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1.
Soft Matter ; 20(31): 6266-6274, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39054893

RESUMO

A correlation between the mechanical properties of cells and various diseases has been emerging in recent years. Atomic force microscopy (AFM) has been widely used to measure a single cell's apparent Young's modulus by treating it as a fully elastic object. More recently, quantitative characterization of the complete viscoelasticity of single cells has become possible. We performed AFM-based nano-indentation experiments on hemocytes isolated from third instar larvae to determine their viscoelasticity and found that live hemocytes, like many other cells, follow a scale-free power-law rheology (PLR) akin to soft glasses. Further, we examined the changes in the rheological response of hemocytes in the presence of pathogenic protein aggregates known to cause neurodegenerative diseases such as Huntington's disorder and amyotrophic lateral sclerosis. Our results show that cells lose their fluidity and appear more solid-like in the presence of certain aggregates, in a manner correlated to actin reorganization. More solid-like cells also display reduced intracellular transport through clathrin-mediated endocytosis (CME). However, the cell's rheology remains largely unaffected and is similar to that of wild-type (WT) hemocytes, if aggregates do not perturb the actin organization and CME. Moreover, the fluid-like nature was significantly recovered when actin organization was rescued by overexpressing specific actin interacting proteins or chaperones. Our study, for the first time, underscores a direct correlation between parameters governing glassy dynamics, actin organization and CME.


Assuntos
Hemócitos , Reologia , Animais , Hemócitos/metabolismo , Agregados Proteicos , Viscosidade , Endocitose , Actinas/metabolismo , Actinas/química , Análise de Célula Única , Microscopia de Força Atômica
2.
Analyst ; 149(10): 2833-2841, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38587502

RESUMO

Sensing and visualization of metabolites and metabolic pathways in situ are significant requirements for tracking their spatiotemporal dynamics in a non-destructive manner. The shikimate pathway is an important cellular mechanism that leads to the de novo synthesis of many compounds containing aromatic rings of high importance such as phenylalanine, tyrosine, and tryptophan. In this work, we present a cost-effective and extraction-free method based on the principles of stable isotope-coupled Raman spectroscopy and hyperspectral Raman imaging to monitor and visualize the activity of the shikimate pathway. We also demonstrated the applicability of this approach for nascent aromatic amino acid localization and tracking turnover dynamics in both prokaryotic and eukaryotic model systems. This method can emerge as a promising tool for both qualitative and semi-quantitative in situ metabolomics, contributing to a better understanding of aromatic ring-containing metabolite dynamics across various organisms.


Assuntos
Ácido Chiquímico , Análise Espectral Raman , Ácido Chiquímico/metabolismo , Ácido Chiquímico/análise , Ácido Chiquímico/análogos & derivados , Análise Espectral Raman/métodos , Imageamento Hiperespectral/métodos , Marcação por Isótopo/métodos , Isótopos de Carbono/química , Escherichia coli/metabolismo
3.
J Phys Chem A ; 128(21): 4233-4241, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38758579

RESUMO

We have designed, synthesized, and characterized a donor-acceptor triad, SPS-PPY-C60, that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and fullerene as an acceptor to seek charge separation upon photoexcitation. The optical absorption spectrum revealed red-shifted Soret and Q-bands of porphyrin due to charge transfer-type interactions involving the two ethynyl bridges carrying electron-rich and electron-poor substituents. The redox properties suggested that the phenothiazine-porphyrin part of the molecule is easier to oxidize and the fullerene part is easier to reduce. DFT calculations supported the redox properties wherein the electron density of the highest molecular orbital (HOMO) was distributed over the donor phenothiazine-porphyrin entity while the lowest unoccupied molecular orbital (LUMO) was distributed over the fullerene acceptor. TD-DFT studies suggested the involvement of both the S2 and S1 states in the charge transfer process. The steady-state emission spectrum, when excited either at porphyrin Soret or visible band absorption maxima, revealed quenched emission both in nonpolar and polar solvents, suggesting the occurrence of excited state events. Finally, femtosecond transient absorption spectral studies were performed to witness the charge separation by utilizing solvents of different polarities. The transient data was further analyzed by GloTarAn by fitting the data with appropriate models to describe photochemical events. From this, the average lifetime of the charge-separated state calculated was found to be 169 ps in benzonitrile, 319 ps in dichlorobenzene, 1.7 ns in toluene for Soret band excitation, and ∼320 ps for Q-band excitation in benzonitrile.

4.
Arch Toxicol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136731

RESUMO

Parkinson disease represents a significant and growing burden on global healthcare systems, necessitating a deeper understanding of their underlying molecular mechanisms for the development of effective treatments. The AKT and ERK pathways play crucial roles in the disease, influencing multiple cellular pathways that support neuronal survival. Researchers have made notable progress in uncovering how these pathways are controlled by upstream kinases and how their downstream effects contribute to cell signalling. However, as we delve deeper into their intricacies, we encounter increasing complexity, compounded by the convergence of multiple signalling pathways. Many of their targets overlap with those of other kinases, and they not only affect specific substrates but also influence entire signalling networks. This review explores the intricate interplay of the AKT/ERK pathways with several other signalling cascades, including oxidative stress, endoplasmic reticulum stress, calcium homeostasis, inflammation, and autophagy, in the context of Parkinson disease. We discuss how dysregulation of these pathways contributes to disease progression and neuronal dysfunction, highlighting potential therapeutic targets for intervention. By elucidating the complex network of interactions between the AKT/ERK pathways and other signalling cascades, this review aims to provide insights into the pathogenesis of Parkinson disease and describe the development of novel therapeutic strategies.

5.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33658331

RESUMO

We evaluate the impacts of implementing and lifting nonpharmaceutical interventions (NPIs) in US counties on the daily growth rate of COVID-19 cases and compliance, measured through the percentage of devices staying home, and evaluate whether introducing and lifting NPIs protecting selective populations is an effective strategy. We use difference-in-differences methods, leveraging on daily county-level data and exploit the staggered introduction and lifting of policies across counties over time. We also assess heterogenous impacts due to counties' population characteristics, namely ethnicity and household income. Results show that introducing NPIs led to a reduction in cases through the percentage of devices staying home. When counties lifted NPIs, they benefited from reduced mobility outside of the home during the lockdown, but only for a short period. In the long term, counties experienced diminished health and mobility gains accrued from previously implemented policies. Notably, we find heterogenous impacts due to population characteristics implying that measures can mitigate the disproportionate burden of COVID-19 on marginalized populations and find that selectively targeting populations may not be effective.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Controle de Doenças Transmissíveis/métodos , COVID-19/economia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Política de Saúde/economia , Política de Saúde/tendências , Humanos , Pandemias , Distanciamento Físico , SARS-CoV-2/isolamento & purificação , Fatores Socioeconômicos , Estados Unidos/epidemiologia
6.
Prostate ; 83(6): 534-546, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36597263

RESUMO

We have shown that decursin, a coumarin compound, induces cell cycle arrest and apoptosis in human prostate cancer cells (PCa); however, its molecular mechanisms are largely unexplored. We studied the mechanisms associated with its anticancer activity in advanced human prostate carcinoma cells. We found that decursin inhibited epidermal growth factor receptor (EGFR) signaling by inhibiting its activating phosphorylation at tyrosine 1068 residue in DU145 and 22Rv1 cells. This inhibition of EGFR was associated with the downregulation of ERK1/2 phosphorylation. Both EGFR and ERK1/2 are known to be deregulated/activated in many human malignancies. Consistent with our earlier study, decursin (25-100 µM) treatment for 24-72 h inhibited DU145 cell proliferation by 49%-87% (p < 0.001) which was associated with strong G1 phase arrest and cell death. It also decreased (p < 0.001) the number of surviving colonies. Decursin moderately increased the expression of Rb-related proteins p107 and p130 but decreased the levels of E2F family transcription factors including E2F-3, E2F-4 and E2F-5. Further, decursin strongly inhibited the growth of androgen-dependent prostate carcinoma 22Rv1 cells from 61% to 79% (p < 0.001) and arrested these cells at G1 phase via induction of cyclin-dependent kinase inhibitor p27/Kip1 and downregulation of CDK2 and CDK4 protein expression. Additionally, EGFR inhibitor erlotinib- and EGF ligand-modulated EGFR activation validated EGFR signaling as a target of decursin-mediated cell growth inhibition and cytotoxicity. Decursin decreased EGF ligand-induced phosphorylation of EGFR (Y-1068) as well as activation of its downstream mediator, ERK1/2. Furthermore, inhibitory targeting of EGFR-ERK1/2 axis by combinatorial treatment of decursin and erlotinib further sensitized DU145 cells for the decursin-induced growth inhibition and cell death. Overall, these findings strongly suggest that anticancer efficacy of decursin against human PCa involves inhibitory targeting of EGFR-ERK1/2 signaling axis, a pathway constitutively active in advanced PCa.


Assuntos
Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Fator de Crescimento Epidérmico , Sistema de Sinalização das MAP Quinases , Próstata/patologia , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/metabolismo , Ligantes , Receptores ErbB/metabolismo , Fosforilação , Neoplasias da Próstata/patologia , Carcinoma/metabolismo
7.
Chemistry ; 29(28): e202203354, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797844

RESUMO

Herein, fullerene (C70 ) is introduced as an effective photoredox catalyst for the construction of a highly functionalised pyrrolo[2,1-a]isoquinoline framework by 1,3-dipolar cycloaddition-aromatisation reaction sequence. The ability of C70 to efficiently harvest visible light, its long-triplet state lifetime, good photostability, and strong singlet oxygen generation potential (Φ▵ ≈1), make it an efficient photoredox catalyst. Upon photoirradiation, C70 promotes the formation of singlet oxygen and superoxide radical by energy transfer (EnT) and single electron transfer (SET) mechanism. The superoxide radical acts as a potential oxidant in the formation of azomethine ylide through the oxidation-deprotonation tandem process. Azomethine ylide further participates in [3+2]-cycloaddition reaction protocol with alkene/alkyne to give the corresponding pyrrolo[2,1-a]isoquinolines. Interestingly, this protocol allows the activation of a wide range of substrates giving access to a diverse library of 48 well-decorated pyrrolo[2,1-a]isoquinolines with good functional group tolerance.

8.
Photochem Photobiol Sci ; 22(2): 379-393, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36264479

RESUMO

A series of phenothiazine-C60/70 dyads containing fulleropyrrolidine tethered to C-3 position (C60-PTZ and C70-PTZ) or to the heteroatom N-position via either phenyl (C60-Ph-PTZ and C70-Ph-PTZ) or phenoxyethyl linkers (C60-PhOEt-PTZ and C70-PhOEt-PTZ) of the phenothiazine were synthesized and light-induced electron transfer events were explored. Optimized studies suggested that the highest molecular orbital (HOMO) resides on donor phenothiazine moiety while lowest molecular orbital (LUMO) on the acceptor fulleropyrrolidine moiety of the dyads. Optical and electrochemical properties suggested no electronic communication between the donor and acceptor moieties in the ground state. However, steady-state emission studies in solvents of varied polarity, involving selective excitation of C60/C70, disclosed that the emission intensity of C60/C70 was quenched in the dyads in the increasing order, C60/70-PTZ > C60/70-Ph-PTZ > C60/70-PhOEt-PTZ as a consequence of the donor-acceptor distance resulted due to spacer lengths. Also, the emission quenching is more pronounced in polar solvents such as DMF compared to a non-polar solvent, toluene. With the support of parallel electrochemical studies, the emission quenching is attributed to intramolecular photo-induced electron transfer occurring from PTZ to (C60/C70)* generating a radical ion pair, PTZ+⋅-C60-⋅/PTZ+⋅-C70-⋅. Finally, bulk heterojunction (BHJ) solar cells devices inverted fashion prepared by employing the dyads as acceptors, and PTB7 as donor, suggested that the devices prepared from C70 derivatives i.e., PTB7:C70-PTZ and PTB7:C70-PhOEt-PTZ exhibited better power conversion efficiency of 2.66% and 2.15%, respectively over C60 derivatives i.e., PTB7:C60-PTZ and PTB7:C60-PhOEt-PTZ with the efficiencies of 1.80 and 1.72%, respectively. AFM studies revealed that the poor performance of PTB7:C60-PTZ- and PTB7:C60-PhOEt-PTZ-based devices can be ascribed to the lower solubility of the dyads in 1,2-DCB solvent leading to rough morphology.

9.
Org Biomol Chem ; 21(24): 4962-4966, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37272266

RESUMO

An expeditious and regioselective approach towards the construction of a spiro-chroman motif is described. Quinone methides underwent a PTSA catalyzed annulation with 2-benzylidene dithiolanes to afford spiro-chroman dithiolanes in high yields. The synthetic versatility of the dithiolane motif was demonstrated by converting the adduct to coumarin, 3,4-dihydrocoumarin and chroman derivatives.

10.
Toxicol Mech Methods ; 33(4): 293-306, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36154553

RESUMO

Nuclear receptors (NRs) are ligand-modulated transcription factors that regulate multiple physiological functions in our body. Many NRs in their unliganded state are localized in the cytoplasm. The ligand-inducible nuclear translocation of NRs provides a valuable tool for studying the NR-ligand interactions and their downstream effects. The translocation response of NRs can be studied irrespective of the nature of the interacting ligand (agonist, antagonist, or a small molecule modulator). These nuclear translocation studies offer an advantage over promoter-reporter-based transcription assays where transcription response is observed only with the activating hormones or agonistic ligands. Globally, milk serves as a major dietary source. However, suspected presence of endocrine/metabolism-disrupting chemicals like bisphenols, parabens, organochlorine pesticides, carbamates, non-steroidal anti-inflammatory drugs, chloramphenicol, brominated flame retardants, etc. has been reported. Considering that these chemicals may impart serious developmental and metabolism-related health concerns, it is essential to develop assays suitable for the detection of xenobiotics present at differing levels in milk. Since milk samples cannot be used directly on cultured cells or for microscopy, a combination of screening strategies has been developed herein based on the revelation that i) lipophilic NR ligands can be successfully retrieved in milk-fat; ii) milk-fat treatment of cells is compatible with live-cell imaging studies; and finally, iii) treatment of cells with xenobiotics-spiked and normal milk derived fat provides a visual and quantifiable response of NR translocation in living cells. Utilizing a milk-fat extraction method and Green Fluorescent Protein (GFP) tagged NRs expressed in cultured mammalian cells, followed by an assessment of NR response proved to be an effective approach for screening xenobiotics present in milk samples.HighlightsDiverse endocrine and metabolism-disrupting chemicals are suspected to contaminate milk.Nuclear receptors serve as 'xenosensors' for assessing the presence of xenobiotics in milk.Nuclear import of steroid receptors with (ant)agonist can be examined in live cells.Lipophilic xenobiotics are extracted and observed enriched in milk-fat fraction.A comprehensive cell-based protocol aids in the detection of xenobiotics in milk.


Assuntos
Disruptores Endócrinos , Receptores de Esteroides , Animais , Leite/química , Leite/metabolismo , Xenobióticos/toxicidade , Ligantes , Receptores Citoplasmáticos e Nucleares , Receptores de Esteroides/metabolismo , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/análise , Mamíferos/metabolismo
11.
World J Microbiol Biotechnol ; 40(1): 28, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057683

RESUMO

Furfuryl alcohol (FA) and other furanic compounds have garnered considerable attention in the quest for sustainable alternatives. FA-based resins have been used in various sectors that entail the release of FA into the environment. Hence, to ensure sustainability in this scenario, devising a dependable approach to its degradation is imperative. Given the crucial role of bacterial strains in the biodegradation of various organic pollutants, this study investigates the microbial degradation of FA, using bacterial strains isolated from sites that are constantly exposed to industrial waste. Three potential isolates were identified as B. paramycoides, B. cereus, and B. tequilensis by 16S rRNA gene sequencing. At a concentration of 300 µg/ml, these isolates demonstrated efficient FA degradation; 60-70% (at 300 µg/ml FA) and 50-60%, (at 500 µg/ml FA). Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC) analysis further supported the result that the bacterial isolates consumed FA as the carbon source. Liquid chromatography-mass spectrometry (LC-MS) facilitates the detection of the major metabolic intermediate product in which FA gets transformed. The prominent peaks at 113 and 119 m/z obtained in the MS spectra of the degraded FA samples indicated the possibility of the conversion of FA into furoic acid or levulinic acid. The phytotoxicity bioassay findings revealed the non-toxic nature of the bio-transformed products as compared to pure FA. This investigation presents the initial documentation of the FA degradative potential of Bacillus strains, thereby augmenting the understanding of the prospective implementation of Bacillus species in industrial waste treatment projects.


Assuntos
Bacillus , Bacillus/genética , Bacillus/metabolismo , Resíduos Industriais , RNA Ribossômico 16S/genética , Estudos Prospectivos , Biodegradação Ambiental
12.
Diabet Med ; 39(10): e14928, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35900906

RESUMO

OBJECTIVES: To assess the cost-effectiveness of the WISDOM self-management intervention for type 2 diabetes compared with care as usual. DESIGN: We performed a difference-in-differences analysis to estimate differences in risk factors for diabetes complications between people in the WISDOM group (n = 25, 276) and a control group (n = 15, 272) using GP records. A decision analytic model was then used to extrapolate differences in risk factors into costs and outcomes in the long term. SETTING: Participating GP practices in West Hampshire and Southampton, UK. PARTICIPANTS: All people diagnosed with type 2 diabetes between January 1990 and March 2020 (n = 40,548). OUTCOMES: Diabetes-related complications, quality-adjusted life years (QALYs) and costs to the English National Health Service at 5 years and lifetime. INTERVENTIONS: The WISDOM intervention included risk stratification, self-management education programme to professionals and people with type 2 diabetes, and monitoring of key treatment targets. RESULTS: WISDOM was associated with less atrial fibrillation [p = 0.001], albuminuria [p = 0.002] and blood pressure [p = 0.098]. Among all people in the intervention group, WISDOM led to 51 [95%CI: 25; 76] QALYs gained and saved £278,036 [95%CI: -631,900; 176,392] in the first 5 years after its implementation compared with care as usual. During those people' lifetime, WISDOM led to 253 [95%CI: 75; 404] QALYs gained and cost saving of £126,380 [95%CI: -1,466,008; 1,339,628]. The gains in QALYs were a result of reduced diabetes-related complications through improved management of the associated risk factors. CONCLUSIONS: The WISDOM risk-stratification and education intervention for type 2 diabetes appear to be cost-effective compared to usual care by reducing diabetes complications.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Medicina Estatal
13.
Neurochem Res ; 47(7): 1816-1829, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35380400

RESUMO

The medicinal plant Mucuna pruriens (Fabaceae) is widely known for its anti-oxidative and anti-inflammatory properties. It is a well-established drug in Ayurveda and has been widely used for the treatment of neurological disorders and male infertility for ages. The seeds of the plant have potent medicinal value and its extract has been tested in different models of neurodegenerative diseases, especially Parkinson's disease (PD). Apart from PD, Mucuna pruriens is now being studied in models of other nervous systems disorders such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and stroke because of its neuroprotective importance. This review briefly discusses the pathogenesis of PD, AD, ALS and stroke. It aims to summarize the medicinal importance of Mucuna pruriens in treatment of these diseases, and put forward the potential targets where Mucuna pruriens can act for therapeutic interventions. In this review, the effect of Mucuna pruriens on ameliorating the neurodegeneration evident in PD, AD, ALS and stroke is briefly discussed. The potential targets for neuroprotection by the plant are delineated, which can be studied further to validate the hypothesis regarding the use of Mucuna pruriens for the treatment of these diseases.


Assuntos
Esclerose Lateral Amiotrófica , Mucuna , Doenças Neurodegenerativas , Doença de Parkinson , Acidente Vascular Cerebral , Esclerose Lateral Amiotrófica/tratamento farmacológico , Humanos , Masculino , Doenças Neurodegenerativas/tratamento farmacológico , Neuroproteção , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes , Acidente Vascular Cerebral/tratamento farmacológico
14.
Org Biomol Chem ; 20(45): 8907-8911, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36321573

RESUMO

PTSA-catalyzed divergent synthetic routes toward 3-aryl coumarins and indenes have been developed using ketene dithioacetals. These transformations are transition-metal and oxidant free, proceed under mild conditions, and provide expeditious access to these important structural motifs.


Assuntos
Indenos , Cumarínicos/química , Etilenos/química , Catálise
15.
Phys Chem Chem Phys ; 24(24): 15110-15120, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35699113

RESUMO

It is an established fact that [1]benzothieno[3,2-b][1]benzothiophene (BTBT) is a champion molecule for high-mobility OFET devices. Recently, it has also been utilized in dye-sensitized solar cells (DSSCs) and organic photovoltaics (OPVs) as an alternative to fullerene (non-fullerene acceptor). Considering the advantageous features of BTBT, we herein report its aggregation-induced emission (AIE) and mechanofluorochromic (MFC) behaviour for the first time. We have designed and synthesized two new BTBT derivatives: [1]benzothieno[3,2-b][1]benzothiophene-tetraphenylethylene (BTBT-TPE) and [1]benzothieno[3,2-b][1]benzothiophene-phenyl-N,N-dimethylamine (BTBT-NMe). The donor-π-acceptor-π-donor-integrated BTBT-TPE showed AIE whereas BTBT-NMe showed aggregation-caused quenching (ACQ), as evident by their quantum yield and lifetime results. BTBT-NMe was found to possess great interaction, resulting in the halochromic (protonation) effect. The theoretical calculation of the electronic distribution and energy investigation were consistent with the experimental outcomes. The electron contribution of the HOMO is high for BTBT-NMe at the donor, which can be attributed to the weaker donating nature of TPE compared to that of the NMe group. Overall, the results indicate the potential of the mechanical stimuli and aggregation response of the studied compounds for further investigation.

16.
Age Ageing ; 51(1)2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34969074

RESUMO

BACKGROUND: hospital level healthcare in the home guided by comprehensive geriatric assessment (CGA) might provide a less costly alternative to hospitalisation for older people. OBJECTIVE: to determine the cost-effectiveness of CGA admission avoidance hospital at home (HAH) compared with hospital admission. DESIGN/INTERVENTION: a cost-effectiveness study alongside a randomised trial of CGA in an admission avoidance HAH setting, compared with admission to hospital. PARTICIPANTS/SETTING: older people considered for a hospital admission in nine locations across the UK were randomised using a 2:1 randomisation schedule to admission avoidance HAH with CGA (N = 700), or admission to hospital with CGA when available (N = 355). MEASUREMENTS: quality adjusted life years, resource use and costs at baseline and 6 months; incremental cost-effectiveness ratios were calculated. The main analysis used complete cases. RESULTS: adjusting for baseline covariates, HAH was less costly than admission to hospital from a health and social care perspective (mean -£2,265, 95% CI: -4,279 to -252), and remained less costly with the addition of informal care costs (mean difference -£2,840, 95% CI: -5,495 to -185). There was no difference in quality adjusted survival. Using multiple imputation for missing data, the mean difference in health and social care costs widened to -£2,458 (95% CI: -4,977 to 61) and societal costs remained significantly lower (-£3,083, 95% CI: -5,880 to -287). There was little change to quality adjusted survival. CONCLUSIONS: CGA HAH is a cost-effective alternative to admission to hospital for selected older people.


Assuntos
Avaliação Geriátrica , Hospitalização , Idoso , Análise Custo-Benefício , Hospitais , Humanos , Anos de Vida Ajustados por Qualidade de Vida
17.
Curr Microbiol ; 79(5): 142, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35322302

RESUMO

Metal-binding proteins occur in the cytosol of most eubacteria. The hypothetical metal responsive protein MreA (PP-2969 gene; NreA) seems responsible for zinc, chromium, cadmium accumulation, and metal ion homeostasis. However, there is a lack of definitive evidence regarding the specific metal-binding sites of MreA protein. The present study aimed to identify putative metal-binding regions for MreA. In silico analysis revealed that amino acids C40, H65, and C69 (CHC region) seem critical for metal-protein interactions. We created site-directed mutants (SDM's) of MreA for interacted amino acids to validate in silico results. The differential scanning fluorimetry (DSF) and atomic absorption spectroscopy (AAS) showed that SDM strains of MreA protein curtailed metal accumulation compared to the wild types indicating C40, H65, and C69 amino acids are critical for metal binding. Thus, we report potential implications for MreA-bioengineered strains of Pseudomonas putida KT2440 for metal ion homeostasis by alleviating metal toxicity in the biological environment.


Assuntos
Pseudomonas putida , Sítios de Ligação , Cádmio/metabolismo , Metais/metabolismo , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Zinco/metabolismo
18.
Water Sci Technol ; 86(9): 2260-2269, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36378179

RESUMO

Widespread use of antibiotics for treating human and animal ailments has increased their discharge in the environment through excreta. Moreover, unscientific disposal of unused antibiotics has further increased their presence in the environmental matrices. Thus, occurrence of used and/or discarded antibiotics in water resources is becoming a growing concern across the globe. Antibiotics and their residues in the aquatic environment are emerging contaminants which pose a serious threat to the aquatic biota as well as human beings by enhancing antibiotic resistance. Various methods are being adopted for the removal of these contaminants. Adsorption over activated carbon is one such promising method which is environmentally friendly, cost-effective, and efficient. However, there are various factors which affect the overall process efficiency, such as, properties of activated carbon/antibiotics/reaction medium etc. In this article, emphasis has been laid down on evaluating these factors, so that the experimental procedures may be optimized to obtain the highest possible removal efficiency for antibiotics in the aqueous media.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Humanos , Adsorção , Antibacterianos/química , Poluentes Químicos da Água/química , Águas Residuárias/química , Água
19.
Environ Geochem Health ; 44(1): 149-177, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34027568

RESUMO

Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants widely used all over the world. These chlorinated hydrocarbons are toxic and often cause detrimental health effects because of their long shelf life and bioaccumulation in the adipose tissues of primates. OCP exposure to humans occurs through skin, inhalation and contaminated foods including milk and dairy products, whereas developing fetus and neonates are exposed through placental transfer and lactation, respectively. In 1960s, OCPs were banned in most developed countries, but because they are cheap and easily available, they are still widely used in most third world countries. The overuse or misuse of OCPs has been rising continuously which pose threats to environmental and human health. This review reports the comparative occurrence of OCPs in human and bovine milk samples around the globe and portrays the negative impacts encountered through the long history of OCP use.


Assuntos
Hidrocarbonetos Clorados , Praguicidas , Animais , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Recém-Nascido , Leite/química , Praguicidas/análise , Placenta , Gravidez
20.
Environ Monit Assess ; 194(11): 803, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121501

RESUMO

Microplastics are one of the emerging and ubiquitous environmental pollutants. Recent studies have proven their co-existence with pharmaceuticals in the environment wherein microplastics act as a potential vector for the transportation of pharmaceuticals. Both microplastics and pharmaceuticals are charged moieties enriched with diverse functional groups resulting in the possibility of multiple interactions. Major interactions could be electrostatic, hydrogen bonding, and hydrophobic, while minor interactions may occur through π-π interaction, cationic bridging mechanism, van der Waals interaction, partition, and pore-filling mechanism. These interactions have both short- and long-term effects over pharmaceutical sorption on microplastics and possibly, ensuing toxicity. This review analyses and summarises the currently reported interactions between microplastic particles and pharmaceuticals as well as establishes the link to various factors affecting the process, viz. pH, salinity, dissolved organic matter, and physiochemical properties of microplastics.


Assuntos
Microplásticos , Poluentes Químicos da Água , Adsorção , Monitoramento Ambiental , Preparações Farmacêuticas , Plásticos/química , Poluentes Químicos da Água/análise
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