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1.
Int J Mol Sci ; 25(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38732264

RESUMO

Pyridoxal and pyridoxal 5'-phosphate are aldehyde forms of B6 vitamin that can easily be transformed into each other in the living organism. The presence of a phosphate group, however, provides the related compounds (e.g., hydrazones) with better solubility in water. In addition, the phosphate group may sometimes act as a binding center for metal ions. In particular, a phosphate group can be a strong ligand for a gold(III) ion, which is of interest for researchers for the anti-tumor and antimicrobial potential of gold(III). This paper aims to answer whether the phosphate group is involved in the complex formation between gold(III) and hydrazones derived from pyridoxal 5'-phosphate. The answer is negative, since the comparison of the stability constants determined for the gold(III) complexes with pyridoxal- and pyridoxal 5'-phosphate-derived hydrazones showed a negligible difference. In addition, quantum chemical calculations confirmed that the preferential coordination of two series of phosphorylated and non-phosphorylated hydrazones to gold(III) ion is similar. The preferential protonation modes for the gold(III) complexes were also determined using experimental and calculated data.


Assuntos
Ouro , Hidrazonas , Piridoxal , Hidrazonas/química , Ouro/química , Piridoxal/química , Fosfato de Piridoxal/química , Complexos de Coordenação/química , Espectrofotometria Ultravioleta , Estrutura Molecular
2.
Am J Hum Genet ; 111(6): 1061-1083, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38723632

RESUMO

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Ovarianas , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/genética , Transcriptoma , Fatores de Risco , Genômica/métodos , Estudos de Casos e Controles , Multiômica
3.
Molecules ; 29(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792252

RESUMO

Sorption technologies are essential for various industries because they provide product quality and process efficiency. New encapsulated microspherical composite sorbents have been developed for resource-saving contact drying of thermolabile materials, particularly grain and seeds of crops. Magnesium sulfate, known for its high water capacity, fast sorption kinetics, and easy regeneration, was used as an active moisture sorption component. To localize the active component, porous carriers with an accessible internal volume and a perforated glass-crystalline shell were used. These carriers were created by acid etching of cenospheres with different structures isolated from fly ash. The amount of magnesium sulfate included in the internal volume of the microspherical carrier was 38 wt % for cenospheres with ring structures and 26 wt % for cenospheres with network structures. Studies of the moisture sorption properties of composite sorbents on wheat seeds have shown that after 4 h of contact drying the moisture content of wheat decreases from 22.5 to 14.9-15.5 wt %. Wheat seed germination after sorption drying was 95 ± 2%. The advantage of composite sorbents is the encapsulation of the desiccant in the inner volume of perforated cenospheres, which prevents its entrainment and contamination and provides easy separation and stable sorption capacity in several cycles.

4.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 80(Pt 3): 201-207, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747314

RESUMO

The crystal structure of superprotonic conductor caesium hydrogen sulfate phosphate [Cs4(HSO4)3(H2PO4)] have been analyzed using neutron diffraction methods. Additionally, its structure and surface layers have been investigated using atomic force microscopy. From the diffraction data obtained, Fourier syntheses of neutron scattering densities were calculated, and the localization of hydrogen atoms and the parameters of three types of hydrogen bonds in the crystal structure were accurately determined. Correlation of surface characteristics of samples obtained by atomic force microscopy with their crystal structure is shown.

5.
JAMA Netw Open ; 7(5): e2411699, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767919

RESUMO

Importance: The Joint Commission Unexpected Complications in Term Newborns measure characterizes newborn morbidity potentially associated with quality of labor and delivery care. Infant exclusions isolate relatively low-risk births, but unexpected newborn complications (UNCs) are not adjusted for maternal factors that may be associated with outcomes independently of hospital quality. Objective: To investigate the association between maternal characteristics and hospital UNC rates. Design, Setting, and Participants: This cohort study was conducted using linked 2016 to 2018 New York City birth and hospital discharge datasets among 254 259 neonates at low risk (singleton, ≥37 weeks, birthweight ≥2500 g, and without preexisting fetal conditions) at 39 hospitals. Logistic regression was used to calculate unadjusted hospital-specific UNC rates and replicated analyses adjusting for maternal covariates. Hospitals were categorized into UNC quintiles; changes in quintile ranking with maternal adjustment were examined. Data analyses were performed from December 2022 to July 2023. Main Outcomes and Measures: UNCs were classified according to Joint Commission International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) criteria. Maternal preadmission comorbidities, obstetric factors, social characteristics, and hospital characteristics were ascertained. Results: Among 254 259 singleton births at 37 weeks or later who were at low risk (125 245 female [49.3%] and 129 014 male [50.7%]; 71 768 births [28.2%] to Hispanic, 47 226 births [18.7%] to non-Hispanic Asian, 42 682 births [16.8%] to non-Hispanic Black, and 89 845 births [35.3%] to non-Hispanic White mothers and 2738 births [1.0%] to mothers with another race or ethnicity), 148 393 births (58.4%) were covered by Medicaid and 101 633 births (40.0%) were covered by commercial insurance. The 2016 to 2018 cumulative UNC incidence in New York City hospitals was 37.1 UNCs per 1000 births. Infants of mothers with preadmission risk factors had increased UNC risk; for example, among mothers with vs without preeclampsia, there were 104.4 and 35.8 UNCs per 1000 births, respectively. Among hospitals, unadjusted UNC rates ranged from 15.6 to 215.5 UNCs per 1000 births and adjusted UNC rates ranged from 15.6 to 194.0 UNCs per 1000 births (median [IQR] change from adjustment, 1.4 [-4.7 to 1.0] UNCs/1000 births). The median (IQR) change per 1000 births for adjusted vs unadjusted rates showed that hospitals with low (<601 deliveries/year; -2.8 [-7.0 to -1.6] UNCs) to medium (601 to <954 deliveries/year; -3.9 [-7.1 to -1.9] UNCs) delivery volume, public ownership (-3.6 [-6.2 to -2.3] UNCs), or high proportions of Medicaid-insured (eg, ≥90.72%; -3.7 [-5.3 to -1.9] UNCs), Black (eg, ≥32.83%; -5.3 [-9.1 to -2.2] UNCs), or Hispanic (eg, ≥6.25%; -3.7 [-5.3 to -1.9] UNCs) patients had significantly decreased UNC rates after adjustment, while rates increased or did not change in hospitals with the highest delivery volume, private ownership, or births to predominantly White or privately insured individuals. Among all 39 hospitals, 7 hospitals (17.9%) shifted 1 quintile comparing risk-adjusted with unadjusted quintile rankings. Conclusions and Relevance: In this study, adjustment for maternal case mix was associated with small overall changes in hospital UNC rates. These changes were associated with performance assessment for some hospitals, and these results suggest that profiling on this measure should consider the implications of small changes in rates for hospitals with higher-risk obstetric populations.


Assuntos
Hospitais , Humanos , Feminino , Recém-Nascido , Adulto , Gravidez , Cidade de Nova Iorque/epidemiologia , Masculino , Hospitais/estatística & dados numéricos , Doenças do Recém-Nascido/epidemiologia , Complicações na Gravidez/epidemiologia , Estudos de Coortes , Nascimento a Termo , Fatores de Risco , Adulto Jovem , Estados Unidos/epidemiologia
6.
JAMA Cardiol ; 9(7): 631-639, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776106

RESUMO

Importance: The use of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been rapidly expanding as an alternative treatment to redo surgical aortic valve replacement (SAVR) for failed bioprosthetic valves despite limited long-term data. Objective: To assess mortality and morbidity in patients undergoing intervention for failed bioprosthetic SAVR. Design, Setting, and Participants: This was a retrospective population-based cohort analysis conducted between January 1, 2015, and December 31, 2020, with a median (IQR) follow-up time of 2.3 (1.1-4.0) years. A total of 1771 patients with a history of bioprosthetic SAVR who underwent ViV-TAVR or redo SAVR in California, New York, and New Jersey were included. Data were obtained from the California Department of Health Care Access and Information, the New York Statewide Planning and Research Cooperative System, and the New Jersey Discharge Data Collection System. Exclusion criteria included undergoing TAVR or redo SAVR within 5 years from initial SAVR, as well as infective endocarditis, concomitant surgical procedures, and out-of-state residency. Propensity matching yielded 375 patient pairs. Data were analyzed from January to December 2023. Interventions: ViV-TAVR vs redo SAVR. Main Outcomes and Measurements: The primary outcome was all-cause mortality. Secondary outcomes were stroke, heart failure hospitalization, reoperation, major bleeding, acute kidney failure, new pacemaker insertion, and infective endocarditis. Results: From 2015 through 2020, the proportion of patients undergoing ViV-TAVR vs redo SAVR increased from 159 of 451 (35.3%) to 498 or 797 (62.5%). Of 1771 participants, 653 (36.9%) were female, and the mean (SD) age was 74.4 (11.3) years. Periprocedural mortality and stroke rates were similar between propensity-matched groups. The ViV-TAVR group had lower periprocedural rates of major bleeding (2.4% vs 5.1%; P = .05), acute kidney failure (1.3% vs 7.2%; P < .001), and new pacemaker implantations (3.5% vs 10.9%; P < .001). The 5-year all-cause mortality rate was 23.4% (95% CI, 15.7-34.1) in the ViV-TAVR group and 13.3% (95% CI, 9.2-18.9) in the redo SAVR group. In a landmark analysis, no difference in mortality was observed up to 2 years (hazard ratio, 1.03; 95% CI, 0.59-1.78), but after 2 years, ViV-TAVR was associated with higher mortality (hazard ratio, 2.97; 95% CI, 1.18-7.47) as well as with a higher incidence of heart failure hospitalization (hazard ratio, 3.81; 95% CI, 1.57-9.22). There were no differences in 5-year incidence of stroke, reoperation, major bleeding, or infective endocarditis. Conclusions and Relevance: Compared with redo SAVR, ViV-TAVR was associated with a lower incidence of periprocedural complications and a similar incidence of all-cause mortality through 2 years' follow-up. However, ViV-TAVR was associated with higher rates of late mortality and heart failure hospitalization. These findings may be influenced by residual confounding and require adjudication in a randomized clinical trial.


Assuntos
Bioprótese , Reoperação , Substituição da Valva Aórtica Transcateter , Humanos , Feminino , Masculino , Idoso , Substituição da Valva Aórtica Transcateter/métodos , Estudos Retrospectivos , Reoperação/estatística & dados numéricos , Idoso de 80 Anos ou mais , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/epidemiologia , Falha de Prótese , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos
7.
Biochemistry (Mosc) ; 89(Suppl 1): S180-S204, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38621750

RESUMO

In many proteins, supplementary metal-binding centers appear under stress conditions. They are known as aberrant or atypical sites. Physico-chemical properties of proteins are significantly changed after such metal binding, and very stable protein aggregates are formed, in which metals act as "cross-linking" agents. Supplementary metal-binding centers in proteins often arise as a result of posttranslational modifications caused by reactive oxygen and nitrogen species and reactive carbonyl compounds. New chemical groups formed as a result of these modifications can act as ligands for binding metal ions. Special attention is paid to the role of cysteine SH-groups in the formation of supplementary metal-binding centers, since these groups are the main target for the action of reactive species. Supplementary metal binding centers may also appear due to unmasking of amino acid residues when protein conformation changing. Appearance of such centers is usually considered as a pathological process. Such unilateral approach does not allow to obtain an integral view of the phenomenon, ignoring cases when formation of metal complexes with altered proteins is a way to adjust protein properties, activity, and stability under the changed redox conditions. The role of metals in protein aggregation is being studied actively, since it leads to formation of non-membranous organelles, liquid condensates, and solid conglomerates. Some proteins found in such aggregates are typical for various diseases, such as Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and some types of cancer.


Assuntos
Metais , Estresse Oxidativo , Metais/química , Metais/metabolismo , Oxirredução , Processamento de Proteína Pós-Traducional
8.
J Am Coll Cardiol ; 83(17): 1656-1668, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38658105

RESUMO

BACKGROUND: Tricuspid valve annuloplasty (TA) during mitral valve repair (MVr) is associated with increased risk of permanent pacemaker (PPM) implantation, but the magnitude of risk and long-term clinical consequences have not been firmly established. OBJECTIVES: This study assesses the incidence rates of PPM implantation after isolated MVr and following MVr with TA as well as the associated long-term clinical consequences of PPM implantation. METHODS: State-mandated hospital discharge databases of New York and California were queried for patients undergoing MVr (isolated or with concomitant TA) between 2004 and 2019. Patients were stratified by whether or not they received a PPM within 90 days of index surgery. After weighting by propensity score, survival, heart failure hospitalizations (HFHs), endocarditis, stroke, and reoperation were compared between patients with or without PPM. RESULTS: A total of 32,736 patients underwent isolated MVr (n = 28,003) or MVr + TA (n = 4,733). Annual MVr + TA volumes increased throughout the study period (P < 0.001, trend), and PPM rates decreased (P < 0.001, trend). The incidence of PPM implantation <90 days after surgery was 7.7% for MVr and 14.0% for MVr + TA. In 90-day conditional landmark-weighted analyses, PPMs were associated with reduced long-term survival among MVr (HR: 1.96; 95% CI: 1.75-2.19; P < 0.001) and MVr + TA recipients (HR: 1.65; 95% CI: 1.28-2.14; P < 0.001). In both surgical groups, PPMs were also associated with an increased risk of HFH (HR: 1.56; 95% CI: 1.27-1.90; P < 0.001) and endocarditis (HR: 1.95; 95% CI: 1.52-2.51; P < 0.001), but not with stroke or reoperation. CONCLUSIONS: Compared to isolated MVr, adding TA to MVr was associated with a higher risk of 90-day PPM implantation. In both surgical groups, PPM implantation was associated with an increase in mortality, HFH, and endocarditis.


Assuntos
Marca-Passo Artificial , Valva Tricúspide , Humanos , Feminino , Masculino , Idoso , Marca-Passo Artificial/efeitos adversos , Valva Tricúspide/cirurgia , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Estudos Retrospectivos , Anuloplastia da Valva Cardíaca/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
9.
Comp Cytogenet ; 18: 51-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601956

RESUMO

Polyploidy is a condition in which a cell has multiple diploid sets of chromosomes. Two forms of polyploidy are known. One of them, generative polyploidy, is characteristic of all cells of the organism, while the other form develops only in some somatic tissues at certain stages of postnatal ontogenesis. Whole genome duplication has played a particularly important role in the evolution of plants and animals, while the role of cellular (somatic) polyploidy in organisms remains largely unclear. In this work we investigated the contribution of cellular polyploidy to the normal and the reparative liver growth of Rattusnorvegicus (Berkenhout, 1769) and Homosapiens Linnaeus, 1758. It is shown that polyploidy makes a significant contribution to the increase of the liver mass both in the course of normal postnatal development and during pathological process.

10.
Biochemistry (Mosc) ; 89(3): 507-522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38648769

RESUMO

Some tricyclic antidepressants (TCAs), including amitriptyline (ATL), clomipramine (CLO), and desipramine (DES), are known to be effective for management of neuropathic pain. It was previously determined that ATL, CLO, and DES are capable of voltage-dependent blocking of NMDA receptors of glutamate (NMDAR), which play a key role in pathogenesis of neuropathic pain. Despite the similar structure of ATL, CLO, and DES, efficacy of their interaction with NMDAR varies significantly. In the study presented here, we applied molecular modeling methods to investigate the mechanism of binding of ATL, CLO, and DES to NMDAR and to identify structural features of the drugs that determine their inhibitory activity against NMDAR. Molecular docking of the studied TCAs into the NMDAR channel was performed. Conformational behavior of the obtained complexes in the lipid bilayer was simulated by the method of molecular dynamics (MD). A single binding site (upper) for the tertiary amines ATL and CLO and two binding sites (upper and lower) for the secondary amine DES were identified inside the NMDAR channel. The upper and lower binding sites are located along the channel axis at different distances from the extracellular side of the plasma membrane. MD simulation revealed that the position of DES in the lower site is stabilized only in the presence of sodium cation inside the NMDAR channel. DES binds more strongly to NMDAR compared to ATL and CLO due to simultaneous interaction of two hydrogen atoms of its cationic group with the asparagine residues of the ion pore of the receptor. This feature may be responsible for the stronger side effects of DES. It has been hypothesized that ATL binds to NMDAR less efficiently compared to DES and CLO due to its lower conformational mobility. The identified features of the structure- and cation-dependent mechanism of interaction between TCAs and NMDAR will help in the further development of effective and safe analgesic therapy.


Assuntos
Antidepressivos Tricíclicos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/química , Antidepressivos Tricíclicos/farmacologia , Antidepressivos Tricíclicos/metabolismo , Antidepressivos Tricíclicos/química , Sítios de Ligação , Amitriptilina/química , Amitriptilina/metabolismo , Amitriptilina/farmacologia , Humanos , Clomipramina/farmacologia , Clomipramina/química , Clomipramina/metabolismo , Cátions/metabolismo , Cátions/química , Desipramina/farmacologia , Ligação Proteica
11.
Micromachines (Basel) ; 15(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38675287

RESUMO

DNA data storage based on synthetic oligonucleotides is a major attraction due to the possibility of storage over long periods. Nowadays, the quantity of data generated has been growing exponentially, and the storage capacity needs to keep pace with the growth caused by new technologies and globalization. Since DNA can hold a large amount of information with a high density and remains stable for hundreds of years, this technology offers a solution for current long-term data centers by reducing energy consumption and physical storage space. Currently, research institutes, technology companies, and universities are making significant efforts to meet the growing need for data storage. DNA data storage is a promising field, especially with the advancement of sequencing techniques and equipment, which now make it possible to read genomes (i.e., to retrieve the information) and process this data easily. To overcome the challenges associated with developing new technologies for DNA data storage, a message encoding and decoding exercise was conducted at a Brazilian research center. The exercise performed consisted of synthesizing oligonucleotides by the phosphoramidite route. An encoded message, using a coding scheme that adheres to DNA sequence constraints, was synthesized. After synthesis, the oligonucleotide was sequenced and decoded, and the information was fully recovered.

12.
J Pediatr Hematol Oncol ; 46(3): e220-e222, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447071

RESUMO

Acquired thrombotic thrombocytopenic (aTTP) purpura is a life-threatening condition that can lead to devastating thromboembolic events. Recently, caplacizumab has been shown to rapidly restore platelet numbers and reduce the risk of severe end-organ damage when added to plasma exchanges (PEXs) and immunosuppression (IST). Here, we report the outcomes in 3 children with aTTP who were treated with caplacizumab in combination with PEXs and IST. In all 3 patients, platelet count increased to >15,000/mm 3 in 24 h and normalized on day 4, whereas normalization of ADAMTS13 activity >50% and elimination of the inhibitor was achieved after 18 to 89 days. Epistaxis was observed in 2 patients and was the only side effect related to caplacizumab. Caplacizumab is a promising agent for first-line treatment of children with aTTP.


Assuntos
Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Criança , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Troca Plasmática , Fator de von Willebrand , Terapia de Imunossupressão , Proteína ADAMTS13
13.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542080

RESUMO

Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements.


Assuntos
Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Humanos , Super Intensificadores , RNA
14.
Macromol Biosci ; : e2400028, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38511568

RESUMO

Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulates the moisture levels of the tissue and is capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal membranes to assess mucoadhesion and muco-penetration of pharmaceutical formulations which may struggle with limited accessibility, reproducibility, and ethical questions. Aiming to develop a platform for the rationale study of the interaction of drugs and delivery systems with mucosal tissues, in this work mucus-mimicking mucin-based hydrogels are synthesized by the tandem chemical and physical crosslinking of mucin aqueous solutions. Chemical crosslinking is achieved with glutaraldehyde (0.3% and 0.75% w/v), while physical crosslinking by one or two freeze-thawing cycles. Hydrogels after one freeze-thawing cycle show water content of 97.6-98.1%, density of 0.0529-0.0648 g cm⁻3, and storage and loss moduli of ≈40-60 and ≈3-5 Pa, respectively, that resemble the properties of native gastrointestinal mucus. The mechanical stability of the hydrogels increases over the number of freeze-thawing cycles. Overall results highlight the potential of this simple, reproducible, and scalable method to produce artificial mucus-mimicking hydrogels for different applications in pharmaceutical research.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38492720

RESUMO

OBJECTIVE: Limited comparative data guide the decision between coronary artery bypass grafting and percutaneous coronary intervention for multivessel revascularization in ischemic cardiomyopathy. The study objective was to compare the long-term outcomes of coronary artery bypass grafting and percutaneous coronary intervention for ischemic cardiomyopathy. METHODS: Clinical registries from the New Jersey Department of Health linked to administrative databases were used to compare all-cause mortality, repeat revascularization, heart failure readmissions, myocardial infarction, and stroke using Cox proportional hazards and propensity matching with competing risk analysis in 5988 patients with ejection fraction 35% or less who underwent coronary artery bypass grafting (3673, 61.3%) or percutaneous coronary intervention (2315, 38.6%) for multivessel coronary disease between 2007 and 2018. Median follow-up time was 5.2 years (range, 0-13 years); the last follow-up date was December 31, 2020. RESULTS: After controlling for completeness of revascularization, at 13 years, mortality was 57% (95% CI, 51-63) after percutaneous coronary intervention and 60% (95% CI, 53-66) after coronary artery bypass grafting (hazard ratio [HR], 1.10; 95% CI, 0.93-1.31; P = .28); risk of repeat revascularization was 18% for percutaneous coronary intervention versus 14% for coronary artery bypass grafting (HR, 1.62; 95% CI, 1.17-2.25; P = .003); risk of readmission for heart failure was 16% after percutaneous coronary intervention and coronary artery bypass grafting (HR, 1.13,95% CI, 0.84-1.51, weighted P = .10); risk of myocardial infarction was 10% versus 6%, respectively (HR, 1.91; 95% CI, 1.18-3.09; P = .007); and stroke risk was 3% versus 4%, respectively (HR, 0.79; 95% CI, 0.41-1.53; P = .52). Rate of complete revascularization was lower after percutaneous coronary intervention than after coronary artery bypass grafting and associated with higher mortality after percutaneous coronary intervention (HR, 1.35; 95% CI, 1.20-1.52; P < .001). CONCLUSIONS: Coronary bypass was associated with similar mortality, stroke, and heart failure readmissions, and reduced repeat revascularization compared with percutaneous coronary intervention in patients with ischemic cardiomyopathy if similar rates of complete revascularization were achieved. These findings support consensus recommendations for coronary artery bypass grafting and medical therapy in patients with multivessel coronary disease and left ventricular dysfunction.

16.
Viruses ; 16(3)2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38543751

RESUMO

Bacteria of the genus Staphylococcus are significant challenge for medicine, as many species are resistant to multiple antibiotics and some are even to all of the antibiotics we use. One of the approaches to developing new therapeutics to treat staphylococcal infections is the use of bacteriophages specific to these bacteria or the lytic enzymes of such bacteriophages, which are capable of hydrolyzing the cell walls of these bacteria. In this study, a new bacteriophage vB_SepP_134 (St 134) specific to Staphylococcus epidermidis was described. This podophage, with a genome of 18,275 bp, belongs to the Andhravirus genus. St 134 was able to infect various strains of 12 of the 21 tested coagulase-negative Staphylococcus species and one clinical strain from the Staphylococcus aureus complex. The genes encoding endolysin (LysSte134_1) and tail tip lysin (LysSte134_2) were identified in the St 134 genome. Both enzymes were cloned and produced in Escherichia coli cells. The endolysin LysSte134_1 demonstrated catalytic activity against peptidoglycans isolated from S. aureus, S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus warneri. LysSte134_1 was active against S. aureus and S. epidermidis planktonic cells and destroyed the biofilms formed by clinical strains of S. aureus and S. epidermidis.


Assuntos
Bacteriófagos , Endopeptidases , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Bacteriófagos/genética , Staphylococcus , Staphylococcus epidermidis , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes
17.
Arch Gerontol Geriatr ; 122: 105397, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38484670

RESUMO

BACKGROUND AND OBJECTIVES: Using US national nursing home data, this cross-sectional study sought to evaluate 1) the association between lack of social engagement and level of cognitive impairment; and 2) the extent to which this association differs by hearing and visual impairment. RESEARCH DESIGN AND METHODS: Our sample included 793,846 nursing home residents aged ≥ 50 years. The Index of Social Engagement was categorized as none/lower (0, 1, 2) or higher levels (3 through 6). Cognitive Performance Scale was grouped as intact/mild (0, 1, 2), moderate (3, 4), or severe (5, 6). Multinomial models provided adjusted odds ratio (aOR) and 95 % confidence intervals (CI) between none/lower social engagement and cognitive impairment. We estimated relative excess risk due to interaction (RERI) to quantify the joint effects of social engagement and sensory impairment types. RESULTS: Overall, 12.6 % had lower social engagement, 30.3 % had hearing impairment, and 40.3 % had visual impairment. Compared to residents with high social engagement, those with lower social engagement were more likely to have moderate/severe cognitive impairment (aORmoderate = 2.21, 95 % CI 2.17-2.26; aORsevere = 6.49, 95 % CI 6.24-6.74). The impact of low social engagement on cognitive impairment was more profound among residents with hearing impairment and/or visual impairment (RERIhearing = 3.89, 95 % CI 3.62-4.17; RERIvisual = 25.2, 95 % CI 23.9-26.6)). DISCUSSION AND IMPLICATIONS: Residents with lower social engagement had higher levels of cognitive impairment. Residents with sensory impairments are potentially more susceptible to the negative impact of lower levels of social engagement on level of cognitive impairment.


Assuntos
Disfunção Cognitiva , Casas de Saúde , Transtornos da Visão , Humanos , Casas de Saúde/estatística & dados numéricos , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Estudos Transversais , Idoso , Transtornos da Visão/epidemiologia , Transtornos da Visão/psicologia , Transtornos da Visão/complicações , Idoso de 80 Anos ou mais , Participação Social/psicologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Perda Auditiva/psicologia , Perda Auditiva/epidemiologia , Instituição de Longa Permanência para Idosos/estatística & dados numéricos
18.
Biomedicines ; 12(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38397896

RESUMO

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

19.
Vet Sci ; 11(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38393109

RESUMO

In this study, we used the Manchurian golden breed of quails. We assessed the efficacy of the food additives of the phytase from Obesumbacterium proteus encapsulated in the recombinant Yarrowia lipolytica yeast, which was supplied at a concentration of 500 phytase activity units per kg of the feed. One hundred fifty one-day-old quails were distributed into six treatment groups. The results showed that adding the O. proteus encapsulated phytase to the quails' diets improved live weight, body weight gain, and feed conversion compared to those in the control groups and the groups using a commercial phytase from Aspergillus ficuum. The results obtained during the experiments indicate a high degree of assimilation of phytate-containing feeds if the encapsulated phytase was fed by the quails compared to that in the other groups. We can conclude that the class D encapsulated phytase is an expedient additive to the diets possessing better kinetic features compared to the PhyA and PhyC classes phytases when it acts inside the quail's chyme.

20.
Microbiol Resour Announc ; 13(3): e0098023, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38329355

RESUMO

We present six whole community shotgun metagenomic sequencing data sets of two types of biological soil crusts sampled at the ecotone of the Mojave Desert and Colorado Desert in California. These data will help us understand the diversity and function of biocrust microbial communities, which are essential for desert ecosystems.

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