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1.
Cell ; 187(12): 2900-2902, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38848673

RESUMEN

In tissue homeostasis, intestinal stem cells (ISCs) undergo continuous self-renewal to sustain rapid cellular turnover. In this issue of Cell, Capdevila et al.1 and Malagola, Vasciaveo, et al.2 identify a new ISC population in the upper crypt that can generate Lgr5+ stem cells during homeostasis.


Asunto(s)
Intestinos , Células Madre , Células Madre/citología , Células Madre/metabolismo , Intestinos/citología , Animales , Humanos , Homeostasis , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Diferenciación Celular
2.
Cell ; 149(6): 1298-313, 2012 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-22682250

RESUMEN

Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging.


Asunto(s)
Envejecimiento/metabolismo , Complemento C1q/metabolismo , Vía de Señalización Wnt , Animales , Complemento C1s/metabolismo , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Ratones , Suero/metabolismo
3.
Nature ; 593(7857): 147-151, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33828301

RESUMEN

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn's disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mouse small intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1-/- or Rag2-/- mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn's disease and defines lymphocyte sub-specialization in the small intestine.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Regulación de la Expresión Génica , Intestino Delgado/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Linfocitos T/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Linfocitos T CD4-Positivos/metabolismo , Receptor de Androstano Constitutivo , Enfermedad de Crohn/metabolismo , Femenino , Ileítis/metabolismo , Inflamación/metabolismo , Interleucina-10/biosíntesis , Interleucina-10/genética , Intestino Delgado/citología , Ratones
4.
Immunity ; 47(6): 1182-1196.e10, 2017 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-29262351

RESUMEN

CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1-/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1-/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn's disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunología , Ácidos y Sales Biliares/inmunología , Linfocitos T CD4-Positivos/inmunología , Enfermedad de Crohn/inmunología , Ileítis/inmunología , Mucosa Intestinal/inmunología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/deficiencia , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Acridinas/farmacología , Adulto , Animales , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Transporte Biológico , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/inmunología , Homeostasis/inmunología , Humanos , Ileítis/genética , Ileítis/patología , Íleon/inmunología , Íleon/patología , Inmunidad Mucosa , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Estrés Oxidativo , Transducción de Señal , Tetrahidroisoquinolinas/farmacología
5.
NMR Biomed ; 37(3): e5063, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37871617

RESUMEN

Recently, intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has also been demonstrated as an imaging tool for applications in neurological and neurovascular diseases. However, the use of single-shot diffusion-weighted echo-planar imaging for IVIM DWI acquisition leads to suboptimal data quality: for instance, geometric distortion and deteriorated image quality at high spatial resolution. Although the recently commercialized multi-shot acquisition methods, such as multiplexed sensitivity encoding (MUSE), can attain high-resolution and high-quality DWI with signal-to-noise ratio (SNR) performance superior to that of the conventional parallel imaging method, the prolonged scan time associated with multi-shot acquisition is impractical for routine IVIM DWI. This study proposes an acquisition and reconstruction framework based on parametric-POCSMUSE to accelerate the four-shot IVIM DWI with 70% reduction of total scan time (13 min 8 s versus 4 min 8 s). First, the four-shot IVIM DWI scan with 17 b values was accelerated by acquiring only one segment per b value except for b values of 0 and 600 s/mm2 . Second, an IVIM-estimation scheme was integrated into the parametric-POCSMUSE to enable joint reconstruction of multi-b images from under-sampled four-shot IVIM DWI data. In vivo experiments on both healthy subjects and patients show that the proposed framework successfully produced multi-b DW images with significantly higher SNRs and lower reconstruction errors than did the conventional acceleration method based on parallel imaging. In addition, the IVIM quantitative maps estimated from the data produced by the proposed framework showed quality comparable to that of fully sampled MUSE-reconstructed images, suggesting that the proposed framework can enable highly accelerated multi-shot IVIM DWI without sacrificing data quality. In summary, the proposed framework can make multi-shot IVIM DWI feasible in a routine MRI examination, with reasonable scan time and improved geometric fidelity.


Asunto(s)
Alprostadil , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Cabeza , Imagen por Resonancia Magnética , Imagen Eco-Planar/métodos , Movimiento (Física)
6.
Int J Neuropsychopharmacol ; 27(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38365306

RESUMEN

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as some of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious adverse effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signaling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signaling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signaling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.


Asunto(s)
Trastornos Mentales , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Sirolimus/farmacología , Antidepresivos/farmacología , Trastornos Mentales/tratamiento farmacológico
7.
Ann Hematol ; 103(5): 1601-1611, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38267561

RESUMEN

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Ciclofosfamida/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antibacterianos/uso terapéutico , Antígenos CD34/metabolismo
9.
Fam Pract ; 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38423070

RESUMEN

BACKGROUND: The effects of integrated care with case management and nutritional counselling for frail patients with nutritional risk are unclear. OBJECTIVES: To assess the impact of the integrated care model for frail patients with nutritional risk in the primary care setting. METHODS: This was a retrospective observational study. We enrolled 100 prefrail or frail patients according to Clinical Frailty Scale (CFS) aged ≥ 60 years with nutritional risk from the geriatric clinic. We implemented the frailty intervention model, including integrated care with comprehensive geriatric assessments (CGA), case management, and nutritional counselling by the dietitian. We obtained measures of CGA components, physical performance, body mass index (BMI), and daily caloric intake before and after the 2-month care program. We used the Wilcoxon signed-rank test to analyse differences after the care program and applied multiple linear regression to determine the predictive factors for CFS improvement. RESULTS: Among the 100 patients (mean age, 75.0 ±â€…7.2 years; females, 71.0%; frail patients, 26%), 93% improved their CFS status, and 91% achieved > 80% of recommended daily caloric intake after the care program. The Mini Nutritional Assessment Short-Form significantly improved after the program. BMI and daily caloric intake increased significantly after nutritional counselling. The post-test short physical performance battery (SPPB) significantly increased with a faster 4 m gait speed. Baseline poor CFS was a significant predictor for CFS improvement. CONCLUSIONS: Integrated care with case management and nutritional counselling for prefrail and frail patients with nutritional risk in the primary care setting may improve physical performance and nutritional status.


Frailty, a state of vulnerability in older adults, can lead to various health issues. Early intervention in poor nutrition can be beneficial in managing frailty. Integrated care with comprehensive assessments has demonstrated its effectiveness in managing frail older adults. However, there are limited models designed for primary care, and nutritional intervention alone may not be adequate. This retrospective observational study, conducted in a specialized primary care unit for geriatric patients, enrolled prefrail and frail individuals at nutritional risk. A multidisciplinary team implemented an integrated care model that included comprehensive geriatric assessments, case management, and nutritional counselling. After the care program, a significant majority of patients exhibited improved Clinical Frailty Scale status, along with a high proportion achieving 80% of their recommended daily caloric intake. The study also revealed improved physical performance measured by the Short Physical Performance Battery, and a faster 4 m gait speed. Additionally, both BMI and daily caloric intake significantly increased after nutritional counselling. These findings highlight the positive impact of integrated care, including comprehensive assessments, case management, and nutritional counselling, on the physical performance and nutritional status of prefrail and frail older adults.

10.
BMC Geriatr ; 24(1): 294, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38549045

RESUMEN

BACKGROUND: Advance care planninganning (ACP) is a priority within palliative care service provision. Nurses working in the community occupy an opportune role to engage with families and patients in ACP. Carers and family members of palliative patients often find ACP discussions difficult to initiate. However, community nurses caring for palliative patients can encourage these discussions, utilising the rapport and relationships they have already built with patients and families. Despite this potential, implementation barriers and facilitators continue to exist. To date, no research synthesis has captured the challenges community nurses face when implementing ACP, nor the facilitators of community nurse-led ACP. Considering this, the review question of: 'What factors contribute to or hinder ACP discussion for nurses when providing care to palliative patients?' was explored. METHOD: To capture challenges and facilitators, a global qualitative scoping review was undertaken in June 2023. The Arksey and O'Malley framework for scoping reviews guided the review methodology. Six databases were searched identifying 333 records: CINAHL (16), MEDLINE (45), PUBMED (195), EMBASE (30), BJOCN (15), IJOPN (32). After de-duplication and title and abstract screening, 108 records remained. These were downloaded, hand searched (adding 5 articles) and subject to a full read. 98 were rejected, leaving a selected dataset of 15 articles. Data extracted into a data extraction chart were thematically analysed. RESULTS: Three key themes were generated: 'Barriers to ACP', 'Facilitators of ACP' and 'Understanding of professional role and duty'. Key barriers were - lack of confidence, competence, role ambiguity and prognostic uncertainty. Key facilitators concerned the pertinence of the patient-practitioner relationship enabling ACP amongst nurses who had both competence and experience in ACP and/or palliative care (e.g., palliative care training). Lastly, nurses understood ACP to be part of their role, however, met challenges understanding the law surrounding this and its application processes. CONCLUSIONS: This review suggests that community nurses' experience and competence are associated with the effective implementation of ACP with palliative patients. Future research is needed to develop interventions to promote ACP uptake in community settings, enable confidence building for community nurses and support higher standards of palliative care via the implementation of ACP.


Asunto(s)
Planificación Anticipada de Atención , Cuidado Terminal , Humanos , Cuidados Paliativos , Relaciones Interpersonales
11.
BMC Geriatr ; 24(1): 403, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714957

RESUMEN

BACKGROUND: Evidence on the effects of plantar intrinsic foot muscle exercise in older adults remains limited. This study aimed to evaluate the effect of an integrated intrinsic foot muscle exercise program with a novel three-dimensional printing foot core training device on balance and body composition in community-dwelling adults aged 60 and above. METHODS: A total of 40 participants aged ≥ 60 years were enrolled in this quasi-experimental, single-group, pretest-posttest design; participants were categorized into two groups, those with balance impairment and those without balance impairment. The participants performed a 4-week integrated intrinsic foot muscle exercise program with a three-dimensional printing foot core training device. The short physical performance battery (SPPB) and timed up and go test were employed to evaluate mobility and balance. A foot pressure distribution analysis was conducted to assess static postural control. The appendicular skeletal muscle mass index and fat mass were measured by a segmental body composition monitor with bioelectrical impedance analysis. The Wilcoxon signed rank test was used to determine the difference before and after the exercise program. RESULTS: Among the 40 enrolled participants (median age, 78.0 years; female, 80.0%; balance-impaired group, 27.5%), the 95% confidence ellipse area of the center of pressure under the eyes-closed condition was significantly decreased (median pretest: 217.3, interquartile range: 238.4; median posttest: 131.7, interquartile range: 199.5; P = 0.001) after the exercise. Female participants without balance impairment demonstrated a significant increase in appendicular skeletal muscle mass index and a decrease in fat mass. Participants in the balance-impaired group exhibited a significant increase in SPPB. CONCLUSIONS: Integrated intrinsic foot muscle exercise with a three-dimensional printing foot core training device may improve balance and body composition in adults aged 60 and above. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05750888 (retrospectively registered 02/03/2023).


Asunto(s)
Composición Corporal , Pie , Vida Independiente , Músculo Esquelético , Equilibrio Postural , Humanos , Femenino , Anciano , Equilibrio Postural/fisiología , Masculino , Composición Corporal/fisiología , Pie/fisiología , Músculo Esquelético/fisiología , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Terapia por Ejercicio/instrumentación , Anciano de 80 o más Años
12.
BMC Biol ; 21(1): 233, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880702

RESUMEN

BACKGROUND: The population structure of crop pathogens such as Puccinia striiformis f. sp. tritici (Pst), the cause of wheat stripe rust, is of interest to researchers looking to understand these pathogens on a molecular level as well as those with an applied focus such as disease epidemiology. Cereal rusts can reproduce sexually or asexually, and the emergence of novel lineages has the potential to cause serious epidemics such as the one caused by the 'Warrior' lineage in Europe. In a global context, Pst lineages in Canada were not well-characterized and the origin of foreign incursions was not known. Additionally, while some Pst mating type genes have been identified in published genomes, there has been no rigorous assessment of mating type diversity and distribution across the species. RESULTS: We used a whole-genome/transcriptome sequencing approach for the Canadian Pst population to identify lineages in their global context and evidence tracing foreign incursions. More importantly: for the first time ever, we identified nine alleles of the homeodomain mating type locus in the worldwide Pst population and show that previously identified lineages exhibit a single pair of these alleles. Consistently with the literature, we find only two pheromone receptor mating type alleles. We show that the recent population shift from the 'PstS1' lineage to the 'PstS1-related' lineage is also associated with the introduction of a novel mating type allele (Pst-b3-HD) to the Canadian population. We also show evidence for high levels of mating type diversity in samples associated with the Himalayan center of diversity for Pst, including a single Canadian race previously identified as 'PstPr' (probable recombinant) which we identify as a foreign incursion, most closely related to isolates sampled from China circa 2015. CONCLUSIONS: These data describe a recent shift in the population of Canadian Pst field isolates and characterize homeodomain-locus mating type alleles in the global Pst population which can now be utilized in testing several research questions and hypotheses around sexuality and hybridization in rust fungi.


Asunto(s)
Basidiomycota , Alelos , Canadá , Basidiomycota/genética , Recombinación Genética , Europa (Continente) , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología
13.
Int Ophthalmol ; 44(1): 130, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38478099

RESUMEN

PURPOSE: This study seeks to build a normative database for the vessel density of the superficial retina (SVD) and evaluate how changes and trends in the retinal microvasculature may be influenced by age and axial length (AL) in non-glaucomatous eyes, as measured with optical coherence tomography angiography (OCTA). METHODS: We included 500 eyes of 290 healthy subjects visiting a county hospital. Each participant underwent comprehensive ophthalmological examinations and OCTA to measure the SVD and thickness of the macular and peripapillary areas. To analyze correlations between SVD and age or AL, multivariable linear regression models with generalized estimating equations were applied. RESULTS: Age was negatively correlated with the SVD of the superior, central, and inferior macular areas and the superior peripapillary area, with a decrease rate of 1.06%, 1.36%, 0.84%, and 0.66% per decade, respectively. However, inferior peripapillary SVD showed no significant correlation with age. AL was negatively correlated with the SVD of the inferior macular area and the superior and inferior peripapillary areas, with coefficients of -0.522%/mm, -0.733%/mm, and -0.664%/mm, respectively. AL was also negatively correlated with the thickness of the retinal nerve fiber layer and inferior ganglion cell complex (p = 0.004). CONCLUSION: Age and AL were the two main factors affecting changes in SVD. Furthermore, AL, a relative term to represent the degree of myopia, had a greater effect than age and showed a more significant effect on thickness than on SVD. This relationship has important implications because myopia is a significant issue in modern cities.


Asunto(s)
Miopía , Vasos Retinianos , Humanos , Retina , Tomografía de Coherencia Óptica/métodos , Fibras Nerviosas , Envejecimiento
14.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1206-1216, 2024 Mar.
Artículo en Zh | MEDLINE | ID: mdl-38621967

RESUMEN

Soil microbiome is a key evaluation index of soil health. Previous studies have shown that organic fertilizer from traditional Chinese medicine(TCM)residues can improve the yield and quality of cultivated traditional Chinese medicinal materials. However, there are few reports on the effects of organic fertilizer from TCM residues on soil microbiome. Therefore, on the basis of evaluating the effects of organic fertilizer from TCM residues on the yield and quality of cultivated Salvia miltiorrhiza, the metagenomic sequencing technique was used to study the effects of organic fertilizer from TCM residues on rhizosphere microbiome community and function of cultivated S. miltiorrhiza. The results showed that:(1) the application of organic fertilizer from TCM residues promoted the growth of S. miltiorrhiza and the accumulation of active components, and the above-ground and underground dry weight and fresh weight of S. miltiorrhiza increased by 371.4%, 288.3%, 313.4%, and 151.9%. The increases of rosmarinic acid and salvianolic acid B were 887.0% and 183.0%.(2)The application of organic fertilizer from TCM residues significantly changed the rhizosphere bacterial and fungal community structures, and the microbial community composition was significantly different.(3)The relative abundance of soil-beneficial bacteria, such as Nitrosospira multiformis, Bacillus subtilis, Lysobacter enzymogenes, and Trichoderma was significantly increased by the application of organic fertilizer from TCM residues.(4)KEGG function prediction analysis showed that metabolism-related microorganisms were more easily enriched in the soil environment after organic fertilizer application. The abundance of functional genes related to nitrification and denitrification could also be increased after the application of organic fertilizer from TCM residues. The results of this study provide guidance for the future application of organic fertilizer from TCM residues in the cultivation of traditio-nal Chinese medicinal materials and enrich the content of green cultivation technology of traditional Chinese medicinal materials.


Asunto(s)
Micobioma , Salvia miltiorrhiza , Suelo/química , Salvia miltiorrhiza/química , Fertilizantes , Medicina Tradicional China , Bacterias/genética , Microbiología del Suelo
15.
Anal Chem ; 95(26): 9787-9796, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37341384

RESUMEN

Distinguishing isomeric saccharides poses a major challenge for analytical workflows based on (liquid chromatography) mass spectrometry (LC-MS). In recent years, many studies have proposed infrared ion spectroscopy as a possible solution as the orthogonal, spectroscopic characterization of mass-selected ions can often distinguish isomeric species that remain unresolved using conventional MS. However, the high conformational flexibility and extensive hydrogen bonding in saccharides cause their room-temperature fingerprint infrared spectra to have broad features that often lack diagnostic value. Here, we show that room-temperature infrared spectra of ion-complexed saccharides recorded in the previously unexplored far-infrared wavelength range (300-1000 cm-1) provide well-resolved and highly diagnostic features. We show that this enables distinction of isomeric saccharides that differ either by their composition of monosaccharide units and/or the orientation of their glycosidic linkages. We demonstrate the utility of this approach from single monosaccharides up to isomeric tetrasaccharides differing only by the configuration of a single glycosidic linkage. Furthermore, through hyphenation with hydrophilic interaction liquid chromatography, we identify oligosaccharide biomarkers in patient body fluid samples, demonstrating a generalized and highly sensitive MS-based method for the identification of saccharides found in complex sample matrices.


Asunto(s)
Errores Innatos del Metabolismo , Oligosacáridos , Humanos , Oligosacáridos/química , Isomerismo , Monosacáridos , Espectrofotometría Infrarroja , Biomarcadores , Iones
16.
Pulm Pharmacol Ther ; 81: 102218, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37201652

RESUMEN

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , eIF-2 Quinasa , Humanos , Estrés del Retículo Endoplásmico/fisiología , Respuesta de Proteína Desplegada , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
17.
Toxicol Pathol ; 51(6): 313-328, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-38288712

RESUMEN

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers.


Asunto(s)
Inteligencia Artificial , Patólogos , Humanos , Reproducibilidad de los Resultados
18.
Pediatr Crit Care Med ; 24(4): 277-288, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36534761

RESUMEN

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.


Asunto(s)
Agotamiento Profesional , COVID-19 , Femenino , Humanos , Niño , Salud Mental , COVID-19/epidemiología , Pandemias , Prevalencia , Estudios Transversales , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Unidades de Cuidado Intensivo Pediátrico , Personal de Salud/psicología
19.
BMC Public Health ; 23(1): 1005, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37254119

RESUMEN

BACKGROUND: To sufficiently house and support persons experiencing homelessness (PEH), deeper understandings of the cultural appropriateness and responsiveness of community resources and the service delivery system is essential. In the case of Metro Vancouver, Canada, the cultural appropriateness and responsiveness of Housing First as a service model for supporting PEH was explored. METHODS: Local service providers and stakeholders (n = 52) participated in three full day service-mapping workshops to identify Housing First supports for older adults, youth, and women experiencing homelessness, as part of a municipal-wide participatory and action-oriented study. Data were analyzed using a structured framework thematic analysis approach and cultural safety and humility lenses. RESULTS: We generated three key themes: (i) insufficient built environments create challenges across gender and age, (ii) cultural safety and humility concerns at the intersection of gender and age, and (iii) implications for a culturally-responsive Housing First implementation. CONCLUSIONS: Findings informed the development of a Culturally-Responsive Planning resource to support housing, health, and social service providers who are implementing Housing First initiatives.


Asunto(s)
Vivienda , Personas con Mala Vivienda , Adolescente , Anciano , Femenino , Humanos , Canadá , Problemas Sociales , Servicio Social , Masculino
20.
J Am Pharm Assoc (2003) ; 63(5): 1634-1642.e3, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37327997

RESUMEN

BACKGROUND: The world is moving fast toward digital transformation as we live in the artificial intelligence (AI) era. The COVID-19 pandemic accelerates this movement. Chatbots were used successfully to help researchers collect data for research purposes. OBJECTIVE: To implement a chatbot on the Facebook platform to establish connections with health care professionals who had subscribed to the chatbot, provide medical and pharmaceutical educational content, and collect data for online pharmacy research projects. Facebook was chosen because it has billions of daily active users, which offers a massive potential audience for research projects. PRACTICE DESCRIPTION: The chatbot was successfully implemented on the Facebook platform following 3 consecutive steps. Firstly, the ChatPion script was installed on the Pharmind website to establish the chatbot system. Secondly, the PharmindBot application was developed on Facebook. Finally, the PharmindBot app was integrated with the chatbot system. PRACTICE INNOVATION: The chatbot responds automatically to public comments and sends subscribers private responses using AI. The chatbot collected quantitative and qualitative data with minimal costs. EVALUATION METHODS: The chatbot's auto-reply function was tested using a post published on a specific page on Facebook. Testers were asked to leave predefined keywords to test its functionality. The chatbot's ability to collect and save data was tested by asking testers to fill out an online survey within Facebook Messenger for quantitative data and answer predefined questions for qualitative data. RESULTS: The chatbot was tested on 1000 subscribers who interacted with it. Almost all testers (n = 990, 99%) obtained a successful private reply from the chatbot after sending a predefined keyword. Also, the chatbot replied privately to almost all public comments (n = 985, 98.5%) which helped to increase the organic reach and to establish a connection with the chatbot subscribers. No missing data were found when the chatbot was used to collect quantitative and qualitative data. CONCLUSIONS: The chatbot reached thousands of health care professionals and provided them with automated responses. At a low cost, the chatbot was able to gather both qualitative and quantitative data without relying on Facebook ads to reach the intended audience. The data collection was efficient and effective. Using chatbots by pharmacy and medical researchers will help do more feasible online studies using AI to advance health care research.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , Humanos , Inteligencia Artificial , Pandemias , Personal de Salud
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