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Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.
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The competition among drugs for binding to plasma proteins is regarded as a pharmacokinetic drug interaction. Competition between antitumor agents and other drugs for plasma protein binding can alter the free concentration of the drug, potentially impacting its efficacy and increasing the risk of toxic side effects. Through a range of spectroscopic techniques, this study examined the interaction between limonin and human serum albumin (HSA) in the context of berberine (Ber) and curcumin (Cur) under physiological conditions to clarify the binding mechanisms of binary and ternary systems at the molecular level. As demonstrated by fluorescence quenching experiments, Static quenching was identified as the mechanism of interaction between HSA and limonin. The results of site competition experiments indicated that the binding site between limonin and HSA was site I, a result further supported by molecular docking simulations. Through the use of thermodynamic data calculations, it was determined that limonin forms a stable complex with HSA by establishing hydrogen bonds and van der Waals forces. Circular dichroism (CD) spectroscopy, three-dimensional (3D) fluorescence spectroscopy, and synchronous fluorescence spectroscopy (SFS) employed to validate the notion that limonin perturbed the microenvironment of amino acids and induced conformational changes in HSA. What's more, the presence of Ber or Cur was found to have further modified the alterations observed in the interaction between the original HSA-limonin binary system. In vitro cellular experiments showed that interaction with HSA reduced the antitumor activity of limonin. In contrast, adding Ber or Cur increased the inhibition rate of tumor cells. The coexistence of both Ber and Cur significantly diminished limonin's binding affinity to HSA. The current investigation enhances comprehension regarding the binding characteristics and interaction mechanisms involving limonin, Ber, Cur, and HSA. It explores the potential of HSA as a versatile drug carrier and furnishes theoretical underpinnings for co-administrative strategies.
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Antineoplásicos , Berberina , Curcumina , Limoninas , Simulación del Acoplamiento Molecular , Unión Proteica , Albúmina Sérica Humana , Espectrometría de Fluorescencia , Humanos , Berberina/farmacología , Berberina/química , Berberina/metabolismo , Curcumina/farmacología , Curcumina/metabolismo , Curcumina/química , Limoninas/farmacología , Limoninas/química , Limoninas/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismo , Albúmina Sérica Humana/metabolismo , Albúmina Sérica Humana/química , Sitios de Unión , Termodinámica , Línea Celular Tumoral , Dicroismo CircularRESUMEN
Li-alloying reactions facilitate the incorporation of a large number of Li atoms into the crystalline structures of electrodes, such as black phosphorus (BP). However, the reactions inevitably induce multistep phase transitions characterized by drastic atomic rearrangements and lattice collapse. Despite many theoretical and experimental studies on alloying mechanisms, long-term debates persist regarding the structures of the intermediate phases, the accurate pathways of phase transitions, the formation of specific configurations, and alloying/dealloying reversibility. Here, through a combination of operando electron diffraction measurements and ab initio simulations at the atomic and electronic scales, we identify key factors that govern the severe structural changes during alloying-dealloying reactions in BP. P-P bonds of three-bond P atoms are continuously broken during lithiation, generating two-bond P atoms with a high ability to accept inserted electrons and Li ions. Consequently, the pristine layered structure in BP is transformed to P7 cages in Li3P7, which then evolve to chain configurations in LiP and finally to isolated P atoms in Li3P. Specifically, the preferential formation of the P7 cage results from its lowest binding energy with three Li ions compared to other cage isomers. Furthermore, only LiP can be reversibly transformed to the crystalline structure of Li3P7 during charge, but it is thermodynamically favorable for Li3P7 and Li3P intermediates to be delithiated to amorphous structures. Our findings offer unique insights into the alloying mechanisms and deepen the fundamental understanding of alloying anode systems.
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Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.
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The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.
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BACKGROUND: Adolescence is marked by an increasing risk of depression and is an optimal window for prevention and early intervention. Personalizing interventions may be one way to maximize therapeutic benefit, especially given the marked heterogeneity in depressive presentations. However, empirical evidence that can guide personalized intervention for youth is lacking. Identifying person-specific symptom drivers during adolescence could improve outcomes by accounting for both developmental and individual differences. OBJECTIVE: This study leverages adolescents' everyday smartphone use to investigate person-specific drivers of depression and validate smartphone-based mobile sensing data against established ambulatory methods. We describe the methods of this study and provide an update on its status. After data collection is completed, we will address three specific aims: (1) identify idiographic drivers of dynamic variability in depressive symptoms, (2) test the validity of mobile sensing against ecological momentary assessment (EMA) and actigraphy for identifying these drivers, and (3) explore adolescent baseline characteristics as predictors of these drivers. METHODS: A total of 50 adolescents with elevated symptoms of depression will participate in 28 days of (1) smartphone-based EMA assessing depressive symptoms, processes, affect, and sleep; (2) mobile sensing of mobility, physical activity, sleep, natural language use in typed interpersonal communication, screen-on time, and call frequency and duration using the Effortless Assessment of Risk States smartphone app; and (3) wrist actigraphy of physical activity and sleep. Adolescents and caregivers will complete developmental and clinical measures at baseline, as well as user feedback interviews at follow-up. Idiographic, within-subject networks of EMA symptoms will be modeled to identify each adolescent's person-specific drivers of depression. Correlations among EMA, mobile sensor, and actigraph measures of sleep, physical, and social activity will be used to assess the validity of mobile sensing for identifying person-specific drivers. Data-driven analyses of mobile sensor variables predicting core depressive symptoms (self-reported mood and anhedonia) will also be used to assess the validity of mobile sensing for identifying drivers. Finally, between-subject baseline characteristics will be explored as predictors of person-specific drivers. RESULTS: As of October 2023, 84 families were screened as eligible, of whom 70% (n=59) provided informed consent and 46% (n=39) met all inclusion criteria after completing baseline assessment. Of the 39 included families, 85% (n=33) completed the 28-day smartphone and actigraph data collection period and follow-up study visit. CONCLUSIONS: This study leverages depressed adolescents' everyday smartphone use to identify person-specific drivers of adolescent depression and to assess the validity of mobile sensing for identifying these drivers. The findings are expected to offer novel insights into the structure and dynamics of depressive symptomatology during a sensitive period of development and to inform future development of a scalable, low-burden smartphone-based tool that can guide personalized treatment decisions for depressed adolescents. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43931.
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Depresión , Evaluación Ecológica Momentánea , Teléfono Inteligente , Humanos , Adolescente , Depresión/diagnóstico , Femenino , Masculino , Actigrafía/instrumentación , Actigrafía/métodos , Aplicaciones MóvilesRESUMEN
We present the development and validation of an impedance-based urine osmometer for accurate and portable measurement of urine osmolality. The urine osmolality of a urine sample can be estimated by determining the concentrations of the conductive solutes and urea, which make up approximately 94% of the urine composition. Our method utilizes impedance measurements to determine the conductive solutes and urea after hydrolysis with urease enzyme. We built an impedance model using sodium chloride (NaCl) and urea at various known concentrations. In this work, we validated the accuracy of the impedance-based urine osmometer by developing a proof-of-concept first prototype and an integrated urine dipstick second prototype, where both prototypes exhibit an average accuracy of 95.5 ± 2.4% and 89.9 ± 9.1%, respectively in comparison to a clinical freezing point osmometer in the hospital laboratory. While the integrated dipstick design exhibited a slightly lower accuracy than the first prototype, it eliminated the need for pre-mixing or manual pipetting. Impedance calibration curves for conductive and non-conductive solutes consistently yielded results for NaCl but underscored challenges in achieving uniform urease enzyme coating on the dipstick. We also investigated the impact of storing urine at room temperature for 24 hours, demonstrating negligible differences in osmolality values. Overall, our impedance-based urine osmometer presents a promising tool for point-of-care urine osmolality measurements, addressing the demand for a portable, accurate, and user-friendly device with potential applications in clinical and home settings.
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Impedancia Eléctrica , Urea , Ureasa , Urea/orina , Urea/química , Concentración Osmolar , Hidrólisis , Humanos , Ureasa/metabolismo , Ureasa/química , Urinálisis/instrumentación , Diseño de EquipoRESUMEN
Here, we present a method for expressing multiple open reading frames (ORFs) from single transcripts using the leaky scanning model of translation initiation. In this approach termed "stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes" (SEMPER), adjacent ORFs are translated from a single mRNA at tunable ratios determined by their order in the sequence and the strength of their translation initiation sites. We validate this approach by expressing up to three fluorescent proteins from one plasmid in two different cell lines. We then use it to encode a stoichiometrically tuned polycistronic construct encoding gas vesicle acoustic reporter genes that enables efficient formation of the multi-protein complex while minimizing cellular toxicity. We also demonstrate that SEMPER enables polycistronic expression of recombinant monoclonal antibodies from plasmid DNA and of two fluorescent proteins from single mRNAs made through in vitro transcription. Finally, we provide a probabilistic model to elucidate the mechanisms underlying SEMPER. A record of this paper's transparent peer review process is included in the supplemental information.
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Sistemas de Lectura Abierta , ARN Mensajero , Ribosomas , ARN Mensajero/genética , Ribosomas/metabolismo , Ribosomas/genética , Sistemas de Lectura Abierta/genética , Humanos , Biosíntesis de Proteínas/genética , Expresión Génica/genética , Plásmidos/genética , Animales , Genes Reporteros/genéticaRESUMEN
Introduction: Borderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations. Methods: A total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: "F1: Affective Instability and Impulsivity", "F2: Interpersonal Unstable and Extreme Reactions", and "F3: Identity Disturbance". Results: Among 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p<0.001). Discussion: Our study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.
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BACKGROUND: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC. METHODS: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins. RESULTS: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated. CONCLUSION: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.
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Objective: This study aims to investigate the elderly digital engagement (acceptance and utilization of technology), with a focus on the widespread application of financial technology: mobile banking (m-banking). Methods: Guided by social influence theory, the research examines the various social dynamics that encourage elderly engagement with m-banking and the moderating effects of their digital literacy. Data was gathered online utilizing a disjunctive approach and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Results: The study reveals that both word-of-mouths (WOMs) and peer engagement significantly influence the elderly's perceived usefulness of the platform, thereby influencing their m-banking engagement. Additionally, the level of digital literacy among older adults was found to impact their perceived usefulness of m-banking services. Interestingly, digital literacy among older adults negatively moderates the positive associations of WOMs and peer engagement on perceived usefulness. Discussion: These insights advance our understanding of how social interactions can steer technological engagement, particularly for the silver generation with diverse levels of digital literacy. As society ages and becomes increasingly digitized, it is imperative to promote digital engagement among the elderly and foster a more inclusive digital environment.
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Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.
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BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivariate Cox regression analysis of AKI and mortality-related risk factors was performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1-3 AKI had significantly lower survival rates than those without AKI (p = 0.0012). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage (p = 0.0012). Age; albumin, D-dimer, and ferritin levels; and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within one month after the disease onset.
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Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.
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Receptores de Hialuranos , Diálisis Peritoneal , Fibrosis Peritoneal , Peritoneo , Transducción de Señal , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/patología , Animales , Ratones , Receptores de Hialuranos/metabolismo , Humanos , Peritoneo/patología , Peritoneo/metabolismo , Diálisis Peritoneal/efectos adversos , Modelos Animales de Enfermedad , Inflamación/metabolismo , Presión/efectos adversos , Masculino , Proliferación Celular , Transición Epitelial-Mesenquimal , Ratones Endogámicos C57BL , Línea Celular , Movimiento CelularRESUMEN
OBJECTIVES: The incidence of chronic kidney disease (CKD) is increasing owing to the ageing population, resulting in an increased demand for dialysis and kidney transplantation, which can be costly. Current research lacks clarity regarding the relationship between residence setting and CKD prevalence or its related risk factors. This study explored the urban-rural disparities in CKD prevalence and risk factors in Taiwan. Our findings will aid the understanding of the distribution of CKD and the design of more effective prevention programmes. DESIGN: This cross-sectional community-based study used the Renal Value Evaluation Awareness and Lift programme, which involves early screening and health education for CKD diagnosis and treatment. CKD prevalence and risk factors including alcohol consumption, smoking and betel nut chewing were compared between urban and rural areas. SETTING: Urbanisation levels were determined based on population density, education, age, agricultural population and medical resources. PARTICIPANTS: A total of 7786 participants from 26 urban and 15 rural townships were included. RESULTS: The prevalence of CKD was significantly higher in rural (29.2%) than urban (10.8%) areas, representing a 2.7-fold difference (p<0.0001). Risk factors including diabetes (rural vs urban: 21.7% and 11.0%), hypertension (59.0% vs 39.9%), hyperuricaemia (36.7% vs 18.6%), alcohol consumption (29.0% vs 19.5%), smoking (15.9% vs 12.0%), betel nut chewing (12.6% vs 2.8%) and obesity (33.6% vs 19.4%) were significantly higher (p<0.0001) in rural areas. CONCLUSIONS: The prevalence of CKD is three times higher in rural versus urban areas. Despite >99% National Health Insurance coverage, disparities in CKD prevalence persist between residential areas. Targeted interventions and further studies are crucial for addressing these disparities and enhancing CKD management across different settings.
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Disparidades en el Estado de Salud , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Masculino , Femenino , Insuficiencia Renal Crónica/epidemiología , Persona de Mediana Edad , Taiwán/epidemiología , Factores de Riesgo , Anciano , Prevalencia , Adulto , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Salud Rural/estadística & datos numéricosRESUMEN
BACKGROUND: As an emerging infectious disease with a heterogenous and uncertain transmission pattern, coronavirus disease 2019 (COVID-19) has created a catastrophe in healthcare-associated infections (HAIs) and posed a significant challenge to infection control practices (ICPs) in healthcare settings. While the unique characteristics of psychiatric patients and clinical settings may make the implementation of ICPs difficult, evidence is lacking for compliance with ICPs among healthcare workers (HCWs) in a psychiatric setting during the COVID-19 pandemic. METHODS: A cross-sectional multi-method study based on participant unobtrusive observation coupled with the completion of a self-administered ICP survey was conducted to assess compliance with ICPs among HCWs in a psychiatric inpatient ward in a regional hospital. An online checklist, called eRub, was used to record the performance of HCWs in hand hygiene (HH) and other essential ICPs. Furthermore, a well-validated questionnaire (i.e., Compliance with Standard Precautions Scale, CSPS) was used to collect the participants' self-reported ICP compliance for later comparison. RESULTS: A total of 2,670 ICP opportunities were observed from January to April 2020. The overall compliance rate was 42.6%. HCWs exhibited satisfactory compliance to the wearing of mask (91.2%) and the handling of clinical waste (87.5%); suboptimal compliance to the handling of sharp objects (67.7%) and linen (72.7%); and poor compliance to HH (3.3%), use of gloves (40.9%), use of personal protective equipment (20%), and disinfection of used surface/area (0.4%). The compliance rates of the nurses and support staff to HH were significantly different (χ2 = 123.25, p < 0.001). In the self-reported survey, the overall compliance rate for ICPs was 64.6%. CONCLUSION: The compliance of HCWs in a psychiatric inpatient ward to ICPs during the COVID-19 pandemic ranged from poor to suboptimal. This result was alarming. Revisions of current ICP guidelines and policies that specifically target barriers in psychiatric settings will be necessary.
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COVID-19 , Adhesión a Directriz , Personal de Salud , Control de Infecciones , Autoinforme , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Estudios Transversales , Control de Infecciones/métodos , Personal de Salud/psicología , Adhesión a Directriz/estadística & datos numéricos , Encuestas y Cuestionarios , Masculino , SARS-CoV-2 , Femenino , Infección Hospitalaria/prevención & control , Higiene de las Manos/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Servicio de Psiquiatría en Hospital , Equipo de Protección Personal/estadística & datos numéricosRESUMEN
Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant advantages for high-risk and relapsed/refractory B cell non-Hodgkin's lymphoma (B-NHL) patients. Currently, a variety of anti-CD19 CAR-T cells have been approved by the FDA for the treatment of B-NHL, such as axicabtagene ciloleucel, tisagenlecucel, lisocababtagene maraleucel and brexucabtagene autoleucel. In addition, many studies are actively exploring and developing different targeted CAR-T cells, which show great potential in B-NHL. This review briefly summarized the latest research progress on the application of CAR-T in common B-NHL.
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Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B/terapia , Antígenos CD19/inmunología , Linfoma no Hodgkin/terapia , Receptores de Antígenos de Linfocitos T , Linfocitos T/inmunología , Inmunoterapia/métodos , Productos BiológicosRESUMEN
Prior research suggests that the effects of specific cognitive-behavioral therapy (CBT) modules on symptom outcomes can be estimated. We conducted a study utilizing idiographic and nomothetic methods to clarify which CBT modules are most effective for youth depression, and for whom they are most effective. Thirty-five youths received modular CBT for depression. Interrupted time series models estimated whether the introduction of each module was associated with changes in internalizing symptoms, whereby significant symptom reduction would suggest a therapeutic response to the module. Regression models were used to explore whether participant characteristics predicted subgroups of youths based on their estimated response to certain types (e.g., cognitive) of modules, and whether group membership was associated with posttreatment outcomes. Thirty youths (86%) had at least one module associated with a significant change in internalizing symptoms from premodule delivery to postmodule delivery. The specific modules associated with these changes varied across youths. Behavioral activation was most frequently associated with symptom decreases (34% of youths). No participant characteristics predicted estimated response to module type, and group membership was not significantly associated with posttreatment outcomes. Youths display highly heterogeneous responses to treatment modules, indicating multiple pathways to symptom improvement for depressed youths.