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1.
Nat Commun ; 15(1): 3903, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724537

RESUMO

Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s-1 day-1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

2.
Cell Commun Signal ; 22(1): 259, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715050

RESUMO

Ubiquitination and deubiquitination are important forms of posttranslational modification that govern protein homeostasis. Deubiquitinating enzymes (DUBs), a protein superfamily consisting of more than 100 members, deconjugate ubiquitin chains from client proteins to regulate cellular homeostasis. However, the dysregulation of DUBs is reportedly associated with several diseases, including cancer. The tumor microenvironment (TME) is a highly complex entity comprising diverse noncancerous cells (e.g., immune cells and stromal cells) and the extracellular matrix (ECM). Since TME heterogeneity is closely related to tumorigenesis and immune evasion, targeting TME components has recently been considered an attractive therapeutic strategy for restoring antitumor immunity. Emerging studies have revealed the involvement of DUBs in immune modulation within the TME, including the regulation of immune checkpoints and immunocyte infiltration and function, which renders DUBs promising for potent cancer immunotherapy. Nevertheless, the roles of DUBs in the crosstalk between tumors and their surrounding components have not been comprehensively reviewed. In this review, we discuss the involvement of DUBs in the dynamic interplay between tumors, immune cells, and stromal cells and illustrate how dysregulated DUBs facilitate immune evasion and promote tumor progression. We also summarize potential small molecules that target DUBs to alleviate immunosuppression and suppress tumorigenesis. Finally, we discuss the prospects and challenges regarding the targeting of DUBs in cancer immunotherapeutics and several urgent problems that warrant further investigation.


Assuntos
Enzimas Desubiquitinantes , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Enzimas Desubiquitinantes/metabolismo , Animais , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/enzimologia , Neoplasias/metabolismo , Evasão Tumoral , Ubiquitinação , Evasão da Resposta Imune
3.
Talanta ; 276: 126215, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38723474

RESUMO

Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.

4.
Tzu Chi Med J ; 36(2): 195-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645789

RESUMO

Objective: Uremic pruritus (UP) is a prevalent and troublesome condition affecting individuals with end-stage renal failure, which results in intense pruritus, depression, as well as poor quality of sleep, significantly impacting their quality of life. According to previous studies, acupuncture and acupoint stimulation have been shown to provide additional benefits in treating UP in dialysis patients. In addition, using acupoints combination may yield superior effectiveness compared to utilizing a singular acupoint. To investigate the potential correlations between acupoint combinations, an association-rule analysis was employed. Materials and Methods: Apriori algorithms stand out as highly potent techniques for identifying associations in databases; this study utilized an association rule mining to examine the association rules of key acupoint groupings that could be employed for treating UP. Results: The analysis utilized information derived from the meta-analysis encompassing 40 randomized controlled trials that used acupuncture to treat UP. In total, 64 acupoints were analyzed, and 71 association rules were found. The following acupoint combinations: Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14) showed the strongest associations. Conclusion: Acupoints involving Auricular shenmen (TF4), Quchi (LI11), Geshu (BL17), Auricular heart (Extra14), Sanyinjiao (SP6), Auricular lung (CO14), and Xuehai (SP10) can be regarded as the core combination of acupuncture points for managing UP.

5.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619255

RESUMO

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.


Assuntos
Candida , Fotoquimioterapia , Humanos , Rosa Bengala/farmacologia , Candida glabrata , Fármacos Fotossensibilizantes/farmacologia
6.
PeerJ ; 12: e17081, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560478

RESUMO

Background: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the Global Initiatives for Chronic Lung Diseases (GOLD) criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox regression with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria during the follow-up period (median (IQR) 597 (331-934.5) days). Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60 ± 2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ≥2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer (hazard ratios (95% C.I.) from 1.03 [1.00-1.06] to 5.45 [3.04-9.79]). The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis, after adjusting for all selected factors except cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. Conclusions: The predictive formula for dead space fraction enables the estimation of VD/VTrest, and the mortality probability formula facilitates the estimation of COPD mortality. However, the clinical implications should be approached with caution until these formulas have been validated.


Assuntos
Neoplasias , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Retrospectivos , Testes de Função Respiratória , Hospitalização
7.
bioRxiv ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38559277

RESUMO

Despite numerous advances in our understanding of zebrafish cardiac regeneration, an aspect that remains less studied is how regenerating cardiomyocytes invade, and eventually replace, the collagen-containing fibrotic tissue following injury. Here, we provide an in-depth analysis of the process of cardiomyocyte invasion using live-imaging and histological approaches. We observed close interactions between protruding cardiomyocytes and macrophages at the wound border zone, and macrophage-deficient irf8 mutant zebrafish exhibited defects in extracellular matrix (ECM) remodeling and cardiomyocyte protrusion into the injured area. Using a resident macrophage ablation model, we show that defects in ECM remodeling at the border zone and subsequent cardiomyocyte protrusion can be partly attributed to a population of resident macrophages. Single-cell RNA-sequencing analysis of cells at the wound border revealed a population of cardiomyocytes and macrophages with fibroblast-like gene expression signatures, including the expression of genes encoding ECM structural proteins and ECM-remodeling proteins. The expression of mmp14b , which encodes a membrane-anchored matrix metalloproteinase, was restricted to cells in the border zone, including cardiomyocytes, macrophages, fibroblasts, and endocardial/endothelial cells. Genetic deletion of mmp14b led to a decrease in 1) macrophage recruitment to the border zone, 2) collagen degradation at the border zone, and 3) subsequent cardiomyocyte invasion. Furthermore, cardiomyocyte-specific overexpression of mmp14b was sufficient to enhance cardiomyocyte invasion into the injured tissue and along the apical surface of the wound. Altogether, our data shed important insights into the process of cardiomyocyte invasion of the collagen-containing injured tissue during cardiac regeneration. They further suggest that cardiomyocytes and resident macrophages contribute to ECM remodeling at the border zone to promote cardiomyocyte replenishment of the fibrotic injured tissue.

8.
J Clin Immunol ; 44(3): 77, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451335

RESUMO

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.


Assuntos
Arterite , Síndrome de Linfonodos Mucocutâneos , Humanos , Animais , Camundongos , Infiltração de Neutrófilos , Óxido Nítrico Sintase Tipo II , Receptores de Interleucina-17/genética , Células Endoteliais , Imunoglobulinas Intravenosas , Interleucina-17 , Leucócitos Mononucleares , Ligantes , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Quimiocinas , RNA Mensageiro
9.
Artigo em Inglês | MEDLINE | ID: mdl-38530870

RESUMO

OBJECTIVE: Drawing on the intergenerational solidarity framework and life course perspective, the authors assessed how mother-child closeness across different life stages is associated with adult children's time and financial assistance to mothers in later life. METHOD: Using children's reports of their perceived closeness to mothers from waves 1 to 4 of the National Longitudinal Study of Adolescent to Adult Health (Add Health) and mothers' reports about adult children's time and financial assistance from wave 2 of the Add Health Parent Study (AHPS) in the United States, the authors investigated how mother-child closeness during adolescence, emerging adulthood, and young adulthood is related to midlife adult children's support with a focus on difference between mother-daughter (N = 934) and mother-son (N = 899) dyads. RESULTS: Closeness during young adulthood was an important determinant of adult children's time assistance to their mothers, regardless of child's gender. Daughters' closeness with mothers during young adulthood also had a direct association with their financial support to mothers but not sons'. In contrast, sons' perceived closeness during emerging adulthood had a direct association with their financial support later in life. Closeness during adolescence had no direct association with later-life transfers of time or money but had an indirect association through its influence on mother-child relationships at subsequent life stages. DISCUSSION: Mother-child closeness is a continuously evolving process. Although mother-child bond formed during adolescence has no direct influence on help to mothers later in life, it shapes the progression of mother-child interactions over time that eventuates in support.

10.
J Med Syst ; 48(1): 35, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530526

RESUMO

This retrospective study assessed the effectiveness and impact of implementing a Modified Early Warning System (MEWS) and Rapid Response Team (RRT) for inpatients admitted to the general ward (GW) of a medical center. This study included all inpatients who stayed in GWs from Jan. 2017 to Feb. 2022. We divided inpatients into GWnon-MEWS and GWMEWS groups according to MEWS and RRT implementation in Aug. 2019. The primary outcome, unexpected deterioration, was defined by unplanned admission to intensive care units. We defined the detection performance and effectiveness of MEWS according to if a warning occurred within 24 h before the unplanned ICU admission. There were 129,039 inpatients included in this study, comprising 58,106 GWnon-MEWS and 71,023 GWMEWS. The numbers of inpatients who underwent an unplanned ICU admission in GWnon-MEWS and GWMEWS were 488 (.84%) and 468 (.66%), respectively, indicating that the implementation significantly reduced unexpected deterioration (p < .0001). Besides, 1,551,525 times MEWS assessments were executed for the GWMEWS. The sensitivity, specificity, positive predicted value, and negative predicted value of the MEWS were 29.9%, 98.7%, 7.09%, and 99.76%, respectively. A total of 1,568 warning signs accurately occurred within the 24 h before an unplanned ICU admission. Among them, 428 (27.3%) met the criteria for automatically calling RRT, and 1,140 signs necessitated the nursing staff to decide if they needed to call RRT. Implementing MEWS and RRT increases nursing staff's monitoring and interventions and reduces unplanned ICU admissions.


Assuntos
Equipe de Respostas Rápidas de Hospitais , Quartos de Pacientes , Humanos , Estudos Retrospectivos , Pacientes Internados , Hospitalização , Unidades de Terapia Intensiva , Mortalidade Hospitalar
11.
Toxicol Appl Pharmacol ; 485: 116888, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452945

RESUMO

Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the molecular mechanism of action of GDC-0152 in cancer cells is still incompletely understood. In this study, we found that the potency of GDC-0152 is unaffected by the expression of ABCB1 in cancer cells. Interestingly, through in silico and in vitro analysis, we discovered that GDC-0152 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multidrug efflux activity at sub-cytotoxic concentrations (i.e., 0.25×IC50 or less). Further investigation revealed that GDC-0152 also decreases BIRC5 expression, induces mitophagy, and lowers intracellular ATP levels in cancer cells at low cytotoxic concentrations (i.e., 0.5×IC50). Co-treatment with GDC-0152 restored the sensitivity to the known ABCB1 substrates, including paclitaxel, vincristine, and YM155 in ABCB1-expressing multidrug-resistant cancer cells, and it also restored the sensitivity to tamoxifen in BIRC5-overexpressing tamoxifen-resistant breast cancer cells in vitro. Moreover, co-treatment with GDC-0152 restored and potentiated the anticancer effects of paclitaxel in ABCB1 and BIRC5 co-expressing xenograft tumors in vivo. In conclusion, GDC-0152 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide essential information to physicians for designing a more patient-specific GDC-0152 clinical trial program in the future.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Benzodioxóis , Resistencia a Medicamentos Antineoplásicos , Indolizinas , Survivina , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Survivina/genética , Survivina/metabolismo , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Camundongos Nus , Camundongos , Antineoplásicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Reguladoras de Apoptose/metabolismo , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Paclitaxel/farmacologia , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Camundongos Endogâmicos BALB C , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Inibidoras de Apoptose/genética
12.
Nat Commun ; 15(1): 2386, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493205

RESUMO

Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.

13.
Gerontologist ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446986

RESUMO

BACKGROUND AND OBJECTIVES: The oldest adults faced the highest risk of death and hospitalization from COVID-19, but less is known about whether they also were the most likely to experience pandemic-related economic, health care, and mental health challenges. Guided by prior research on vulnerability versus resilience among older adults, the current study investigated age differences in economic hardship, delays in medical care, and mental health outcomes among adults aged 55 and older. RESEARCH DESIGN AND METHODS: Data were from the COVID-19 module and Leave Behind Questionnaire in the 2020 Health and Retirement Study (HRS). We estimated linear probability models to examine differences in experiences of pandemic-related economic and health challenges by age group (55-64, 65-74, 75+) with and without controls for preexisting sociodemographic, social program, health, and economic characteristics from the 2018 HRS. Models accounting for differential mortality also were estimated. RESULTS: Adults aged 65-74 and 75+ experienced fewer economic and mental health challenges and those aged 75+ were less likely to delay medical care than adults aged 55-64. Age gradients were consistent across a broad range of measures and were robust to including controls. For all age groups, economic challenges were less common than delays in medical care or experiences of loneliness, stress, or being emotionally overwhelmed. DISCUSSION AND IMPLICATIONS: Even though the oldest adults were at the greatest risk of death and hospitalization from COVID-19, they experienced fewer secondary pandemic-related challenges. Future research should continue to explore the sources of this resilience for older adults.

14.
Nat Commun ; 15(1): 1742, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453921

RESUMO

Super Typhoon Mangkhut, which traversed the North Equatorial Current (NEC; 8-17 °N) in the western North Pacific in 2018, was the most intense Category-5 tropical cyclone (TC) with the longest duration in history-3.5 days. Here we show that the combination of two factors-high ocean heat content (OHC) and increased stratification - makes the NEC region the most favored area for a rapid intensification (RI) of super typhoons, instead of the Eddy Rich Zone (17-25 °N), which was considered the most relevant for RI occurrence. The high OHC results from a northward deepening thermocline in geostrophic balance with the westward-flowing NEC. The stratification is derived from precipitation associated with the Inter-Tropical Convergence Zone in the summer peak typhoon season. These factors, which are increasingly significant over the past four decades, impede the TC-induced sea surface cooling, thus enhancing RI of TCs and simultaneously maintaining super typhoons over the NEC region.

15.
Front Med (Lausanne) ; 11: 1305579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482530

RESUMO

Dry eye disease (DED) is a common multifactorial disease affecting a substantial proportion of the population worldwide. Objective tests and subjective symptoms evaluation are necessary to assess DED. Although various treatments have been introduced, accurately evaluating the efficacy of those treatments is difficult because of the disparity between diagnostic tests and patient-reported symptoms. We reviewed the questionnaires used to evaluate DED and the improvements of quality of life with various treatments. In addition, we highlighted the importance of patient-reported outcomes (PRO) assessments for evaluating the effect of DED treatments. Given that the assessment of DED treatment effectiveness substantially relies on individual ocular experiences, acquiring qualitative PRO data is essential for comprehensive evaluation and optimal treatment management. Clinicians should not only focus on improving objective symptoms but also prioritize the well-being of patients in clinical management.

16.
Matrix Biol ; 127: 23-37, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331051

RESUMO

BACKGROUND: The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. METHODS: Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5-/- (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. RESULTS: In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5-/- (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. CONCLUSIONS: We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.


Assuntos
Nefropatias , Macrófagos , Camundongos , Animais , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Macrófagos/metabolismo , Rim/metabolismo , Inflamação/metabolismo , Nefropatias/metabolismo , RNA/metabolismo
17.
Pituitary ; 27(2): 141-150, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38315244

RESUMO

CONTEXT: Patients with Cushing's disease (CD) face challenges living with and receiving appropriate care for this rare, chronic condition. Even with successful treatment, many patients experience ongoing symptoms and impaired quality of life (QoL). Different perspectives and expectations between patients and healthcare providers (HCPs) may also impair well-being. OBJECTIVE: To examine differences in perspectives on living with CD between patients and HCPs, and to compare care goals and unmet needs. DESIGN: Memorial Sloan Kettering Pituitary Center established an annual pituitary symposium for pituitary patients and HCPs. Through anonymous pre-program surveys distributed at the 2020 and 2022 symposia, patients and HCPs answered questions related to their own sense, or perception of their patients' sense, of hope, choice, and loneliness in the context of living with CD. PARTICIPANTS: From 655 participants over two educational events, 46 patients with CD and 116 HCPs were included. Median age of both groups was 51 years. 78.3% of the patients were female vs. 53.0% of the HCPs. RESULTS: More patients than HCPs reported they had no choices in their treatment (21.7% vs. 0.9%, P < 0.001). More patients reported feeling alone living with CD than HCPs' perception of such (60.9% vs. 45.5%, P = 0.08). The most common personal care goal concern for patients was 'QoL/mental health,' vs. 'medical therapies/tumor control' for HCPs. The most common CD unmet need reported by patients was 'education/awareness' vs. 'medical therapies/tumor control' for HCPs. CONCLUSIONS: CD patients experience long term symptoms and impaired QoL which may in part be due to a perception of lack of effective treatment options and little hope for improvement. Communicating experiences and care goals may improve long term outcomes for CD patients.


Assuntos
Neoplasias , Hipersecreção Hipofisária de ACTH , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hipersecreção Hipofisária de ACTH/terapia , Hipersecreção Hipofisária de ACTH/diagnóstico , Qualidade de Vida/psicologia , Estudos Longitudinais , Motivação
18.
Medicine (Baltimore) ; 103(6): e35376, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335411

RESUMO

Accurate assessment of wound areas is crucial in making therapeutic decisions, as the prognosis and changes in the size of the wound over time play a significant role. An ideal assessment method should possess qualities such as speed, affordability, accuracy, user-friendliness for both patients and healthcare professionals, and suitability for daily clinical practice. This study aims to introduce a handheld 3-dimensional (3D) scanner and evaluate its accuracy in measuring wound areas. Engineers from the Industrial Technology Research Institute in Taiwan developed a handheld 3D scanner with the intention of extending its application to the medical field. A project was conducted to validate the accuracy of this 3D scanner. We utilized a smartphone (Asus ZenFone 2 with a 13-million-pixel rear camera), a digital single-lens reflex digital camera (Nikon, D5000, Tokyo, Japan), and the 3D scanner to repeatedly measure square papers of known size that were affixed to the curved surface of life-size facial mask or medical teaching breast models. The "Image J" software was employed for 2-dimensional image measurements, while the "3D Edit" software was used to assess the "area of interest" on 3D objects. By using square papers with predetermined dimensions, the measurement-associated error rate (ER) could be calculated for each image. Three repeated measurements were performed using the "Image J" software for each square paper. The ERs of the 3D scan images were all below 3%, with an average ER of 1.64% in this study. The close-up mode of the smartphone exhibited the highest ER. It was observed that as the area increased, the ER also increased in the digital single-lens reflex camera group. The extension distortion effect caused by the wide-angle lens on the smartphone may increase the ER. However, the definition of a healthy skin edge may vary, and different algorithms for calculating the measurement area are employed in various 3D measurement software. Therefore, further validation of their accuracy for medical purposes is necessary. Effective communication with software engineers and discussions on meeting clinical requirements are crucial steps in enhancing the functionality of the 3D scanner.


Assuntos
Algoritmos , Software , Humanos , Face , Pele , Imageamento Tridimensional , Acreditação
19.
J Affect Disord ; 350: 340-349, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199411

RESUMO

BACKGROUND: Patients with major depressive disorder (MDD) exhibit atypical brain activities in the frontal, temporal, and parietal lobes. The study aimed to investigate the effects of standardized weighted low-resolution electromagnetic tomography Z-score neurofeedback (swLZNFB) on symptoms of depression and anxiety, electroencephalography (EEG) parameters, and deep brain activities in patients with MDD. METHOD: Forty-eight patients with MDD comorbid with anxiety symptoms were assigned to the swLZNFB group and the control group. Participants completed the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) and a 5-minute resting EEG at the pre-and post-tests. The swLZNFB group received ten sessions of one-hour treatment twice weekly. The control group received treatment as usual. The scores for BDI-II and BAI, number of EEG abnormalities, percentage of EEG abnormalities, and current source density (CSD) measured in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and amygdala were compared at pre-and post-tests between the two groups. RESULTS: There were decreased scores of BDI-II and BAI, number of EEG abnormalities, and percentage of EEG abnormalities at post-test compared with pre-test in the swLZNFB group, and lower scores of BDI-II and BAI at post-test in the swLZNFB group compared with the control group. Moreover, decreased CSD of beta1 and beta3 in the PFC, ACC, PCC, and amygdala at post-test compared to pre-test in the swLZNFB group. LIMITATIONS: Not a randomized controlled trial. CONCLUSION: Ten sessions of swLZNFB reduced clinical symptoms and atypical brain activities, it serves as a potential psychological intervention for patients with MDD.


Assuntos
Transtorno Depressivo Maior , Neurorretroalimentação , Humanos , Neurorretroalimentação/métodos , Transtorno Depressivo Maior/terapia , Ansiedade/terapia , Eletroencefalografia , Transtornos de Ansiedade/terapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-38204236

RESUMO

BACKGROUND: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. AIM: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. OBJECTIVE: The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. METHODS: Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. RESULTS: FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. CONCLUSION: The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

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