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1.
Metab Eng ; 83: 193-205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631458

RESUMO

Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and Clostridium thermocellum is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by C. thermocellum is approached with co-cultures, because C. thermocellum does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered C. thermocellum to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different ß-xylosidase enzymes originating from Thermoanaerobacterium saccharolyticum into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the ß-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported C. thermocellum strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.


Assuntos
Clostridium thermocellum , Engenharia Metabólica , Polissacarídeos , Clostridium thermocellum/metabolismo , Clostridium thermocellum/genética , Polissacarídeos/metabolismo , Polissacarídeos/genética , Xilose/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Celulose/metabolismo , Xilosidases/metabolismo , Xilosidases/genética
2.
PNAS Nexus ; 2(3): pgad066, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37007711

RESUMO

Natural thermal geysers are hot springs that periodically erupt liquid water, steam, and gas. They are found in only a few locations worldwide, with nearly half located in Yellowstone National Park (YNP). Old Faithful geyser (OFG) is the most iconic in YNP and attracts millions of visitors annually. Despite extensive geophysical and hydrological study of geysers, including OFG, far less is known of the microbiology of geysed waters. Here, we report geochemical and microbiological data from geysed vent water and vent water that collects in a splash pool adjacent to OFG during eruptions. Both waters contained microbial cells, and radiotracer studies showed that they fixed carbon dioxide (CO2) when incubated at 70°C and 90°C. Shorter lag times in CO2 fixation activity were observed in vent and splash pool waters incubated at 90°C than 70°C, suggesting cells are better adapted or acclimated to temperatures like those in the OFG vent (∼92-93°C). 16S rDNA and metagenomic sequence data indicated that both communities are dominated by the autotroph Thermocrinis, which likely fuels productivity through the aerobic oxidation of sulfide/thiosulfate in erupted waters or steam. Dominant OFG populations, including Thermocrinis and subdominant Thermus and Pyrobaculum strains, exhibited high-strain level genomic diversity (putative ecotypes) relative to populations from nongeysing YNP hot springs that is attributed to the temporal chemical and temperature dynamics caused by eruptions. These findings show that OFG is habitable and that its eruption dynamics promote genomic diversity, while highlighting the need to further research the extent of life in geyser systems such as OFG.

3.
FEMS Microbiol Ecol ; 99(1)2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36565717

RESUMO

The influence of mineralogy on the assembly of microbial communities in glacial environments has been difficult to assess due to complications in isolating mineralogy from other variables. Here we assess the abundance and composition of microbial communities that colonized defined minerals incubated for 12 months in two meltwater streams (N and S) emanating from Kaldalónsjökull (Kal), a basalt-hosted glacier in Iceland. The two streams shared similar meltwater geochemistry as well as bedrock and proglacial sediment elemental compositions. Yet genomic DNA and PCR-amplifiable 16S rRNA genes were detected only in Kal S. The amount of recoverable DNA was highest for hematite incubated in Kal S and the composition of 16S rRNA genes recovered from Kal S sediments was most like those recovered from hematite and magnetite, an effect driven largely by similarities in the relative abundance of the putative hydrogenotrophic iron reducer Rhodoferax. We suggest this is attributable to comminution and weathering reactions involving exposed iron silicate minerals that generate and release hydrogen and Fe(III) that can be coupled to support microbial metabolism in Kaldalónsjökull, and possibly other basaltic habitats. The low abundance of cells in Kal N could be due to low availability of Fe(III) or another substrate.


Assuntos
Ferro , Microbiota , Ferro/metabolismo , Compostos Férricos/metabolismo , RNA Ribossômico 16S/genética , Minerais/metabolismo , Silicatos
4.
Nat Commun ; 13(1): 3773, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773279

RESUMO

Trace metals have been an important ingredient for life throughout Earth's history. Here, we describe the genome-guided cultivation of a member of the elusive archaeal lineage Caldarchaeales (syn. Aigarchaeota), Wolframiiraptor gerlachensis, and its growth dependence on tungsten. A metagenome-assembled genome (MAG) of W. gerlachensis encodes putative tungsten membrane transport systems, as well as pathways for anaerobic oxidation of sugars probably mediated by tungsten-dependent ferredoxin oxidoreductases that are expressed during growth. Catalyzed reporter deposition-fluorescence in-situ hybridization (CARD-FISH) and nanoscale secondary ion mass spectrometry (nanoSIMS) show that W. gerlachensis preferentially assimilates xylose. Phylogenetic analyses of 78 high-quality Wolframiiraptoraceae MAGs from terrestrial and marine hydrothermal systems suggest that tungsten-associated enzymes were present in the last common ancestor of extant Wolframiiraptoraceae. Our observations imply a crucial role for tungsten-dependent metabolism in the origin and evolution of this lineage, and hint at a relic metabolic dependence on this trace metal in early anaerobic thermophiles.


Assuntos
Archaea , Tungstênio , Anaerobiose , Archaea/metabolismo , Metagenoma , Filogenia
5.
Appl Environ Microbiol ; 87(23): e0159821, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34586901

RESUMO

Little is known of how the confluence of subsurface and surface processes influences the assembly and habitability of hydrothermal ecosystems. To address this knowledge gap, the geochemical and microbial composition of a high-temperature, circumneutral hot spring in Yellowstone National Park was examined to identify the sources of solutes and their effect on the ecology of microbial inhabitants. Metagenomic analysis showed that populations comprising planktonic and sediment communities are archaeal dominated, are dependent on chemical energy (chemosynthetic), share little overlap in their taxonomic composition, and are differentiated by their inferred use of/tolerance to oxygen and mode of carbon metabolism. The planktonic community is dominated by putative aerobic/aerotolerant autotrophs, while the taxonomic composition of the sediment community is more evenly distributed and comprised of anaerobic heterotrophs. These observations are interpreted to reflect sourcing of the spring by anoxic, organic carbon-limited subsurface hydrothermal fluids and ingassing of atmospheric oxygen that selects for aerobic/aerotolerant organisms that have autotrophic capabilities in the water column. Autotrophy and consumption of oxygen by the planktonic community may influence the assembly of the anaerobic and heterotrophic sediment community. Support for this inference comes from higher estimated rates of genome replication in planktonic populations than sediment populations, indicating faster growth in planktonic populations. Collectively, these observations provide new insight into how mixing of subsurface waters and atmospheric oxygen create dichotomy in the ecology of hot spring communities and suggest that planktonic and sediment communities may have been less differentiated taxonomically and functionally prior to the rise of oxygen at ∼2.4 billion years ago (Gya). IMPORTANCE Understanding the source and availability of energy capable of supporting life in hydrothermal environments is central to predicting the ecology of microbial life on early Earth when volcanic activity was more widespread. Little is known of the substrates supporting microbial life in circumneutral to alkaline springs, despite their relevance to early Earth habitats. Using metagenomic and informatics approaches, water column and sediment habitats in a representative circumneutral hot spring in Yellowstone were shown to be dichotomous, with the former largely hosting aerobic/aerotolerant autotrophs and the latter primarily hosting anaerobic heterotrophs. This dichotomy is attributed to influx of atmospheric oxygen into anoxic deep hydrothermal spring waters. These results indicate that the ecology of microorganisms in circumneutral alkaline springs sourced by deep hydrothermal fluids was different prior to the rise of atmospheric oxygen ∼2.4 Gya, with planktonic and sediment communities likely to be less differentiated than contemporary circumneutral hot springs.


Assuntos
Atmosfera , Fontes Termais , Microbiota , Carbono , Fontes Termais/microbiologia , Metagenômica , Oxigênio , Wyoming
6.
J Vet Intern Med ; 34(6): 2232-2241, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32945575

RESUMO

BACKGROUND: Triple therapy (TT) consisting of furosemide, pimobendan, and an angiotensin-converting enzyme inhibitor (ACEI) frequently is recommended for the treatment of congestive heart failure (CHF) attributable to myxomatous mitral valve disease (MMVD). However, the effect of adding an ACEI to the combination of pimobendan and furosemide (dual therapy [DT]) so far has not been evaluated prospectively. HYPOTHESIS: Triple therapy will extend survival time compared to DT in dogs with CHF secondary to MMVD. ANIMALS: Client-owned dogs presented with the first episode of CHF caused by MMVD. METHODS: Prospective, single-blinded, randomized multicenter study. One-hundred and fifty-eight dogs were recruited and prospectively randomized to receive either DT (furosemide and pimobendan) or TT (furosemide, pimobendan, and ramipril). The primary endpoint was a composite of cardiac death, euthanasia for heart failure, or treatment failure. RESULTS: Seventy-seven dogs were randomized to receive DT and 79 to receive TT. Two dogs were excluded from analysis. The primary endpoint was reached by 136 dogs (87%; 66 dogs, DT; 70 dogs, TT). Median time to reach the primary endpoint for all dogs in the study was 214 days (95% confidence interval [CI], 168-259 days). Median time to reach the primary endpoint was not significantly different between the DT group (227 days; interquartile range [IQR], 103-636 days) compared with TT group (186 days; IQR, 72-453 days; P = .42). CONCLUSIONS AND CLINICAL IMPORTANCE: Addition of the ACEI ramipril to pimobendan and furosemide did not have any beneficial effect on survival time in dogs with CHF secondary to MMVD.


Assuntos
Doenças do Cão , Insuficiência Cardíaca , Animais , Doenças do Cão/tratamento farmacológico , Cães , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Valva Mitral , Estudos Prospectivos , Piridazinas , Ramipril/uso terapêutico
7.
Biotechnol Bioeng ; 117(12): 3799-3808, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32770740

RESUMO

The production of volatile industrial chemicals utilizing metabolically engineered extreme thermophiles offers the potential for processes with simultaneous fermentation and product separation. An excellent target chemical for such a process is acetone (Tb = 56°C), ideally produced from lignocellulosic biomass. Caldicellulosiruptor bescii (Topt 78°C), an extremely thermophilic fermentative bacterium naturally capable of deconstructing and fermenting lignocellulose, was metabolically engineered to produce acetone. When the acetone pathway construct was integrated into a parent strain containing the bifunctional alcohol dehydrogenase from Clostridium thermocellum, acetone was produced at 9.1 mM (0.53 g/L), in addition to minimal ethanol 3.3 mM (0.15 g/L), along with net acetate consumption. This demonstrates that C. bescii can be engineered with balanced pathways in which renewable carbohydrate sources are converted to useful metabolites, primarily acetone and H2 , without net production of its native fermentation products, acetate and lactate.


Assuntos
Acetona/metabolismo , Biomassa , Caldicellulosiruptor/metabolismo , Hidrogênio/metabolismo , Lignina/metabolismo , Engenharia Metabólica , Caldicellulosiruptor/genética
8.
J Exp Med ; 217(10)2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32609329

RESUMO

The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function.


Assuntos
Diversidade de Anticorpos , Linfócitos B/metabolismo , Genes de Imunoglobulinas/genética , Animais , Linfócitos B/imunologia , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Morte Celular , Diferenciação Celular , Linhagem Celular , Feminino , Imunofluorescência , Edição de Genes , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
9.
Extremophiles ; 24(4): 511-518, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32415359

RESUMO

The key difference in the modified Embden-Meyerhof glycolytic pathway in hyperthermophilic Archaea, such as Pyrococcus furiosus, occurs at the conversion from glyceraldehyde-3-phosphate (GAP) to 3-phosphoglycerate (3-PG) where the typical intermediate 1,3-bisphosphoglycerate (1,3-BPG) is not present. The absence of the ATP-yielding step catalyzed by phosphoglycerate kinase (PGK) alters energy yield, redox energetics, and kinetics of carbohydrate metabolism. Either of the two enzymes, ferredoxin-dependent glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR) or NADP+-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), responsible for this "bypass" reaction, could be deleted individually without impacting viability, albeit with differences in native fermentation product profiles. Furthermore, P. furiosus was viable in the gluconeogenic direction (growth on pyruvate or peptides plus elemental sulfur) in a ΔgapnΔgapor strain. Ethanol was utilized as a proxy for potential heterologous products (e.g., isopropanol, butanol, fatty acids) that require reducing equivalents (e.g., NAD(P)H, reduced ferredoxin) generated from glycolysis. Insertion of a single gene encoding the thermostable NADPH-dependent primary alcohol dehydrogenase (adhA) (Tte_0696) from Caldanaerobacter subterraneus, resulted in a strain producing ethanol via the previously established aldehyde oxidoreductase (AOR) pathway. This strain demonstrated a high ratio of ethanol over acetate (> 8:1) at 80 °C and enabled ethanol production up to 85 °C, the highest temperature for bio-ethanol production reported to date.


Assuntos
Pyrococcus furiosus , Fermentação , Gliceraldeído 3-Fosfato , Glicólise , Engenharia Metabólica
10.
Appl Environ Microbiol ; 86(10)2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32198176

RESUMO

Microbial mat communities are associated with extensive (∼700 km2) and morphologically variable carbonate structures, termed microbialites, in the hypersaline Great Salt Lake (GSL), Utah. However, whether the composition of GSL mat communities covaries with microbialite morphology and lake environment is unknown. Moreover, the potential adaptations that allow the establishment of these extensive mat communities at high salinity (14% to 17% total salts) are poorly understood. To address these questions, microbial mats were sampled from seven locations in the south arm of GSL representing different lake environments and microbialite morphologies. Despite the morphological differences, microbialite-associated mats were taxonomically similar and were dominated by the cyanobacterium Euhalothece and several heterotrophic bacteria. Metagenomic sequencing of a representative mat revealed Euhalothece and subdominant Thiohalocapsa populations that harbor the Calvin cycle and nitrogenase, suggesting they supply fixed carbon and nitrogen to heterotrophic bacteria. Fifteen of the next sixteen most abundant taxa are inferred to be aerobic heterotrophs and, surprisingly, harbor reaction center, rhodopsin, and/or bacteriochlorophyll biosynthesis proteins, suggesting aerobic photoheterotrophic (APH) capabilities. Importantly, proteins involved in APH are enriched in the GSL community relative to that in microbialite mat communities from lower salinity environments. These findings indicate that the ability to integrate light into energy metabolism is a key adaptation allowing for robust mat development in the hypersaline GSL.IMPORTANCE The earliest evidence of life on Earth is from organosedimentary structures, termed microbialites, preserved in 3.481-billion-year-old (Ga) rocks. Phototrophic microbial mats form in association with an ∼700-km2 expanse of morphologically diverse microbialites in the hypersaline Great Salt Lake (GSL), Utah. Here, we show taxonomically similar microbial mat communities are associated with morphologically diverse microbialites across the lake. Metagenomic sequencing reveals an abundance and diversity of autotrophic and heterotrophic taxa capable of harvesting light energy to drive metabolism. The unexpected abundance of and diversity in the mechanisms of harvesting light energy observed in GSL mat populations likely function to minimize niche overlap among coinhabiting taxa, provide a mechanism(s) to increase energy yield and osmotic balance during salt stress, and enhance fitness. Together, these physiological benefits promote the formation of robust mats that, in turn, influence the formation of morphologically diverse microbialite structures that can be imprinted in the rock record.


Assuntos
Bactérias/classificação , Fenômenos Fisiológicos Bacterianos , Lagos/microbiologia , Microbiota , Cianobactérias/classificação , Cianobactérias/fisiologia , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Salinidade , Utah
11.
Z Orthop Unfall ; 158(6): 625-629, 2020 Dec.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-31556077

RESUMO

BACKGROUND: Today, nearly two thirds of inpatients in trauma surgery hospitals are over 70 years old and at significant risk for comorbidities. These patients frequently suffer delirium. Delirium occurs in 15 - 30% of these trauma patients and increases the risk of mortality in up to 15 - 25% of cases. Conversation, attention, and activity significantly reduce this risk. OBJECTIVES: Thus, the Centre for Geriatric Traumatology and the District Seniors Council have initiated a new project of a visiting service, to prevent delirium and anxiety conditions in elderly inpatients. Volunteers from the welfare program offer daily care for selected patients. METHODS: They care for and interact with the patients for approximately one hour per day. They accompany the patients in the hospital and during mobilization, explain, read aloud, converse, or simply listen, and thus provide calm, support, and company. The attendants are volunteers who have been previously trained by the clinic, who regularly attend team meetings and draw up reports from each admission. All patients and relatives are informed prior to these visits and are notified with an accompanying letter. There are structured visiting plans for each week. RESULTS: From July 17 to May 19, 4031 patients in our clinic and in three other hospitals have been accompanied in the program. None of the patients suffered delirium. The patients and attendants found the care very good and personally satisfying. Evaluations of the volunteers for the success of their work, using the German school-grading system, was an average 1.3. Noticeable was the markedly reduced frequency of patient calls to nursing, who were thus relieved. Travel expenses and insurance costs for the volunteers were reimbursed. CONCLUSION: In times of skilled labour shortages, patient support provided by volunteer patient attendants enables innovative care for patients at risk for delirium. The assistance of the attendants alone reduced the workload on the nursing staff.


Assuntos
Delírio , Delírio/prevenção & controle , Hospitalização , Humanos , Seguridade Social , Traumatologia , Carga de Trabalho
12.
Environ Microbiol ; 21(10): 3696-3710, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31188531

RESUMO

Species in the archaeal order Sulfolobales thrive in hot acid and exhibit remarkable metabolic diversity. Some species are chemolithoautotrophic, obtaining energy through the oxidation of inorganic substrates, sulphur in particular, and acquiring carbon through the 3-hydroxypropionate/4-hydroxybutyrate (3-HP/4-HB) CO2 -fixation cycle. The current model for sulphur oxidation in the Sulfolobales is based on the biochemical analysis of specific proteins from Acidianus ambivalens, including sulphur oxygenase reductase (SOR) that disproportionates S° into H2 S and sulphite (SO3 2- ). Initial studies indicated SOR catalyses the essential first step in oxidation of elemental sulphur, but an ancillary role for SOR as a 'recycle' enzyme has also been proposed. Here, heterologous expression of both SOR and membrane-bound thiosulphate-quinone oxidoreductase (TQO) from Sulfolobus tokodaii 'restored' sulphur oxidation capacity in Sulfolobus acidocaldarius DSM639, but not autotrophy, although earlier reports indicate this strain was once capable of chemolithoautotrophy. Comparative transcriptomic analyses of Acidianus brierleyi, a chemolithoautotrophic sulphur oxidizer, and S. acidocaldarius DSM639 showed that while both share a strong transcriptional response to elemental sulphur, S. acidocaldarius DSM639 failed to upregulate key 3-HP/4-HB cycle genes used by A. brierleyi to drive chemolithoautotrophy. Thus, the inability for S. acidocaldarius DSM639 to grow chemolithoautotrophically may be rooted more in gene regulation than the biochemical capacity.


Assuntos
Crescimento Quimioautotrófico , Sulfolobales/metabolismo , Enxofre/metabolismo , Processos Autotróficos , Oxirredução , Oxirredutases/metabolismo , Tiossulfatos/metabolismo
13.
Mol Cell ; 72(4): 636-649.e8, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30293785

RESUMO

Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super-enhancer, 3' regulatory region (3'RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here, we identify the chromatin reader ZMYND8 as an essential regulator of the 3'RR. In B cells, ZMYND8 binds promoters and super-enhancers, including the Igh enhancers. ZMYND8 controls the 3'RR activity by modulating the enhancer transcriptional status. In its absence, there is increased 3'RR polymerase loading and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3'RR. Thus, ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3' Igh super-enhancer.


Assuntos
Montagem e Desmontagem da Cromatina/genética , Switching de Imunoglobulina/genética , Cadeias Pesadas de Imunoglobulinas/genética , Proteínas Supressoras de Tumor/genética , Animais , Linfócitos B , Linhagem Celular , Cromatina/genética , Cromatina/metabolismo , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , DNA/genética , Elementos Facilitadores Genéticos , Rearranjo Gênico , Humanos , Domínios MYND , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Nucleico , Hipermutação Somática de Imunoglobulina/genética , Proteínas Supressoras de Tumor/metabolismo
14.
MDM Policy Pract ; 3(2): 2381468318801565, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349874

RESUMO

Background. A preference-based quality-of-life index for non-small cell lung cancer was developed with a subset of Functional Assessment of Cancer Therapy (FACT)-General (G) and FACT-Lung (L) items, based on clinician input and the literature. Design. A total of 236 non-small cell lung carcinoma patients contributed their preferences, randomly allocated among three survey groups to decrease burden. The FACT-L Utility Index (FACT-LUI) was constructed with two methods: 1) multiattribute utility theory (MAUT), where a visual analog scale (VAS)-based index was transformed to standard gamble (SG); and 2) an unweighted index, where items were summed, normalized to a 0 to 1.0 scale, and the result transformed to a scale length equivalent to the VAS or SG MAUT-based model on a Dead to Full Health scale. Agreement between patients' direct utility and the indexes for current health was assessed. Results. The agreement of the unweighted index with direct SG was superior to the MAUT-based index (intraclass correlation for absolute agreement: 0.60 v. 0.35; mean difference: 0.03 v. 0.19; and mean absolute difference 0.09 v. 0.21, respectively). Mountain plots showed substantial differences, with the unweighted index demonstrating a median bias of 0.02 versus the MAUT model at 0.2. There was a significant difference (P = 0.0002) between early (I-II) and late stage (III-IV) patients, the mean difference for both indexes being greater than distribution-based estimates of minimal important difference. Limitations. The population was limited to non-small cell lung cancer patients. However, most quality-of-life literature consulted and the FACT instruments do not differentiate between lung cancer cell types. Minorities were also limited in this sample. Conclusions. The FACT-LUI shows early evidence of validity for informing economic analysis of lung cancer treatments.

15.
Chemistry ; 24(42): 10756-10765, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29691932

RESUMO

Herein we report general methods allowing the synthesis of various perfluoroalkylated corannulenes with a specific substitution pattern. Variable temperature NMR spectroscopic investigations revealed dynamic behavior which was analyzed by line shape analysis. The activation parameters of these dynamic processes were determined. For a tetrasubstituted compound it was possible to observe through space scalar coupling. The packing motifs were elucidated by X-ray crystallography, showing that the substitution pattern as well as the size of substituents strongly influence intermolecular π-stacking. The reduction potentials of the perfluoroalkylated compounds were determined by cyclic voltammetry.

16.
J Cancer Res Clin Oncol ; 144(3): 579-586, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29305709

RESUMO

PURPOSE: Physical activity can impact the immune system in different ways, e.g. by alteration of the humoral and cellular immune response. Physical activity at medium intensity enhances numbers of cytotoxic T cells, NK cells and macrophages in healthy people. The aim of this study was to compare the effects of endurance and resistance training on the immune system in breast cancer patients during adjuvant chemotherapy. METHODS: In a prospective, controlled and randomized intervention exploratory trial, 12-week supervised endurance or resistance training were compared with usual care twice a week. Endpoints were the absolute numbers of the immune cells such as CD3+ T lymphocytes including CD4+- and CD8+, αß T cells, γδT cells, CD3-/CD16+/56+ NK cells and CD19+ B cells, before and after 12 weeks of treatment. Cell numbers were analyzed using fluorescence-activated cell sorting. RESULTS: Despite different physical interventions in all groups immune cell count decreased in CD3 T cells including TCR αß and CD4 T cells, NK cells and CD19 B cells 12 weeks after initiation of chemotherapy and start of the physical intervention program, while the reduction of γδ T cells and CD8 T cells is less prominent in the RT and UC group. CONCLUSION: Chemotherapy led to a decrease in nearly all measured immune cells. In this study, physical intervention with endurance or resistance training did not suppress cellular immunity any further. Larger multicenter trials are needed to evaluate the exact impact of sports intervention on immune cell subpopulations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Imunidade Celular/fisiologia , Adulto , Idoso , Linfócitos B/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Células Matadoras Naturais/patologia , Contagem de Linfócitos , Pessoa de Meia-Idade , Resistência Física , Treinamento Resistido , Linfócitos T Citotóxicos/patologia
17.
Clin J Oncol Nurs ; 21(3 Suppl): 31-53, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28524906

RESUMO

BACKGROUND: Chronic and refractory cancer pain are significant issues and can increase patient suffering and compromise quality of life. A variety of evidence-based pharmacologic strategies can be used routinely to control cancer pain. 
. OBJECTIVES: The purpose of this study is to conduct a systematic review of the pharmacologic evidence in the management of chronic and refractory cancer pain. 
. METHODS: The Oncology Nursing Society's Putting Evidence Into Practice pain team conducted a search of 184 systematic reviews, meta-analyses, research studies, and guidelines and classified the evidence into weight-of-evidence categories. 
. FINDINGS: Opioids are the mainstay of cancer pain management, but evidence supports the use of coanalgesics and adjuvants to improve overall pain management. Complementary pharmacologic strategies, such as caffeine and herbal preparations, are under investigation, but additional research is needed to recommend these modalities.
.


Assuntos
Analgésicos Opioides/uso terapêutico , Analgésicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Medicina Baseada em Evidências/métodos , Enfermagem Oncológica/métodos , Dor Intratável/tratamento farmacológico , Educação Continuada em Enfermagem , Humanos , Manejo da Dor/métodos
18.
J Am Coll Radiol ; 14(2): 274-281, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27927589

RESUMO

PURPOSE: The Radiology Process Model (RPM) was previously described in terms of its conceptual basis and proposed survey items. The current study describes the first pilot application of the RPM in the field and the results of initial psychometric analysis. METHODS: We used an Institutional Review Board-approved pilot RPM survey in 100 patients having outpatient interventional radiology procedures. The 24 survey items had 4 or 5 levels of severity. We assessed for missing data, items that patients found confusing, any suggestions by patients for additional items and clarity of items from patient feedback. Factor analysis was performed and internal consistency measured. Construct validity was assessed by correlation of patient responses to the items as a summated scale with a visual analog scale (VAS) they completed indicating their interventional radiology experience. RESULTS: The visual analog scale and the RPM summated scale were strongly correlated (r = 0.7). Factor analysis showed four factors: interactions with facility and doctors/staff, time-sensitive aspects, pain, and anxiety. The items showed high internal consistency (alpha: 0.86) as a group and approximately 0.7 to 0.9 by the factors. Analysis shows that two items could be deleted (cost and communication between radiologist and referrers). Revision of two items and potential addition of others are discussed. CONCLUSIONS: The RPM shows initial evidence of psychometric validity and internal consistency reliability. Minor changes are anticipated before wider use.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Dor/psicologia , Satisfação do Paciente/estatística & dados numéricos , Assistência Centrada no Paciente/estatística & dados numéricos , Qualidade de Vida/psicologia , Radiografia Intervencionista/psicologia , Radiografia Intervencionista/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Boston/epidemiologia , Simulação por Computador , Feminino , Pesquisas sobre Atenção à Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Dor/diagnóstico , Dor/epidemiologia , Projetos Piloto , Avaliação de Processos em Cuidados de Saúde/métodos , Psicometria/métodos , Radiologia/organização & administração
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