Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.045
Filtrar
1.
Nature ; 601(7892): 217-222, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35022589

RESUMO

The use of lithium metal anodes in solid-state batteries has emerged as one of the most promising technologies for replacing conventional lithium-ion batteries1,2. Solid-state electrolytes are a key enabling technology for the safe operation of lithium metal batteries as they suppress the uncontrolled growth of lithium dendrites. However, the mechanical properties and electrochemical performance of current solid-state electrolytes do not meet the requirements for practical applications of lithium metal batteries. Here we report a class of elastomeric solid-state electrolytes with a three-dimensional interconnected plastic crystal phase. The elastomeric electrolytes show a combination of mechanical robustness, high ionic conductivity, low interfacial resistance and high lithium-ion transference number. The in situ-formed elastomer electrolyte on copper foils accommodates volume changes for prolonged lithium plating and stripping processes with a Coulombic efficiency of 100.0 per cent. Moreover, the elastomer electrolytes enable stable operation of the full cells under constrained conditions of a limited lithium source, a thin electrolyte and a high-loading LiNi0.83Mn0.06Co0.11O2 cathode at a high voltage of 4.5 volts at ambient temperature, delivering a high specific energy exceeding 410 watt-hours per kilogram of electrode plus electrolyte. The elastomeric electrolyte system presents a powerful strategy for enabling stable operation of high-energy, solid-state lithium batteries.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35023627

RESUMO

The globally dominant N2 -fixing cyanobacteria Trichodesmium and Crocosphaera provide vital nitrogen supplies to subtropical and tropical oceans, but little is known about how they will be affected by long-term ocean warming. We tested their thermal responses using experimental evolution methods during 2 years of selection at optimal (28°C), supra-optimal (32°C) and suboptimal (22°C) temperatures. After several hundred generations under thermal selection, changes in growth parameters, as well as N and C fixation rates, suggested that Trichodesmium did not adapt to the three selection temperature regimes during the 2-year evolution experiment, but could instead rapidly and reversibly acclimate to temperature shifts from 20°C to 34°C. In contrast, over the same timeframe apparent thermal adaptation was observed in Crocosphaera, as evidenced by irreversible phenotypic changes as well as whole-genome sequencing and variant analysis. Especially under stressful warming conditions (34°C), 32°C-selected Crocosphaera cells had an advantage in survival and nitrogen fixation over cell lines selected at 22°C and 28°C. The distinct strategies of phenotypic plasticity versus irreversible adaptation in these two sympatric diazotrophs are both viable ways to maintain fitness despite long-term temperature changes, and so could help to stabilize key ocean nitrogen cycle functions under future warming scenarios.

5.
Am J Otolaryngol ; 43(1): 103228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34537509

RESUMO

OBJECTIVE: To perform a systematic review of the diagnosis and treatment of patients with pulsatile tinnitus secondary to middle ear myoclonus. DATABASES REVIEWED: PubMed, EMBASE, and Scopus. METHODS: A systematic review was performed using standardized methodology. Computerized and manual searches were performed to identify studies of all ages (patients) who had middle ear myoclonus (intervention). All study designs were assessed. Extracted data included demographics, clinical features, duration of followup as well as the diagnosis and reversibility of symptoms with medical or surgical intervention. Studies were included if they included subjects with middle ear myoclonus. Exclusion criteria included letters/commentaries and reviews. RESULTS: Twenty articles representing 115 subjects with middle ear myoclonus were included. The mean age was 29.7 (range 6-67). The follow-up period ranged from 5 weeks to 36 months. Primary treatment consists of medical therapy utilising anxiolytics, antiepileptics, botulinum toxin and surgical treatment involving division of middle ear muscular tendon(s). In total, 60 patients underwent middle ear muscular tenotomies, with division of both stapedius and tensor tympani tendons being the most prevalent (88%). Limitations in the data arose from study design, related comorbidities such as palatal myoclonus, and concomitant drug administration. No study provided any objective criteria to diagnose this condition or evaluate post-treatment outcome. CONCLUSION: Middle ear myoclonus is an entity that is poorly assessed in the literature. There is a lack of consensus regarding the criteria and strategies for both diagnosing and treating this condition. Although level of evidence of current studies remains modest, it is felt that a stepwise approach is deemed best, with therapeutic decisions being made on an individual basis, evaluating each patient's specific circumstances and priorities.

6.
Glia ; 70(2): 368-378, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34726298

RESUMO

Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aß) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aß on astroglial and neuronal network function remains unknown. Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aß on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aß density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aß, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hypo-responsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.

7.
Nat Commun ; 12(1): 7016, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853318

RESUMO

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or "Nissle") exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin's affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the pH increases. Thus, our results indicate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to commensal and pathogenic Enterobacteriaceae.

8.
Nanoscale ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34853844

RESUMO

Solar-driven interfacial steam generation (SISG) has attracted much attention in recent years as a solution to freshwater scarcity and the energy crisis. Currently, research interests are mainly focused on standard conditions under "1-sun" illumination, which we believe are insufficient on their own. Gaining insight and understanding about SISG under both weak and strong irradiation have important implications for real-world use that are rarely presented in relevant discussions. In this review, we aim to discuss SISG under weak (<1 sun) and strong solar irradiation (>1 sun), both of which are often undervalued but necessary for real application. By analyzing state-of-the-art techniques and recent research progress, we provide some possible strategies, in terms of both energy and water management, for improving the performance of SISG under different irradiation powers. Finally, we also give a summary and our perspectives on the directions that the future development of this exciting field might take.

9.
Front Immunol ; 12: 744763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867967

RESUMO

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.

10.
JAMA Intern Med ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34870676

RESUMO

Importance: Visual function is important for older adults. Interventions to preserve vision, such as cataract extraction, may modify dementia risk. Objective: To determine whether cataract extraction is associated with reduced risk of dementia among older adults. Design, Setting, and Participants: This prospective, longitudinal cohort study analyzed data from the Adult Changes in Thought study, an ongoing, population-based cohort of randomly selected, cognitively normal members of Kaiser Permanente Washington. Study participants were 65 years of age or older and dementia free at enrollment and were followed up biennially until incident dementia (all-cause, Alzheimer disease, or Alzheimer disease and related dementia). Only participants who had a diagnosis of cataract or glaucoma before enrollment or during follow-up were included in the analyses (ie, a total of 3038 participants). Data used in the analyses were collected from 1994 through September 30, 2018, and all data were analyzed from April 6, 2019, to September 15, 2021. Exposures: The primary exposure of interest was cataract extraction. Data on diagnosis of cataract or glaucoma and exposure to surgery were extracted from electronic medical records. Extensive lists of dementia-related risk factors and health-related variables were obtained from study visit data and electronic medical records. Main Outcomes and Measures: The primary outcome was dementia as defined by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Multivariate Cox proportional hazards regression analyses were conducted with the primary outcome. To address potential healthy patient bias, weighted marginal structural models incorporating the probability of surgery were used and the association of dementia with glaucoma surgery, which does not restore vision, was evaluated. Results: In total, 3038 participants were included (mean [SD] age at first cataract diagnosis, 74.4 (6.2) years; 1800 women (59%) and 1238 men (41%); and 2752 (91%) self-reported White race). Based on 23 554 person-years of follow-up, cataract extraction was associated with significantly reduced risk (hazard ratio, 0.71; 95% CI, 0.62-0.83; P < .001) of dementia compared with participants without surgery after controlling for years of education, self-reported White race, and smoking history and stratifying by apolipoprotein E genotype, sex, and age group at cataract diagnosis. Similar results were obtained in marginal structural models after adjusting for an extensive list of potential confounders. Glaucoma surgery did not have a significant association with dementia risk (hazard ratio, 1.08; 95% CI, 0.75-1.56; P = .68). Similar results were found with the development of Alzheimer disease dementia. Conclusions and Relevance: This cohort study found that cataract extraction was significantly associated with lower risk of dementia development. If validated in future studies, cataract surgery may have clinical relevance in older adults at risk of developing dementia.

11.
J Proteome Res ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855411

RESUMO

Ocean microbial communities are important contributors to the global biogeochemical reactions that sustain life on Earth. The factors controlling these communities are being increasingly explored using metatranscriptomic and metaproteomic environmental biomarkers. Using published proteomes and transcriptomes from the abundant colony-forming cyanobacterium Trichodesmium (strain IMS101) grown under varying Fe and/or P limitation in low and high CO2, we observed robust correlations of stress-induced proteins and RNAs (i.e., involved in transport and homeostasis) that yield useful information on the nutrient status under low and/or high CO2. Conversely, transcriptional and translational correlations of many other central metabolism pathways exhibit broad discordance. A cellular RNA and protein production/degradation model demonstrates how biomolecules with small initial inventories, such as environmentally responsive proteins, achieve large increases in fold-change units as opposed to those with a higher basal expression and inventory such as metabolic systems. Microbial cells, due to their immersion in the environment, tend to show large adaptive responses in both RNA and protein that result in transcript-protein correlations. These observations and model results demonstrate multi-omic coherence for environmental biomarkers and provide the underlying mechanism for those observations, supporting the promise for global application in detecting responses to environmental stimuli in a changing ocean.

12.
J Pediatr Orthop ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34857723

RESUMO

BACKGROUND: Predictors of outcomes in adolescent athletes undergoing hip arthroscopy have not been established. The purpose of this study was to identify factors correlated with achieving the Patient Acceptable Symptomatic State (PASS) for the Hip Outcome Score-Sports Specific Subscale (HOS-SSS) at a minimum 5-year follow-up in adolescent athletes undergoing primary hip arthroscopy. METHODS: Data were reviewed on adolescent (below 18 y old) athletes who underwent primary hip arthroscopy for femoroacetabular impingement syndrome between March 2008 and October 2015. Patients were included if they participated in sport within 1 year before surgery and had preoperative, 2-year, and minimum 5-year postoperative patient-reported outcome (PRO) scores for the modified Harris Hip Score, HOS-SSS, Visual Analog Scale for pain (VAS), and Non-Arthritic Hip Score (NAHS). Patients were divided into 2 groups based on whether they achieved PASS for HOS-SSS. Demographics, intraoperative findings, radiographic variables, surgical treatments, and PRO were compared. Multivariate logistic regression with corresponding odds ratios (ORs) quantified the correlation between variables and achievement of the PASS. RESULTS: A total of 123 athletes with a mean age of 16.2±1.1 years were included. These athletes demonstrated significant imrpovement from preoperative to minimum 5-year follow-up for all recorded PROs (P<0.001). The multivariate logistic regression model identified preoperative NAHS (P=0.019, OR: 1.033), 2-year postoperative HOS-SSS (P=0.014, OR: 1.037), and 2-year postoperative VAS (P=0.003, OR: 0.590) as statistically significantly correlated with achieving the PASS. Athletes with a 2-year postoperative VAS pain score ≤2 achieved PASS at a rate of 81.9%, while those with a score >2 achieved PASS at a rate of 24.1% (P<0.001, OR: 14.2, 95% confidence interval: 5.23-38.7). CONCLUSIONS: Favorable outcome were achieved at mid-term follow-up in adolescent athletes undergoing primary hip arthroscopy. Preoperative NAHS, 2-year postoperative HOS-SSS, and 2-year postoperative VAS pain scores were correlated with achieving the PASS for HOS-SSS at a minimum 5-year follow-up. Patients with 2-year postoperative VAS ≤2 were significantly more likely to achieve the PASS at 5-year follow-up than those with scores >2. LEVEL OF EVIDENCE: Level III-case-control study.

13.
Arthroscopy ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863903

RESUMO

PURPOSE: (1) To report minimum 2- and 5-year outcomes of high-level athletes who did not RTS after hip arthroscopy for reasons unrelated to their hip (T athletes) and (2) to benchmark these findings against a propensity-matched control group of high-level athletes who returned to sport (RTS athletes). METHODS: Data were prospectively collected and retrospectively reviewed for professional, collegiate, and high school athletes between April 2008 and October 2015 who underwent primary hip arthroscopy. Athletes were considered eligible if they did not return to sport for reasons unrelated to their hip such as loss of interest, graduation, or a lifestyle transition (T athletes). Inclusion criteria were preoperative and minimum 5-year postoperative PROs for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), and the Visual Analog Scale (VAS) for pain. Clinical outcomes were assessed using the minimal clinically important difference (MCID) and maximum outcome improvement satisfaction threshold (MOIST). T athletes were then propensity-matched to a control group of high-level athletes who returned to sport after hip arthroscopy (RTS athletes) for comparison. RESULTS: Twenty-seven T hips (25 patients) were included in the analysis with a mean follow-up time of 38.9 ± 16.8 and 72.1 ± 16.8 months for minimum 2- and 5-year outcomes, respectively. They demonstrated significant improvement in all measured PROs. When compared to a propensity-matched control group of RTS athletes, T athletes demonstrated similar improvement in PROs (mHHS, NAHS and HOS-SSS) and achieved MCID at similar rates for NAHS (T: 77.8% vs RTS: 68.8%, P = 0.570) and HOS-SSS (T: 70.3% vs RTS: 76.6%, P = .824) compared to RTS athletes; however T athletes demonstrated higher rates of achieving MCID for mHHS (T: 88.9% vs RTS: 72.9% P = .033). CONCLUSION: Athletes who did not return to sport for reasons unrelated to their hip demonstrated favorable outcomes at minimum 2- and 5-year follow-up. They had similar PROs and rates of achieving MCID for HOS-SSS compared to a propensity-matched control group of high-level athletes who returned to sport. LEVEL OF EVIDENCE: III, retrospective cohort study.

14.
Biomaterials ; 280: 121270, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34890973

RESUMO

Three-dimensional (3D) hydrogels made from synthetic polymers have emerged as in vitro cell culture platforms capable of representing the extracellular geometry, modulus, and water content of tissues in a tunable fashion. Hydrogels made from these otherwise non-bioactive polymers can be decorated with short peptides derived from proteins naturally found in tissues to support cell viability and direct phenotype. We identified two key limitations that limit the ability of this class of materials to recapitulate real tissue. First, these environments typically display between 1 and 3 bioactive peptides, which vastly underrepresents the diversity of proteins found in the extracellular matrix (ECM) of real tissues. Second, peptides chosen are ubiquitous in ECM and not derived from proteins found in specific tissues, per se. To overcome this critical limitation in hydrogel design and functionality, we developed an approach to incorporate the complex and specific protein signature of bone marrow into a poly (ethylene glycol) (PEG) hydrogel. This bone marrow hydrogel mimics the elasticity of marrow and has 20 bone marrow-specific and cell-instructive peptides. We propose this tissue-centric approach as the next generation of 3D hydrogel design for applications in tissue engineering and beyond.

15.
AsiaIntervention ; 7(1): 54-59, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34913003

RESUMO

Aims: The aim of the study was to report the clinical experience, 30-day mortality and acute outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) in the Asia Pacific region. Methods and results: The Asia Pacific TAVI registry is an international, multicentre, prospective, observational registry managed under the auspices of the Asian Pacific Society of Interventional Cardiology (APSIC). Patients undergoing TAVI in seven centres from Hong Kong, Japan, Philippines, Singapore and Taiwan, treated with TAVI devices for severe symptomatic aortic stenosis, were assessed. This first review presents the acute results and 30-day mortality. A multivariable analysis was also performed to identify independent predictors of early all-cause mortality. The enrolment was from 2009 to 2017 and a total of 1,125 patients were recruited. The 30-day mortality rate was 2.5%. Baseline logistic EuroSCORE more than 16 was independently associated with a 2.8-times increased risk of 30-day all-cause mortality (p=0.016). Post-procedural stroke (HR 4.9, p=0.008) was also associated with increased mortality. Conclusions: This initial report of the Asia Pacific TAVI registry demonstrated good acute success and low 30-day mortality. The preprocedural logistic EuroSCORE and post-procedural stroke incidence were strongly associated with acute mortality. Further attempts to reduce post-procedural stroke should be explored.

16.
Am J Cardiol ; 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34949471

RESUMO

Fractional flow reserve (FFR) determines the functional significance of epicardial stenoses assuming negligible venous pressure (Pv) and microvascular resistance. However, these assumptions may be invalid in end-stage liver disease (ESLD) because of fluctuating Pv and vasodilation. Accordingly, all patients with ESLD who underwent right-sided cardiac catheterization and coronary angiography with FFR as part of their orthotopic liver transplantation evaluation between 2013 and 2018 were included in the present study. Resting mean distal coronary pressure (Pd)/mean aortic pressure (Pa), FFR, and Pv were measured. FFR accounting for Pv (FFR - Pv) was defined as (Pd - Pv)/(Pa - Pv). The hyperemic effect of adenosine was defined as resting Pd/Pa - FFR. The primary outcome was all-cause mortality at 1 year. In 42 patients with ESLD, 49 stenoses were interrogated by FFR (90% were <70% diameter stenosis). Overall, the median model for ESLD score was 16.5 (10.8 to 25.5), FFR was 0.87 (0.81 to 0.94), Pv was 8 mm Hg (4 to 14), FFR-Pv was 0.86 (0.80 to 0.94), and hyperemic effect of adenosine was 0.06 (0.02 to 0.08). FFR-Pv led to the reclassification of 1 stenosis as functionally significant. There was no significant correlation between the median model for ESLD score and the hyperemic effect of adenosine (R = 0.10). At 1 year, 13 patients had died (92% noncardiac in etiology), and patients with FFR ≤0.80 had significantly higher all-cause mortality (73% vs 17%, p = 0.001. In conclusion, in patients with ESLD who underwent orthotopic liver transplantation evaluation, Pv has minimal impact on FFR, and the hyperemic effect of adenosine is preserved. Furthermore, even in patients with the predominantly angiographically-intermediate disease, FFR ≤0.80 was an independent predictor of all-cause mortality.

17.
Brain ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34957475

RESUMO

Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.

18.
Arthroscopy ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34920010

RESUMO

PURPOSE: To report minimum two-year patient-reported outcome measures (PROMs) following primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and painful external snapping hip (ESH) treatment and ESH resolution, and to compare these PROMs to a benchmark FAIS propensity-matched control group without ESH. METHODS: Data were prospectively collected and retrospectively reviewed between November 2009 and April 2018. Patients were eligible if they were preoperatively diagnosed with FAIS and painful ESH and received primary hip arthroscopy to address these pathologies. Inclusion criteria were baseline and minimum two-year follow-up scores for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Sport Specific Subscale, and Visual Analog Scale for pain. Exclusion criteria were Tönnis grade >1, and previous hip conditions. A secondary sub-analysis was performed to benchmark these outcomes to a FAIS propensity-matched control group without ESH according to age, sex, body mass index (BMI), Tönnis grade, and preoperative lateral center-edge and alpha angles using a 1:3 ratio. The minimal clinically important difference (MCID) and the maximum outcome improvement (MOI) rates were reported. RESULTS: Twenty-two hips (21 patients) were included. The mean age, BMI, and follow-up were 31.3 years ± 14.0, 26 kg/m2 ± 5.0, and 31.4 months ± 4.4, respectively, with 68.2% being female. ESH was resolved in 100% of patients. Significant improvement for all PROMs at a minimum two-year (P < 0.001) was reported. The minimum two-year PROMs and the rate of achieving the MCID and MOI threshold were comparable to the control group. CONCLUSION: Following primary hip arthroscopy for FAIS and painful ESH, patients demonstrated significant improvement in all PROMs and the rate of resolution of ESH was 100% at minimum two-year follow-up. Functional outcomes and rates of MCID and MOI achievement were comparable to a FAIS propensity-matched benchmark control group without ESH.

19.
Br J Surg ; 109(1): 30-36, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921604

RESUMO

BACKGROUND: Despite persistently poor oncological outcomes, approaches to the management of T4 colonic cancer remain variable, with the role of neoadjuvant therapy unclear. The aim of this review was to compare oncological outcomes between direct-to-surgery and neoadjuvant therapy approaches to T4 colon cancer. METHODS: A librarian-led systematic search of MEDLINE, Embase, the Cochrane Library, Web of Science, and CINAHL up to 11 February 2020 was performed. Inclusion criteria were primary research articles comparing oncological outcomes between neoadjuvant therapies or direct to surgery for primary T4 colonic cancer. Based on PRISMA guidelines, screening and data abstraction were undertaken in duplicate. Quality assessment was carried out using Cochrane risk-of-bias tools. Random-effects models were used to pool effect estimates. This study compared pathological resection margins, postoperative morbidity, and oncological outcomes of cancer recurrence and overall survival. RESULTS: Four studies with a total of 43 063 patients met the inclusion criteria. Compared with direct to surgery, neoadjuvant therapy was associated with increased rates of margin-negative resection (odds ratio (OR) 2.60, 95 per cent c.i. 1.12 to 6.02; n = 15 487) and 5-year overall survival (pooled hazard ratio 1.42, 1.10 to 1.82, I2 = 0 per cent; n = 15 338). No difference was observed in rates of cancer recurrence (OR 0.42, 0.15 to 1.22; n = 131), 30-day minor (OR 1.12, 0.68 to 1.84; n = 15 488) or major (OR 0.62, 0.27 to 1.44; n = 15 488) morbidity, or rates of treatment-related adverse effects. CONCLUSION: Compared with direct to surgery, neoadjuvant therapy improves margin-negative resection rates and overall survival.

20.
Dev Biol ; 483: 66-75, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34968443

RESUMO

In recent years CRISPR-Cas9 knockouts (KO) have become increasingly ultilised to study gene function. MicroRNAs (miRNAs) are short non-coding RNAs, 20-22 nucleotides long, which affect gene expression through post-transcriptional repression. We previously identified miRNAs-196a and -219 as implicated in the development of Xenopus neural crest (NC). The NC is a multipotent stem-cell population, specified during early neurulation. Following EMT, NC cells migrate to various points in the developing embryo where they give rise to a number of tissues including parts of the peripheral nervous system, pigment cells and craniofacial skeleton. Dysregulation of NC development results in many diseases grouped under the term neurocristopathies. As miRNAs are so small, it is difficult to design CRISPR sgRNAs that reproducibly lead to a KO. We have therefore designed a novel approach using two guide RNAs to effectively 'drop out' a miRNA. We have knocked out miR-196a and miR-219 and compared the results to morpholino knockdowns (KD) of the same miRNAs. Validation of efficient CRISPR miRNA KO and phenotype analysis included use of whole-mount in situ hybridization of key NC and neural plate border markers such as Pax3, Xhe2, Sox10 and Snail2, q-RT-PCR and Sanger sequencing. To show specificity we have also rescued the knockout phenotype using miRNA mimics. MiRNA-219 and miR-196a KO's both show loss of NC, altered neural plate and hatching gland phenotypes. Tadpoles show gross craniofacial and pigment phenotypes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...