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1.
Bull World Health Organ ; 102(7): 476-485C, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38933479

RESUMO

Objective: To assess the availability of information on indicators of the World Health Organization and United Nations Children's Fund primary health-care measurement framework in Bangladesh, India, Nepal, Pakistan and Sri Lanka and to outline the opportunities for and challenges to using the framework in these countries. Methods: We reviewed global and national data repositories for quantitative indicators of the framework and conducted a desk review of country documents for qualitative indicators in February-April 2023. We assessed data sources and cross-sectional survey tools to suggest possible sources of information on framework indicators that were not currently reported in the countries. We also identified specific indicators outside the framework on which information is collected in the countries and which could be used to measure primary health-care performance. Findings: Data on 54% (32/59) of the quantitative indicators were partially or completely available for the countries, ranging from 41% (24/59) in Pakistan to 64% (38/59) in Nepal. Information on 41% (66/163) of the qualitative subindicators could be acquired through desk reviews of country-specific documents. Information on input indicators was more readily available than on process and output indicators. The feasibility of acquiring information on the unreported indicators was moderate to high through adaptation of data collection instruments. Conclusion: The primary health-care measurement framework provides a platform to readily assess and track the performance of primary health care. Countries should improve the completeness, quality and use of existing data for strengthening of primary health care.


Assuntos
Atenção Primária à Saúde , Nações Unidas , Organização Mundial da Saúde , Humanos , Atenção Primária à Saúde/organização & administração , Nepal , Bangladesh , Paquistão , Índia , Estudos Transversais , Sri Lanka , Indicadores de Qualidade em Assistência à Saúde
2.
ACS Appl Bio Mater ; 7(6): 4162-4174, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38769764

RESUMO

The escalating threat of antimicrobial resistance has become a global health crisis. Therefore, there is a rising momentum in developing biomaterials with self-sanitizing capabilities and inherent antibacterial properties. Despite their promising antimicrobial properties, metal nanoparticles (MNPs) have several disadvantages, including increased toxicity as the particle size decreases, leading to oxidative stress and DNA damage that need consideration. One solution is surface functionalization with biocompatible organic ligands, which can improve nanoparticle dispersibility, reduce aggregation, and enable targeted delivery to microbial cells. The existing research predominantly concentrates on the advancement of peptide-based hydrogels for coating materials to prevent bacterial infection, with limited exploration of developing surface coatings using organogels. Herein, we have synthesized organogel-based coatings doped with MNPs that can offer superior hydrophobicity, oleophobicity, and high stability that are not easily achievable with hydrogels. The self-assembled gels displayed distinct morphologies, as revealed by scanning electron microscopy and atomic force microscopy. The cross-linked matrix helps in the controlled and sustained release of MNPs at the site of bacterial infection. The synthesized self-assembled gel@MNPs exhibited excellent antibacterial properties against harmful bacteria such as Escherichia coli and Staphylococcus aureus and reduced bacterial viability up to 95% within 4 h. Cytotoxicity testing against metazoan cells demonstrated that the gels doped with MNPs were nontoxic (IC50 > 100 µM) to mammalian cells. Furthermore, in this study, we coated the organogel@MNPs on cotton fabric and tested it against Gram +ve and Gram -ve bacteria. Additionally, the developed cotton fabric exhibited superhydrophobic properties and developed a barrier that limits the interaction between bacteria and the surface, making it difficult for bacteria to adhere and colonize, which holds potential as a valuable resource for self-cleaning coatings.


Assuntos
Antibacterianos , Cobre , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Prata , Propriedades de Superfície , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Cobre/química , Cobre/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Géis/química
3.
J Exp Bot ; 75(10): 2773-2775, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764322
4.
Chemistry ; : e202401239, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818941

RESUMO

Herein, we describe water-soluble heteroaryl azopyridinium ionic photoswitches (HAPIPs). We aim to combine variations in five-membered heterocycles, their substitutions, N-alkyl groups at pyridinium nitrogen, the position of pyridinium center relative to azo group, counterions, and solvents, in achieving better photoswitching. Through these studies, we successfully tuned the half-life of Z isomers of the resultant HAPIPs between seconds to days in water. Extensive spectroscopic studies and density functional theory (DFT) computations unravelled the factors responsible for thermal relaxation behavior. Considering the versatility of these photoswitches, the tunability of half-lives and photoswitching in aqueous medium allows the scope of applications in several fields.

5.
Langmuir ; 40(25): 12911-12924, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38691550

RESUMO

Multifunctional carbon-based materials exhibit a large number of unprecedented active sites via an electron transfer process and act as a desired platform for exploring high-performance electroactive material. Herein, we exemplify the holistic design of a heterometallic nanostructured material (MWCNTs@KR-6/Mn/Sn/Pb) formed by the integration of metals (Mn2+, Sn2+, and Pb2+) and a dipodal ligand (KR-6) at the surface of multiwalled carbon nanotubes (MWCNTs). First, MWCNTs@KR-6 was readily synthesized via a noncovalent approach, which was further sequentially doped by Mn2+, Sn2+, and Pb2+ to give MWCNTs@KR-6/Mn/Sn/Pb. The designed material showed excellent electrochemical activity for the discrimination of insecticides belonging to structurally different classes. In contrast to that of the individual building components, both the stability and electrochemical activity of heterometallic nanostructured material were remarkably enhanced, resulting in a magnificent electrochemical performance of the developed material. Hence, the current work reports a comprehensive synthetic approach for MWCNTs@KR-6/Mn/Sn/Pb synthesis by synergizing unique properties of the heterometallic complex with MWCNTs. This work also offers a new insight into the design of multifunctional carbon-based materials for discrimination of different analytes on the basis of their redox potential.

6.
Chem Asian J ; 19(12): e202400258, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629210

RESUMO

Chemosensing, an interdisciplinary scientific domain, plays a pivotal role ranging from environmental monitoring to healthcare diagnostics and (inter)national security. Metal-organic gels (MOGs) are recognized for their stability, selectivity, and responsiveness, making them valuable for chemosensing applications. Researchers have explored the development of MOGs based on different metal ions and ligands, allowing for tailored properties and sensitivities, and have even demonstrated their applications as portable sensors such as paper-based test strips for practical use. Herein, several studies related to MOGs development and their applications in the chemosensing field via UV-visible or luminance along with electrochemical approach are presented. These papers explored MOGs as versatile materials with their use in sensing bio or environmental analytes. This review provides a foundational understanding of key concepts, methodologies, and recent advancements in this field, fostering the scientific community.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38635134

RESUMO

The current study was designed to describe usual clinical care for youth with primary anxiety problems in community mental health centers. The observer-rated Therapy Process Observational Coding System for Child Psychotherapy - Revised Strategies scale (TPOCS-RS), designed to assess therapeutic techniques from five theory-based domains, was used to code sessions (N = 403) from the usual clinical care group of two randomized effectiveness trials: (a) Youth Anxiety Study (YAS) with 21 youth (M age = 10.44 years, SD = 1.91; 49.2% Latinx; 46.6%, 53.4% male) and 16 clinicians (77.5% female; 43.8% White), and (b) Child STEPS Multisite Trial with 17 youth (M age = 10.00 years, SD = 1.87; 58.8% male; 41.2% White) and 13 clinicians (M age = 40.00 years; SD = 9.18; 76.9% female; 61.5% White). The average number of TPOCS-RS items observed per treatment session was more than 10, and multiple techniques were used together in each session. All TPOCS-RS items were observed at least once throughout a clinical case, and most items reoccurred (i.e., observed in two or more sessions). The dosage of TPOCS-RS in all items was below 5 on a 7-point scale. In conclusion, clinicians in both usual care samples used a wide range of techniques from several theory-based domains at a low to medium dose. However, the type and dosage of the techniques used did vary across the two samples.

8.
Cureus ; 16(3): e57112, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38681316

RESUMO

Background The outbreak of the COVID-19 pandemic led to the rise of various social issues apart from medical ones. Several myths regarding COVID-19 vaccination were found worldwide, and some of the common ones identified were abortions, birth defects, bad pregnancy outcomes such as abortions, ectopic pregnancy, risk of infertility, and irregular menstrual cycles. Although no scientific theories or data backed those myths, pregnancy was still omitted from trials for a long time as any drug/vaccine given during pregnancy may affect the fetus. Objective The objective of this study was to evaluate the vaccination status of pregnant women (PW) regarding COVID-19 and explore the factors influencing those who chose not to get the initial dose, second dose, or booster dose. Methodology A total of 747 PW were enrolled in the current study. Information related to sociodemographic data, clinical data, COVID-19 vaccine status, and rationale for choosing not to receive the COVID-19 vaccination was analyzed using a prestructured and validated Performa. Results The mean age and gestational age of the women enrolled for the study was 27.39 ± 3.75 years and 30.21 ± 7.30 weeks, respectively. The first dose of the COVID-19 vaccine was not received by 40 (5.4%) subjects, and the second dose was pending in 142 (19%) women, and none of them received booster dose. The prevalent cause for abstaining from receiving the COVID-19 vaccination was the fear of abortion in 179 (24%) subjects, followed by the fear of vaccine-related side effects in 142 (19%) subjects. There was a significant correlation between acceptance of COVID-19 vaccination and education and employment. Conclusion The present study indicated that most women have taken the COVID-19 vaccine before conception and that none received the first, second, or booster dose during pregnancy, even if it was due. Women need to be educated about the benefits of vaccination to enhance the compliance rate of COVID-19 vaccination and reduce COVID-19-related morbidity and mortality during pregnancy.

9.
Molecules ; 29(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474626

RESUMO

The current study describes a novel and eco-conscious method to synthesize 1,4-dihydropyridine derivatives utilizing an aqueous micellar solution containing aluminum dodecyl sulfate, Al(DS)3, using readily available starting material. The final products were synthesized with excellent yields within remarkably quick reaction durations, promoting remarkable atom economy and minimizing environmental impacts. The present protocol has several advantages over other methodologies in terms of high yield (up to 97%) with excellent purity. Further, the synthesized 1,4-DHPs exhibit favorable to excellent resistance against examined bacterial and fungal species. Intriguingly, polar groups on the phenyl ring (5b, 5c, 5i and 5j) make the 1,4-DHPs equally potent against the microbes as compared to the standard drugs.


Assuntos
Di-Hidropiridinas , Compostos Heterocíclicos , Micro-Ondas , Alumínio
10.
Langmuir ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319126

RESUMO

In recent years, the issue of pharmaceutical contaminants in water bodies has emerged as a significant environmental concern owing to the potential negative impacts on both aquatic ecosystems and human health. Consequently, the development of efficient and eco-friendly methods for their determination and removal is of paramount importance. In this context, the development of a surfactant ensemble sensor has been explored for hard-to-sense amphiphilic drug, i.e., amitriptyline. Herein, a pyrene-based amphiphile chemoreceptor was synthesized and characterized through various spectroscopic techniques such as 1H, 13C NMR, single-crystal XRD, FTIR, and ES-mass spectrometry. Then, dodecanoic acid (DA) and a pyrene-based receptor in a THF/water solvent system were used to generate reverse micelle-based self-aggregates of SUPRAS (SUPRAmolecular Solvent). The structural aspects, such as morphology and size, along with the stability of the SUPRAS aggregates were unfolded through spectroscopic and microscopic insights. The present investigation describes a synergistic approach that combines the unique properties of premicellar concentration of supramolecular solvent with the promising potential of pyrene-based receptor for enhanced amitriptyline extraction with simultaneous determination from water (LOD = 12 nM). To evaluate the effectiveness of the developed aggregates in real-world scenarios, experiments were conducted to determine the sensing efficiency among various pharmaceutical pollutants commonly found in water sources. The results reveal that the synergistic nanoensemble exhibits remarkable sensing ability, toward the amitriptyline (AMT) drug outperforming conventional methods.

11.
Fungal Biol Biotechnol ; 11(1): 2, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409036

RESUMO

BACKGROUND: Fusarium Head Blight (FHB) is a destructive floral disease of different cereal crops. The Ascomycete fungus Fusarium graminearum (Fg) is one of the main causal agents of FHB in wheat and barley. The role(s) in virulence of Fg genes include genetic studies that involve the transformation of the fungus with different expression cassettes. We have observed in several studies where Fg genes functions were characterised that integration of expression cassettes occurred randomly. Random insertion of a cassette may disrupt gene expression and/or protein functions and hence the overall conclusion of the study. Target site integration (TSI) is an approach that consists of identifying a chromosomal region where the cassette can be inserted. The identification of a suitable locus for TSI in Fg would avert the potential risks of ectopic integration. RESULTS: Here, we identified a highly conserved intergenic region on chromosome 1 suitable for TSI. We named this intergenic region TSI locus 1. We developed an efficient cloning vector system based on the Golden Gate method to clone different expression cassettes for use in combination with TSI locus 1. We present evidence that integrations in the TSI locus 1 affects neither fungal virulence nor fungal growth under different stress conditions. Integrations at the TSI locus 1 resulted in the expression of different gene fusions. In addition, the activities of Fg native promoters were not altered by integration into the TSI locus 1. We have developed a bespoke bioinformatic pipeline to analyse the existence of ectopic integrations, cassette truncations and tandem insertions of the cassette that may occurred during the transformation process. Finally, we established a protocol to study protein secretion in wheat coleoptiles using confocal microscopy and the TSI locus 1. CONCLUSION: The TSI locus 1 can be used in Fg and potentially other cereal infecting Fusarium species for diverse studies including promoter activity analysis, protein secretion, protein localisation studies and gene complementation. The bespoke bioinformatic pipeline developed in this work together with PCR amplification of the insert could be an alternative to Southern blotting, the gold standard technique used to identify ectopic integrations, cassette truncations and tandem insertions in fungal transformation.

12.
Adv Rheumatol ; 64(1): 1, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167388

RESUMO

BACKGROUND: Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. METHODS: We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and non-hospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. RESULTS: We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. CONCLUSIONS: Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Feminino , Humanos , Masculino , Doenças do Tecido Conjuntivo/complicações , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/terapia , Escleroderma Sistêmico/complicações , Hospitalização , Prontuários Médicos
13.
Anal Methods ; 16(7): 1111-1122, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38293839

RESUMO

Ochratoxin A (OTA) is the most abundant and harmful toxin found in agriculture and processed food. The environment and human health are both harmed by this mycotoxin. As a result, in various scenarios, selective detection and biodegradation of ochratoxin A are essential. The current study reveals the morphogenesis of a peptidic-benzimidazolium dipodal receptor (SS4) and its application as a catalytic and sensing unit for the detection and degradation of OTA in an aqueous medium. Initially, a facile and scalable method was executed to synthesize SS4, and solvent-directed morphogenesis were examined under SEM analysis. Consequently, molecular recognition properties of self-assembled architectures were explored using UV-visible absorption, fluorescence spectroscopy, and atomic force microscopy (AFM). The designed probe showed a ratiometric response for OTA and served as a catalytic unit for the degradation of OTA at a short interval of 25 min. The biodegradation pathway for OTA was accomplished using LC-MS analysis. Furthermore, the reliability of the developed method was checked by determining the spiked concentrations of the OTA in cereals and wine samples. The results obtained are in good agreement with the % recovery and RSD values. The present work provides a robust, selective, and sensitive method of detection and degradation for OTA.


Assuntos
Contaminação de Alimentos , Ocratoxinas , Humanos , Solventes , Reprodutibilidade dos Testes , Contaminação de Alimentos/análise , Ocratoxinas/análise
14.
Clin Nephrol ; 101(3): 152-154, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214175

RESUMO

Opportunistic infections are common in transplant recipients, but gastrointestinal bleed is rarely reported to be due to opportunistic fungal infections, and hence could present as a diagnostic challenge. We report a case of disseminated histoplasmosis in a kidney transplant recipient whose initial presentation was acute lower gastrointestinal bleeding with no other symptoms. The colonoscopy showed scattered punchout circular colonic ulcers with biopsy revealing budding yeasts consistent with a diagnosis of histoplasmosis. The patient was successfully treated with a prolonged course of intravenous amphotericin B followed by oral itraconazole.


Assuntos
Histoplasmose , Transplante de Rim , Humanos , Antifúngicos/uso terapêutico , Transplante de Rim/efeitos adversos , Transplantados , Itraconazol , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/patologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/tratamento farmacológico
15.
J Econ Entomol ; 117(2): 609-617, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38284646

RESUMO

The clover seed weevil, Tychius picirostris Fabricius, a serious pest of white clover, Trifolium repens L., grown for seed in western Oregon, causing feeding damage to flowers and developing seeds. Since 2017, white clover seed producers have anecdotally reported T. picirostris control failures using foliar pyrethroid insecticide applications. This mode of action (MoA) is an important chemical control option for T. picirostris management. To evaluate insecticide resistance selection to pyrethroids (bifenthrin) and other MoAs labeled for T. picirostris management (malathion and chlorantraniliprole), adult populations were collected from 8 commercial white clover grown for seed fields in the Willamette Valley, OR, in 2022 and 2023. Among collected Oregon populations, very high resistance ratios (RR50 = 178.00-725.67) were observed to technical grade bifenthrin and low to high resistance ratios (RR50 = 7.80-32.80) to malathion in surface contact assays compared to a susceptible Canadian field population. Moreover, >2.73 times the labeled rate of formulated product containing bifenthrin as the sole MoA was required to kill >50% of T. picirostris in topical assays. Synergistic assays with a mixed-function oxidase inhibitor, an esterase inhibitor, and a glutathione-S-transferase inhibitor revealed phase I and II detoxification enzymes are present in Oregon T. picirostris populations and confer metabolic resistance to bifenthrin. This is the first report of T. picirostris insecticide resistance selection to pyrethroid and organophosphate insecticides. Results will inform continued monitoring and insecticide resistance management strategies to slow the evolution of T. picirostris insecticide resistance selection in Oregon's white clover seed production.


Assuntos
Besouros , Inseticidas , Piretrinas , Trifolium , Gorgulhos , Animais , Malation , Oregon , Canadá , Piretrinas/farmacologia , Inseticidas/farmacologia , Resistência a Inseticidas , Produtos Agrícolas
16.
Perit Dial Int ; : 8968608231209850, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38179591

RESUMO

The global unmet need for kidney replacement therapy means that millions of people die every year as they cannot afford treatment. Peritoneal dialysis (PD) offers comparable survival to haemodialysis and is often more affordable, but one barrier to increasing access is that conventional manufacturing and distribution of PD fluid is costly. Here we report the results from a pilot proof-of-principal study demonstrating for the first time that the Ellen Medical Devices Point-of-Care system can be used by patients to produce sterile PD fluid at the point-of-care. With further development, this low-cost system could offer a solution to the many millions of people around the world who currently cannot afford treatment for kidney failure.

17.
J Fluoresc ; 34(2): 935-943, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37432582

RESUMO

A naked eye and fluorescence turn-on 1,8-naphtahlimide based chemosensor,1, possessing Schiff base linkage was utilized for the rapid detection of highly toxic triphosgene. The proposed sensor selectively detected triphosgene over various other competitive analytes including phosgene with the detection limit of 6.15 and 1.15 µM measured using UV-vis and fluorescence spectrophotometric techniques, respectively. Colorimetric changes observed in solution phase were processed by image analysis using smartphone leading to on-site and inexpensive determination of triphosgene. Further, solid phase sensing of triphosgene was carried out by 1 loaded PEG membranes and silica gel.


Assuntos
Fosgênio , Fosgênio/análogos & derivados , Fosgênio/análise , Corantes Fluorescentes , Smartphone , Espectrometria de Fluorescência/métodos
18.
Adv Rheumatol ; 64: 1, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1533544

RESUMO

Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

19.
Sci Transl Med ; 15(726): eadf9561, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091405

RESUMO

Immunoglobulin E (IgE) is a key driver of type 1 hypersensitivity reactions and allergic disorders, which are globally increasing in number and severity. Although eliminating pathogenic IgE may be a powerful way to treat allergy, no therapeutic strategy reported to date can fully ablate IgE production. Interleukin-4 receptor α (IL-4Rα) signaling is required for IgE class switching, and IL-4Rα blockade gradually reduces, but does not eliminate, IgE. The persistence of IgE after IL-4Rα blockade may be due to long-lived IgE+ plasma cells that maintain serological memory to allergens and thus may be susceptible to plasma cell-targeted therapeutics. We demonstrate that transient administration of a B cell maturation antigen x CD3 (BCMAxCD3) bispecific antibody markedly depletes IgE, as well as other immunoglobulins, by ablating long-lived plasma cells, although IgE and other immunoglobulins rapidly rebound after treatment. Concomitant IL-4Rα blockade specifically and durably prevents the reemergence of IgE by blocking IgE class switching while allowing the restoration of other immunoglobulins. Moreover, this combination treatment prevented anaphylaxis in mice. Together with additional cynomolgus monkey and human data, our studies demonstrate that allergic memory is primarily maintained by both non-IgE+ memory B cells that require class switching and long-lived IgE+ plasma cells. Our combination approach to durably eliminate pathogenic IgE has potential to benefit allergy in humans while preserving antibody-mediated immunity.


Assuntos
Anafilaxia , Imunoglobulina E , Camundongos , Humanos , Animais , Macaca fascicularis , Plasmócitos , Alérgenos
20.
Plant Physiol Biochem ; 203: 108084, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37832370

RESUMO

Brassica rapa L. (2n = 20; AA) is a vegetable and oilseed crop that is grown all over the world. Its leaves, shoots, and seeds store significant amounts of minerals. We used inductively coupled plasma-optical emission spectroscopy (ICP-OES) to determine the concentrations of eleven minerals in the leaves and seeds of 195 advanced generation inbred lines, of which 92 represented natural (NR) B. rapa and the remaining 103 were derived (DR) from a set of mother genotypes originally extracted from an allotetraploid B. juncea (2n = 36; AABB). The inbred lines differed for the composition of leaf and seed minerals. Leaf concentrations of N, K, Zn, and Se were higher in the DR subpanel as compared to NR subpanel, along with high seed accumulations of K and Se. DArT genotyping and genome wide association mapping led to the identification of SNPs associated with leaf and seed mineral compositions. Chromosomes A03, A05, and A10 harboured the most associated loci. Annotations of the regions adjacent to respective GWAS peaks allowed prediction of genes known for acquisition, transport, and accumulation of minerals and heavy metal detoxification. Transcriptome analysis revealed differential expression patterns of the predicted candidates, with most genes either down-regulated in derived genotypes relative to natural forms or their expression being comparable between the two. General downregulation may be a consequence of extracting B. rapa from allotetraploid B. juncea through genome resection. Some of the identified SNPs may be used as DNA markers for breeding programmes designed to modify the leaf and seed mineral compositions.


Assuntos
Brassica rapa , Brassica rapa/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Folhas de Planta/genética , Sementes/genética , Minerais
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