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1.
Nat Commun ; 15(1): 8210, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294117

RESUMO

Aliphatic diols such as ethylene and propylene glycol are the key products in the chemical industry for manufacturing polymers. The synthesis of these molecules usually implies sequential processes, including epoxidation of olefins using hydrogen peroxide or oxygen with subsequent hydrolysis to glycols. Direct hydroxylation of olefins by cheap and green oxidants is an economically attractive and environmentally friendly route for the synthesis of diols. Here, we report a photocatalytic reaction for the dihydroxylation of ethylene and propylene to their glycols at room temperature using water as the oxidant. The photocatalyst contains Pd clusters stabilized by sub-nanometric polyoxometalate with TiO2 as the host material. Under light irradiation, it results in production rates of ethylene glycol and propylene glycols of 146.8 mmol·gPd-1·h-1 and 28.6 mmol·gPd-1·h-1 with liquid-phase selectivities of 63.3 % and 80.0 %, respectively. Meanwhile, green hydrogen derived from water is produced as another valuable product. Combined spectroscopy investigation suggests that the reaction proceeds via π-bonded adsorption of olefins over Pd clusters with hydroxylation by hydroxyl radicals formed by photocatalytic dissociation of water.

2.
Int J Biol Macromol ; 279(Pt 3): 135295, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233153

RESUMO

Lignin, a biopolymer derived from plant biomass, is recognized as a highly promising substance for developing self-healing polymers owing to its dynamic linkages and functional groups. This paper provides a thorough review of lignin-based self-healing polymer, from the process of extracting lignin, chemical modification, synthesis techniques such as via reversible addition-fragmentation chain transfer (RAFT) polymerization, crosslinking with polymers like polyvinyl alcohol (PVA) and chitosan, and reactions with isocyanates to create lignin-based networks with reversible interactions. This work also summarizes the optimization of self-healing ability, such as including dynamic copolymers, encapsulating healing agents like dicyclopentadiene and polycaprolactone (PCL), and chain extenders with disulfide or Diels-Alder (DA) moieties. The material's characterization focuses on its capacity to recover via hydrogen bonding and dynamic re-associations, improved mechanical properties from lignin's rigid structure, and enhanced temperature resistance. Primary obstacles involve the optimization of lignin extraction, enhancement of polymer compatibility, and the establishment of efficient procedures for synthesis and characterization. Overall, lignin shows great potential as a renewable component of self-healing polymers, with plenty of opportunities for further development.

3.
Cureus ; 16(8): e66323, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39238736

RESUMO

The complex connection between some infectious illnesses and some psychiatric disorders is an important area of study, with infections known to cause a diverse range of psychiatric symptoms. This association poses significant challenges for physicians in differentiating between mental illnesses induced by infections and those stemming from underlying psychiatric conditions. This study systematically synthesizes literature from various databases that explain the relationship between certain infectious diseases and specific psychiatric disorders. The systematic review explores mechanisms such as neuroinflammation, direct central nervous system (CNS) infection, and the interaction between the immune system and psychiatric conditions. The study examines various infectious pathogens, including viruses, bacteria, parasites, prion diseases, and fungi. An analysis of these findings is presented in the study's discussion section, along with a review of therapeutic methods such as drug use and psychological treatment. The review emphasizes the need for multidisciplinary teamwork and thorough clinical examinations in managing psychiatric symptoms caused by infections. It also highlights the significant role of public health measures in mitigating the impact of psychiatric diseases related to infectious illnesses. The study finds that current therapeutic methods include pharmacological and psychological treatments, which can effectively manage these conditions. The study has concluded that psychiatric manifestations are prevalent across various infectious diseases, including those caused by viruses, bacteria, parasites, and fungi. Key mechanisms identified include neuroinflammation, direct infection of the CNS, and the immuno-psychiatric interface, all of which contribute to the development of psychiatric symptoms. The future of managing these complex conditions lies in a comprehensive approach that combines clinical, therapeutic, and public health strategies.

4.
Curr Probl Cardiol ; 49(11): 102792, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39137880

RESUMO

BACKGROUND: Studies exploring predictors of arrhythmias in the population primarily hospitalized for SARS-CoV-2 (COVID-19) are scarce. Understanding this is crucial for risk stratification and appropriate management. METHODS: Using the 2020 National Inpatient Sample (NIS) database, we identified primary admissions for COVID-19. A 'greedy neighbor' 1:1 propensity-score matching (PSM) accounted for baseline differences. Then, multivariable logistic regression models were employed to account for confounders and estimate the probability of arrhythmia. RESULTS: There were a total of 1,058,815 admissions for COVID-19 (mean age 64.3 years ±16.8), 47.2% female, 52.5% (107698) White, 18.5% (37973) Blacks, and 20.7% (42,447) Hispanics. Atrial fibrillation was the most prevalent arrhythmia, 15.1% (31,942). After PSM, 166,405 arrhythmia hospitalizations were matched to 166,405 hospitalizations without arrhythmia. Sick sinus syndrome 4.9 (4.4-5.5), dyslipidemia 1.2 (1.2-1.3), cardiac arrest 1.3 (1.1-1.4), invasive mechanical ventilation 1.9 (1.8-2.0) and obesity 1.3 (1.2-1.4), (p<0.0001, all) were all independent predictors of arrhythmias. CONCLUSIONS: Our analysis revealed a notable proportion of hospitalized COVID-19 patients with arrhythmias. Dyslipidemia, obesity, sick sinus syndrome, invasive mechanical ventilation, and cardiac arrest were independent predictors of arrhythmias.


Assuntos
Arritmias Cardíacas , COVID-19 , Hospitalização , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Arritmias Cardíacas/epidemiologia , Hospitalização/estatística & dados numéricos , Idoso , Fatores de Risco , Estados Unidos/epidemiologia , Medição de Risco/métodos
5.
J Child Health Care ; : 13674935241252479, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718378

RESUMO

With a growing 25.5 million people in the United States experiencing limited-English proficiency (LEP), there is a concern over these individuals' experiences in healthcare. Health outcomes of LEP status are well-documented for adults in hospitals; however, less is known about patient experience, pediatric populations, and primary care settings. This study investigated differences in caregiver satisfaction between families with and without LEP receiving healthcare for their child. A sample of 25,118 caregivers whose children from birth to 17 years had met with any healthcare providers in the past year was used. Analyses consisted of unpaired t-tests comparing mean satisfaction of LEP and English-proficient (EP) caregivers in the domains of how often primary healthcare providers spent enough time with the child, listened, provided specific information, demonstrated sensitivity to the family's values, and made the respondent feel like a partner. In all aspects of caregiver satisfaction, mean satisfaction scores were significantly lower for LEP caregivers than EP caregivers. The largest drops were seen in perceived time and sensitivity. These results highlight a need to ensure LEP families receive equitable and high-quality primary care services, ultimately building trust in the healthcare system and improving children's health and well-being.

6.
Hum Resour Health ; 22(1): 25, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632567

RESUMO

BACKGROUND: Health workforce projection models are integral components of a robust healthcare system. This research aims to review recent advancements in methodology and approaches for health workforce projection models and proposes a set of good practice reporting guidelines. METHODS: We conducted a systematic review by searching medical and social science databases, including PubMed, EMBASE, Scopus, and EconLit, covering the period from 2010 to 2023. The inclusion criteria encompassed studies projecting the demand for and supply of the health workforce. PROSPERO registration: CRD 42023407858. RESULTS: Our review identified 40 relevant studies, including 39 single countries analysis (in Australia, Canada, Germany, Ghana, Guinea, Ireland, Jamaica, Japan, Kazakhstan, Korea, Lesotho, Malawi, New Zealand, Portugal, Saudi Arabia, Serbia, Singapore, Spain, Thailand, UK, United States), and one multiple country analysis (in 32 OECD countries). Recent studies have increasingly embraced a complex systems approach in health workforce modelling, incorporating demand, supply, and demand-supply gap analyses. The review identified at least eight distinct types of health workforce projection models commonly used in recent literature: population-to-provider ratio models (n = 7), utilization models (n = 10), needs-based models (n = 25), skill-mixed models (n = 5), stock-and-flow models (n = 40), agent-based simulation models (n = 3), system dynamic models (n = 7), and budgetary models (n = 5). Each model has unique assumptions, strengths, and limitations, with practitioners often combining these models. Furthermore, we found seven statistical approaches used in health workforce projection models: arithmetic calculation, optimization, time-series analysis, econometrics regression modelling, microsimulation, cohort-based simulation, and feedback causal loop analysis. Workforce projection often relies on imperfect data with limited granularity at the local level. Existing studies lack standardization in reporting their methods. In response, we propose a good practice reporting guideline for health workforce projection models designed to accommodate various model types, emerging methodologies, and increased utilization of advanced statistical techniques to address uncertainties and data requirements. CONCLUSIONS: This study underscores the significance of dynamic, multi-professional, team-based, refined demand, supply, and budget impact analyses supported by robust health workforce data intelligence. The suggested best-practice reporting guidelines aim to assist researchers who publish health workforce studies in peer-reviewed journals. Nevertheless, it is expected that these reporting standards will prove valuable for analysts when designing their own analysis, encouraging a more comprehensive and transparent approach to health workforce projection modelling.


Assuntos
Mão de Obra em Saúde , Humanos , Mão de Obra em Saúde/normas , Necessidades e Demandas de Serviços de Saúde , Atenção à Saúde/normas , Previsões , Pessoal de Saúde , Modelos Teóricos
7.
Drug Deliv Transl Res ; 14(8): 2188-2202, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38578378

RESUMO

Nanoparticles (NPs) engineered as drug delivery systems continue to make breakthroughs as they offer numerous advantages over free therapeutics. However, the poor understanding of the interplay between the NPs and biomolecules, especially blood proteins, obstructs NP translation to clinics. Nano-bio interactions determine the NPs' in vivo fate, efficacy and immunotoxicity, potentially altering protein function. To fulfill the growing need to investigate nano-bio interactions, this study provides a systematic understanding of two key aspects: (i) protein corona (PC) formation and (ii) NP-induced modifications on protein's structure and stability. A methodology was developed by combining orthogonal techniques to analyze both quantitative and qualitative aspects of nano-bio interactions, using human serum albumin (HSA) as a model protein. Protein quantification via liquid chromatography-mass spectrometry, and capillary zone electrophoresis (CZE) clarified adsorbed protein quantity and stability. CZE further unveiled qualitative insights into HSA forms (native, glycated HSA and cysteinylated), while synchrotron radiation circular dichroism enabled analyzing HSA's secondary structure and thermal stability. Comparative investigations of NP cores (organic vs. hybrid), and shells (with or without polyethylene glycol (PEG)) revealed pivotal factors influencing nano-bio interactions. Polymeric NPs based on poly(lactic-co-glycolic acid) (PLGA) and hybrid NPs based on metal-organic frameworks (nanoMOFs) presented distinct HSA adsorption profiles. PLGA NPs had protein-repelling properties while inducing structural modifications on HSA. In contrast, HSA exhibited a high affinity for nanoMOFs forming a PC altering thereby the protein structure. A shielding effect was gained through PEGylation for both types of NPs, avoiding the PC formation as well as the alteration of unbound HSA structure.


Assuntos
Nanopartículas , Albumina Sérica Humana , Humanos , Nanopartículas/química , Albumina Sérica Humana/química , Coroa de Proteína/química , Estabilidade Proteica , Polímeros/química , Eletroforese Capilar , Dicroísmo Circular
8.
Bioorg Chem ; 146: 107295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513326

RESUMO

A concise asymmetric synthesis of clickable enantiomeric pyrrolidines was achieved using Crabbé-Ma allenation. The synthesized iminosugars were grafted by copper-free strain-promoted alkyne-azide cycloaddition onto phosphorus dendrimers. The hexavalent and dodecavalent pyrrolidines were evaluated as ß-glucocerebrosidase inhibitors. The level of inhibition suggests that monofluorocyclooctatriazole group may contribute to the affinity for the protein leading to potent multivalent inhibitors. Docking studies were carried out to rationalize these results. Then, the iminosugars clusters were evaluated as pharmacological chaperones in Gaucher patients' fibroblasts. An increase in ß-glucocerebrosidase activity was observed with hexavalent and dodecavalent pyrrolidines at concentrations as low as 1 µM and 0.1 µM, respectively. These iminosugar clusters constitute the first example of multivalent pyrrolidines acting as pharmacological chaperones against Gaucher disease.


Assuntos
Doença de Gaucher , Imino Açúcares , Humanos , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase , Pirrolidinas/farmacologia , Inibidores Enzimáticos/farmacologia
9.
Front Immunol ; 15: 1285063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455053

RESUMO

Paraprobiotics that benefit human health have the capacity to modulate innate and adaptive immune systems. In this study, we prepared the paraprobiotic from Bacillus velezensis GV1 using the heat-killing method and investigated its effects on immunity and gut microbiota in vitro and in vivo. The morphology of inactivated strain GV1 was observed using scanning electron microscopy. Treatment with GV1 promoted nitric oxide production and augmented cytokine (IL-6, IL-1ß, and TNF-α) expression and secretion in RAW 264.7 macrophages. Moreover, the strain GV1 could alleviate cyclophosphamide monohydrate (CTX)-induced immunosuppression by reversing spleen damage and restoring the immune organ index, as well as by increasing the expression of immune-related cytokines (TNF-α, IL-1ß, IFN-γ, and IL-2) in the spleen and thymus, respectively. Furthermore, GV1 treatment dramatically healed the CTX-damaged colon and regulated gut microbiota by increasing the relative abundance of beneficial bacterial families (Lactobacillaceae, Akkermansiaceae, and Coriobacteriaceae) and decreasing that of harmful bacterial families (Desulfovibrionaceae, Erysipelotrichaceae, and Staphylococcaceae). Thus, the heat-killed GV1 can be considered a potential immunoregulatory agent for use as a functional food or immune-enhancing medicine.


Assuntos
Bacillus , Microbioma Gastrointestinal , Fator de Necrose Tumoral alfa , Camundongos , Humanos , Animais , Ciclofosfamida/farmacologia , Citocinas/metabolismo , Macrófagos , Imunidade
10.
ACS Appl Mater Interfaces ; 16(12): 14852-14863, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501567

RESUMO

Among semiconductor nanomaterials, titanium dioxide is at the forefront of heterogeneous photocatalysis, but its catalytic activity greatly suffers from the loss of photoexcited charge carriers through deleterious recombination processes. Here, we investigate the impact of an external electric field (EEF) applied to conventional P25 TiO2 nanopowder with or without Au nanoparticles (NPs) to circumvent this issue. The study of two redox reactions in the gas phase, water splitting and toluene degradation, reveals an enhancement of the photocatalytic activity with rather modest electric fields of a few volt/centimeters only. Such an improvement arises from the electric-field-induced quenching of the green emission in anatase, allowing the photoexcited charge carriers to be transferred to the adsorbed reactants instead of pointless radiative recombinations. Applying an EEF across a trap-rich metal oxide material, such as TiO2, which, when impregnated with Au NPs, leads, respectively, to 12- and 6-fold enhancements in the production of hydrogen and the oxidation of toluene for an electric field of 8 V/cm, without any electrolysis, is a simple and elegant strategy to meet higher photocatalytic efficiencies.

11.
J Neurol Sci ; 457: 122864, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38185014

RESUMO

Congenital myopathy with tremor (MYOTREM) is a recently described disorder characterized by mild myopathy and a postural and intention tremor present since early infancy. MYOTREM is associated with pathogenic variants in MYBPC1 which encodes slow myosin-binding protein C, a sarcomere protein with regulatory and structural roles. Here, we describe a family with three generations of variably affected members exhibiting a novel variant in MYBPC1 (c.656 T > C, p.Leu219Pro). Among the unique features of affected family members is the persistence of tremor in sleep. We also present the first muscle magnetic resonance images for this disorder, and report muscle atrophy and fatty infiltration.


Assuntos
Doenças Musculares , Tremor , Humanos , Família , Mutação/genética , Tremor/diagnóstico por imagem , Tremor/genética
12.
Child Care Health Dev ; 50(1): e13169, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658639

RESUMO

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.


Assuntos
Baclofeno , Paralisia Cerebral , Criança , Humanos , Hipertonia Muscular , Gabapentina , Canadá
13.
Int J Biol Macromol ; 257(Pt 2): 128687, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101655

RESUMO

Synthetic biodegradable and bio-based polymers have emerged as sustainable alternatives to nonrenewable petroleum-derived polymers which cause serious environmental issues. In particular, polyhydroxyalkanoates (PHA) are promising biopolymers owing to their outstanding biodegradability and biocompatibility. The production of the homopolymer poly(3-hydroxybutyrate) (PHB) and copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from type II methanotrophs via microbial fermentation was presented. For the efficient extraction and recovery of intracellular PHA from methanotrophs, different extraction approaches were investigated including solvent extraction using 1,3-dioxolane as a green solvent, integrated cell lysis and solvent extraction, and cell digestion without the use of organic solvents. Among various extraction approaches, the integrated method exhibited the highest extraction performance, with PHA recovery and purity exceeding 91 % and 93 %, respectively, even when the PHA content of the cells was low. Furthermore, the molecular weight, thermal stability, and mechanical properties of the recovered PHA were comprehensively analyzed to suggest its suitable practical applications. The obtained properties were comparable to that of the commercial PHA products and PHA produced from other microbial species, indicating an efficient recovery of high-quality PHA produced from methanotrophs.


Assuntos
Poli-Hidroxialcanoatos , Biopolímeros , Ácido 3-Hidroxibutírico , Hidroxibutiratos , Solventes
14.
PLoS One ; 18(11): e0294048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37934745

RESUMO

Evaluating the risks and benefits of using traditional medicinal plants is of utmost importance for a huge fraction of the human population, in particular in Northern Vietnam. Zebrafish are increasingly used as a simple vertebrate model for testing toxic and physiological effects of compounds, especially on development. Here, we tested 12 ethanolic extracts from popular medicinal plants collected in northern Vietnam for their effects on zebrafish survival and development during the first 4 days after fertilization. We characterized more in detail their effects on epiboly, hatching, growth, necrosis, body curvature, angiogenesis, skeletal development and mostly increased movement behavior. Finally, we confirm the effect on epiboly caused by the Mahonia bealei extract by staining the actin filaments and performing whole genome gene expression analysis. Further, we show that this extract also inhibits cell migration of mouse embryo fibroblasts. Finally, we analyzed the chemical composition of the Mahonia bealei extract and test the effects of its major components. In conclusion, we show that traditional medicinal plant extracts are able to affect zebrafish early life stage development to various degrees. In addition, we show that an extract causing delay in epiboly also inhibits mammalian cell migration, suggesting that this effect may serve as a preliminary test for identifying extracts that inhibit cancer metastasis.


Assuntos
Plantas Medicinais , Animais , Embrião não Mamífero , Larva , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Vietnã , Peixe-Zebra/genética
15.
Lancet Microbe ; 4(11): e953-e962, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683688

RESUMO

Whole-genome sequencing (WGS) has resulted in improvements to pathogen characterisation for the rapid investigation and management of disease outbreaks and surveillance. We conducted a systematic review to synthesise the economic evidence of WGS implementation for pathogen identification and surveillance. Of the 2285 unique publications identified through online database searches, 19 studies met the inclusion criteria. The economic evidence to support the broader application of WGS as a front-line pathogen characterisation and surveillance tool is insufficient and of low quality. WGS has been evaluated in various clinical settings, but these evaluations are predominantly investigations of a single pathogen. There are also considerable variations in the evaluation approach. Economic evaluations of costs, effectiveness, and cost-effectiveness are needed to support the implementation of WGS in public health settings.


Assuntos
Infecção Hospitalar , Vigilância em Saúde Pública , Humanos , Análise Custo-Benefício , Sequenciamento Completo do Genoma/métodos , Surtos de Doenças , Saúde Pública
16.
Cureus ; 15(8): e43189, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37692610

RESUMO

Colon cancer is one of the most common cancers in the United States of America. In addition to conventional treatment approaches such as surgery, chemotherapy, and radiation for colorectal cancer, immunotherapy has gained recognition over the past few years. However, its effectiveness in colorectal cancer treatment is controversial. Our study investigates the survival and progression-free rates of immunotherapy for different types of colorectal cancer over the last 10 years. We conducted literature reviews from various clinical trials and research studies to evaluate immunotherapy's role in colorectal cancer treatment. We also investigated how it affects clinical outcomes. We discovered a range of effective immunotherapy approaches targeting various growth factors and signaling pathways. These modalities include monoclonal antibodies aimed at growth factors such as epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), human epidermal growth factor receptor 2 (HER2), and downstream signaling pathways such as mitogen-activated protein kinase (MAPK), kirsten rat sarcoma viral oncogene (KRAS), B-raf proto-oncogene, serine/threonine kinase (BRAF), and phosphatase and tensin homolog (PTEN). Additionally, we identified immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors, as well as target therapy and adoptive cell therapy as promising immunotherapeutic options. Nevertheless, the application of immunotherapy remains highly limited due to various factors influencing survival and progression-free rates, including tumor microenvironment, microsatellite instability, immune checkpoint expression, and gut microbiome. Additionally, its effectiveness is restricted to a small subgroup of patients, accompanied by side effects and the development of drug resistance mechanisms. To unlock its full potential, further clinical trials and research on molecular pathways in colorectal cancer are imperative. This will ultimately enhance drug discovery success and lead to more effective clinical management approaches.

17.
Chemistry ; 29(53): e202301210, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37313991

RESUMO

The first phosphorus dendrimers built on a cyclotriphosphazene core and decorated with six or twelve monofluorocyclooctyne units were prepared. A simple stirring allowed the grafting of N-hexyl deoxynojirimycin inhitopes onto their surface by copper-free strain promoted alkyne-azide cycloaddition click reaction. The synthesized iminosugars clusters were tested as multivalent inhibitors of the biologically relevant enzymes ß-glucocerebrosidase and acid α-glucosidase, involved in Gaucher and Pompe lysosomal storage diseases, respectively. For both enzymes, all the multivalent compounds were more potent than the reference N-hexyl deoxynojirimycin. Remarkably, the final dodecavalent compound proved to be one of the best ß-glucocerebrosidase inhibitors described to date. These cyclotriphosphazene-based deoxynojirimycin dendrimers were then evaluated as pharmacological chaperones against Gaucher disease. Not only did these multivalent constructs cross the cell membranes but they were also able to increase ß-glucocerebrosidase activity in Gaucher cells. Notably, dodecavalent compound allowed a 1.4-fold enzyme activity enhancement at a concentration as low as 100 nM. These new monofluorocyclooctyne-presenting dendrimers may further find numerous applications in the synthesis of multivalent objects for biological and pharmacological purposes.


Assuntos
Dendrímeros , Doença de Gaucher , Humanos , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/metabolismo , Glucosilceramidase/uso terapêutico , Inibidores Enzimáticos/metabolismo
18.
J Adv Vet Anim Res ; 10(1): 132-143, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37155534

RESUMO

Objectives: This study aimed to determine the antibiotic-resistant profile and to identify molecular characterization of some virulence genes of Klebsiella spp. isolated from mastitis samples in Vietnam. Materials and Method: A total of 468 samples from clinical mastitis cases were collected and submitted to the Laboratory. All samples were cultured, and Klebsiella spp. was identified through biochemical reactions and confirmed by Polymerase chain reaction (PCR). Antimicrobial resistance was tested by disk diffusion method, and virulence and resistance genes were tested by PCR. Results: An antibiogram study showed that a high proportion of isolates are multidrug-resistant (94%). All isolates were resistant to lincomycin and sulfamethoxazole, followed by ampicillin (94%), sulphonamide (66%), amoxicillin (56%), streptomycin (52%), polymyxin B (28%), colistin sulfate (12%), tetracycline (6%), ciprofloxacin (4%), florfenicol (4%), enrofloxacin (4%), piperacillin (2%), trimethoprim (2%), nalidixic acid (2%), imipenem (2%), and sulfamethoxazole/trimethoprim (2%). In contrast, all isolates showed sensitivity to gentamicin and ceftiofur. The appearance of an efflux pump system, extended-spectrum beta-lactamase (ESBL), tetracycline, and sulphonamides-resistant genes was reconfirmed using different specific primers. Capsular serotype K1 and virulence genes magA, fimH, and entB, responsible for hypermucoviscosity production, adherence, and enterobactin production, were confirmed in isolates. Multidrug resistance and virulence potential in Klebsiella spp. are changing this mastitis pathogen into a superbug and making its management harder. Conclusions: Klebsiella spp. associated with bovine mastitis in Nghe An province were mostly multidrug-resistant and carried virulence genes including fimH, entB, and antimicrobials resistant genes (bla SHV, acrAKp, tetA, etc.), but these isolates were not ESBL producers.

19.
Neurology ; 100(19): e1976-e1984, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36990719

RESUMO

BACKGROUND AND OBJECTIVES: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE. METHODS: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders. RESULTS: Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, p = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, p = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p > 0.1). DISCUSSION: Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes.


Assuntos
Lesões Encefálicas , Epilepsia , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Lactente , Criança , Recém-Nascido , Humanos , Estudos Prospectivos , Convulsões/etiologia , Convulsões/complicações , Epilepsia/complicações , Lesões Encefálicas/complicações , Eletroencefalografia , Hipóxia-Isquemia Encefálica/complicações
20.
J Health Econ ; 88: 102737, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36758392

RESUMO

Do wealthier individuals use more health care services than those less affluent? Our paper addresses this question by examining the relationship between housing wealth and health care utilization. Exploiting fluctuations in the U.S. housing market, we estimate the effect of unanticipated wealth shocks on older adults' health care utilization, using county-year variation in house prices to construct an instrumental variable. Using data from the 1996-2016 Health and Retirement Study, we find that an increase in wealth significantly increases numbers of doctor visits, prescription drugs, outpatient surgery, and dental services. Notably, an economic downturn like that in the Great Recession, when housing wealth declined by 16 percent on average, could reduce the utilization of prescription drugs by 0.4 percent, outpatient services by 0.5 percent, dental care by 0.6 percent, and numbers of doctor visits by 0.5 visits annually.


Assuntos
Habitação , Medicamentos sob Prescrição , Humanos , Idoso , Aposentadoria , Aceitação pelo Paciente de Cuidados de Saúde
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