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1.
Sci Total Environ ; 806(Pt 3): 151256, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717998

RESUMO

Applying biochar in association with crop residues might optimize costs and effectiveness in the reclamation of saline soils. Here, we explored the potential effects of biochar in association with crop residue amendments on soil greenhouse gas (GHG) emissions, and microbial communities. Previously, we found that soil N2O emission significantly increased with increasing salinity levels followed by cotton straw addition. In the present study, microcosm experiments were performed to investigate the interaction of salinity (0 and 1.2% salt) with the aging of biochar following soil amendments over an incubation period of 80 days. The results indicated that N2O emissions were approximately 5-10 times higher in saline soils than in non-saline soils, and the cumulative N2O emissions following two straw amendments treatment were the highest of all the treatments. Salinity increased the contribution of nitrification to soil N2O emissions stimulated by the cotton straw amendments, and aged biochar performed better in decreasing soil N2O emissions in saline soils than in non-saline soils. In addition, aged biochar increased soil C mineralization and CO2 emissions under saline conditions. Soil CO2 and N2O emissions were affected by both soil abiotic and biotic factors under non-saline and saline conditions. Moreover, much more specific but fewer microbial groups survived and utilized crop residues under saline than non-saline conditions, and aged biochar decreased salt stress in soil microorganisms. These findings indicated that aged biochar and crop residues together would be an optimal way to address soil C storage and mitigate N2O emissions under saline conditions.


Assuntos
Gases de Efeito Estufa , Solo , Agricultura , Carvão Vegetal , Fertilizantes , Gases de Efeito Estufa/análise , Laboratórios , Óxido Nitroso/análise
3.
ANZ J Surg ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676664

RESUMO

Post-operative ileus (POI) is a syndrome of impaired gastrointestinal transit which occurs following abdominal surgery. There are few effective targeted therapies for ileus, and research has been limited by inconsistent definitions and an incomplete understanding of the underlying pathophysiology. Despite considerable effort, there remains no widely-adopted definition of ileus, and recent work has identified variation in outcome reporting is a major source of heterogeneity in clinical trials. Outcomes should be clearly-defined, clinically-relevant, and reflective of the underlying biology, impacts on hospital resources and quality of life. Further collaborative efforts will be needed to develop consensus definitions and a core outcome set for postoperative gastrointestinal recovery. Investigation into the pathophysiology of POI has been hindered by use of low-resolution techniques and difficulties linking cellular mechanisms to dysmotility patterns and clinical symptoms. Recent evidence has suggested the common assumption of post-operative GI paralysis is incorrect, and that the distal colon becomes hyperactive following surgery. The post-operative inflammatory response is important in the pathophysiology of ileus, but the time course of this in humans remains unclear, with the majority of evidence coming from animal models. Future work should investigate dysmotility patterns underlying ileus, and identify biomarkers which may be used to diagnose, monitor and stratify patients with ileus.

4.
BMJ Open ; 11(7): e046313, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290065

RESUMO

INTRODUCTION: Ileus is a common and distressing condition characterised by gut dysfunction after surgery. While a number of interventions have aimed to curtail its impact on patients and healthcare systems, ileus is still an unmet challenge. Electrical stimulation of the vagus nerve is a promising new treatment due to its role in modulating the neuro-immune axis through a novel anti-inflammatory reflex. The protocol for a feasibility study of non-invasive vagus nerve stimulation (nVNS), and a programme of mechanistic and qualitative studies, is described. METHODS AND ANALYSIS: This is a participant-blinded, parallel-group, randomised, sham-controlled feasibility trial (IDEAL Stage 2b) of self-administered nVNS. One hundred forty patients planned for elective, minimally invasive, colorectal surgery will be randomised to four schedules of nVNS before and after surgery. Feasibility outcomes include assessments of recruitment and attrition, adequacy of blinding and compliance to the intervention. Clinical outcomes include bowel function and length of hospital stay. A series of mechanistic substudies exploring the impact of nVNS on inflammation and bowel motility will inform the design of the final stimulation schedule. Semistructured interviews with participants will explore experiences and perceptions of the intervention, while interviews with patients who decline participation will explore barriers to recruitment. ETHICS AND DISSEMINATION: The protocol has been approved by the Tyne and Wear South National Health Service (NHS) Research Ethics Committee (19/NE/0217) on 2 July 2019. Feasibility, mechanistic and qualitative findings will be disseminated to national and international partners through peer-reviewed publications, academic conferences, social media channels and stakeholder engagement activities. The findings will build a case for or against progression to a definitive randomised assessment as well as informing key elements of study design. TRIAL REGISTRATION NUMBER: ISRCTN62033341.


Assuntos
Cirurgia Colorretal , Íleus , Estimulação do Nervo Vago , Estudos de Viabilidade , Humanos , Íleus/etiologia , Íleus/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina Estatal , Resultado do Tratamento
5.
Drug Test Anal ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022102

RESUMO

Lysergic acid diethylamide (LSD) is a potent psychoactive substance that has attracted great interest in clinical research. As the pharmacological exploration of LSD analogs continues to grow, some of those analogs have appeared on the street market. Given that LSD analogs are uncontrolled in many jurisdictions, it is important that these analogs be differentiated from LSD. This report presents the analysis of blotters found to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA), and techniques to differentiate it from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography (GC)-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion also provided sufficient information to distinguish the three isomers on mass spectral grounds alone, where chromatographic separation proved challenging. Derivatization with 2,2,2-trifluoro-N,N-bis (trimethylsilyl)acetamide (BSTFA) also led to improved GC separation. Liquid chromatography single quadrupole mass spectrometry (LC-Q-MS) and in-source collision-induced dissociation allowed for the differentiation between MIPLA and LAMPA based on distinct m/z 239 ion ratios when co-eluting. An alternative LC-MS/MS method improved the separation between all three lysergamides, but LSD was found to co-elute with iso-LSD. However, a comparison of ion ratios recorded for transitions at m/z 324.2 > 223.2 and m/z 324.2 > 208.2 facilitated their differentiation. The analysis of two blotters by LC-Q-MS revealed the presence of 180 and 186 µg MIPLA per blotter. These procedures may be used to avoid inadvertent misidentification of MIPLA or LAMPA as LSD.

6.
Sci Total Environ ; 788: 147773, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34029806

RESUMO

The anaerobic oxidation of methane (AOM) mediated by microorganisms is a key process in the reduction of methane emissions, and AOM-coupled electron acceptors have been shown to regulate methane emissions into the atmosphere in marine systems. Paddy fields are a significant source of methane and account for 20% of global methane emissions, but the effect of electron acceptors on the methane emission process in flooded paddy fields has been poorly characterized. This study aimed to determine whether the electron acceptors ferric iron and nitrate, and biochar, acting as an electron shuttle, can regulate the AOM process in paddy soil, with or without interaction between biochar and these two electron acceptors. We also aimed to characterize which microorganisms are actively involved. Here, we added 13C-labeled CH4 (13CH4) into anaerobic microcosms to evaluate the role of electron acceptors by measuring the methane oxidation rate and the enrichment of 13C-labeled CO2 (13CO2). We then combined DNA-stable isotope probing with amplicon sequencing to study the active microorganisms. We found for the first time that, in addition to nitrate, ferric iron can also effectively promote AOM in paddy soil. However, there was no significant effect of biochar. Ferric iron-dependent AOM was mainly carried out by iron-reducing bacteria (Geobacter, Ammoniphilus and Clostridium), and nitrate-dependent AOM was mainly by nitrate-reducing bacteria (Rhodanobacter, Paenibacillus and Planococcus). Our results demonstrate that the AOM process, regulated by the electron acceptors ferric iron and nitrate, can alleviate methane emission from paddy soil. The potentially active microorganisms related to electron acceptor reduction may be crucial for this methane sink and deserve further research.


Assuntos
Metano , Microbiota , Anaerobiose , Archaea , Ferro , Nitratos , Oxirredução , Solo
7.
ACS Pharmacol Transl Sci ; 4(2): 533-542, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33860183

RESUMO

The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine), there has been little systematic investigation of the structure-activity relationships (SAR) of 4-substituted tryptamine derivatives. In addition, structural analogs of psilocybin containing a 4-acetoxy group, such as 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), have appeared as new designer drugs, but almost nothing is known about their pharmacological effects. To address the gap of information, studies were conducted with 17 tryptamines containing a variety of symmetrical and asymmetrical N,N-dialkyl substituents and either a 4-hydroxy or 4-acetoxy group. Calcium mobilization assays were conducted to assess functional activity at human and mouse 5-HT2 subtypes. Head-twitch response (HTR) studies were conducted in C57BL/6J mice to assess 5-HT2A activation in vivo. All of the compounds acted as full or partial agonists at 5-HT2 subtypes, displaying similar potencies at 5-HT2A and 5-HT2B receptors, but some tryptamines with bulkier N-alkyl groups had lower potency at 5-HT2C receptors and higher 5-HT2B receptor efficacy. In addition, O-acetylation reduced the in vitro 5-HT2A potency of 4-hydroxy-N,N-dialkyltryptamines by about 10- to 20-fold but did not alter agonist efficacy. All of the compounds induce head twitches in mice, consistent with an LSD-like behavioral profile. In contrast to the functional data, acetylation of the 4-hydroxy group had little effect on HTR potency, suggesting that O-acetylated tryptamines may be deacetylated in vivo, acting as prodrugs. In summary, the tryptamine derivatives have psilocybin-like pharmacological properties, supporting their classification as psychedelic drugs.

8.
Colorectal Dis ; 23(5): 1225-1232, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33539637

RESUMO

AIM: Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of self-administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery. METHOD: A parallel-group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self-administered bilaterally over the cervical surface landmarks for 5 days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien-Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery. RESULTS: Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7 ± 0.9 days out of 5 days in the Sham group and 4.7 ± 1.1 in the Active group. Compliance with treatment after surgery was 4.1 ± 1.1 and 4.4 ± 1.5, respectively. Participants considered the intervention to be 'acceptable' according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35 ± 1.32 vs 1.65 ± 0.88) and tolerance of solid diet (2.18 ± 2.21 vs 1.75 ± 0.91) for Sham and Active groups, respectively. CONCLUSION: This study supports the safety, treatment compliance and usability of self-administered nVNS in patients undergoing major colorectal surgery.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Íleus , Estimulação do Nervo Vago , Humanos , Íleus/etiologia , Íleus/prevenção & controle , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversos
9.
J Clin Epidemiol ; 133: 94-100, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33484839

RESUMO

OBJECTIVE: To explore the approach to participant coenrolment in publicly funded randomized controlled trials (RCTs) and to consider its impact on study recruitment. STUDY DESIGN AND SETTING: A cross-sectional study of the UK National Institute for Health Research Journals Library was undertaken. RCTs funded between 2010 and 2019 were eligible. The reporting of coenrolment criteria was assessed through inspection of publicly available study protocols. Where present, the approach to coenrolment was examined, including circumstances in which it was permitted/prohibited and the mechanism for decision-making. For completed RCTs, the impact on recruitment was explored by comparing rates of early recruitment (completion before the expected end date) and extensions (completion after the expected end date) between studies, which did and did not permit coenrolment. RESULTS: Of 219 eligible protocols, coenrolment was addressed in 94 (42.9%). Twenty-three (24.5%) of these did not allow recruitment to multiple studies, while 71 (75.5%) permitted it according to a series of caveats, including considerations of study outcomes, intervention type, and patient burden. The final decision for coenrolment rested with the local recruitment team in 57 (60.6%) and with the central organizing team in 37 (39.4%). Early completion of recruitment occurred in 8 of 64 (12.5%) RCTs where coenrolment was permitted and 5 of 20 (25.0%) where it was not (P = 0.285). An extension to recruitment time was required in 31 of 64 (48.4%) RCTs where coenrolment was permitted and 9 of 11 (45.0%) where it was not (P = 0.788). CONCLUSIONS: The reporting of coenrolment in protocols of publicly funded RCTs is infrequent, and where present, the approach to decision-making is widely variable. In this study, policies of coenrolment were not associated with gains in trial recruitment.


Assuntos
Financiamento Governamental/estatística & dados numéricos , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Projetos de Pesquisa , Reino Unido
10.
Sci Total Environ ; 762: 144118, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33360472

RESUMO

Rice straw is considered as a renewable biomass energy source and its efficient utilization is still a topic worthy of attention. Black soldier fly larvae, Hermetia illucens (L.), (Diptera: Stratiomydiae) is a kind of saprophytic insect, which can effectively digest organic wastes. Here we report that alkaline peroxide-pretreatment improves the digestion of rice straw by these larvae, especially the decomposition of cellulose, which was at 70.9% compared to 58.2% without pretreatment. After conversion, the effective conversion rates of rice straw to larvae were 10.7% and 11.4%, for raw rice straw and rice straw with pretreatment, respectively. With pretreatment the composition of larval gut microorganisms was altered where Actinomyces, Dysgonomonas, Devosia and Pelagibacterium were the dominant flora for digesting rice straw. In addition, metabolism, environmental information processing and genetic information processing were the major gut microbial functions. These findings demonstrate that chemical pretreatment for the removal of lignin and hemicellulose was an effective measure for the digestion and consumption of rice straw by black soldier fly larvae.


Assuntos
Dípteros , Microbioma Gastrointestinal , Oryza , Animais , Biomassa , Larva
11.
Colorectal Dis ; 23(4): 975-981, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33249732

RESUMO

AIM: The provision of information to patients is an important part of recovery after colorectal surgery. This study aimed to define patient information needs, barriers to effective understanding and insights into how information provision may be improved. METHOD: A patient focus group was convened. This comprised a broad, convenience sample of 11 participants from across the United Kingdom with experience of major colorectal surgery. A semistructured topic guide was used to facilitate discussion about previous experiences of information provision and how this may be improved. Data were analysed thematically and are presented as major themes. RESULTS: Overall, participants felt that their information needs are poorly prioritized by healthcare professionals. Barriers to understanding and retaining information include highly emotional situations (such as receiving bad news) and inappropriate information design (such as the use of inaccessible language). Participants expressed how information resources should: (a) address patients' individual information needs; (b) empower patients to take an active role in their recovery; (c) support patients with meaningful education and sign-posted resources; and (d) recognize patients' heightened need for information during recovery at home. CONCLUSION: This study provides key insights into the information needs of patients undergoing colorectal surgery. These should inform the development of future information resources, whose format, timing and design are currently supported by low-quality evidence.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Grupos Focais , Pessoal de Saúde , Humanos , Reino Unido
12.
Ann Surg ; 274(6): e1223-e1229, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097165

RESUMO

OBJECTIVE: To investigate the incidence of LARS in patients undergoing elective anterior resection within the MRC/NIHR ROLARR trial and to explore perioperative variables that might be associated with major LARS. SUMMARY BACKGROUND DATA: Sphincter-preserving rectal cancer surgery is frequently accompanied by defaecatory dysfunction known as Low anterior resection syndrome (LARS). This is distressing for patients and is an unmet clinical challenge. METHODS: An international, retrospective cohort study of patients undergoing anterior resection within the ROLARR trial was undertaken. Trial participants with restoration of gastrointestinal continuity and free from disease recurrence completed the validated LARS questionnaire between August 2015 and April 2017. The primary outcome was the incidence of LARS and secondary outcome was severity (minor versus major). RESULTS: LARS questionnaires were received from 132/155 (85%) eligible patients. The median time from surgery to LARS assessment was 1065 days (range 174-1655 d). The incidence of LARS was 82.6% (n = 109/132), which was minor in 26/132 (19.7%) and major in 83/132 (62.9%). The most common symptoms were incontinence to flatus (n = 86/132; 65.2%) and defaecatory clustering (88/132; 66.7%). In a multivariate model, predictors of major LARS were: 1 cm decrease in tumor height above the anal verge (OR = 1.290, 95% CI: 1.101,1.511); and an ASA grade greater than 1 (OR = 2.920, 95% CI: 1.239, 6.883). Treatment allocation (laparoscopic vs robotic) did not predict major LARS. CONCLUSIONS: LARS is a common after rectal cancer surgery and patients should be appropriately counselled preoperatively, particularly before surgery for low tumors or in comorbid populations.

13.
BMJ Open Respir Res ; 7(1)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32928787

RESUMO

The SARS-CoV-2 can lead to severe illness with COVID-19. Outcomes of patients requiring mechanical ventilation are poor. Awake proning in COVID-19 improves oxygenation, but on data clinical outcomes is limited. This single-centre retrospective study aimed to assess whether successful awake proning of patients with COVID-19, requiring respiratory support (continuous positive airways pressure (CPAP) or high-flow nasal oxygen (HFNO)) on a respiratory high-dependency unit (HDU), is associated with improved outcomes. HDU care included awake proning by respiratory physiotherapists. Of 565 patients admitted with COVID-19, 71 (12.6%) were managed on the respiratory HDU, with 48 of these (67.6%) requiring respiratory support. Patients managed with CPAP alone 22/48 (45.8%) were significantly less likely to die than patients who required transfer onto HFNO 26/48 (54.2%): CPAP mortality 36.4%; HFNO mortality 69.2%, (p=0.023); however, multivariate analysis demonstrated that increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. The mortality of patients with COVID-19 requiring respiratory support is considerable. Data from our cohort managed on HDU show that CPAP and awake proning are possible in a selected population of COVID-19, and may be useful. Further prospective studies are required.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Infecções por Coronavirus/terapia , Oxigenoterapia/métodos , Posicionamento do Paciente/métodos , Pneumonia Viral/terapia , Decúbito Ventral , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva/métodos , Razão de Chances , Pandemias , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , Reino Unido , Vigília
14.
Environ Pollut ; 265(Pt A): 115106, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806403

RESUMO

The conversion of natural forests to tea plantations largely affects soil nitrous oxide (N2O) emissions and soil microbial communities. However, the impacts of this conversion on the contribution of fungi to N2O emission and on fungal community structure remain unclear. In this study, we determined the soil N2O emission rate, N2O production by fungi, associated fungal community diversity, and related ecological factors in chronological changes of tea crop systems (3, 36 and 105 years old tea orchards named T3, T36 and T105, respectively), and in an adjacent soil from a natural forest. The results indicate that the tea plantations significantly enhanced soil N2O production compared with the forest soil. Tea plantations significantly decreased soil pH and C/N ratio, but increased soil inorganic nitrogen (N). Furthermore, they increased the fungal contribution to the production of soil N2O, but decreased the bacterial counterpart. We also observed that fungal community and functional composition differed distinctly between tea plantations and forest. Additionally, most of the fungal groups in high N2O emission soils (T36 and T105) were identified as the genus Fusarium, which were positively correlated with soil N2O emissions. The variation in N2O emission response could be well explained by NO3--N, soil organic carbon (SOC), C/N, and Fusarium, which contributed to up to 97% of the observed variance. Altogether, these findings provide significant direct evidence that the increase of soil N2O emissions and fungal communities be attributed to the conversion of natural forest to tea plantations.


Assuntos
Micobioma , Carbono/análise , Florestas , Fungos , Solo , Microbiologia do Solo , Chá
15.
Learn Publ ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32836910

RESUMO

This study explores the response to COVID-19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross-sectional bibliometric review of COVID-19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission-to-acceptance time and availability of original data. Publisher-responsiveness was assessed by measuring the acceptance-to-publication time and the provision of open access. Three hundred and ninety-eight of 2,835 COVID-19 and 55 of 1,513 MERS search results were eligible. Most COVID-19 studies were clinical reports (n = 242; 60.8%). The submission-to-acceptance [median: 5 days (IQR: 3-11) versus 71.5 days (38-106); P < .001] and acceptance-to-publication [median: 5 days (IQR: 2-8) versus 22.5 days (4-48·5-; P < .001] times were strikingly shorter for COVID-19. Almost all COVID-19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open-access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID-19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one-in-four were published alongside original data, which is a key target for improvement.

16.
Int J Mycobacteriol ; 9(1): 48-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474488

RESUMO

Background: Treatment of Mycobacterium abscessus pulmonary disease (PD) is challenging with frequent side effects and uncertain rates of success. Methods: We performed a retrospective review of all patients at our center with at least one respiratory sample positive for M. abscessus between 2014 and 2019. Electronic health records were reviewed to determine factors associated with M. abscessus infection and clinical outcomes. Results: Thirty-seven patients were identified including 24 with cystic fibrosis (CF), 10 with bronchiectasis, two with chronic obstructive PD (COPD), and one with asthma. American Thoracic Society/Infectious Diseases Society of America criteria for nontuberculous mycobacteria PD were met in 21/37 (56.8%) of cases. Evidence of Aspergillus lung disease was noted in 18 (75.0%) CF patients compared with 3 (23.1%) non-CF patients (P = 0.005). Induction therapy for M. abscessus was given to 22/37 (59.5%) patients (18/24 [75%] with CF and 4/13 [30.8%] without CF). Median duration of induction therapy was 6 weeks (range 3-12). Maintenance antibiotic therapy was prescribed to 17/22 (77.3%) of treated patients. Culture conversion was seen in 15/24 (62.5%) of CF patients compared with 3/13 (23.1%) in the non-CF group (P = 0.034). Culture conversion occurred in 10/22 (45.5%) of treated patients compared with 8/15 (53.3%) untreated patients. Three patients (8.1%) died during follow-up: one with CF and two with COPD. Conclusions: Culture conversion following isolation of M. abscessus from respiratory samples not only is more common in CF than in patients without CF but also frequently occurs spontaneously in both groups. Targeted treatment for M. abscessus did not clearly impact rates of culture conversion.


Assuntos
Antibacterianos/uso terapêutico , Pulmão/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/mortalidade , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/patogenicidade , Estudos Retrospectivos , Escarro/microbiologia , Resultado do Tratamento , Adulto Jovem
17.
Environ Int ; 142: 105834, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540627

RESUMO

As a saprophytic insect, the black soldier fly can digest organic waste efficiently in an environmentally friendly way. However, the ability and efficiency of this insect, and the microbial mechanisms involved, in the degradation of antibiotics are largely uncharacterized. To obtain further details during the degradation of OTC (oxytetracycline) by black soldier fly larvae (larvae), the changes in intestinal bacterial communities were examined. Both ARGs (antibiotic resistance genes) and MGEs (mobile genetic elements) were found within the larval guts. At the end of the degradation period, 82.7%, 77.6% and 69.3% of OTC was degraded by larvae when the initial concentrations were 100, 1000 and 2000 mg kg-1 (dry weight), respectively, which was much higher than the degradation efficiencies (19.3-22.2%) without larvae. There was no obvious effect of OTC on the development of the larvae. Although the larval gut microorganisms were affected by OTC, they adapted to the altered environment. Enterococcus, Ignatzschineria, Providencia, Morganella, Paenalcaligenes and Actinomyces in the gut responded strongly to antibiotic exposure. Interestingly, numerous ARGs (specifically, 180 ARGs and 10 MGEs) were discovered, and significantly correlated with those of both integron-integrase gene and transposases in the larval gut. Of all the detected ARGs, tetracycline resistance genes expressed at relatively high levels and accounted for up to 67% of the total ARGs. In particular, Enterococcus, Ignatzschineria, Bordetella, Providencia and Proteus were all hosts of enzymatic modification genes of tetracycline in the guts that enabled effective degradation of OTC. These findings demonstrate that OTC can be degraded effectively and prove that the bioremediation of antibiotic contamination is enhanced by larvae. In addition, the abundance of ARGs and MGEs formed should receive attention and be considered in environmental health risk assessment systems.


Assuntos
Microbioma Gastrointestinal , Simuliidae , Animais , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Microbioma Gastrointestinal/genética , Genes Bacterianos , Incidência , Larva , Simuliidae/genética
18.
Int J Numer Method Biomed Eng ; 36(3): e3315, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32031302

RESUMO

The subtle relationship between vascular network structure and mass transport is vital to predict and improve the efficacy of anticancer treatments. Here, mathematical homogenisation is used to derive a new multiscale continuum model of blood and chemotherapy transport in the vasculature and interstitium of a vascular tumour. This framework enables information at a range of vascular hierarchies to be fed into an effective description on the length scale of the tumour. The model behaviour is explored through a demonstrative case study of a simplified representation of a dorsal skinfold chamber, to examine the role of vascular network architecture in influencing fluid and drug perfusion on the length scale of the chamber. A single parameter, P, is identified that relates tumour-scale fluid perfusion to the permeability and density of the capillary bed. By fixing the topological and physiological properties of the arteriole and venule networks, an optimal value for P is identified, which maximises tumour fluid transport and is thus hypothesised to benefit chemotherapy delivery. We calculate the values for P for eight explicit network structures; in each case, vascular intervention by either decreasing the permeability or increasing the density of the capillary network would increase fluid perfusion through the cancerous tissue. Chemotherapeutic strategies are compared and indicate that single injection is consistently more successful compared with constant perfusion, and the model predicts optimal timing of a second dose. These results highlight the potential of computational modelling to elucidate the link between vascular architecture and fluid, drug distribution in tumours.


Assuntos
Tratamento Farmacológico/métodos , Modelos Teóricos , Simulação por Computador , Humanos , Neoplasias Vasculares
19.
Genes Immun ; 21(1): 63-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462703

RESUMO

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.


Assuntos
Antígenos HLA/genética , Cadeias alfa de HLA-DQ/genética , Infecções Estreptocócicas/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genes MHC da Classe II , Predisposição Genética para Doença/genética , Antígenos HLA/imunologia , Cadeias alfa de HLA-DQ/metabolismo , Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade
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