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1.
Sci Data ; 11(1): 1117, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39389959

RESUMO

This study reports the methodology for reconstructing anomalous temperature index series of China in 1368-1911 based on the REACHES database which digitizes the Chinese records quoted in the Compendium of Meteorological Records of China in the Last 3000 Years. The reconstruction adopts an ordinal scale index approach ranging from -2 (very cold) to 1 (warm). Based on the grading criteria, a total of 12,871 records were retrieved through a standard coding system established at REACHES. Sensitivity experiments were performed to test robustness of the index system and a reasonability test was conducted to develop an appropriate method for deriving areal mean temperature index. The reconstructed series were validated through comparison with early instrumental data from Global Historical Climatology Network which shows good correlations and reliability of the REACHES reconstructed index data. Annual and semi-annual (winter and summer) temperature index data series were released for the whole domain as well as the 3- and 15-subregion geographical domains in China.

2.
J Biomed Sci ; 31(1): 94, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39379923

RESUMO

Recent breakthroughs in cancer immunotherapies have emphasized the importance of harnessing the immune system for treating cancer. Vaccines, which have traditionally been used to promote protective immunity against pathogens, are now being explored as a method to target cancer neoantigens. Over the past few years, extensive preclinical research and more than a hundred clinical trials have been dedicated to investigating various approaches to neoantigen discovery and vaccine formulations, encouraging development of personalized medicine. Nucleic acids (DNA and mRNA) have become particularly promising platform for the development of these cancer immunotherapies. This shift towards nucleic acid-based personalized vaccines has been facilitated by advancements in molecular techniques for identifying neoantigens, antigen prediction methodologies, and the development of new vaccine platforms. Generating these personalized vaccines involves a comprehensive pipeline that includes sequencing of patient tumor samples, data analysis for antigen prediction, and tailored vaccine manufacturing. In this review, we will discuss the various shared and personalized antigens used for cancer vaccine development and introduce strategies for identifying neoantigens through the characterization of gene mutation, transcription, translation and post translational modifications associated with oncogenesis. In addition, we will focus on the most up-to-date nucleic acid vaccine platforms, discuss the limitations of cancer vaccines as well as provide potential solutions, and raise key clinical and technical considerations in vaccine development.


Assuntos
Antígenos de Neoplasias , Vacinas Anticâncer , Neoplasias , Medicina de Precisão , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Medicina de Precisão/métodos , Antígenos de Neoplasias/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Desenvolvimento de Vacinas/métodos , Ácidos Nucleicos/imunologia , Imunoterapia/métodos
3.
Nutrients ; 16(18)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39339781

RESUMO

OBJECTIVES: This study aimed to assess the current neonatal nutritional practices in Taiwan and promote consensus on standardized protocols. METHODS: An online questionnaire comprising 95 items on parenteral nutrition (PN) and enteral nutrition (EN) practices was distributed to neonatal care units across Taiwan via email between August and December 2022. The responses were compared with the recommendations from the European Society for Pediatric Gastroenterology Hepatology and Nutrition for preterm infant care. RESULTS: Most of the 35 neonatal units, comprising 17 level III and 18 level II units, that participated in this study adhered to standard PN protocols; however, only 30% of units used protein-containing solutions as the initial fluid. Over half of the neonatal units provided calcium, phosphate, and magnesium at less than the recommended dosage. Trophic feeding commenced within 48 h in 88% of the units, with the mother's milk used as the first choice. All the units preferred commencing advanced feeding at <25 mL/kg/day. CONCLUSIONS: Most nutrient protocols for preterm infants in neonatal units in Taiwan meet recent guidelines, but discrepancies such as lower mineral supplements in PN and a slower advancement of enteral feeding increase nutritional risk. These issues warrant further research.


Assuntos
Nutrição Enteral , Fidelidade a Diretrizes , Recém-Nascido Prematuro , Nutrição Parenteral , Humanos , Taiwan , Recém-Nascido , Nutrição Enteral/normas , Nutrição Enteral/métodos , Nutrição Parenteral/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Inquéritos e Questionários , Fenômenos Fisiológicos da Nutrição do Lactente , Feminino , Guias de Prática Clínica como Assunto , Unidades de Terapia Intensiva Neonatal/normas , Masculino , Leite Humano
4.
ChemSusChem ; : e202401568, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327838

RESUMO

The encapsulation of protein enzymes in metal-organic frameworks (MOFs) has been recognized as an effective enzyme immobilization approach. In this study, we demonstrated the influence of enzyme amount and the isoelectric points (pI) of different enzymes on the enzyme loading capacity in both mechanochemical (ball-milling) and water-based approaches. We found that increasing enzyme amounts enhances MOF enzyme loading without compromising activity, while the MOF shell protects encapsulated enzymes from proteinase K degradation through its size-sheltering mechanism. However, an excess of enzymes can hinder the formation of ZIF-90. Moreover, enzymes with low pI values (e.g., catalase, pI 5.4) facilitate encapsulation in MOFs, whereas enzymes with high pI values (e.g., lysozyme, pI 11.35) are more challenging to encapsulate. The simulation results revealed that increasing the enzyme amounts and pI values raises the activation energy necessary for MOF formation. This study highlights the crucial role of enzyme properties in the encapsulation process within MOFs, providing valuable insights for fabricating enzyme-MOF biocomposites for diverse applications, such as protein drug delivery.

5.
Lab Chip ; 24(19): 4536-4548, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39221473

RESUMO

Akin to the impact that digital microelectronics had on electronic devices for information technology, digital microfluidics (DMF) was anticipated to transform fluidic devices for lab-on-a-chip (LoC) applications. However, despite a wealth of research and publications, electrowetting-on-dielectric (EWOD) DMF has not achieved the anticipated wide adoption, and commercialization has been painfully slow. By identifying the technological and resource hurdles in developing DMF chip and control systems as the culprit, we envision democratizing DMF by building a standardized design and manufacturing platform. To achieve this vision, we introduce a proof-of-concept cloud platform that empowers any user to design, obtain, and operate DMF chips (https://edroplets.org). For chip design, we establish a web-based EWOD chip design platform with layout rules and automated wire routing. For chip manufacturing, we build a web-based EWOD chip manufacturing platform and fabricate four types of EWOD chips (i.e., glass, paper, PCB, and TFT) to demonstrate the foundry service workflow. For chip control, we introduce a compact EWOD control system along with web-based operating software. Although industrial fabrication services are beyond the scope of this work, we hope this perspective will inspire academic and commercial stakeholders to join the initiative toward a DMF ecosystem for the masses.

6.
Health Econ Rev ; 14(1): 71, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235715

RESUMO

INTRODUCTION: This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic. METHODS: Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period. RESULTS: The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%. CONCLUSIONS: The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals.

7.
J Multidiscip Healthc ; 17: 3981-3991, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161542

RESUMO

Objective: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature. Background: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia's few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation. Methods: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer's presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4-6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual's progress, at an intensity 4-6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥50% of their maximum inspiratory pressure). Discussion: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts. Conclusion: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual's symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.


Long COVID affects 5-10% of people following COVID infection. There is little specific guidance on how exercise can be safely prescribed in Long COVID. This paper is the first to provide a detailed description of an Australian multidisciplinary Long COVID clinic, including specific tools and guidance about how exercise can be prescribed while minimising post-exertional symptom exacerbation. The tools described could be valuable to other health facilities striving to optimise multidisciplinary care for people with Long COVID, incorporating safe exercise prescription.

8.
Int J Surg ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39166950

RESUMO

BACKGROUND: Blood-brain barrier (BBB) breakdown is associated with neurodegeneration and cognitive impairment. Cerebral small vessel disease (CSVD) is also common in idiopathic normal pressure hydrocephalus (iNPH). Biomarkers in the cerebrospinal fluid (CSF) may reflect the severity of neuropathological damage and indicate a relationship between BBB integrity and iNPH and its surgical outcome. We investigated the association of CSVD and comorbidity-related CSF biomarkers with shunt outcomes in iNPH. MATERIALS AND METHODS: This prospective cohort study recruited 53 patients with iNPH, who were subgrouped by CSVD severity. CSF proteins were analyzed, including soluble platelet-derived growth factor receptor-ß (sPDGFR-ß), Alzheimer's disease biomarkers, neurofilament light chain (NfL), and triggering receptor expressed on myeloid cells 2 (Trem2). We assessed symptom improvement, investigated its association with biomarkes levels, calculated protein cutoffs for surgical outcomes using receiver operating characteristic (ROC) curves, and compared model predictions using different proteins using hierarchical regression analysis. RESULTS: Among patients with iNPH, 74% had comorbid CSVD. Patients with severe CSVD exhibited significantly higher sPDGFR-ß levels (P=0.019) and better postoperative performance (ß=0.332, t=2.174, P=0.039; r=0.573, P=0.001). Analysis of the predictive potential of the biomarkers showed that sPDGFR-ß was predictive of surgical outcomes (area under curve=0.82, sensitivity=66.8%, specificity=94.7%). A Comparison of the models revealed a greater effect of sPDGFR-ß (Adjusted R2=0.247, ∆R2=0.160, ∆F(1, 37)=8.238, P=0.007) on cognitive improvement. CONCLUSION: This study highlighted the relevance of CSF biomarkers in assessing CSVD severity and predicting iNPH surgical outcome. CSF shunt surgery may provide an alternative treatment for neurodegenerative diseases with BBB breakdown and dysfunctional CSF clearance.

9.
BMC Geriatr ; 24(1): 694, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164655

RESUMO

BACKGROUND: This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur. METHODS: The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke. RESULTS: The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology. CONCLUSIONS: This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden.


Assuntos
Acidentes por Quedas , Humanos , Acidentes por Quedas/prevenção & controle , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Família/psicologia , Pessoa de Meia-Idade , Pesquisa Qualitativa , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cuidadores/psicologia
10.
Sensors (Basel) ; 24(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39123891

RESUMO

Maintenance and damage detection of structures are crucial for ensuring their safe usage and longevity. However, damage hidden beneath the surface can easily go unnoticed during inspection and assessment processes. This study proposes a detection method based on image techniques to detect and assess internal structural damage, breaking the limitation of traditional image methods that only analyze the structure's surface. The proposed method combines full-field response on the structure's surface with finite element model updating to reconstruct the structural model, using the reconstructed model to detect and assess hidden structural damage. Initially, numerical experiments are conducted to generate known damaged areas and parameter distributions. Data from these experiments are used to update the finite element model, establish and validate the proposed model updating method, and assess its accuracy in evaluating hidden damage, achieving an accuracy rate of 90%. Furthermore, discussions on more complex damage scenarios are carried out through numerical experiments to demonstrate the feasibility and applicability of the proposed method in reconstructing different forms of damage. Ultimately, this study utilizes stereoscopic digital imaging techniques to acquire full-field information on surfaces, and applies the proposed method to reconstruct the structure, enabling the detection and assessment of hidden damage with an accuracy rate of 86%.

11.
Cell Chem Biol ; 31(9): 1699-1713.e8, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-38991619

RESUMO

Mounting evidence indicates that proteotoxic stress is a primary activator of the CARD8 inflammasome, but the complete array of signals that control this inflammasome have not yet been established. Notably, we recently discovered that several hydrophobic radical-trapping antioxidants (RTAs), including JSH-23, potentiate CARD8 inflammasome activation through an unknown mechanism. Here, we report that these RTAs directly alkylate several cysteine residues in the N-terminal disordered region of CARD8. These hydrophobic modifications destabilize the repressive CARD8 N-terminal fragment and accelerate its proteasome-mediated degradation, thereby releasing the inflammatory CARD8 C-terminal fragment from autoinhibition. Consistently, we also found that unrelated (non-RTA) hydrophobic electrophiles as well as genetic mutation of the CARD8 cysteine residues to isoleucines similarly potentiate inflammasome activation. Overall, our results not only provide further evidence that protein folding stress is a key CARD8 inflammasome-activating signal, but also indicate that the N-terminal cysteines can play key roles in tuning the response to this stress.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Interações Hidrofóbicas e Hidrofílicas , Inflamassomos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas Adaptadoras de Sinalização CARD/química , Inflamassomos/metabolismo , Humanos , Células HEK293 , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Animais , Camundongos , Cisteína/química , Cisteína/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/química
12.
Adv Sci (Weinh) ; 11(36): e2407061, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39083301

RESUMO

We have achieved a significant breakthrough in the preparation and development of two-dimensional nanocomposites with P-N heterojunction interfaces as efficient cathode catalysts for electrochemical hydrogen evolution reaction (HER) and iodide oxidation reaction (IOR). P-type acid-doped polyaniline (PANI) and N-type exfoliated molybdenum disulfide (MoS2) nanosheets can form structurally stable composites due to formation of P-N heterojunction structures at their interfaces. These P-N heterojunctions facilitate charge transfer from PANI to MoS2 structures and thus significantly enhance the catalytic efficiency of MoS2 in the HER and IOR. Herein, by combining efficient sodium-functionalized chitosan-assisted MoS2 exfoliation, electropolymerization of PANI on nickel foam (NF) substrate, and electrochemical activation, controllable and scalable Na-Chitosan/MoS2/PANI/NF electrodes are successfully constructed as non-noble metal-based electrochemical catalysts. Compared to a commercial platinum/carbon (Pt/C) catalyst, the Na-Chitosan/MoS2/PANI/NF electrode exhibits significantly lower resistance and overpotential, a similar Tafel slope, and excellent catalytic stability at high current densities, demonstrating excellent catalytic performance in the HER under acidic conditions. More importantly, results obtained from proton exchange membrane fuel cell devices confirm the Na-Chitosan/MoS2/PANI/NF electrode exhibits a low turn-on voltage, high current density, and stable operation at 2 V. Thus, this system holds potential as a replacement for Pt/C with feasibility for applications in energy-related fields.

14.
Pediatr Gastroenterol Hepatol Nutr ; 27(4): 246-257, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035403

RESUMO

Purpose: Administering early parenteral amino acids to very low birth weight (VLBW) premature infants (birth body weight [BBW]<1,500 g) is challenging due to factors such as holidays, cost, and access to sterile compounding facilities. Using advance-prepared parenteral nutrition (PN) may address this issue and should be evaluated for its safety and potential benefits. Methods: We extracted data from medical records collected between July 2015 and August 2019. VLBW infants received PN for at least seven days and were split into two groups: the traditional group (n=30), which initially received a glucose solution and then PN on workdays, and the pre-preparation group (n=16), which received advance-prepared PN immediately upon admission to the neonatal intensive care unit. Results: The median BBWs of the traditional and pre-preparation groups were 1,180.0 vs. 1,210.0 g. In the initial two days, the pre-preparation group had a significantly higher amino acid intake (2.23 and 2.24 g/kg/d) than the traditional group (0 and 1.78 g/kg/d). The pre-preparation group exhibited greater head circumference growth ratio relative to birth (7th day: 1.21% vs. -3.57%, p=0.014; 21st day: 7.71% vs. 3.31%, p=0.017). No significant differences in metabolic tolerance were observed. Conclusion: Advanced preparation of PN can be safely implemented in VLBW preterm infants, offering advantages such as early, higher amino acid intake and improved head circumference growth within the first 21 days post-birth. This strategy may serve as a viable alternative in settings where immediate provision of sterile compounding facilities is challenging.

15.
Ecotoxicol Environ Saf ; 281: 116650, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964064

RESUMO

Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 µm (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.


Assuntos
Poluentes Atmosféricos , Material Particulado , Encurtamento do Telômero , Humanos , Material Particulado/toxicidade , Encurtamento do Telômero/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Telomerase , Linhagem Celular , Criança , Tamanho da Partícula , Estudos de Coortes , Células Epiteliais/efeitos dos fármacos , Masculino , Fatores de Tempo , Exposição Ambiental/efeitos adversos , Feminino
16.
IEEE Trans Biomed Eng ; PP2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949935

RESUMO

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

17.
Lasers Surg Med ; 56(6): 557-563, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38890780

RESUMO

BACKGROUND AND OBJECTIVES: Considering the pulse widths of picosecond and nanosecond lasers used in cutaneous laser surgery differ by approximately one order of magnitude, can nanosecond lasers produce the optical effect in human skin similar to laser-induced optical breakdown (LIOB) caused by picosecond lasers? METHODS: Cutaneous changes induced by a focused fractional nanosecond 1064-nm Nd:YAG laser were evaluated by VISIA-CR imaging, histological examination, and harmonic generation microscopy (HGM). RESULTS: A focused fractional nanosecond 1064-nm Nd:YAG laser can generate epidermal vacuoles or dermal cavities similar to the phenomenon of LIOB produced by picosecond lasers. The location and extent of photodisruption can be controlled by the laser fluence and focus depth. Moreover, laser-induced shock wave propagation and thermal degeneration of papillary collagen can be observed by HGM imaging. CONCLUSION: Focused fractional nanosecond lasers can produce an optical effect on human skin similar to LIOB caused by picosecond lasers. With techniques of application, the treatment can induce epidermal and dermal repair mechanisms in a tunable fashion to improve skin texture, wrinkles, scars, and dyspigmentation, without disrupting the epidermal surface.


Assuntos
Lasers de Estado Sólido , Pele , Humanos , Lasers de Estado Sólido/uso terapêutico , Pele/efeitos da radiação , Terapia a Laser/métodos , Terapia a Laser/instrumentação
19.
Cancer Res Commun ; 4(7): 1726-1737, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38934093

RESUMO

To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. SIGNIFICANCE: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Resistencia a Medicamentos Antineoplásicos , Doença de Hodgkin , Ipilimumab , Nivolumabe , Humanos , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Doença de Hodgkin/sangue , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Ipilimumab/uso terapêutico , Ipilimumab/administração & dosagem , Ipilimumab/farmacologia , Feminino , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-38875081

RESUMO

Zebrafish has been considered as an essential small-animal model for investigating the mechanism of heart regeneration. Due to the small size of zebrafish heart, high-frequency ultrasound (HFUS) imaging is often required for in vivo evaluations of its dynamic functions. Although commercial HFUS systems are available for myocardial velocity and strain measurement, only the outer myocardial region can be quantified due to the complex structure of zebrafish heart. In this study, a high-resolution 2-D myocardial tissue Doppler and strain imaging based on ultrafast HFUS imaging was developed for zebrafish heart imaging during heart regeneration. The cardiac flow region was first extracted to recognize the myocardial region, and the myocardial velocity and strain were then determined through vector Doppler estimation. Adult AB-line zebrafish was used for in vivo experiments, and cryoinjury was induced in the apical region of the heart. Both the myocardial velocity and strain of the whole ventricle after cryoinjury were directly visualized over 28 days. Myocardial velocity (during later diastolic motion) and strain, respectively, were significantly decreased (anterior wall: -2.0 mm/s and -3.3%; apical region: -2.0 mm/s and -4.5%; and posterior wall (PW): -1.7 mm/s and -4.3%) at the first three days after cryoinjury, which indicates weak myocardial beating due to heart injury. However, these all returned to the baseline values at 14 days after cryoinjury. All of the experimental results indicate that the proposed method is a useful tool for heart regeneration studies in adult zebrafish. In particular, it allows for the noninvasive evaluation of regional dynamic heart function.


Assuntos
Coração , Peixe-Zebra , Animais , Coração/diagnóstico por imagem , Coração/fisiologia , Ecocardiografia Doppler/métodos
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