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1.
Int Emerg Nurs ; 76: 101502, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39126884

RESUMO

BACKGROUND: In pediatric emergency units, intramuscular injection is one of the most common procedures that cause pain and fear in children. Reducing pain and fear is important for patient comfort. OBJECTIVE: This randomized controlled experimental study aimed to determine the effects of ShotBlocker® and the Helfer skin tap technique on the pain and fear experienced by children aged 6-12 years during intramuscular injection in pediatric emergency units. METHODS: This study was conducted from April 2022 to October 2023 among 177 children aged 6-12 years. ShotBlocker and the Helfer skin tap technique were applied during intramuscular injection among children in the intervention groups (ShotBlocker group: n = 59, Helfer skin tap technique group: n = 59), while children in the control group received routine injections. (n = 59). The levels of pain and fear were measured. RESULTS: In the analysis of the age distribution of the children, the average age of the Helfer skin tap technique group was found to be 8.54 ± 2.00 years; ShotBlocker group, 8.46 ± 1.99 years; and control group, 9.19 ± 2.01 years. There was a significant difference in the post-intervention Wong-Baker Pain Scale and Child Fear Scale scores based on the evaluation of the children, parents, and observer nurses between the groups (p < 0.05). The pain and fear scores of the ShotBlocker group were lower than those of the control group (p < 0.05). CONCLUSIONS: ShotBlocker is more effective in reducing pain than the Helfer skin tap technique among children receiving intramuscular injection. These cheap and easy-to-use methods are recommended for use in emergency units.

2.
Infant Ment Health J ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39099255

RESUMO

This study examined the associations between maternal depression and oxytocin in pregnancy, caregiving sensitivity and adult attachment style, and infant temperament. One hundred and six women recruited from a public hospital antenatal clinic in Australia, and their infants completed assessments at three time points (Time 1: pregnancy; Time 2: 3-month postpartum; Time 3: 12-month postpartum). Mothers completed self-report questionnaires assessing maternal depression symptom severity at Time 1-3, adult attachment style at Time 2, and infant temperament at Time 3. At Time 1, they also provided a blood sample to assess peripheral oxytocin levels, and at Time 2, participated in a parent-child interaction session, which was later coded for caregiving behavior (sensitivity). Neither maternal depression nor lower levels of oxytocin during pregnancy predicted difficult infant temperament; rather, it was predicted by non-Caucasian ethnicity. When all other variables were free to vary, adult attachment avoidance mediated an association between maternal depression during pregnancy and difficult infant temperament. Results highlight the potential value of interventions focusing on adult attachment insecurity for pregnant women and raise questions about associations between culture/ethnicity and infant temperament.


Cette étude a examiné les liens entre la dépression maternelle et l'oxytocine durant la grossesse, la sensibilité de la personne prenant soin de l'enfant, le style d'attachement adulte et le tempérament du nourrisson. Cent six femmes recrutées dans une clinique prénatale d'un hôpital public et leurs nourrissons ont rempli des évaluations à trois moments (Moment 1 : la grossesse; Moment 2 : 3 mois postpartum; Moment 3 12 mois postpartum). Les mères ont rempli des questionnaires d'auto­évaluation évaluant la sévérité du symptôme de dépression maternelle aux Moments 1, 2, et 3, le style d'attachement adulte au Moment 2, et le tempérament du nourrisson au Moment 3. Au Moment 1 elles ont aussi donné un échantillon de sang afin d'évaluer les niveaux périphériques d'oxytocine, et au Moment 2 elles ont participé à une séance d'interaction parent­enfant qui fut plus tard codée pour le comportement de soin (sensibilité). Ni la dépression maternelle ni des niveaux plus bas d'oxytocine durant la grossesse ont prédit un tempérament difficile du nourrisson. En fait ce dernier s'est avéré prédit par une ethnicité non blanche. Lorsque toutes les autres variables étaient libres de varier le fait d'éviter l'attachement adulte a servi de médiation dans le lien entre la dépression maternelle durant la grossesse et le tempérament difficile du nourrisson. Les résultats mettent en lumière la valeur potentielle des interventions qui mettent l'accent sur l'insécurité de l'attachement adulte pour les femmes enceintes et soulèvent des questions quant aux liens entre la culture/l'ethnicité et le tempérament du nourrisson.


Este estudio examinó las asociaciones entre depresión materna y oxitocina en el embarazo, la sensibilidad acerca de la prestación de cuidado y el estilo de afectividad adulta, así como el temperamento del infante. Ciento seis mujeres, reclutadas de la clínica antenatal de un hospital público, y sus infantes, completaron un instrumento evaluativo en 3 momentos (Momento 1: embarazo; Momento 2: 2­3 meses después del parto; Momento 3: 12 meses después del parto). Las madres completaron cuestionarios de autoinforme en los que evaluaban la severidad de los síntomas de depresión materna en los Momentos 1, 2 y 3, el estilo de afectividad adulta al Momento 2, así como el temperamento del infante al Momento 3. Al Momento 1, ellas también aportaron una muestra de sangre para evaluar los niveles perimetrales de oxitocina, y al Momento 2, participaron en una sesión de interacción progenitor­infante que luego fue codificada en cuanto al comportamiento de prestación de cuidado (sensibilidad). Ni la depresión materna ni los bajos niveles de oxitocina durante el embarazo predijeron el temperamento difícil del infante; más bien, eso lo predijo la etnicidad no caucásica. Cuando todas las otras variables estaban libres para variar, la evasión de la afectividad adulta sirvió de mediadora en una asociación entre depresión materna durante el embarazo y temperamento difícil del infante. Los resultados subrayan el valor potencial de intervenciones que se enfoquen en la inseguridad de la afectividad adulta para mujeres embarazadas y plantean preguntas acerca de las asociaciones entre cultura/etnicidad y el temperamento del infante.

3.
J Am Heart Assoc ; 13(15): e034821, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39101497

RESUMO

BACKGROUND: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media complex (IM-GSM), is a novel subclinical atherosclerosis marker with lower values indicating greater lipid deposition. Our longitudinal study investigated IM-GSM from childhood to adulthood and its associated risk factors. METHODS AND RESULTS: A total of 240 participants from the Southern California CHS (Children's Health Study) underwent carotid artery ultrasounds in 2008 (mean age±SD): (11.2±0.6 years), and again around 2022 (24.2±1.6 years) to assess IM-GSM, carotid artery intima-media thickness, and carotid artery distensibility. Questionnaires and anthropometric and blood pressure measurements were completed by participants at both times. Mean and SD of IM-GSM were 108.2±24.6 in childhood and 75.6±15.8 in adulthood. Each 1-year increase in age was associated with -2.52 change in IM-GSM (95% CI, -2.76 to -2.27). Childhood and adulthood IM-GSMs were highly correlated (ß=0.13 [95% CI, 0.05-0.22]). In childhood, Hispanic ethnicity, lower parental education levels and prenatal father smoking were significantly associated with lower IM-GSM. In adulthood, higher systolic blood pressure, carotid artery intima-media thickness, hypertension, and lower distensibility were significantly associated with lower IM-GSM. Weight status exhibited a consistent association with both childhood and adulthood IM-GSM. During the transition from childhood to adulthood, individuals who shifted from normal weight to overweight/obese or normal blood pressure to hypertension or experienced an increase in carotid artery intima-media thickness displayed lower levels of IM-GSM in adulthood. CONCLUSIONS: IM-GSM decreases with age. Maintaining healthy weight and blood pressure levels in children could potentially aid in preventing subclinical atherosclerosis.


Assuntos
Artérias Carótidas , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Humanos , Feminino , Masculino , Criança , Estudos Longitudinais , Adulto Jovem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/fisiopatologia , Fatores de Risco , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Adolescente , California/epidemiologia , Fatores Etários , Pressão Sanguínea/fisiologia , Adulto , Valor Preditivo dos Testes
4.
Hematology ; 29(1): 2379597, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39056503

RESUMO

BACKGROUND: Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells. METHODS: Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2. RESULTS: Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells. CONCLUSION: EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Vesículas Extracelulares , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Mesilato de Imatinib/farmacologia , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
5.
J Am Soc Mass Spectrom ; 35(8): 1991-2001, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39056469

RESUMO

Ion mobility (IM) is often combined with LC-MS experiments to provide an additional dimension of separation for complex sample analysis. While highly complex samples are better characterized by the full dimensionality of LC-IM-MS experiments to uncover new information, downstream data analysis workflows are often not equipped to properly mine the additional IM dimension. For many samples the data acquisition benefits of including IM separations are all that is necessary to uncover sample information and the full dimensionality of the data is not required for data analysis. Postacquisition reduction and adaptation of the dimensions of LC-IM-MS and IM-MS experiments into an LC-MS format opens the possibility to use a plethora of existing software tools. In this work, we developed data file conversion tools to reduce the complexity of IM data analysis. Three data file transformations are introduced in the PNNL PreProcessor software: (1) mapping the IM axis to the LC axis for IM-MS data, (2) converting the drift time vs m/z space to CCS/z vs m/z space, and (3) transforming All Ions IM/MS mobility aligned fragmentation data to a standard LC-MS DDA data file format. These new data file conversions are demonstrated with corresponding lipidomics and proteomics workflows that leverage existing LC-MS data analysis software to highlight the benefits of the data transformations.

7.
Pflege ; 2024 Jun 18.
Artigo em Alemão | MEDLINE | ID: mdl-38887916

RESUMO

Demands, resources, and work engagement of lower and middle level nurse managers: a cross-sectional study Abstract. Background: Given their responsibilities, lower- and middle-level nurse managers hold a key role in the health care system. Their performance and health are affected by their work engagement, which according to the Job-Demands-Resources-Model depends on job-related demands and resources. To date, there is a lack of studies on the demands, resources, and work engagement of nurse managers in Germany. Objective: First, the study aimed to describe the job demands and resources as well as the work engagement of lower and mid-level nurse managers in hospitals and geriatric care facilities in Germany. Second, the aim was to explore potential differences in these areas between different groups, particularly regarding gender, age, and management level. Methods: The study used a cross-sectional design. Data were collected by an online survey. N = 408 cases could be evaluated. Results: Work overload is the most prominent demand, followed by emotional demands. In terms of resources, nurse managers can primarily draw on positive social relationships. The available professional resources are rated critically. Work engagement is moderate. Conclusions: The study indicates a clear need for action regarding an improvement in work engagement. In particular, work overload and professional resources need to be addressed by appropriate systemwide and organization-related measures.

8.
Cureus ; 16(5): e60329, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38883093

RESUMO

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), is a common viral illness among adolescents and young adults. IM typically presents with symptoms such as fever, lymphadenopathy, and pharyngitis. We present a case of a 32-year-old woman who developed a maculopapular rash following ibuprofen administration, revealing an underlying undiagnosed IM. Laboratory investigations confirmed EBV infection. This represents the first documented case linking non-steroidal anti-inflammatory drugs (NSAIDs) to IM presentation. Awareness of this association is crucial for timely diagnosis and management, especially when evaluating patients with unexplained skin reactions to medications.

9.
Hum Vaccin Immunother ; 20(1): 2346390, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38691025

RESUMO

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.


Assuntos
Anticorpos Antivirais , Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Nanopartículas , Dióxido de Silício , Vacinas de DNA , Vacinas Virais , Animais , Vacinas de DNA/imunologia , Vacinas de DNA/genética , Vacinas de DNA/administração & dosagem , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Camundongos , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Virais/administração & dosagem , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Dióxido de Silício/química , Camundongos Endogâmicos BALB C , Feminino , Humanos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Desenvolvimento de Vacinas
10.
EFSA J ; 22(5): e8759, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38751503

RESUMO

Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the EFSA PPR Panel published a statement following a request from the European Commission to advise on human health or the environment based on new scientific evidence presented by France during the decision-making phase. In July 2022, by means of a further mandate received from the European Commission, EFSA was requested to provide advice if new information and any other scientific evidence that has become available since the assessment conducted for the renewal in 2018 warrant re-evaluation of (i) toxicological parameters used for the risk assessment of acetamiprid during the renewal process, including toxicological endpoints; (ii) the residue definition for acetamiprid in products of plant origin; and (iii) the safety of existing maximum residue levels (MRLs). Meanwhile, the applicant of acetamiprid in the EU submitted new toxicology studies regarding the toxicological profile of the metabolite IM-2-1. Furthermore, the European Commission was made aware that several recent publications in scientific literature were made available after the literature searches conducted by EFSA. As the new data could affect the advice that EFSA was expected to deliver through the 2022 mandate, EFSA was further requested to consider this information by means of a revised mandate received in September 2023. As regards re-evaluation of point (i) in this statement, this was addressed by an EFSA Working Group integrating all the available evidence. The results of the weight of evidence indicated that there are major uncertainties in the body of evidence for the developmental neurotoxicity (DNT) properties of acetamiprid and further data are therefore needed to come to a more robust mechanistic understanding to enable appropriate hazard and risk assessment. In view of these uncertainties, the EFSA WG proposed to lower the acceptable daily intake (ADI) and acute reference dose (ARfD) from 0.025 to 0.005 mg/kg body weight (per day). A revised residue definition for risk assessment was proposed for leafy and fruit crops as sum of acetamiprid and N-desmethyl-acetamiprid (IM-2-1), expressed as acetamiprid. Regarding pulses/oilseeds, root crops and cereals, the new data received did not indicate a need to modify the existing residue definition for risk assessment, which therefore remains as parent acetamiprid. Regarding the residue definition for enforcement, the available data did not indicate a need to modify the existing definition because acetamiprid is still a sufficient marker of the residues in all crop groups. Considering the new health-based guidance values derived in the present statement, a risk for consumer has been identified for 38 MRLs currently in place in the EU Regulation. Consequently, EFSA recommended to lower the existing MRLs for 38 commodities based on the assessment of fall-back Good Agricultural Practices received within an ad hoc data call. Some fall-back MRLs proposals require further risk management considerations.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38751672

RESUMO

Background and Objective: While the axillary nodal basin is the most common lymphatic drainage pathway of the breast, the internal mammary (IM) lymph node chain plays a significant role in breast cancer staging and treatment. It has been identified as sentinel nodal drainage in approximately 13-37% of patients. Despite this, the data is still limited with regard to diagnosis and management when there is suspicion or confirmation of IM lymph node (IMLN) involvement by metastatic breast cancer. The objective of this publication is to provide a comprehensive assessment of the current body of literature surrounding the diagnosis, management and prognostic value of IMLNs in breast cancer treatment. Methods: Review of the literature published regarding IMLN diagnosis, significance, and management was completed in PubMed. Additional focus was placed on reviewing articles published within the past 10 years as foundation for an update regarding the current practice and future directions in this space. Key Content and Findings: Improved imaging techniques, with positron emission tomography-computed tomography and magnetic resonance imaging, have led to increase in the identification of IM lymphadenopathy, yielding surgical staging of the IM nodes nearly obsolete. While IM nodal metastases may play a role in overall survival (OS), it has not been demonstrated to be an independent risk factor for increased locoregional recurrence. IM nodal irradiation (IMNI) therapy has been a mainstay in the treatment of IM disease in the context of breast cancer. IMNI has demonstrated improvement in OS and risk of distant recurrence. Wide variations in radiation practices for patients with IM lymphadenopathy exist internationally, highlighting the lack of clear data driven consensus guidelines. Conclusions: Herein, we provide an updated assessment of the current diagnosis, clinical significance, and management of IM lymphadenopathy for breast cancer patients.

12.
J Mass Spectrom ; 59(6): e5040, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38736147

RESUMO

In addition to providing critical knowledge of the accurate mass of ions, ion mobility-mass spectrometry (IM-MS) delivers complementary data relating to the conformation and size of ions in the form of an ion mobility spectrum and derived parameters, namely, the ion's mobility (K) and the IM-derived collision cross section (CCS). However, the maximum amount of information obtained in IM-MS measurements is not currently transferred into analytical databases including the full mobility spectra (CCS distributions) as well as capturing of additional ion species (e.g., adducts) into the same compound entry. We introduce CCSfind, a new tool for building comprehensive databases from experimental IM-MS measurements of small molecules. CCSfind allows predicted ion species to be chosen for input chemical formulae, which are then targeted by CCSfind after parsing open source mzML input files to provide a unified set of results within a single data processing step. CCSfind can handle both chromatographically separated isomers and IM separation of isomeric ions (e.g., "protomers" or conformers of the same ion species) with simple user control over the output for new database entries in SQL format. Files of up to 1 GB can be processed in less than 2 min on a desktop computer with 32 GB RAM with computational time scaling linearly with the size of the input mzML file or the number of input molecular formulae. Results are manually reviewed, annotated with experimental settings, before committing the database where the full dataset can be retrieved.

13.
Foods ; 13(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38731776

RESUMO

This paper reports the preparation of margarine fat using Lipozyme TL IM as a catalyst and peony seed oil (PSO), palm stearin (PS) and coconut oil (CO) as raw materials. The results indicate that there were no significant changes in fatty acid composition before or after interesterification of the oil samples. However, the total amount of medium- and long-chain triglycerides (MLCTs) increased from 2.92% to 11.38% in sample E1 after interesterification, mainly including LaLaO, LaMO, LaPM, LaOO, LaPO and LaPP. Moreover, the slip melting point (SMP) of sample E1 decreased from 45.9 °C (B1) to 33.5 °C. The solid fat content (SFC) of all the samples at 20 °C was greater than 10%, indicating that they could effectively prevent oil exudation. After interesterification, the samples exhibited a ß' crystal form and could be used to prepare functional margarine.

14.
Front Oncol ; 14: 1388575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764572

RESUMO

Background: Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. Methods: A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. Results: We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). Conclusion: These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

15.
Cureus ; 16(3): e56720, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646314

RESUMO

This case report describes necrotizing enterocolitis (NEC) in an infant with a history of twin-twin transfusion syndrome (TTTS). TTTS is a volume imbalance where the anastomosis at the vascular equator between the two placentae shifts from the donor to the recipient twin. This causes a higher risk for NEC, a marked inflammation caused by bacterial infection into the intestinal wall, from prematurity and intestinal hypoperfusion. Complications include sepsis, bowel necrosis, perforation, peritonitis, and death. NEC is a leading cause of morbidity in preterm infants. A 3-month-old female with a history of TTTS and prematurity presented with her mother to the pediatric emergency department (ED) for bloody diarrhea, emesis, lack of appetite, and lethargy for 4 days. The pediatrician changed the formula due to a possible milk allergy, however, she continued to have bloody diarrhea. Over the 2 days, the patient had nonbilious and non-bloody emesis and couldn't tolerate oral intake. In the ED, labs showed neutropenia and sepsis. She had a positive fecal occult blood test (FOBT) and an abdominal x-ray that revealed dilated loops of bowel and pneumatosis intestinalis. She was started on intravenous (IV) fluids for maintenance of hydration. She was started on broad-spectrum antibiotics including intravenous (IV) vancomycin and meropenem, and had her feedings temporarily stopped. The patient was transferred to the pediatric intensive care unit (PICU) at a tertiary care/children's hospital that evening where she had a laparotomy performed to resect the diseased intestine. She was discharged 10 days after the surgery for home recovery with clinical follow-up.

16.
J Mass Spectrom ; 59(5): e5026, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38656572

RESUMO

Identification and specific quantification of isomers in a complex biological matrix by mass spectrometry alone is not an easy task due to their identical chemical formula and therefore their same mass-to-charge ratio (m/z). Here, the potential of direct introduction combined with ion mobility-mass spectrometry (DI-IM-MS) for rapid quantification of isomers as human milk oligosaccharides (HMOs) was investigated. Differences in HMO profiles between various analyzed breast milk samples were highlighted using the single ion mobility monitoring (SIM2) acquisition for high ion mobility resolution detection. Furthermore, the Se+ (secretor) or Se- (non-secretor) phenotype could be assigned to breast milk samples studied based on their HMO contents, especially on the response of 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I). The possibility of quantifying a specific isomer in breast milk by DI-IM-MS was also investigated. The standard addition method allowed the determination of the 2'-FL despite the presence of other oligosaccharides, including 3-fucosyllactose (3-FL) isomer in breast milk. This proof-of-concept study demonstrated the high potential of such an approach for the rapid and convenient quantification of isomers in complex mixtures.


Assuntos
Espectrometria de Mobilidade Iônica , Leite Humano , Oligossacarídeos , Trissacarídeos , Leite Humano/química , Humanos , Trissacarídeos/análise , Trissacarídeos/química , Oligossacarídeos/análise , Oligossacarídeos/química , Isomerismo , Feminino , Espectrometria de Mobilidade Iônica/métodos , Espectrometria de Massas/métodos
17.
Heliyon ; 10(7): e28736, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586342

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that seriously affects the life quality of patients. As a patent medicine of Chinese traditional medicine, YuXueBi capsule (YXBC) is widely used for treating RA with significant effects. However, its active compounds and therapeutic mechanisms are not fully illuminated, encumbering the satisfactory clinical application. In this study, we developed a method for identifying the chemical compounds of YXBC and the absorbed compounds into blood of rats using ultra performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) combined with UNIFI analysis software. A total of 58 compounds in YXBC were unambiguously or tentatively identified, 16 compounds from which were found in serum of rats after administration of YXBC. By network pharmacology, these prototype compounds identified in serum were predicted to regulate 30 main pathways (including HIF-1 signaling pathway, neuroactive ligand-receptor interaction, IL-17 signaling pathway, and so on) through 146 targets, resulting in promoting blood circulation and removing blood stasis, analgesia, and anti-inflammatory activities. This study provides a scientific basis for the clinical efficacy of YXBC in the treatment of RA.

18.
BMC Pregnancy Childbirth ; 24(1): 252, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589796

RESUMO

BACKGROUND: Preterm birth is a leading cause of infant morbidity and mortality worldwide. The burden of prematurity underscores the need for effective risk reduction strategies. The purpose of this study is to evaluate the efficacy of progesterone therapy, both intramuscular 17-α-hydroxyprogesterone caproate (IM 17-OHPC) and vaginal progesterone, in the prevention of recurrent spontaneous preterm birth (sPTB). The co-primary outcomes included: recurrent spontaneous PTB < 37 and < 34 weeks' gestation. METHODS: This retrospective cohort study included 637 pregnant patients that delivered at any of the three hospitals within the Los Angeles County healthcare system between October 2015 and June 2021. We compared frequencies of measured variables between each of the progesterone treated groups to no treatment using Pearson chi-squared tests and independent t-tests for categorical and continuous variables, respectively. We estimated crude and adjusted associations between each specific treatment (versus no treatment) and primary outcomes using logistic regression. RESULTS: Recurrent sPTB < 37 weeks' gestation occurred in 22.3% (n = 64) of those in the no treatment group, 29.1% (n = 86, p = .077) in the 17-OHPC group, and 14.3% (n = 6, p = 0.325) in the vaginal progesterone group. Recurrent sPTB < 34 weeks' gestation was 6.6% (n = 19) in the no treatment group, 11.8% (n = 35, p = .043) in the 17-OHPC group, and 7.1% (n = 3, p = 1) in the vaginal progesterone group. Among all participants, neither 17-OHPC nor vaginal progesterone was significantly associated with a reduction in recurrent sPTB at any time point. Among those with a short cervix, IM 17-OHPC was positively associated with recurrent sPTB < 37 weeks' gestation (aOR 5.61; 95% CI 1.16, 42.9). CONCLUSIONS: Progesterone therapy of any type did not reduce the risk of recurrent sPTB < 34 or < 37 weeks' gestation compared to no progesterone therapy.


Assuntos
Nascimento Prematuro , Progesterona , Gravidez , Feminino , Humanos , Recém-Nascido , Progesterona/uso terapêutico , Estudos Retrospectivos , Nascimento Prematuro/prevenção & controle , Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Recém-Nascido Prematuro
19.
J Am Soc Mass Spectrom ; 35(6): 1076-1088, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38660944

RESUMO

A recently developed proteolytic reactor, designed for protein structural investigation, was coupled to ion mobility mass spectrometry to monitor collisional cross section (CCS) evolution of model proteins undergoing trypsin-mediated mono enzymatic digestion. As peptides are released during digestion, the CCS of the remaining protein structure may deviate from the classical 2/3 power of the CCS-mass relationship for spherical structures. The classical relationship between CCS and mass (CCS = A × M2/3) for spherical structures, assuming a globular shape in the gas phase, may deviate as stabilizing elements are lost during digestion. In addition, collision-induced unfolding (CIU) experiments on partially digested proteins provided insights into the CCS resilience in the gas phase to ion activation, potentially due to the presence of stabilizing elements. The study initially investigated a model peptide ModBea (3 kDa), assessing the impact of disulfide bridges on CCS resilience in both reduced and oxidized forms. Subsequently, ß-lactoglobulin (2 disulfide bridges), calmodulin (Ca2+ coordination cation), and cytochrome c (heme) were selected to investigate the influence of common structuring elements on CCS resilience. CIU experiments probed the unfolding process, evaluating the effect of losing specific peptides on the energy landscapes of partially digested proteins. Comparisons of the TWCCSN2→He to trend curves describing the CCS/mass relationship revealed that proteins with structure-stabilizing elements consistently exhibit TWCCSN2→He and greater resilience toward CIU compared to proteins lacking these elements. The integration of online digestion, ion mobility, and CIU provides a valuable tool for identifying structuring elements in biopolymers in the gas phase.


Assuntos
Calmodulina , Espectrometria de Mobilidade Iônica , Desdobramento de Proteína , Proteínas , Espectrometria de Mobilidade Iônica/métodos , Proteínas/química , Calmodulina/química , Calmodulina/metabolismo , Lactoglobulinas/química , Lactoglobulinas/metabolismo , Citocromos c/química , Citocromos c/análise , Espectrometria de Massas/métodos , Peptídeos/química , Peptídeos/análise , Tripsina/química , Tripsina/metabolismo , Animais , Conformação Proteica
20.
J Integr Neurosci ; 23(4): 86, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38682220

RESUMO

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects.


Assuntos
Momordica charantia , Momordica charantia/química , Humanos , Animais , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Extratos Vegetais/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo
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