Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
Cureus ; 16(6): e61689, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975450

RESUMEN

Pneumomediastinum (PM) and subcutaneous emphysema are characterized by extra-alveolar air within the mediastinum and subcutaneous tissue. PM may occur spontaneously or due to trauma or an underlying airway disease. Spontaneous pneumomediastinum (SPM) may be caused by intractable vomiting, forceful coughing, child birthing, or performing a Valsalva maneuver. However, there are limited studies or case reports that present a combination of influenza A infection and electronic cigarette (e-cigarette)-induced SPM. This case report presents SPM in a previously healthy 20-year-old female with untreated influenza A infection and a history of e-cigarette use who presented to the emergency department with fever, cough, chest pain, dyspnea, and vomiting. Her physical examination was significant for neck tenderness, subcutaneous neck crepitus, and increased respiratory effort. Diagnostic evaluation included a chest X-ray and chest computed tomography that revealed PM with subcutaneous emphysema extending into the neck, as well as a negative Gastrografin study. She was treated conservatively and discharged after two days, with a follow-up scheduled at a pulmonary clinic. This case report highlights the need for a detailed substance use history, particularly e-cigarette use, when determining the etiology of SPM in a previously healthy patient. Management for SPM is conservative and should include addressing underlying etiologies with special attention to cessation and education of e-cigarettes and illicit substances.

2.
bioRxiv ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38853942

RESUMEN

BimC family proteins are bipolar motor proteins belonging to the kinesin superfamily which promote mitosis by crosslinking and sliding apart antiparallel microtubules. Understanding the binding mechanism between the kinesin and the microtubule is crucial for researchers to make advances in the treatment of cancer and other malignancies. Experimental research has shown that the ion concentration affects the function of BimC significantly. But the insights of the ion-dependent function of BimC remain unclear. By combining molecular dynamics (MD) simulations with a series of computational approaches, we studied the electrostatic interactions at the binding interfaces of BimC and the microtubule under different KCl concentrations. We found the electrostatic interaction between BimC and microtubule is stronger at 0 mM KCl compared to 150 mM KCl, which is consistent with experimental conclusions. Furthermore, important salt bridges and residues at the binding interfaces of the complex were identified, which illustrates the details of the BimC-microtubule interactions. Molecular dynamics analyses of salt bridges identified that the important residues on the binding interface of BimC are positively charged, while those residues on the binding interface of the tubulin heterodimer are negatively charged. The finding in this work reveals some important mechanisms of kinesin-microtubule binding, which helps the future drug design for cancer therapy.

3.
Biology (Basel) ; 13(6)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38927251

RESUMEN

Auditory temporal processing is a vital component of auditory stream segregation, or the process in which complex sounds are separated and organized into perceptually meaningful objects. Temporal processing can degrade prior to hearing loss, and is suggested to be a contributing factor to difficulties with speech-in-noise perception in normal-hearing listeners. The current study tested this hypothesis in middle-aged adults-an under-investigated cohort, despite being the age group where speech-in-noise difficulties are first reported. In 76 participants, three mechanisms of temporal processing were measured: peripheral auditory nerve function using electrocochleography, subcortical encoding of periodic speech cues (i.e., fundamental frequency; F0) using the frequency following response, and binaural sensitivity to temporal fine structure (TFS) using a dichotic frequency modulation detection task. Two measures of speech-in-noise perception were administered to explore how contributions of temporal processing may be mediated by different sensory demands present in the speech perception task. This study supported the hypothesis that temporal coding deficits contribute to speech-in-noise difficulties in middle-aged listeners. Poorer speech-in-noise perception was associated with weaker subcortical F0 encoding and binaural TFS sensitivity, but in different contexts, highlighting that diverse aspects of temporal processing are differentially utilized based on speech-in-noise task characteristics.

4.
Cureus ; 16(4): e57501, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707069

RESUMEN

Myasthenia gravis is an autoimmune disease of the neuromuscular junction caused by autoantibodies directed against the acetylcholine receptors. It presents with skeletal muscle weakness, often initially presenting with ocular symptoms such as ptosis and diplopia. When myasthenia gravis is isolated to only ocular symptoms, it is referred to as ocular myasthenia gravis (OMG). Here, we present an atypical initial presentation of OMG in a 68-year-old male patient presenting with isolated abducens nerve palsy at the initial onset. With this case report, we highlight the importance of a thorough history and clinical assessment necessary for a timely diagnosis of OMG in patients who present with isolated abducens nerve palsy.

5.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38446738

RESUMEN

The family of Janus Kinases (JAKs) associated with the JAK-signal transducers and activators of transcription signaling pathway plays a vital role in the regulation of various cellular processes. The conformational change of JAKs is the fundamental steps for activation, affecting multiple intracellular signaling pathways. However, the transitional process from inactive to active kinase is still a mystery. This study is aimed at investigating the electrostatic properties and transitional states of JAK1 to a fully activation to a catalytically active enzyme. To achieve this goal, structures of the inhibited/activated full-length JAK1 were modelled and the energies of JAK1 with Tyrosine Kinase (TK) domain at different positions were calculated, and Dijkstra's method was applied to find the energetically smoothest path. Through a comparison of the energetically smoothest paths of kinase inactivating P733L and S703I mutations, an evaluation of the reasons why these mutations lead to negative or positive regulation of JAK1 are provided. Our energy analysis suggests that activation of JAK1 is thermodynamically spontaneous, with the inhibition resulting from an energy barrier at the initial steps of activation, specifically the release of the TK domain from the inhibited Four-point-one, Ezrin, Radixin, Moesin-PK cavity. Overall, this work provides insights into the potential pathway for TK translocation and the activation mechanism of JAK1.


Asunto(s)
Transducción de Señal , Mutación , Dominios Proteicos
6.
Cureus ; 16(2): e53894, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38465024

RESUMEN

Hemispherectomy is a neurosurgical procedure that is frequently performed in pediatric patients diagnosed with Rasmussen's encephalitis. Postoperative complications include immediate complications such as hydrocephalus and hemorrhage and behavioral complications such as language impairments and contralateral weakness. However, there are limited studies or case reports that address the potential endocrinopathies associated with this and other pediatric epileptic surgeries. This case report describes the endocrinopathies following an anatomical hemispherectomy procedure. A four-year-old African-American female had a right anatomical hemispherectomy for the treatment of Rasmussen's encephalitis in 2020. The postoperative course was immediately complicated by central diabetes insipidus which was stabilized with desmopressin. The patient's labs in 2021 were consistent with central precocious puberty with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Additionally, the patient was found to have secondary adrenal insufficiency in which she failed a low-dose adrenocorticotropic hormone (ACTH) stimulation test. Oral hydrocortisone therapy was initiated for secondary adrenal insufficiency in addition to initiating leuprolide injections for central precocious puberty. Furthermore, at the age of seven years, the patient had her first menarche. This case report emphasizes the need for closer and long-term surveillance for endocrine issues in postepileptic surgical pediatric patients as well as a surveillance plan for the development of other potential endocrine abnormalities throughout the patient's life.

7.
Neurosci Insights ; 19: 26331055241228308, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38304551

RESUMEN

The auditory brainstem response (ABR) is important for both clinical and basic auditory research. It is a non-invasive measure of hearing function with millisecond-level precision. The ABR can not only measure the synchrony, speed, and efficacy of auditory physiology but also detect different modalities of hearing pathology and hearing loss. ABRs are easily acquired in vertebrate animal models like reptiles, birds, and mammals, and complement existing molecular, developmental, and systems-level research. One such model system is the chicken; an excellent animal for studying auditory development, structure, and function. However, the ABR for chickens was last reported nearly 4 decades ago. The current study examines how decades of ABR characterization in other animal species support findings from the chicken ABR. We replicated and expanded on previous research using 43 chicken hatchlings 1- and 2-day post-hatch. We report that click-evoked chicken ABRs presented with a peak waveform morphology, amplitude, and latency like previous avian studies. Tone-evoked ABRs were found for frequencies from 250 to 4000 Hertz (Hz) and exhibited a range of best sensitivity between 750 and 2000 Hz. Objective click-evoked and tone-evoked ABR thresholds were comparable to subjective thresholds. With these revisited measurements, the chicken ABR still proves to be an excellent example of precocious avian development that complements decades of molecular, neuronal, and systems-level research in the same model organism.

8.
Audiol Res ; 13(6): 978-988, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38131810

RESUMEN

Cochlear synaptic loss (termed cochlear synaptopathy) has been suggested to contribute to suprathreshold hearing difficulties. However, its existence and putative effects in humans remain inconclusive, largely due to the heterogeneous methods used across studies to indirectly evaluate the health of cochlear synapses. There is a need to standardize proxies of cochlear synaptopathy to appropriately compare and interpret findings across studies. Early auditory evoked potentials (AEPs), including the compound action potential (AP)/Wave I of the auditory brainstem response are a popular proxy, yet remain variable based on technical considerations. This study evaluated one such consideration-electrode array (i.e., montage)-to optimize the use of early AEP waveforms. In 35 young adults, electrocochleography (ECochG) responses were collected using vertical and horizontal montages. Standard ECochG measures and AP/Wave I and Wave II peak-to-trough amplitudes and latencies were compared between montages. Vertical montage recordings consistently produced significantly larger AP/Wave I peak-to-trough amplitudes compared to horizontal recordings. These findings support the use of a vertical electrode montage for optimal recordings of peripheral cochlear nerve activity. As cochlear synaptopathy continues to be explored in humans, the methods highlighted here should be considered in the development of a standardized assessment.

9.
Biophys J ; 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38160255

RESUMEN

Drosophila Ncd proteins are motor proteins that play important roles in spindle organization. Ncd and the tubulin dimer are highly charged. Thus, it is crucial to investigate Ncd-tubulin dimer interactions in the presence of ions, especially ions that are bound or restricted at the Ncd-tubulin dimer binding interfaces. To consider the ion effects, widely used implicit solvent models treat ions implicitly in the continuous solvent environment without focusing on the individual ions' effects. But highly charged biomolecules such as the Ncd and tubulin dimer may capture some ions at highly charged regions as bound ions. Such bound ions are restricted to their binding sites; thus, they can be treated as part of the biomolecules. By applying multiscale computational methods, including the machine-learning-based Hybridizing Ions Treatment-2 program, molecular dynamics simulations, DelPhi, and DelPhiForce, we studied the interaction between the Ncd motor domain and the tubulin dimer using a hybrid solvent model, which considers the bound ions explicitly and the other ions implicitly in the solvent environment. To identify the importance of treating bound ions explicitly, we also performed calculations using the implicit solvent model without considering the individual bound ions. We found that the calculations of the electrostatic features differ significantly between those of the hybrid solvent model and the pure implicit solvent model. The analyses show that treating bound ions at highly charged regions explicitly is crucial for electrostatic calculations. This work proposes a machine-learning-based approach to handle the bound ions using the hybrid solvent model. Such an approach is not only capable of handling kinesin-tubulin complexes but is also appropriate for other highly charged biomolecules, such as DNA/RNA, viral capsid proteins, etc.

10.
Fam Process ; : e12904, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37323008

RESUMEN

The transition to parenthood (TP) interview and coparenting capacity (CC) coding scheme is a mixed method approach to evaluating readiness for the interpersonal challenges of parenthood. This paper focuses on the validation of the TP-CC system with a diverse sample of 140 young expectant father/mother pairs. The TP interview is designed to assist expectant parents in expressing their thoughts and feelings about parenthood and coparenting and the CC coding scheme is designed to assess a new parent's capacity for expressing fondness, acceptance, growth, cohesion, and commitment in their relationship with their coparenting partner. Convergent validation of the TP-CC system involved measuring self- and partner-reported relationship quality, relationship security, and observed warmth and hostility during the pregnancy. Predictive validation focused on the same set of variables, measured at the 6-month postbirth follow-up. Results supported the convergent validity of the TP-CC system for mothers and fathers, with higher-specific CC scores correlating with higher relationship quality, relationship security and warmth scores, as well as lower hostility scores. Results partially supported predictive validity, with fathers' total CC scores predicting fathers' interpersonal hostility and mothers' relationship quality, relationship security, hostility, and warmth at follow-up. Consistently positive and significant correlations between both mothers and fathers prebirth and postbirth CC scores provide evidence for the test-retest reliability of the TP-CC system. Generally, findings demonstrate the potential utility of the TP-CC system for evaluating coparenting readiness across the transition to parenthood.

11.
Life (Basel) ; 13(4)2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37109511

RESUMEN

Janus Kinase 3 (JAK3) plays a key role in the development, proliferation, and differentiation of various immune cells. It regulates gene expression by phosphorylation of Signal Transducers and Activators of Transcriptions (STATs) via the JAK/STAT pathway. Recently, we found a new JAK3 phosphorylation site, tyrosine 841 (Y841). The results showed that pY841 helps the kinase domain flip around the pseudo kinase domain, which may cause JAK3 conformational changes. It also reduces the size of the cleft between the N-lobe and the C-lobe of the JAK3 kinase domain. However, pY841 was found to enlarge the cleft when ATP/ADP was bound to the kinase. The increase in the cleft size suggested that pY841 enhanced the elasticity of the kinase domain. For unphosphorylated JAK3 (JAK3-Y841), the binding forces between the kinase domain and ATP or ADP were similar. After phosphorylation of Y841, JAK3-pY841 exhibited more salt bridges and hydrogen bonds between ATP and the kinase than between ADP and the kinase. Consequently, the electrostatic binding force between ATP and the kinase was higher than that between ADP and the kinase. The result was that compared to ADP, ATP was more attractive to JAK3 when Y841 was phosphorylated. Therefore, JAK3-pY841 tended to bind ATP rather than ADP. This work provides new insights into the role of phosphorylation in kinase activation and ATP hydrolysis and sheds light on the importance of understanding the molecular mechanisms that regulate the kinase function.

12.
Comput Struct Biotechnol J ; 21: 1383-1389, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817955

RESUMEN

Electrostatic features are fundamental to protein functions and protein-protein interactions. Studying highly charged biomolecules is challenging given the heterogeneous distribution of the ionic cloud around such biomolecules. Here we report a new computational method, Hybridizing Ions Treatment-2 (HIT-2), which is used to model biomolecule-bound ions using the implicit solvation model. By modeling ions, HIT-2 allows the user to calculate important electrostatic features of the biomolecules. HIT-2 applies an efficient algorithm to calculate the position of bound ions from molecular dynamics simulations. Modeling parameters were optimized by machine learning methods from thousands of datasets. The optimized parameters produced results with errors lower than 0.2 Å. The testing results on bound Ca2+ and Zn2+ in NAMD simulations also proved that HIT-2 can effectively identify bound ion types, numbers, and positions. Also, multiple tests performed on HIT-2 suggest the method can handle biomolecules that undergo remarkable conformational changes. HIT-2 can significantly improve electrostatic calculations for many problems in computational biophysics.

13.
Cells ; 12(2)2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36672172

RESUMEN

Microtubules are key players in several stages of the cell cycle and are also involved in the transportation of cellular organelles. Microtubules are polymerized by α/ß tubulin dimers with a highly dynamic feature, especially at the plus ends of the microtubules. Therefore, understanding the interactions among tubulins is crucial for characterizing microtubule dynamics. Studying microtubule dynamics can help researchers make advances in the treatment of neurodegenerative diseases and cancer. In this study, we utilize a series of computational approaches to study the electrostatic interactions at the binding interfaces of tubulin monomers. Our study revealed that among all the four types of tubulin-tubulin binding modes, the electrostatic attractive interactions in the α/ß tubulin binding are the strongest while the interactions of α/α tubulin binding in the longitudinal direction are the weakest. Our calculations explained that due to the electrostatic interactions, the tubulins always preferred to form α/ß tubulin dimers. The interactions between two protofilaments are the weakest. Thus, the protofilaments are easily separated from each other. Furthermore, the important residues involved in the salt bridges at the binding interfaces of the tubulins are identified, which illustrates the details of the interactions in the microtubule. This study elucidates some mechanistic details of microtubule dynamics and also identifies important residues at the binding interfaces as potential drug targets for the inhibition of cancer cells.


Asunto(s)
Microtúbulos , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Electricidad Estática , Microtúbulos/metabolismo
14.
J Prev (2022) ; 43(6): 801-821, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36301450

RESUMEN

The misuse of substances by adolescents is a serious public health concern in the United States, and the three most used substances by adolescents are alcohol, cannabis, and electronic cigarettes. In accordance with the Social Development Model, a better understanding of the risk and protective factors across these three substances can assist in predicting potential substance use as well as strategies for prevention. The purpose of the current study is to examine the similar or differential influence that a specific set of risk and protective factors (i.e., favorable attitudes toward substance use, perceived risk of harm, peer substance use, interaction with prosocial peers, parental favorable attitudes toward substance use, family management, perceived availability substances, and rewards for prosocial involvement) have on past 30-day alcohol, cannabis, and e-cigarette use by adolescents. The present study is based on a secondary data analysis of the 2019 Prevention Needs Assessment Survey, which is administered every two years in the State of Utah to a large sample of students in grades 6, 8, 10, and 12 grades. A subsample of students (n = 44,728) was included in the present analysis. Logistic regression was used to examine the predictive relation for the set of four risk and four protective factors on past 30-day use of alcohol, cannabis, and e-cigarette use. In general, the results indicated that endorsement of the four risk factors predicted increases in the use of each substance whereas endorsement of the four protective factors predicted decreases in use. Implications of these findings suggest that there may be more similarities in risk and protective factors across alcohol, cannabis, and electronic cigarettes than between them. In addition, this study adds to the budding literature on the risk and protective factors associated with adolescent e-cigarette use.


Asunto(s)
Cannabis , Sistemas Electrónicos de Liberación de Nicotina , Trastornos Relacionados con Sustancias , Vapeo , Adolescente , Humanos , Estados Unidos , Factores Protectores , Trastornos Relacionados con Sustancias/prevención & control , Etanol
15.
Comput Struct Biotechnol J ; 20: 4305-4314, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051882

RESUMEN

Kinesins are microtubule-based motor proteins that play important roles ranging from intracellular transport to cell division. Human Kinesin-5 (Eg5) is essential for mitotic spindle assembly during cell division. By combining molecular dynamics (MD) simulations with other multi-scale computational approaches, we systematically studied the interaction between Eg5 and the microtubule. We find the electrostatic feature on the motor domains of Eg5 provides attractive interactions to the microtubule. Additionally, the folding and binding energy analysis reveals that the Eg5 motor domain performs its functions best when in a weak acidic environment. Molecular dynamics analyses of hydrogen bonds and salt bridges demonstrate that, on the binding interfaces of Eg5 and the tubulin heterodimer, salt bridges play the most significant role in holding the complex. The salt bridge residues on the binding interface of Eg5 are mostly positive, while salt bridge residues on the binding interface of tubulin heterodimer are mostly negative. Such salt bridge residue distribution is consistent with electrostatic potential calculations. In contrast, the interface between α and ß-tubulins is dominated by hydrogen bonds rather than salt bridges. Compared to the Eg5/α-tubulin interface, the Eg5/ß-tubulin interface has a greater number of salt bridges and higher occupancy for salt bridges. This asymmetric salt bridge distribution may play a significant role in Eg5's directionality. The residues involved in hydrogen bonds and salt bridges are identified in this work and may be helpful for anticancer drug design.

16.
J Vis Exp ; (185)2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35913132

RESUMEN

The chicken embryo is a widely accepted animal model to study the auditory brainstem, composed of highly specialized microcircuitry and neuronal topology differentially oriented along a tonotopic (i.e., frequency) axis. The tonotopic axis permits the segregated encoding of high-frequency sounds in the rostral-medial plane and low-frequency encoding in caudo-lateral regions. Traditionally, coronal brainstem slices of embryonic tissue permit the study of relative individual iso-frequency lamina. Although sufficient to investigate anatomical and physiological questions pertaining to individual iso-frequency regions, the study of tonotopic variation and its development across larger auditory brainstem areas is somewhat limited. This protocol reports brainstem slicing techniques from chicken embryos that encompass larger gradients of frequency regions in the lower auditory brainstem. The utilization of different slicing methods for chicken auditory brainstem tissue permits electrophysiological and anatomical experiments within one brainstem slice, where larger gradients of tonotopic properties and developmental trajectories are better preserved than coronal sections. Multiple slicing techniques allow for improved investigation of the diverse anatomical, biophysical, and tonotopic properties of auditory brainstem microcircuits.


Asunto(s)
Corteza Auditiva , Pollos , Estimulación Acústica , Animales , Vías Auditivas/fisiología , Tronco Encefálico , Embrión de Pollo , Neuronas/fisiología
17.
J Vis Exp ; (182)2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35435914

RESUMEN

The auditory brainstem response (ABR) is an invaluable assay in clinical audiology, non-human animals, and human research. Despite the widespread use of ABRs in measuring auditory neural synchrony and estimating hearing sensitivity in other vertebrate model systems, methods for recording ABRs in the chicken have not been reported in nearly four decades. Chickens provide a robust animal research model because their auditory system is near functional maturation during late embryonic and early hatchling stages. We have demonstrated methods used to elicit one or two-channel ABR recordings using subdermal needle electrode arrays in chicken hatchlings. Regardless of electrode recording configuration (i.e., montage), ABR recordings included 3-4 positive-going peak waveforms within the first 6 ms of a suprathreshold click stimulus. Peak-to-trough waveform amplitudes ranged from 2-11 µV at high-intensity levels, with positive peaks exhibiting expected latency-intensity functions (i.e., increase in latency as a function of decreased intensity). Standardized earphone position was critical for optimal recordings as loose skin can occlude the ear canal, and animal movement can dislodge the stimulus transducer. Peak amplitudes were smaller, and latencies were longer as animal body temperature lowered, supporting the need for maintaining physiological body temperature. For young hatchlings (<3 h post-hatch day 1), thresholds were elevated by ~5 dB, peak latencies increased ~1-2 ms, and peak to trough amplitudes were decreased ~1 µV compared to older hatchlings. This suggests a potential conductive-related issue (i.e., fluid in the middle ear cavity) and should be considered for young hatchlings. Overall, the ABR methods outlined here permit accurate and reproducible recording of in-vivo auditory function in chicken hatchlings that could be applied to different stages of development. Such findings are easily compared to human and mammalian models of hearing loss, aging, or other auditory-related manipulations.


Asunto(s)
Pollos , Potenciales Evocados Auditivos del Tronco Encefálico , Estimulación Acústica/métodos , Animales , Umbral Auditivo/fisiología , Nervio Coclear/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Audición/fisiología , Mamíferos
18.
IDCases ; 25: e01235, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34377669

RESUMEN

Capnocytophaga canimorsus, a commensal organism in canine flora, is most frequently transmitted to humans via animal bite. Infection can lead to multiorgan failure, disseminated intravascular coagulation, and uncommonly mycotic aneurysm. We present a case of a 65-year-old male who presented to the emergency department with right lower quadrant abdominal pain, nausea with vomiting, and diarrhea that began the evening prior to presentation. A computed tomography (CT) scan of the abdomen and pelvis with contrast demonstrated a 4.3 cm fusiform infrarenal aortic aneurysm concerning for a mycotic aneurysm. Vascular surgery felt there was a low likelihood of rupture and empiric antimicrobials were started. Eventually blood cultures grew a Capnocytophaga species and antimicrobials were then narrowed to imipenem. No surgical intervention was performed. Serial imaging showed stability of aneurysm with improvement and later complete resolution of inflammatory changes one month after onset of symptoms. This is the first reported case of Capnocytophaga mycotic aneurysm that was treated with antimicrobials alone and no surgical intervention.

19.
J Chem Inf Model ; 61(9): 4190-4199, 2021 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-34397210

RESUMEN

Signaling bias is a feature of many G protein-coupled receptor (GPCR) targeting drugs with potential clinical implications. Whether it is therapeutically advantageous for a drug to be G protein biased or ß-arrestin biased depends on the context of the signaling pathway. Here, we explored GPCR ligands that exhibit biased signaling to gain insights into scaffolds and pharmacophores that lead to bias. More specifically, we considered BiasDB, a database containing information about GPCR biased ligands, and focused our analysis on ligands which show either a G protein or ß-arrestin bias. Five different machine learning models were trained on these ligands using 15 different sets of features. Molecular fragments which were important for training the models were analyzed. Two of these fragments (number of secondary amines and number of aromatic amines) were more prevalent in ß-arrestin biased ligands. After training a random forest model on HierS scaffolds, we found five scaffolds, which demonstrated G protein or ß-arrestin bias. We also conducted t-SNE clustering, observing correspondence between unsupervised and supervised machine learning methods. To increase the applicability of our work, we developed a web implementation of our models, which can predict bias based on user-provided SMILES, drug names, or PubChem CID. Our web implementation is available at: drugdiscovery.utep.edu/biasnet.


Asunto(s)
Receptores Acoplados a Proteínas G , Transducción de Señal , Ligandos , Unión Proteica , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/metabolismo
20.
Psychol Addict Behav ; 35(7): 797-802, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33734782

RESUMEN

OBJECTIVE: Substance use treatment for adolescents may decrease not only substance use, but also other related outcomes such as externalizing behaviors. Although positively correlated to substance use in youth, externalizing behaviors are not commonly measured as outcomes in the context of substance use treatment. This study seeks to generalize the outcomes of substance use treatment to externalizing behaviors in a sample of Latino/a adolescents who participated in a randomized clinical trial. METHOD: Secondary data analysis was conducted using a longitudinal mixed model to test the outcomes of two versions of a cognitive-behavioral substance use treatment (i.e., standard and culturally accommodated) on externalizing behaviors. Participants were Latino/a adolescents (N = 70) diagnosed with a substance use disorder randomized into one of the two study conditions. RESULTS: The results indicated that Latino/a adolescents in both treatment conditions significantly decreased in self-reported externalizing behaviors from pretreatment to 12-months posttreatment. CONCLUSIONS: Implications from this study suggest that participation in substance use treatment for Latino/a adolescents may also generalize to other outcomes such as externalizing behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Asunto(s)
Terapia Cognitivo-Conductual , Trastornos Relacionados con Sustancias , Adolescente , Hispánicos o Latinos , Humanos , Autoinforme , Trastornos Relacionados con Sustancias/terapia , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...