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1.
Z Orthop Unfall ; 2024 Oct 02.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-39357846

RESUMO

The aim of this study was to develop a simple and reliable score which supports decision making between non-operative and operative treatment in patients with osteoporotic pelvic fractures.Between 2018 to 2020, the OF Pelvis Score was developed during a total of 5 meetings of the Working Group on Osteoporotic Fractures of the Spine Section of the German Society of Orthopaedics and Trauma. The OF Pelvis Score as a decision aid between non-surgical and surgical treatment was developed by expert consensus after analysis of numerous geriatric sacral and pelvic ring fractures from several hospitals. Subsequently, retrospective evaluation of the score was performed on consecutive patients from three hospitals.The following parameters were considered relevant to decision making between non-surgical and surgical treatment and were incorporated into the score: fracture morphology using the OF Pelvis Classification, pain status, level of mobilisation, fracture-related neurological deficits, health status, and the modifiers already integrated into the OF Pelvis classification. If the score is < 8, non-surgical therapy is recommended; if the score is > 8, surgical therapy is recommended; if the score is 8, there is a relative indication for surgery. The OF Pelvis Score was then evaluated retrospectively in a total of 107 patients, according to records. The OF Pelvis Score was 8 points in 4 patients (3.7%), all of whom received surgical treatment. Of the remaining 103 patients, 93 received score-compliant therapy (90.3%). Among these, 4 of the patients who did not receive score-compliant care refused the recommended surgery, so the actual therapy recommendation was score-compliant in 94.2%.The OF Pelvis Score can be used to derive a therapy recommendation in many patients in clinical practice. Because of the possible change of clinical parameters during the course of the disease, the score has a dynamic character. In the retrospective evaluation, the recommendations from the OF Pelvis Score were in close accordance with the therapy actually performed.

2.
Neurochem Int ; 180: 105878, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39389472

RESUMO

The dynamic protective capacity of (poly)phenols, attributed to their potent antioxidant and anti-inflammatory properties, has been consistently reported. Due to their capacity to alter gut microbiome composition, further actions of (poly)phenols may be exerted through the modulation of the microbiota-gut-brain axis. However, the underlying mechanisms remain poorly defined. Here, we investigated the protective effect of a (poly)phenol-rich grape and blueberry extract (Memophenol™), on the microbiota-gut-brain axis in a model of chronic low-grade inflammation (0.5 mg/kg/wk lipopolysaccharide (LPS) for 8 weeks). Dietary supplementation of male C57BL/6 J mice with Memophenol™ prevented LPS-induced increases in the microbe-derived uremia-associated molecules, indoxyl sulfate (IS) and trimethylamine N-oxide (TMAO). These changes coincided with shifts in gut microbiome composition, notably Romboutsia and Desulfovibrio abundance, respectively. In the brain, LPS exposure disrupted the marginal localisation of the endothelial tight junction ZO-1 and downregulated ZO-1 mRNA expression to an extent closely correlated with TMAO and IS levels; a process prevented by Memophenol™ intake. Hippocampal mRNA sequencing analysis revealed significant downregulation in regulatory pathways of neurodegeneration with Memophenol™ intake. These findings may indicate a novel protective role of the (poly)phenol-rich grape and blueberry extract on the endothelial tight junction component ZO-1, acting through modulation of gut microbial metabolism.

3.
Respir Res ; 25(1): 363, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379950

RESUMO

BACKGROUND: In recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning. METHODS: A retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses. RESULTS: A total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032). CONCLUSION: The analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.


Assuntos
Desmame do Respirador , Humanos , Masculino , Desmame do Respirador/métodos , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Fatores de Tempo , Fatores de Risco , Fatores Sexuais , Caracteres Sexuais , Idoso de 80 Anos ou mais
4.
Front Cell Neurosci ; 18: 1465531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39473491

RESUMO

Spreading depolarization (SD) causes a massive neuronal/glial depolarization, disturbs ionic homeostasis and deranges neuronal network function. The metabolic burden imposed by SD may also generate marked amounts of reactive oxygen species (ROS). Yet, proper optical tools are required to study this aspect with spatiotemporal detail. Therefore, we earlier generated transgenic redox indicator mice. They express in excitatory projection neurons the cytosolic redox-sensor roGFP, a reduction/oxidation sensitive green fluorescent protein which is ratiometric by excitation and responds reversibly to redox alterations. Using adult male roGFPc mice, we analyzed SD-related ROS production in CA1 stratum pyramidale of submerged slices. SD was induced by K+ microinjection, O2 withdrawal or mitochondrial uncoupling (FCCP). The extracellular DC potential deflection was accompanied by a spreading wavefront of roGFP oxidation, confirming marked neuronal ROS generation. Hypoxia-induced SD was preceded by a moderate oxidation, which became intensified as the DC potential deflection occurred. Upon K+-induced SD, roGFP oxidation slowly recovered within 10-15 min in some slices. Upon FCCP-or hypoxia-induced SD, recovery was limited. Withdrawing extracellular Ca2+ markedly dampened the SD-related roGFP oxidation and improved its reversibility, confirming a key-role of neuronal Ca2+ load in SD-related ROS generation. Neither mitochondrial uncoupling, nor inhibition of NADPH oxidase or xanthine oxidase abolished the SD-related roGFP oxidation. Therefore, ROS generation during SD involves mitochondria as well as non-mitochondrial sources. This first-time analysis of SD-related ROS dynamics became possible based on quantitative redox imaging in roGFP mice, an advanced approach, which will contribute to further decipher the molecular understanding of SD in brain pathophysiology.

5.
Epilepsy Behav ; 161: 110061, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39306983

RESUMO

BACKGROUND: Seizure frequency and cognitive function are common parameters in assessing epilepsy surgery outcomes. However, psychobehavioral outcomes, such as symptoms of depression and quality of life (QOL), have not found equal attention yet. OBJECTIVE: To assess the effect of seizure frequency, the extent of resection, and cognitive function on the psychobehavioral outcome of patients after temporal lobe surgery for pharmacoresistant epilepsy. METHODS: We retrospectively reviewed all consecutive patients who underwent surgery for intractable temporal lobe epilepsy between 09/2015 and 07/2019. We examined seizure outcome, surgical plan, resection volume, cognitive functions, and psychobehavioral outcome. RESULTS: This study included 77 patients (31 males, 46 females) who underwent temporal lobe surgery. One year after surgery, 53 patients (68.8 %) were completely seizure-free (Engel IA) and 92.2 % of patients showed a worthwhile improvement in seizure frequency (Engel I-III). Resection volume was significantly negatively correlated with QOL (r =  - 0.284, p = 0.041). However, after controlling for the effect of seizure outcome, no significant correlation remained. Patients with a worthwhile improvement in seizure frequency showed significantly fewer symptoms of depression (p = 0.024) and a significantly higher QOL (p = 0.012) one year after surgery. The differences in symptoms of depression (p = 0.044) and QOL (p = 0.030) between patients with and without improvements in seizure frequency remained significant after controlling for the effect of resection volume. After procedures sparing the amygdala and hippocampus (neocortical resection), patients presented significantly fewer symptoms of depression (p = 0.044) and significantly better QOL (p = 0.008) than patients after procedures involving mesial-temporal structures, independent of the resection volume, and after controlling for the side of the procedure (dominant vs. non-dominant). After also controlling for seizure outcome, the difference remained for QOL (p = 0.014) but not for symptoms of depression. CONCLUSIONS: A patient's emotional well-being one year after surgery for pharmacoresistant temporal lobe epilepsy strongly depends on their seizure outcome. As an individual factor, the extent of neocortical resection negatively affects postsurgical emotional well-being, but a favorable seizure outcome outweighs this effect, independent of the resection volume. A favorable seizure outcome even outweighs the negative effects of procedures involving mesial-temporal structures on symptoms of depression.

6.
Energy Fuels ; 38(17): 16504-16519, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39257466

RESUMO

The release of alkali metals (K, Na) and nonmetals (S, Cl) during a calcium looping (CaL) gasification process of waste derived-hydrochars, water-leached samples, and CaO-biomass blends was investigated. Special attention was paid to biomasses that are not particularly promising for gasification requirements but have a large occurrence in Europe, including Grape Bagasse, Organic Fraction of Municipal Solid Waste (OFMSW), Green Waste, and Out-of-use woods from construction debris and discarded furniture. The release experiments were performed at 650 °C in a flow channel reactor to investigate the behavior of inorganic trace substances. Hot-gas analysis was performed by Molecular Beam Mass Spectrometry (MBMS). Thermodynamic equilibrium calculations via FactSage indicate H2S, carbonyl sulfide (COS), KCl, NaCl, and HCl as the main inorganic impurities. Thus, the focus of the experiments was placed on these species. It was found that the concentrations of trace elements released during gasification at 650 °C, such as H2S, SO2, KCl, and NaCl, are hardly affected by intense water-leaching. In contrast, carbonaceous materials from hydrothermal carbonization exhibit a higher concentration of trace potassium substances (K, KCl, and K2Cl+). When biomass samples are combined with CaO, the total amount of inorganic trace compounds (K, Na, and S compounds) in the resulting syngas could be decreased.

7.
J Med Educ Curric Dev ; 11: 23821205241277334, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246599

RESUMO

OBJECTIVES: Life-sustaining treatments (LST) aim to prolong life without reversing the underlying medical condition. Being associated with a high risk of developing unwanted adverse outcomes, decisions about LST are routinely discussed with patients at hospital admission, particularly when it comes to cardiopulmonary resuscitation. Physicians may encounter many challenges when enforcing shared decision-making in this domain. In this study, we map out how junior physicians in Southern Switzerland refer to their experiences when conducting LST discussions with hospitalized patients and their learning strategies related to this. METHODS: In this qualitative exploratory study, we conducted semi-directive interviews with junior physicians working at the regional public hospital in Southern Switzerland and analyzed them with an inductive thematic analysis. RESULTS: Nine physicians participated. We identified 3 themes: emotional burden, learning strategies and practices for conducting discussions. Participants reported feeling unprepared and often distressed when discussing LST with patients. Factors associated with emotional burden were related to the context and to how physicians developed and managed their emotions. Participants signaled having received insufficient education to prepare for discussing LST. They reported learning to discuss LST essentially through trial and error but particularly appreciated the possibility of mentoring and experiential training. Explanations that physicians gave about LST took into account patients' frequent misconceptions. Physicians reported feeling under pressure to ensure that decisions documented were medically indicated and being more at ease when patients decided by themselves to limit treatments. Communication was deemed as an important skill. CONCLUSIONS: Junior physicians experienced conducting LST discussions as challenging and felt caught between advocating for medically relevant decisions and respecting patients' autonomy. Participants reported a substantive emotional burden and feeling unprepared for this task, essentially because of a lack of adequate training. Interventions aiming to ameliorate junior physicians' competency in discussing LST can positively affect their personal experiences and decisional outcomes.

8.
Curr Opin Chem Biol ; 82: 102510, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128325

RESUMO

Mushroom-forming fungi exhibit a distinctive ecology, which is unsurprisingly also reflected in unique and divergent biosynthetic pathways. We review this phenomenon through the lens of the polyketide metabolism, where mushrooms often deviate from established principles and challenge conventional paradigms. This is evident not only by non-canonical enzyme architectures and functions but also by their propensity for multi-product synthases rather than single-product pathways. Nevertheless, mushrooms also feature many polyketides familiar from plants, bacteria, and fungi of their sister division Ascomycota, which, however, are the result of an independent evolution. In this regard, the captivating biosynthetic pathways of mushrooms might even help us understand the biological pressures that led to the simultaneous production of the same natural products (via convergent evolution, co-evolution, and/or metaevolution) and thus address the question of their raison d'être.


Assuntos
Agaricales , Policetídeo Sintases , Policetídeo Sintases/metabolismo , Policetídeo Sintases/genética , Agaricales/enzimologia , Agaricales/metabolismo , Policetídeos/metabolismo , Policetídeos/química , Vias Biossintéticas , Produtos Biológicos/metabolismo , Produtos Biológicos/química
10.
Brain Res ; 1844: 149170, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39163895

RESUMO

Alzheimer's Disease (AD), responsible for 62% of all dementia cases, is a progressive neurodegenerative condition that leads to cognitive dysfunction. The prevalence of AD is consistently higher in women suggesting they are disproportionately affected by this disease. Despite this, our understanding of this female AD vulnerability remains limited. Menopause has been identified as a potential contributing factor to AD in women, with earlier menopause onset associated with greater AD risk. However, the underlying mechanisms responsible for this increased risk are not fully understood. This review examines the potential role of menopause in the development of Alzheimer's Disease providing a mechanistic overview of the available literature from hormones to pathology. While literature is now emerging that indicates a role of hormonal shifts, gut dysbiosis, lipid dysregulation and inflammation, more research is needed to fully elucidate the mechanisms involved.


Assuntos
Doença de Alzheimer , Menopausa , Humanos , Doença de Alzheimer/metabolismo , Menopausa/fisiologia , Feminino , Suscetibilidade a Doenças , Disbiose , Animais
11.
Angew Chem Int Ed Engl ; 63(42): e202403535, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-38951114

RESUMO

Many bacterial natural products contain C-branched sugars, including components from the outer cell wall or antibiotically active metabolites. The enzymatic C-branching of keto sugars leading to longer side chains (≥C2) is catalyzed by thiamine diphosphate (ThDP)-dependent enzymes. Chiral tertiary α-hydroxy ketones are formed in this process. The ThDP-dependent enzymes that catalyze C-branching reactions belong to one of three enzymatic superfamilies: decarboxylases, transketolases, and α-ketoacid dehydrogenases 2, but branching of keto sugars has only been demonstrated for decarboxylases. In this study, we showed that an α-ketoacid dehydrogenase is responsible for C-branching of the deoxyketo sugar amycolose in the biosynthesis of kibdelomycin in Kibdelosporangium sp. MA7385. In addition, we characterized an amino transferase in the same biosynthetic gene cluster (BGC) that accepts a sterically demanding tertiary α-hydroxy ketone in a downstream reaction. Subsequently, we identified approximately 400 similar BGCs in silico, suggesting that there is a large diversity of possible ThDP-dependent enzymes catalyzing the C-branching of keto sugars and subsequent modifications.


Assuntos
Actinomyces , Família Multigênica , Pirróis , Pirrolidinonas , Actinomyces/química , Actinomyces/genética , Pirrolidinonas/química , Pirróis/química
12.
Angew Chem Int Ed Engl ; 63(42): e202407425, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-38963262

RESUMO

Bioactive dimeric (pre-)anthraquinones are ubiquitous in nature and are found in bacteria, fungi, insects, and plants. Their biosynthesis via oxidative phenol coupling (OPC) is catalyzed by cytochrome P450 enzymes, peroxidases, or laccases. While the biocatalysis of OPC in molds (Ascomycota) is well-known, the respective enzymes in mushroom-forming fungi (Basidiomycota) are unknown. Here, we report on the biosynthesis of the atropisomers phlegmacin A1 and B1 of the mushroom Cortinarius odorifer. The biosynthesis of these unsymmetrically 7,10'-homo-coupled dihydroanthracenones was heterologously reconstituted in the mold Aspergillus niger. Methylation of the parental monomer atrochrysone to its 6-O-methyl ether torosachrysone by the O-methyltransferase CoOMT1 precedes the regioselective homocoupling to phlegmacin, catalyzed by the enzyme CoUPO1 annotated as an "unspecific peroxygenase" (UPO). Our results reveal an unprecedented UPO reaction, thereby expanding the biocatalytic portfolio of oxidative phenol coupling beyond the commonly reported enzymes. The results show that Basidiomycota use peroxygenases to selectively couple aryls independently of and convergently to any other group of organisms, emphasizing the central role of OPC in natural processes.


Assuntos
Agaricales , Oxigenases de Função Mista , Oxirredução , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/química , Agaricales/enzimologia , Estereoisomerismo , Fenóis/metabolismo , Fenóis/química , Fenol/química , Fenol/metabolismo
13.
Chembiochem ; 25(19): e202400258, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38887142

RESUMO

S-adenosyl-l-methionine-dependent methyltransferases (MTs) are involved in the C-methylation of a variety of natural products. The MTs SgvM from Streptomyces griseoviridis and MrsA from Pseudomonas syringae pv. syringae catalyze the methylation of the ß-carbon atom of α-keto acids in the biosynthesis of the antibiotic natural products viridogrisein and 3-methylarginine, respectively. MrsA shows high substrate selectivity for 5-guanidino-2-oxovalerate, while other α-keto acids, such as the SgvM substrates 4-methyl-2-oxovalerate, 2-oxovalerate, and phenylpyruvate, are not accepted. Here we report the crystal structures of SgvM and MrsA in the apo form and bound with substrate or S-adenosyl-l-methionine. By investigating key residues for substrate recognition in the active sites of both enzymes and engineering MrsA by site-directed mutagenesis, the substrate range of MrsA was extended to accept α-keto acid substrates of SgvM with uncharged and lipophilic ß-residues. Our results showcase the transfer of the substrate scope of α-keto acid MTs from different biosynthetic pathways by rational design.


Assuntos
Cetoácidos , Metiltransferases , Engenharia de Proteínas , Streptomyces , Metiltransferases/metabolismo , Metiltransferases/química , Metiltransferases/genética , Especificidade por Substrato , Streptomyces/enzimologia , Streptomyces/genética , Cetoácidos/metabolismo , Cetoácidos/química , Pseudomonas syringae/enzimologia , Modelos Moleculares , Cristalografia por Raios X , Mutagênese Sítio-Dirigida , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Domínio Catalítico , Staphylococcus aureus Resistente à Meticilina/enzimologia
14.
Food Funct ; 15(14): 7468-7477, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912918

RESUMO

Dietary fiber has been shown to have multiple health benefits, including a positive effect on longevity and the gut microbiota. In the present study, Drosophila melanogaster has been chosen as an in vivo model organism to study the health effects of dietary fiber supplementation (DFS). DFS extended the mean half-life of male and female flies, but the absolute lifespan only increased in females. To reveal the underlying mechanisms, we examined the effect of DFS on gut microbiota diversity and abundance, local gut immunity, and the brain proteome. A significant difference in the gut microbial community was observed between groups with and without fiber supplementation, which reduced the gut pathogenic bacterial load. We also observed an upregulated expression of dual oxidase and a modulated expression of Attacin and Diptericin genes in the gut of older flies, possibly delaying the gut dysbiosis connected to the age-related gut immune dysfunction. Brain proteome analysis showed that DFS led to the modulation of metabolic processes connected to mitochondrial biogenesis, the RhoV-GTPase cycle, organelle biogenesis and maintenance, membrane trafficking and vesicle-mediated transport, possibly orchestrated through a gut-brain axis interaction. Taken together, our study shows that DFS can prolong the half-life and lifespan of flies, possibly by promoting a healthier gut environment and delaying the physiological dysbiosis that characterizes the ageing process. However, the RhoV-GTPase cycle at the brain level may deserve more attention in future studies.


Assuntos
Fibras na Dieta , Suplementos Nutricionais , Drosophila melanogaster , Microbioma Gastrointestinal , Longevidade , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Feminino , Masculino , Fibras na Dieta/farmacologia , Fibras na Dieta/metabolismo , Encéfalo/metabolismo
15.
Opt Express ; 32(10): 17424-17432, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858926

RESUMO

Resonant enhancement inside an optical cavity has been a wide-spread approach to increase efficiency of nonlinear optical conversion processes while reducing the demands on the driving laser power. This concept has been particularly important for high harmonic generation XUV sources, where passive femtosecond enhancement cavities allowed significant increase in repetition rates required for applications in photoelectron spectroscopy, XUV frequency comb spectroscopy, including the recent endeavor of thorium nuclear clock development. In addition to passive cavities, it has been shown that comparable driving conditions can be achieved inside mode-locked thin-disk laser oscillators, offering a simplified single-stage alternative. This approach is less sensitive to losses thanks to the presence of gain inside the cavity and should thus allow higher conversion efficiencies through tolerating higher intensity in the gas target. Here, we show that the intra-oscillator approach can indeed surpass the much more mature technology of passive enhancement cavities in terms of XUV flux, even reaching comparable values to single-pass sources based on chirped-pulse fiber amplifier lasers. Our system operates at 17 MHz repetition rate generating photon energies between 60 eV and 100 eV. Importantly, this covers the highly attractive wavelength for the silicon industry of 13.5 nm at which our source delivers 60 nW of outcoupled average power per harmonic order.

16.
Angew Chem Int Ed Engl ; 63(34): e202404045, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-38874074

RESUMO

The thiamine diphosphate (ThDP)-binding motif, characterized by the canonical GDG(X)24-27N sequence, is highly conserved among ThDP-dependent enzymes. We investigated a ThDP-dependent lyase (JanthE from Janthinobacterium sp. HH01) with an unusual cysteine (C458) replacing the first glycine of this motif. JanthE exhibits a high substrate promiscuity and accepts long aliphatic α-keto acids as donors. Sterically hindered aromatic aldehydes or non-activated ketones are acceptor substrates, giving access to a variety of secondary and tertiary alcohols as carboligation products. The crystal structure solved at a resolution of 1.9 Šreveals that C458 is not primarily involved in cofactor binding as previously thought for the canonical glycine. Instead, it coordinates methionine 406, thus ensuring the integrity of the active site and the enzyme activity. In addition, we have determined the long-sought genuine tetrahedral intermediates formed with pyruvate and 2-oxobutyrate in the pre-decarboxylation states and deciphered the atomic details for their stabilization in the active site. Collectively, we unravel an unexpected role for the first residue of the ThDP-binding motif and unlock a family of lyases that can perform valuable carboligation reactions.


Assuntos
Tiamina Pirofosfato , Tiamina Pirofosfato/metabolismo , Tiamina Pirofosfato/química , Liases/metabolismo , Liases/química , Motivos de Aminoácidos , Domínio Catalítico , Cristalografia por Raios X , Especificidade por Substrato , Modelos Moleculares
17.
Gut Microbes ; 16(1): 2363011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835220

RESUMO

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with their capacity to affect gut microbiota speciation and metabolism. Mediated through the gut brain axis, this modulation of the microbiota may partly contribute to the neuroprotective properties of the MD. To explore this potential interaction, we evaluated the neuroprotective properties of a novel bioactive blend (Neurosyn240) resembling the Mediterranean diet in a rodent model of chronic low-grade inflammation. Behavioral tests of cognition, brain proteomic analysis, 16S rRNA sequencing, and 1H NMR metabolomic analyses were employed to develop an understanding of the gut-brain axis interactions involved. Recognition memory, as assessed by the novel object recognition task (NOR), decreased in response to LPS insult and was restored with Neurosyn240 supplementation. Although the open field task performance did not reach significance, it correlated with NOR performance indicating an element of anxiety related to this cognitive change. Behavioral changes associated with Neurosyn240 were accompanied by a shift in the microbiota composition which included the restoration of the Firmicutes: Bacteroidota ratio and an increase in Muribaculum, Rikenellaceae Alloprevotella, and most notably Akkermansia which significantly correlated with NOR performance. Akkermansia also correlated with the metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, and adenosine monophosphate, which in turn significantly correlated with NOR performance. The proteomic profile within the brain was dramatically influenced by both interventions, with KEGG analysis highlighting oxidative phosphorylation and neurodegenerative disease-related pathways to be modulated. Intriguingly, a subset of these proteomic changes simultaneously correlated with Akkermansia abundance and predominantly related to oxidative phosphorylation, perhaps alluding to a protective gut-brain axis interaction. Collectively, our results suggest that the bioactive blend Neurosyn240 conferred cognitive and microbiota resilience in response to the deleterious effects of low-grade inflammation.


Assuntos
Cognição , Dieta Mediterrânea , Suplementos Nutricionais , Modelos Animais de Doenças , Microbioma Gastrointestinal , Inflamação , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Masculino , Cognição/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/dietoterapia , Suplementos Nutricionais/análise , Camundongos Endogâmicos C57BL , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/metabolismo , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética
18.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794738

RESUMO

As the population ages, the incidence of age-related neurodegenerative diseases is rapidly increasing, and novel approaches to mitigate this soaring prevalence are sorely needed. Recent studies have highlighted the importance of gut microbial homeostasis and its impact on brain functions, commonly referred to as the gut-brain axis, in maintaining overall health and wellbeing. Nonetheless, the mechanisms by which this system acts remains poorly defined. In this review, we will explore how (poly)phenols, a class of natural compounds found in many plant-based foods and beverages, can modulate the gut-brain axis, and thereby promote neural health. While evidence indicates a beneficial role of (poly)phenol consumption as part of a balanced diet, human studies are scarce and mechanistic insight is still lacking. In this regard, we make the case that dietary (poly)phenols should be further explored to establish their therapeutic efficacy on brain health through modulation of the gut-brain axis, with much greater emphasis on carefully designed human interventions.


Assuntos
Envelhecimento , Eixo Encéfalo-Intestino , Dieta , Microbioma Gastrointestinal , Polifenóis , Humanos , Envelhecimento/fisiologia , Polifenóis/farmacologia , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/fisiologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Doenças Neurodegenerativas , Animais
19.
BMC Geriatr ; 24(1): 461, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38797837

RESUMO

BACKGROUND: Fragility fractures of the pelvis (FFPs) represent a significant health burden, particularly for the elderly. The role of sarcopenia, an age-related loss of muscle mass and function, in the development and impact of these fractures is not well understood. This study aims to investigate the prevalence and impact of osteoporosis and sarcopenia in patients presenting with FFPs. METHODS: This retrospective study evaluated 140 elderly patients with FFPs. The diagnosis of sarcopenia was assessed by psoas muscle area (PMA) and the height-adjusted psoas muscle index (PMI) measured on computed tomography (CT) scans. Clinical data, radiological findings and functional outcomes were recorded and compared with the presence or absence of sarcopenia and osteoporosis. RESULTS: Our study cohort comprised 119 female (85.0%) and 21 (15.0%) male patients. The mean age at the time of injury or onset of symptoms was 82.26 ± 8.50 years. Sarcopenia was diagnosed in 68.6% (n = 96) patients using PMA and 68.8% (n = 88) using PMI. 73.6% (n = 103) of our study population had osteoporosis and 20.0% (n = 28) presented with osteopenia. Patients with sarcopenia and osteoporosis had longer hospital stays (p < 0.04), a higher rate of complications (p < 0.048) and functional recovery was significantly impaired, as evidenced by a greater need for assistance in daily living (p < 0.03). However, they were less likely to undergo surgery (p < 0.03) and the type of FFP differed significantly (p < 0.04). There was no significant difference in mortality rate, pre-hospital health status, age or gender. CONCLUSION: Our study highlights the important role of sarcopenia in FFPs in terms of the serious impact on health and quality of life in elderly patients especially when osteoporosis and sarcopenia occur together. Identifying and targeting sarcopenia in older patients may be an important strategy to reduce pelvic fractures and improve recovery. Further research is needed to develop effective prevention and treatment approaches that target muscle health in the elderly.


Assuntos
Sarcopenia , Humanos , Sarcopenia/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Idoso , Fatores de Risco , Ossos Pélvicos/lesões , Ossos Pélvicos/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Músculos Psoas/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Prevalência , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/complicações
20.
BMC Med Educ ; 24(1): 420, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641835

RESUMO

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.


Assuntos
Instrução por Computador , Humanos , Desmame do Respirador , Aprendizagem , Pessoal de Saúde/educação , Cuidados Críticos
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