time, stance time, distance, and pressure outside of a laboratory setting. However, the reliability of instrumented pressure walkways in measuring spatial and temporal variables during single-legged hop tests is unknown. This study aimed to determine if the Zeno walkway can reliably measure spatiotemporal (ST) characteristics of hop tests. Study Design: Cross-Sectional Study. Methods: Individuals (n=38) in this cross-sectional study performed single, triple, and 6m hop tests on a pressure-sensitive Zeno walkway. Twenty-one participants completed follow-up testing between one and 14 days later. Intraclass correlation coefficients (ICC(3,k)) were used to assess test-retest reliability of ST variables. The accuracy of vertical jump height and 6m hop timing were also measured. Results: All ST variables demonstrated excellent test-retest reliability (ICC > 0.86) with small minimal detectable change (MDC) values during single-legged hop tests. Six-meter hop time and jump height during a bilateral drop jump were also accurately measured by the walkway. Conclusion: An instrumented pressure walkway is a novel tool to reliably assess non-traditional parameters of clinically relevant hop and jump tests such as flight time, stance time, and jump height after lower extremity injury, surgery, and rehabilitation. Level of Evidence: 3b.
RESUMO
Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H2O2 treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.
RESUMO
Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.
Assuntos
Antioxidantes , Músculo Esquelético , Estresse Oxidativo , Doença Arterial Periférica , Espécies Reativas de Oxigênio , Transdução de Sinais , Humanos , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/terapia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/uso terapêutico , Animais , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismoRESUMO
We conducted a research campaign in a neotropical rainforest in Costa Rica throughout the drought phase of an El-Nino Southern Oscillation event to determine microbial community dynamics and soil C fluxes. Our study included nests of the leafcutter ant Atta cephalotes, as soil disturbances made by these ecosystem engineers may influence microbial drought response. Drought decreased the diversity of microbes and the abundance of core microbiome taxa, including Verrucomicrobial bacteria and Sordariomycete fungi. Despite initial responses of decreasing diversity and altered composition, 6 months post-drought the microbiomes were similar to pre-drought conditions, demonstrating the resilience of soil microbial communities to drought events. A. cephalotes nests altered fungal composition in the surrounding soil, and reduced both fungal mortality and growth of Acidobacteria post-drought. Drought increased CH4 consumption in soils due to lower soil moisture, and A. cephalotes nests decrease the variability of CH4 emissions in some soil types. CH4 emissions were tracked by the abundance of methanotrophic bacteria and fungal composition. These results characterize the microbiome of tropical soils across both time and space during drought and provide evidence for the importance of leafcutter ant nests in shaping soil microbiomes and enhancing microbial resilience during climatic perturbations.
Assuntos
Formigas , Bactérias , Secas , Fungos , Microbiota , Floresta Úmida , Microbiologia do Solo , Clima Tropical , Formigas/microbiologia , Formigas/fisiologia , Animais , Fungos/classificação , Fungos/fisiologia , Fungos/isolamento & purificação , Costa Rica , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Solo/química , FlorestasRESUMO
Dominant microorganisms of the Sargasso Sea are key drivers of the global carbon cycle. However, associated viruses that shape microbial community structure and function are not well characterised. Here, we combined short and long read sequencing to survey Sargasso Sea phage communities in virus- and cellular fractions at viral maximum (80 m) and mesopelagic (200 m) depths. We identified 2,301 Sargasso Sea phage populations from 186 genera. Over half of the phage populations identified here lacked representation in global ocean viral metagenomes, whilst 177 of the 186 identified genera lacked representation in genomic databases of phage isolates. Viral fraction and cell-associated viral communities were decoupled, indicating viral turnover occurred across periods longer than the sampling period of three days. Inclusion of long-read data was critical for capturing the breadth of viral diversity. Phage isolates that infect the dominant bacterial taxa Prochlorococcus and Pelagibacter, usually regarded as cosmopolitan and abundant, were poorly represented.
Assuntos
Bacteriófagos , Metagenoma , Metagenômica , Oceanos e Mares , Água do Mar , Metagenômica/métodos , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/classificação , Água do Mar/virologia , Água do Mar/microbiologia , Metagenoma/genética , Genoma Viral/genética , Filogenia , Prochlorococcus/virologia , Prochlorococcus/genética , Microbiota/genética , Bactérias/genética , Bactérias/virologia , Bactérias/classificação , Bactérias/isolamento & purificaçãoRESUMO
PURPOSE: To determine if subchondral rafting wires retained as adjunctive tibial plateau fracture fixation affect postoperative articular subsidence. METHODS: A retrospective cohort study was conducted at one Level 1 trauma center and one academic university hospital. Consecutive adults with closed, displaced OTA/AO 41B/C tibial plateau fractures treated between 2018 and 2023 with open reduction internal fixation were included. Patients who were not ambulatory, with contralateral injuries limiting weight bearing, and without follow-up radiographs of the injured extremity were excluded. The intervention was retention of subchondral rafting wires as definitive fixation. The primary outcome was linear articular surface subsidence between postoperative and follow-up AP knee radiographs. Linear subsidence was compared between groups using Welch's two sample t test. Associations of linear subsidence with patient, injury, and treatment characteristics were assessed by multivariable linear regression. RESULTS: We identified 179 patients of a mean age of 44 ± 14 years, of whom 15 (8.4%) received subchondral rafting wires. Median follow-up was 121 days. No patients who received rafting wires as definitive implants experienced linear subsidence ≥ 2 mm, while 22 patients (13.4%) who did not receive rafting wires experienced linear subsidence ≥ 2 mm (p = 0.130). Subchondral rafting wires were associated with less linear subsidence (0.3 mm [95% confidence interval - 0.3-0.9 mm] vsersus 1.0 mm [- 0.9-2.9 mm], p < 0.001). The depth of linear subsidence was significantly associated on multivariable regression with male sex, depressed plateau area, active smoking, and retained rafting wires. CONCLUSION: Subchondral rafting wires were associated with a small reduction in articular subsidence after internal fixation of tibial plateau fractures. Routine rafting wires may be useful for patients and fractures at high risk of articular subsidence.
Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas , Fraturas da Tíbia , Humanos , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Adulto , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Pessoa de Meia-Idade , Radiografia , Fraturas do Planalto TibialRESUMO
Reversible phosphorylation is a fundamental mechanism for controlling protein function. Despite the critical roles phosphorylated proteins play in physiology and disease, our ability to study individual phospho-proteoforms has been hindered by a lack of versatile methods to efficiently generate homogeneous proteins with site-specific phosphoamino acids or with functional mimics that are resistant to phosphatases. Genetic code expansion (GCE) is emerging as a transformative approach to tackle this challenge, allowing direct incorporation of phosphoamino acids into proteins during translation in response to amber stop codons. This genetic programming of phospho-protein synthesis eliminates the reliance on kinase-based or chemical semisynthesis approaches, making it broadly applicable to diverse phospho-proteoforms. In this comprehensive review, we provide a brief introduction to GCE and trace the development of existing GCE technologies for installing phosphoserine, phosphothreonine, phosphotyrosine, and their mimics, discussing both their advantages as well as their limitations. While some of the technologies are still early in their development, others are already robust enough to greatly expand the range of biologically relevant questions that can be addressed. We highlight new discoveries enabled by these GCE approaches, provide practical considerations for the application of technologies by non-GCE experts, and also identify avenues ripe for further development.
Assuntos
Código Genético , Fosforilação , Fosfoaminoácidos/metabolismo , Fosfoaminoácidos/química , Fosfoaminoácidos/genética , Proteínas/metabolismo , Proteínas/química , Proteínas/genética , HumanosRESUMO
The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system.
RESUMO
Borrelia burgdorferi, the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here, we show that mice infected with B. burgdorferi and concomitantly immunized with recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein had an abrogated antibody response to the immunization. To further define how long this humoral immune suppression lasts, mice were immunized at 2, 4, and 6 weeks post-infection. Suppression of host antibody production against the SARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. Antibody responses against the SARS-CoV-2 spike protein were also assessed following antibiotic treatment to determine whether this immune suppression persists or resolves following clearance of B. burgdorferi. Host antibody production against the SARS-CoV-2 spike protein returned to baseline following antibiotic treatment; however, anti-SARS-CoV-2 IgM remained high, comparable to levels found in B. burgdorferi-infected but untreated mice. Thus, our data demonstrate restored IgG responses following antibiotic treatment but persistently elevated IgM levels, indicating lingering effects of B. burgdorferi infection on the immune system following treatment.
Assuntos
Borrelia burgdorferi , Doença de Lyme , Glicoproteína da Espícula de Coronavírus , Camundongos , Humanos , Animais , Imunidade Humoral , Imunoglobulina M , Antibacterianos , Anticorpos AntibacterianosRESUMO
BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela , Excisão de Linfonodo , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Hormônios/uso terapêutico , Axila/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
BACKGROUND: An especially significant event in the patient-oncologist relationship is the initial consultation, where many complex topics-diagnosis, treatment intent, and often, prognosis-are discussed in a relatively short period of time. This study aimed to measure patients' understanding of the information discussed during their first medical oncology visit and their satisfaction with the communication from medical oncologists. METHODS: Between January and August 2021, patients without prior systemic treatment of their gastrointestinal malignancy (GI) attending the Princess Margaret Cancer Centre (PMCC) were approached within 24 h of their initial consultation to complete a paper-based questionnaire assessing understanding of their disease (diagnosis, treatment plan/intent, and prognosis) and satisfaction with the consultation. Medical oncology physicians simultaneously completed a similar questionnaire about the information discussed at the initial visit. Matched patient-physician responses were compared to assess the degree of concordance. RESULTS: A total of 184 matched patient-physician surveys were completed. The concordance rates for understanding of diagnosis, treatment plan, treatment intent, and prognosis were 92.9%, 59.2%, 66.8%, and 59.8%, respectively. After adjusting for patient and physician variables, patients who reported treatment intent to be unclear at the time of the consultation were independently associated with lower satisfaction scores (global p = 0.014). There was no statistically significant association between patient satisfaction and whether prognosis was disclosed (p = 0.08). CONCLUSION: An in-depth conversation as to what treatment intent and prognosis means is reasonable during the initial medical oncology consultation to ensure patients and caregivers have a better understanding about their cancer.
Assuntos
Neoplasias , Médicos , Humanos , Satisfação do Paciente , Oncologia , Relações Médico-Paciente , Neoplasias/diagnóstico , Neoplasias/terapia , Comunicação , Encaminhamento e ConsultaRESUMO
Collaborations between ecosystem ecologists and engineers have led to impressive progress in developing complex models of biogeochemical fluxes in response to global climate change. Ecology and engineering iteratively inform and transform each other in these efforts. Nested data streams from local sources, adjacent networks, and remote sensing sources together magnify the capacity of ecosystem ecologists to observe systems in near real-time and address questions at temporal and spatial scales that were previously unobtainable. We describe our research experiences working in a Costa Rican rainforest ecosystem with the challenges presented by constant high humidity, 4300 mm of annual rainfall, flooding, small invertebrates entering the tiniest openings, stinging insects, and venomous snakes. Over the past two decades, we faced multiple challenges and learned from our mistakes to develop a broad program of ecosystem research at multiple levels of integration. This program involved integrated networks of diverse sensors on a series of canopy towers linked to multiple belowground soil sensor arrays that could transport sensor data streams from the forest directly to an off-site location via a fiber optic cable. In our commentary, we highlight three components of our work: (1) the eddy flux measurements using canopy towers; (2) the soil sensor arrays for measuring the spatial and temporal patterns of CO2 and O2 fluxes at the soil-atmosphere interface; and (3) focused investigations of the ecosystem impact of leaf-cutter ants as "ecosystem engineers" on carbon fluxes.
Assuntos
Ecossistema , Floresta Úmida , Florestas , Ecologia , Solo/química , Dióxido de CarbonoRESUMO
The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-α, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.
RESUMO
Leaf-cutter ants (LCAs) are widely distributed and alter the physical and biotic architecture above and below ground. In neotropical rainforests, they create aboveground and belowground disturbance gaps that facilitate oxygen and carbon dioxide exchange. Within the hyperdiverse neotropical rainforests, arbuscular mycorrhizal (AM) fungi occupy nearly all of the forest floor. Nearly every cubic centimeter of soil contains a network of hyphae of Glomeromycotina, fungi that form arbuscular mycorrhizae. Our broad question is as follows: how can alternative mycorrhizae, which are-especially ectomycorrhizae-essential for the survival of some plant species, become established? Specifically, is there an ant-mycorrhizal fungus interaction that facilitates their establishment in these hyperdiverse ecosystems? In one lowland Costa Rican rainforest, nests of the LCA Atta cephalotes cover approximately 1.2% of the land surface that is broadly scattered throughout the forest. On sequencing the DNA from soil organisms, we found the inocula of many AM fungi in their nests, but the nests also contained the inocula of ectomycorrhizal, orchid mycorrhizal, and ericoid mycorrhizal fungi, including Scleroderma sinnamariense, a fungus critical to Gnetum leyboldii, an obligate ectomycorrhizal plant. When the nests were abandoned, new root growth into the nest offered opportunities for new mycorrhizal associations to develop. Thus, the patches created by LCAs appear to be crucial sites for the establishment and survival of shifting mycorrhizal plant-fungal associations, in turn facilitating the high diversity of these communities. A better understanding of the interactions of organisms, including cross-kingdom and ant-mycorrhizal fungal interactions, would improve our understanding of how these ecosystems might tolerate environmental change.
RESUMO
BACKGROUND: There are few contemporary studies on the time taken to complete dental procedures, those most heavily relied on in the United Kingdom date back to 1999. OBJECTIVES: This work aimed to establish how long members of the dental team took to complete specific dental procedures, relevant to their scope of practice. METHODS: Data were collected via a purposive sample of 96 dentists, dental hygienists/therapists and dental nurses. Via an online survey, participants were asked to state the mean, minimum and maximum time they estimated that they took to complete individual dental procedures. RESULTS: The mean time taken to complete procedures common to both dentists and dental hygienists/therapists ranged from 3.7 to 4 min respectively for clinical note reading prior to seeing patients to 30.1 and 28 min to undertake root surface debridement. There were no significant differences between the time taken by dentists and dental hygienists/therapists to treat adult patients. However, in all but one procedure, dental hygienists/therapists reported taking longer (p = 0.04) to treat child patients. CONCLUSIONS: The data provided here represent an up to date assessment of the time taken to complete specific tasks by different members of the dental team. These data will be of value to service planners and commissioners interested in evolving a dental care system that employs a greater degree of skill-mix and preventively oriented care.
Assuntos
Assistência Odontológica , Higienistas Dentários , Adulto , Criança , Humanos , Estudos Transversais , Reino Unido , Inquéritos e Questionários , OdontólogosRESUMO
We evaluated the impact of a philanthropic program investing in the conservation of sites along the Pacific Americas Flyway, which spans >16,000 km of coastline and is used by millions of shorebirds. Using a quasi-experimental, mixed methods approach, we estimated what would have happened to shorebird populations at 17 wintering sites without the sustained and additional investment they received. We modeled shorebird populations across the entire flyway and at sites with and without investment. Combining shorebird abundance estimates with a land-cover classification model, we used the synthetic control method to create counterfactuals for shorebird trends at the treatment sites. We found no evidence of an overall effect across three outcome variables. Species- and site-level treatment effects were heterogeneous, with a few cases showing evidence of a positive effect, including a site with a high level of overall investment. Results suggest six shorebirds declined across the entire flyway, including at many Latin American sites. However, the percentage of flyway populations present at the sites remained stable, and the percentage at the treatment sites was higher (i.e., investment sites) than at control sites. Multiple mechanisms behind our results are possible, including that investments have yet to mitigate impacts and negative impacts at other sites are driving declines at the treatment sites. A limitation of our evaluation is the sole focus on shorebird abundance and the lack of data that prohibits the inclusion of other outcome variables. Monitoring infrastructure is now in place to design a more robust and a priori shorebird evaluation framework across the entire flyway. With this framework, it will prove easier to prioritize limited dollars to result in the most positive conservation outcomes.
Evaluación del impacto de la inversión para la conservación enfocada en especies migratorias de largo recorrido Resumen Evaluamos el impacto de un programa filantrópico que invierte en la conservación de sitios a lo largo de la Ruta Migratoria Pacífico-Américas, la cual abarca >16,000 km de la línea costera y millones de aves playeras la usan. Estimamos con una estrategia cuasiexperimental y de métodos mixtos lo que habría pasado con las poblaciones de estas aves en 17 sitios invernales sin la inversión adicional y continua que recibieron. Modelamos estas poblaciones en toda la ruta y en sitios con y sin inversión. Combinamos las estimaciones de aves playeras con el modelo de clasificación de la cobertura del suelo y usamos el método de control sintético para crear contrafactuales para las tendencias de las aves playeras en sitios de tratamiento. No encontramos evidencia alguna de un efecto generalizado en las tres variables de los resultados. Los efectos del tratamiento de especies y de sitio fueron heterogéneos, con unos cuantos casos que mostraron evidencia de un efecto positivo, incluido un sitio con un nivel elevado de inversión general. Los resultados sugieren que seis especies de aves playeras declinaron a lo largo de toda la ruta, incluyendo en varios sitios de América Latina. Sin embargo, el porcentaje de poblaciones de la ruta presentes en los sitios permaneció estable y el porcentaje en los sitios de tratamiento (sitios de inversión) fue más elevado que en los sitios control. Muchos mecanismos son posibles detrás de nuestros resultados, incluidas las inversiones que todavía no han mitigado impactos y los impactos negativos en otros sitios que están causando las declinaciones en los sitios de tratamiento. Una limitación en nuestra evaluación es el enfoque único en la abundancia de aves playeras y la falta de datos que impiden la inclusión de otras variables de los resultados. El monitoreo de la infraestructura ahora está en una posición en la que puede diseñar un marco de evaluación más robusto y a priori de las aves playeras a lo largo de toda la ruta. Con este marco, será más fácil priorizar los dólares limitados para que los resultados de conservación sean lo más positivos posible.
RESUMO
HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.