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1.
Front Cell Dev Biol ; 12: 1422764, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966426

RESUMEN

Purpose: Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Methods: Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9-39 weeks. Charge balanced, biphasic, current pulses (100 µA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3-34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Conclusion: Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.

2.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1033-1039, 2024 Jun 20.
Artículo en Chino | MEDLINE | ID: mdl-38977332

RESUMEN

OBJECTIVE: To evaluate the predictive value of global longitudinal strain (GLS) measured by cardiac magnetic resonance (CMR) feature-tracking technique for left ventricular remodeling (LVR) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 403 patients undergoing PCI for acute STEMI were prospectively recruited from multiple centers in China.CMR examinations were performed one week (7±2 days) and 6 months after myocardial infarction to obtain GLS, global radial strain (GRS), global circumferential strain (GCS), ejection fraction (LVEF) and infarct size (IS).The primary endpoint was LVR, defined as an increase of left ventricle end-diastolic volume by ≥20% or an increase of left ventricle end-systolic volume by ≥15% from the baseline determined by CMR at 6 months.Logistic regression analysis was performed to evaluate the predictive value of CMR parameters for LVR. RESULTS: LVR occurred in 101 of the patients at 6 months after myocardial infarction.Compared with those without LVR (n=302), the patients in LVR group exhibited significantly higher GLS and GCS (P < 0.001) and lower GRS and LVEF (P < 0.001).Logistic regression analysis indicated that both GLS (OR=1.387, 95%CI: 1.223-1.573;P < 0.001) and LVEF (OR=0.951, 95%CI: 0.914-0.990;P=0.015) were independent predictors of LVR.ROC curve analysis showed that at the optimal cutoff value of-10.6%, GLS had a sensitivity of 74.3% and a specificity of 71.9% for predicting LVR.The AUC of GLS was similar to that of LVEF for predicting LVR (P=0.146), but was significantly greater than those of other parameters such as GCS, GRS and IS (P < 0.05);the AUC of LVEF did not differ significantly from those of the other parameters (P>0.05). CONCLUSION: In patients receiving PCI for STEMI, GLS measured by CMR is a significant predictor of LVR occurrence with better performance than GRS, GCS, IS and LVEF.


Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Remodelación Ventricular , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/cirugía , Estudios Prospectivos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Volumen Sistólico , Función Ventricular Izquierda/fisiología , Tensión Longitudinal Global
3.
J Thorac Oncol ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39067700

RESUMEN

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I non-small cell lung cancer (NSCLC). Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in SBRT-treated stage I NSCLC patients and develop prediction models for these outcomes. METHODS: Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017-2021 were included. Acute toxicity was assessed, defined as grade ≥2 radiation-pneumonitis or grade ≥3 non-hematologic toxicity ≤90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. RESULTS: Among 7,279 patients, the mean age was 72.5 years, with 21.6% being >80 years. Most were female (50.7%), had WHO scores 0-1 (73.3%), and cT1a-b tumors (64.6%), predominantly in upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO ≥2, lower FEV1 and DLCO, no pathology confirmation, middle/lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Female gender, WHO ≥2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). CONCLUSIONS: This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in SBRT-treated stage I NSCLC patients. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.

4.
Curr Biol ; 34(12): 2657-2671.e7, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38810639

RESUMEN

Animals need to detect threats, initiate defensive responses, and, in parallel, remember where the threat occurred to avoid the possibility of re-encountering it. By probing animals capable of detecting and avoiding a shock-related threatening location, we were able to reveal a septo-hippocampal-hypothalamic circuit that is also engaged in ethological threats, including predatory and social threats. Photometry analysis focusing on the dorsal premammillary nucleus (PMd), a critical interface of this circuit, showed that in freely tested animals, the nucleus appears ideal to work as a threat detector to sense dynamic changes under threatening conditions as the animal approaches and avoids the threatening source. We also found that PMd chemogenetic silencing impaired defensive responses by causing a failure of threat detection rather than a direct influence on any behavioral responses and, at the same time, updated fear memory to a low-threat condition. Optogenetic silencing of the main PMd targets, namely the periaqueductal gray and anterior medial thalamus, showed that the projection to the periaqueductal gray influences both defensive responses and, to a lesser degree, contextual memory, whereas the projection to the anterior medial thalamus has a stronger influence on memory processes. Our results are important for understanding how animals deal with the threat imminence continuum, revealing a circuit that is engaged in threat detection and that, at the same time, serves to update the memory process to accommodate changes under threatening conditions.


Asunto(s)
Miedo , Hipocampo , Memoria , Animales , Miedo/fisiología , Memoria/fisiología , Masculino , Hipocampo/fisiología , Vías Nerviosas/fisiología , Hipotálamo/fisiología , Optogenética , Ratas/fisiología
5.
Sci Total Environ ; 915: 169863, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38190906

RESUMEN

Decentralised wastewater treatment is becoming a suitable strategy to reduce cost and environmental impact. In this research, the performance of two technologies treating black water (BW) and grey water (GW) fractions of urban sewage is carried out in a decentralised treatment of the wastewater produced in three office buildings. An Anaerobic Membrane Bioreactor (AnMBR) treating BW and a Hybrid preanoxic Membrane Bioreactor (H-MBR) containing small plastic carrier elements, treating GW were operated at pilot scale. Their potential on reducing the release of contaminants of emerging concern (CECs) such as Organic Micropollutants (OMPs), Antibiotic Resistance Genes (ARGs) and pathogens was studied. After 226 d of operation, a stable operation was achieved in both systems: the AnMBR removed 92.4 ± 2.5 % of influent COD, and H-MBR removed 89.7 ± 3.5 %. Regarding OMPs, the profile of compounds differed between BW and GW, being BW the matrix with more compounds detected at higher concentrations (up to µg L-1). For example, in the case of ibuprofen the concentrations in BW were 23.63 ± 3.97 µg L-1, 3 orders of magnitude higher than those detected in GW. The most abundant ARGs were sulfonamide resistant genes (sul1) and integron class 1 (intl1) in both BW and GW. Pathogenic bacteria counts were reduced between 1 and 3 log units in the AnMBR. Bacterial loads in GW were much lower than in BW, being no bacterial re-growth observed for the GW effluents after treatment in the H-MBR. None of the selected enteric viruses was detected in GW treatment line.


Asunto(s)
Antibacterianos , Purificación del Agua , Agua , Aguas Residuales , Aguas del Alcantarillado/microbiología , Farmacorresistencia Microbiana/genética , Genes Bacterianos , Reactores Biológicos/microbiología , Eliminación de Residuos Líquidos
7.
Sci Rep ; 13(1): 21196, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38040917

RESUMEN

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.

8.
Zhonghua Nei Ke Za Zhi ; 62(12): 1458-1464, 2023 Dec 01.
Artículo en Chino | MEDLINE | ID: mdl-38044073

RESUMEN

Objectives: Microvascular obstruction (MVO) is a specific cardiac magnetic resonance (CMR) imaging feature in patients with acute myocardial infarction. The purpose of this study was to elucidate the predictive value of MVO in left ventricular adverse remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 167 patients with STEMI undergoing primary PCI in the Chinese PLA General Hospital from 2016 to 2020 were enrolled in this prospective cohort study, the average age of study patients was 57±10 years old, with 151 males (90.4%) and 16 females (9.6%). The patients were divided into the MVO group (n=81) and non-MVO group (n=86) according to the presence or absence of MVO on CMR imaging, respectively. The primary endpoint of the study was the occurrence of left ventricular adverse remodeling, which was defined as an increase in left ventricular end diastolic volume (LVEDV) by >20% at 6 months after primary PCI compared with the baseline. Patients who completed follow-up were diagnosed as left ventricular adverse remodeling or no left ventricular adverse remodeling according to CMR. The baseline data, perioperative data, and related data of end points were compared between the MVO group and non-MVO group. Finally, the predictive value of MVO in left ventricular adverse remodeling was calculated by receiver operating characteristic curve analysis. Results: In the baseline data, preoperative thrombolysis in myocardial infarction (TIMI) flow (χ2=13.74, P=0.003) and postoperative TIMI flow (χ2=14.87, P=0.001) were both obviously decreased in the MVO group. After 6 months of follow-up, the incidence of left ventricular adverse remodeling in the MVO group was significantly higher than that in the non-MVO group [37.0%(27/73) vs. 18.9%(14/74), χ2=5.96, P=0.015]. The left ventricular end systolic volume at 6 months post infarction in the MVO group was significantly larger than that in the non-MVO group [(94±32) vs. (68±20) ml, t=-5.98, P<0.001], as well as the LVEDV [(169±38) vs. (143±29) ml, t=-4.74, P<0.001]. Receiver operating characteristic curve showed that the area under the curve of MVO size for predicting left ventricular adverse remodeling was 0.637. Conclusion: The risk of left ventricular adverse remodeling is significantly increased in patients with MVO after primary PCI for acute STEMI.


Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio con Elevación del ST/diagnóstico , Estudios Prospectivos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Circulación Coronaria , Remodelación Ventricular , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Microcirculación , Función Ventricular Izquierda
9.
Zhonghua Bing Li Xue Za Zhi ; 52(12): 1223-1229, 2023 Dec 08.
Artículo en Chino | MEDLINE | ID: mdl-38058038

RESUMEN

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.


Asunto(s)
Inteligencia Artificial , Neoplasias Urológicas , Humanos , Urotelio/patología , Citodiagnóstico , Células Epiteliales/patología , Sensibilidad y Especificidad , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patología , Neoplasias Urológicas/orina
10.
Med J Malaysia ; 78(6): 793-802, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38031223

RESUMEN

INTRODUCTION: There has been an observed number of readmissions after an index COVID-19 admission, including admissions after an initial home quarantine. The purpose of this study was to identify the clinical characteristics and outcomes of COVID-19 patients who were readmitted or admitted after an initial home quarantine between 21 and 90 days of illness. MATERIALS AND METHODS: This was a single-centre retrospective cohort study comprising patients admitted to a state hospital in Selangor, Malaysia, between August and October 2021. The demographic data, clinical characteristics, presenting complaints, laboratory tests, organ dysfunction, use of invasive ventilation, intensive care unit (ICU) admissions, length of hospitalisation and mortality were collected and analysed. RESULTS: The analysis involved a total of 195 cases. More than a quarter of the cases (52 [26.7%]) were related to the initial COVID-19 infection. Nine cases (4.6%) required mechanical ventilation, while eight cases (4.1%) were admitted to the ICU. The overall mortality was 17 cases (8.7%). Surviving patients were younger (49.5 vs. 58.4 years), less likely to have diabetes mellitus (48.3% vs. 82.4%), or chronic kidney disease (12.9% vs. 41.2%); had higher levels of admission haemoglobin (12.6 vs. 9.1g/dL) and albumin (33.0 vs. 21.0g/L); lower white blood cells (10.2 vs. 13.0 × 109/L), creatinine (81.2 vs. 151.9µmol/L) and C-reactive protein (18.2 vs. 135.0mg/L) at admission; less likely to have MI (6.7% vs. 23.5%), sepsis (3.4% vs. 47.1%), or acute kidney injury (3.4% vs. 17.6%) and organ dysfunction (25.3% vs. 94.1%). CONCLUSION: Approximately a quarter of patients were admitted or readmitted due to direct COVID-19 complications between 21 and 90 days of illness. The baseline oxygen requirements at admission were independently associated with mortality, invasive mechanical ventilation and ICU admissions. Further research is needed to establish a risk model for patients returning to a hospital to predict their risk of post-COVID complications.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Readmisión del Paciente , Insuficiencia Multiorgánica , Hospitalización
11.
Zhonghua Yi Xue Za Zhi ; 103(37): 2947-2951, 2023 Oct 10.
Artículo en Chino | MEDLINE | ID: mdl-37752054

RESUMEN

Objective: To investigate the diagnostic value of anti-Sa antibody and anti-carbonylated protein (CarP) antibody for rheumatoid arthritis (RA). Methods: A retrospective selection of 180 patients with RA who came to Qinghai Provincial People's Hospital from September 2022 to February 2023. Grouped according to the Disease Activity Score of 28 joints (DAS28), 101 of them were patients with RA in high activity (RAH group), 24 males and 77 females, aged 18-79 (53.2±12.2), and 79 patients with RA in low activity (RAL group), 23 males and 56 females, aged 24-78 (49.0±12.9).A total of 90 patients with other autoimmune diseases in the hospital in the same period were choosed as the other immune disease group, and 90 healthy physical examiners were as the healthy control group. The levels of serum anti-Sa and anti-CarP antibodies were measured by ELISA, RF by immunoscattering turbidimetry, anti-CCP by chemiluminescence, and ESR by Weil's method in four groups of patients. The area under the subject operating characteristic (ROC) curve (AUC) was applied to assess the sensitivity and specificity of each index alone or in combination for the diagnosis of RA. Results: In the RAH group, RAL group, other immune disease group, and healthy control group, the RF levels were 117.6 (61.0, 161.1), 92.7 (48.1, 92.7), 10.1 (5.3, 24.6), and 8.1 (6.0, 12.8) U/ml, anti-CCP antibody levels were 202.7 (67.1, 594.4), 212.9 (98.3, 416.2), 9.4 (6.6, 11.8), 1.9 (0.8, 4.9) U/ml, anti-Sa antibody levels were 305.3 (120.4, 614.9), 235.8 (161.6, 336.9), 123.9 (41.8, 240.5), 165.1 (71.1, 237.5) U/ml, and anti-CarP antibody levels were 11.7 (7.9, 21.6), 5.2 (3.3, 7.7), 5.1 (3.9, 6.5), and 5.8 (3.8, 7.5) mg/L, respectively, and their differences were statistically significant (all P<0.001). The level of anti-CarP antibody was higher in the RAH group than in the RAL group (P<0.001), and the difference in anti-Sa antibody was not statistically significant (P>0.05). The critical value of anti-Sa antibody at 181.45 µg/L showed a sensitivity of 67.2%, specificity of 65.6% and AUC of 0.710 (95%CI: 0.645-0.775); The sensitivity was 52.8% and the specificity was 88.9% with an AUC of 0.706 (95%CI: 0.646-0.766) at a critical value of 7.98 U/ml for the anti-CarP antibody. The AUC for the combined RF, anti-CCP antibody and anti-CarP antibody assay was 0.986 (95%CI: 0.977-0.996). Conclusion: Anti-CarP antibody is clinically significant in distinguishing active RA. RF, anti-CCP, and anti-CarP antibodies can be detected together with high AUC results, suggesting the potential for developing an improved method for diagnosing RA.


Asunto(s)
Anticuerpos Antiproteína Citrulinada , Artritis Reumatoide , Femenino , Humanos , Masculino , Artritis Reumatoide/diagnóstico , Autoanticuerpos , Péptidos Cíclicos , Proteínas , Estudios Retrospectivos , Factor Reumatoide , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano
12.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(9): 1440-1446, 2023 Sep 10.
Artículo en Chino | MEDLINE | ID: mdl-37743279

RESUMEN

Objective: To understand the etiological characteristics of 2 serotypes of Salmonella strains isolated from a foodborne disease outbreak. Methods: A total of 11 anal swabs of the cases, 13 suspected contaminated food and 10 environmental samples were collected from a foodborne disease outbreak occurred on September 8, 2022 in a school. The anal swabs were enriched with selenite brilliant green enrichment broth (SBG) and brain heart infusion broth (BHI) respectively. PCR detection and culture of common intestinal pathogens were carried out. The suspected food samples were tested according to national standards for food safety. Multiple suspected Salmonella colonies were obtained and selected for serotype determination and whole genome sequencing. Serotypes were determined based on the whole-genome sequence, and clustering analysis was performed based on core genome single nucleotide polymorphism (SNP). Results: The positive rates of Salmonella in anal swabs and suspected food samples were 9/11 and 5/13 respectively. Both Salmonella Uganda and Salmonella Idikan were isolated from 4 anal swabs and 4 suspected food samples. For the remaining samples, only Salmonella Uganda or Salmonella Idikan was isolated in each sample. The positive rate of Salmonella in 11 anal swabs of the cases after BHI enrichment for 12 h and 24 h were all 9/11 in real-time PCR, same to the culture results. Salmonella Uganda and Salmonella Idikan formed two independent and genetically distant lineages in the clustering tree based on core genome SNP, and 0-14 and 0-23 SNP were observed in Salmonella Uganda and Salmonella Idikan respectively. Conclusions: This foodborne disease outbreak was probably caused by Salmonella Uganda and Salmonella Idikan, which both exhibited strong genetic diversity. The PCR based pathogen screening strategy plus pathogen enrichment for cases' annal swabs can be used in the routine outbreak investigation.


Asunto(s)
Enfermedades Transmitidas por los Alimentos , Humanos , Serogrupo , Causalidad , Enfermedades Transmitidas por los Alimentos/epidemiología , Brotes de Enfermedades , Salmonella/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
13.
Eur Rev Med Pharmacol Sci ; 27(16): 7768-7780, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37667955

RESUMEN

OBJECTIVE: The aim of this study was to systematically assess the effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety of patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This study searched for case-control trials of TNBC patients from January 2010 to May 2022. Two researchers independently extracted data. RevMan 5.3 statistical software was used for analysis. RESULTS: This study included a total of 7 clinical controlled studies, containing 620 samples. The results showed that compared with the control group, the study group showed significant differences in objective response rate [OR = 2.44, 95% CI (1.69, 3.5), p < 0.00001], 1-year survival rate [OR = 3.59, 95% CI (2.01, 6.39), p < 0.0001], progression-free survival (PFS) [MD = 2.04, 95% CI (1.68, 2.41), p < 0.00001], with statistical significance (p < 0.05), while there are no significant differences in overall survival [MD = 6.33, 95% CI (-1.65, 14.30), p = 0.12] and incidence of adverse events [OR = 0.73, 95% CI (0.52, 1.02), p = 0.006] (p > 0.05). CONCLUSIONS: Targeted therapy associated with adjuvant chemotherapy can remarkably enhance the outcome of patients with advanced TNBC, prolonging their progression-free survival (PFS) and overall survival (OS) without increasing adverse effects. The validity of this research, however, will require higher quality studies and longer follow-ups.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Quimioterapia Adyuvante , Pacientes , Supervivencia sin Progresión
14.
JID Innov ; 3(5): 100214, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37554517

RESUMEN

Tralokinumab, a fully human mAb specifically targeting the IL-13 cytokine, has demonstrated clinical efficacy and safety in patients with moderate-to-severe atopic dermatitis. Tralokinumab binds IL-13 with high affinity, which prevents the interaction of IL-13 with IL-13Rα1 and subsequent signaling. Similarly, tralokinumab-bound IL-13 cannot bind to IL-13Rα2, a proposed decoy receptor that is reported to bind IL-13 with extraordinarily high affinity. It has however not been fully elucidated to what extent tralokinumab interferes with the endogenous regulation of IL-13 through IL-13Rα2. In this mechanistic study, we used biophysical, biochemical, and cellular assays to investigate the effect of tralokinumab on the interaction between IL-13 and IL-13Rα1 and IL-13Rα2, respectively, as well as the effects on IL-13Rα2-mediated IL-13 internalization. We demonstrate that IL-13Rα2 binds IL-13 with exceptionally high affinity and that tralokinumab is unable to displace IL-13 from IL-13Rα2. In contrast to this, tralokinumab is able to disrupt the IL-13/IL-13Rα1 and IL-13Rα1/IL-13/IL-4Rα complex. Furthermore, we demonstrate that whereas the IL-13/tralokinumab complex is unable to bind IL-13Rα2, any IL-13 that is not bound by tralokinumab (i.e., free IL-13) can be bound by IL-13Rα2 and subsequently internalized, regardless of the presence of tralokinumab. In summary, our study indicates that tralokinumab does not interfere with endogenous IL-13Rα2-mediated regulation of free IL-13.

16.
Toxins (Basel) ; 15(6)2023 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-37368676

RESUMEN

Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs.


Asunto(s)
Anopheles , Antimaláricos , Malaria , Plasmodium , Toxinas Biológicas , Femenino , Humanos , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Ponzoñas/farmacología , Ponzoñas/uso terapéutico , Mosquitos Vectores , Malaria/tratamiento farmacológico , Toxinas Biológicas/uso terapéutico , Plasmodium falciparum
17.
Zhonghua Zhong Liu Za Zhi ; 45(6): 514-518, 2023 Jun 23.
Artículo en Chino | MEDLINE | ID: mdl-37355470

RESUMEN

Objective: To investigate the oncologic and surgical safety of the fused fascia method for immediate breast reconstruction with implants. Methods: The clinical data of 343 patients with immediate breast reconstruction with implants in Tianjin Medical University Cancer Hospital from 2014-2017 were retrospectively analyzed to compare the 5-year local recurrence-free survival, 5-year disease-free survival and 5-year overall survival of patients with breast reconstruction by fusion fascia and other methods, and to analyze the complication incidences of implant removal between different implant groups. Results: Of the 343 patients with breast reconstruction, 95 were in the fused fascia group (fascia group) and 248 were in the non-fascia group (25 in the bovine pericardial patch group and 223 in the muscle flap group). At a median follow-up of 49 months, the differences in 5-year local recurrence-free survival (90.1% and 94.9%, respectively), 5-year disease-free survival (89.2% and 87.6%, respectively), and 5-year overall survival (95.2% and 95.1%, respectively) between patients in the fascial and non-fascial groups were not statistically significant (P>0.05). The complication incidence of implant removal was 24.0% (6/25) in the patch group and 2.1% (2/95) and 2.2% (5/223) in the fascia and muscle flap groups, respectively. Conclusion: Immediate breast reconstruction with fused fascial combined with implant is safe and feasible, less invasive than muscle flaps, more economical and with fewer complications than patches.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Animales , Bovinos , Femenino , Mastectomía/efectos adversos , Mastectomía/métodos , Estudios Retrospectivos , Implantes de Mama/efectos adversos , Estudios de Factibilidad , Mamoplastia/efectos adversos , Mamoplastia/métodos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Resultado del Tratamiento , Complicaciones Posoperatorias/cirugía
18.
Int J Numer Method Biomed Eng ; 39(7): e3715, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37151128

RESUMEN

Cell proliferation is vital for the development and homeostasis of the human body. For such to occur, cells go through the cell cycle during which they replicate their genetic material and ultimately complete cellular division, when one cell divides into two new cells with equal genetic material. However, if there are some errors or abnormalities during the cell cycle that disrupt the balance between cell death and proliferation, severe problems can occur, such as tumour development, which is currently one of the leading causes of death in the world. Nowadays, mathematical and computational models are used to understand and study several biological mechanisms and processes, namely cellular proliferation. Over the last forty-five years, several models have attempted to describe cell proliferation and its regulation. Due to the complexity of the process, numerous assumptions and simplifications have been considered. This work presents a review of some of these models, focusing mainly on mammalian or generic eukaryotic models. Previously published continuum, discrete and hybrid approaches are presented and compared, in order to understand and highlight the relevance and capabilities of these models, their shortcomings and future challenges.


Asunto(s)
Modelos Biológicos , Neoplasias , Animales , Humanos , Ciclo Celular , Proliferación Celular , Mamíferos
19.
Transl Vis Sci Technol ; 12(3): 20, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36943168

RESUMEN

Purpose: Accurate mapping of phosphene locations from visual prostheses is vital to encode spatial information. This process may involve the subject pointing to evoked phosphene locations with their finger. Here, we demonstrate phosphene mapping for a retinal implant using eye movements and compare it with retinotopic electrode positions and previous results using conventional finger-based mapping. Methods: Three suprachoroidal retinal implant recipients (NCT03406416) indicated the spatial position of phosphenes. Electrodes were stimulated individually, and the subjects moved their finger (finger based) or their eyes (gaze based) to the perceived phosphene location. The distortion of the measured phosphene locations from the expected locations (retinotopic electrode locations) was characterized with Procrustes analysis. Results: The finger-based phosphene locations were compressed spatially relative to the expected locations all three subjects, but preserved the general retinotopic arrangement (scale factors ranged from 0.37 to 0.83). In two subjects, the gaze-based phosphene locations were similar to the expected locations (scale factors of 0.72 and 0.99). For the third subject, there was no apparent relationship between gaze-based phosphene locations and electrode locations (scale factor of 0.07). Conclusions: Gaze-based phosphene mapping was achievable in two of three tested retinal prosthesis subjects and their derived phosphene maps correlated well with the retinotopic electrode layout. A third subject could not produce a coherent gaze-based phosphene map, but this may have revealed that their phosphenes were indistinct spatially. Translational Relevance: Gaze-based phosphene mapping is a viable alternative to conventional finger-based mapping, but may not be suitable for all subjects.


Asunto(s)
Movimientos Oculares , Prótesis Visuales , Humanos , Fosfenos , Trastornos de la Visión , Retina/cirugía
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(2): 229-235, 2023 Feb 06.
Artículo en Chino | MEDLINE | ID: mdl-36797581

RESUMEN

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.


Asunto(s)
Proteasas de Ácido Aspártico , Mariposas Nocturnas , Animales , Ovinos , Larva/microbiología , Virulencia , Candida glabrata , Agar , Mariposas Nocturnas/microbiología , Esterasas , Lipasa
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