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1.
Int J Obstet Anesth ; 60: 104227, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-39018741

RESUMEN

BACKGROUND: Patient satisfaction and quality of recovery (QoR) are important patient-reported outcomes and quality metrics. The relationship between these two outcomes is complex, with studies showing a weak correlation between them in the non-obstetric population. We sought to evaluate the correlation between patient satisfaction and QoR scores in the obstetric population after caesarean delivery. As secondary aims, we aimed to determine the influence of urgency of procedure and mode of anaesthetic on patient satisfaction and QoR scores as well as determining drivers of satisfaction and dissatisfaction. METHODS: Women were invited to complete the Maternal Satisfaction Scale for Caesarean Section (MSCS) and Obstetric Quality of Recovery Score (ObsQoR-11) questionnaires at 24 h after caesarean delivery. Correlations were analysed using Spearman's rank tests. Qualitative data were analyzed using thematic content analysis. RESULTS: Data were collected from 300 women. There was a significant but weak positive correlation between ObsQoR-11 and MSCS scores (r = 0.31, P < 0.001). Correlation was significantly influenced by mode of anaesthesia (P < 0.001) and urgency of procedure (P = 0.005), with greater satisfaction amongst patients receiving spinal anaesthesia and those undergoing scheduled caesarean deliveries for a given QoR score. Quality of communication, interactions with staff and aspects of the postpartum physical environment were significant determinants of satisfaction and dissatisfaction. CONCLUSION: Maternal satisfaction and obstetric QoR are distinct entities with a weak correlation between the two variables. Urgency of procedure and mode of anaesthesia are significant predictors of the correlation between satisfaction and quality of recovery scores. Many of the drivers of satisfaction were modifiable including quality of communication and a comfortable physical space for postpartum recovery.

2.
Biophys J ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39021073

RESUMEN

Signaling through the Ras-MAPK pathway can exhibit switch-like activation, which has been attributed to the underlying positive feedback and bimodality in the activation of RasGDP to RasGTP by SOS. SOS contains both catalytic and allosteric Ras binding sites, and a common assumption is that allosteric activation selectively by RasGTP provides the mechanism of positive feedback. However, recent single-molecule studies have revealed that SOS catalytic rates are independent of the nucleotide state of Ras in the allosteric binding site, raising doubt about this as a positive feedback mechanism. Here, we perform detailed kinetic analyses of receptor-mediated recruitment of full-length SOS to the membrane while simultaneously monitoring its catalytic activation of Ras. These results, along with kinetic modeling, expose the autoinhibition release step in SOS, rather than either recruitment or allosteric activation, as the underlying mechanism giving rise to positive feedback in Ras activation.

3.
J Phys Chem A ; 128(28): 5668-5675, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38968412

RESUMEN

Kinetics of the lanthanide cations (Ln+ = La+-Lu+ excluding Pm+) reacting with molecular oxygen were measured in a selected-ion flow tube apparatus from 300 to 600 K. Where exothermic, these reactions occur efficiently, producing LnO+ + O. The reactions display positive temperature dependences consistent with Arrhenius equation behavior and show small activation energies (0-2 kJ mol-1) that are strongly correlated to promotion energies of the Ln+ atoms. Reanalysis of literature data on neutral Ln + O2 reactions show a similar correlation with slightly larger activation energies (0-10 kJ mol-1). The data are explained by a common mechanism controlling oxidation by molecular oxygen in these systems, as well as in gas-phase reactions of transition metal and posttransition metal cluster anions, neutral clusters deposited on surfaces, and for oxygen incident on metal surfaces. It is posited that across these systems, the height of an early barrier along the reaction coordinate is predictable based on knowledge of the electronic states of the reactants and may be used to either promote or inhibit oxygen activation.

4.
Expert Opin Drug Discov ; : 1-27, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004919

RESUMEN

INTRODUCTION: Small molecules often bind to multiple targets, a behavior termed polypharmacology. Anticipating polypharmacology is essential for drug discovery since unknown off-targets can modulate safety and efficacy - profoundly affecting drug discovery success. Unfortunately, experimental methods to assess selectivity present significant limitations and drugs still fail in the clinic due to unanticipated off-targets. Computational methods are a cost-effective, complementary approach to predict polypharmacology. AREAS COVERED: This review aims to provide a comprehensive overview of the state of polypharmacology prediction and discuss its strengths and limitations, covering both classical cheminformatics methods and bioinformatic approaches. The authors review available data sources, paying close attention to their different coverage. The authors then discuss major algorithms grouped by the types of data that they exploit using selected examples. EXPERT OPINION: Polypharmacology prediction has made impressive progress over the last decades and contributed to identify many off-targets. However, data incompleteness currently limits most approaches to comprehensively predict selectivity. Moreover, our limited agreement on model assessment challenges the identification of the best algorithms - which at present show modest performance in prospective real-world applications. Despite these limitations, the exponential increase of multidisciplinary Big Data and AI hold much potential to better polypharmacology prediction and de-risk drug discovery.

5.
Explor Target Antitumor Ther ; 5(3): 581-599, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966179

RESUMEN

Passaged cell lines represent currently an integral component in various studies of malignant neoplasms. These cell lines are utilized for drug screening both in monolayer cultures or as part of three-dimensional (3D) tumor models. They can also be used to model the tumor microenvironment in vitro and in vivo through xenotransplantation into immunocompromised animals. However, immortalized cell lines have some limitations of their own. The homogeneity of cell line populations and the extensive passaging in monolayer systems make these models distant from the original disease. Recently, there has been a growing interest among scientists in the use of primary cell lines, as these are passaged directly from human tumor tissues. In this case, cells retain the morphological and functional characteristics of the tissue from which they were derived, an advantage often not observed in passaged cultures. This review highlights the advantages and limitations of passaged and primary cell cultures, their similarities and differences, as well as existing test systems that are based on primary and passaged cell cultures for drug screening purposes.

6.
Environ Sci Technol ; 58(28): 12575-12584, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38952258

RESUMEN

There is a notable lack of continuous monitoring of air pollutants in the Global South, especially for measuring chemical composition, due to the high cost of regulatory monitors. Using our previously developed low-cost method to quantify black carbon (BC) in fine particulate matter (PM2.5) by analyzing reflected red light from ambient particle deposits on glass fiber filters, we estimated hourly ambient BC concentrations with filter tapes from beta attenuation monitors (BAMs). BC measurements obtained through this method were validated against a reference aethalometer between August 2 and 23, 2023 in Addis Ababa, Ethiopia, demonstrating a very strong agreement (R2 = 0.95 and slope = 0.97). We present hourly BC for three cities in sub-Saharan Africa (SSA) and one in North America: Abidjan (Côte d'Ivoire), Accra (Ghana), Addis Ababa (Ethiopia), and Pittsburgh (USA). The average BC concentrations for the measurement period at the Abidjan, Accra, Addis Ababa Central summer, Addis Ababa Central winter, Addis Ababa Jacros winter, and Pittsburgh sites were 3.85 µg/m3, 5.33 µg/m3, 5.63 µg/m3, 3.89 µg/m3, 9.14 µg/m3, and 0.52 µg/m3, respectively. BC made up 14-20% of PM2.5 mass in the SSA cities compared to only 5.6% in Pittsburgh. The hourly BC data at all sites (SSA and North America) show a pronounced diurnal pattern with prominent peaks during the morning and evening rush hours on workdays. A comparison between our measurements and the Goddard Earth Observing System Composition Forecast (GEOS-CF) estimates shows that the model performs well in predicting PM2.5 for most sites but struggles to predict BC at an hourly resolution. Adding more ground measurements could help evaluate and improve the performance of chemical transport models. Our method can potentially use existing BAM networks, such as BAMs at U.S. Embassies around the globe, to measure hourly BC concentrations. The PM2.5 composition data, thus acquired, can be crucial in identifying emission sources and help in effective policymaking in SSA.


Asunto(s)
Contaminantes Atmosféricos , Ciudades , Monitoreo del Ambiente , Material Particulado , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , África , Carbono/análisis , Hollín/análisis
7.
J Neurosurg Sci ; 68(4): 482-491, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38949058

RESUMEN

INTRODUCTION: Arachnoid cysts are primarily dysembryogenetic splitting or duplication of the embryonic meningeal mesenchyme, hence the paediatric preponderance. Neuroendoscopic cysto-cisternostomy is now the favoured treatment option. We pooled data on middle fossa arachnoid cysts (MCFAC) demographics, clinical presentations, cyst characteristics, neuro-endoscopic cysto-cisternostomy and its outcomes. EVIDENCE ACQUISITION: Using search words (from the keywords; 'endoscopic treatment' and 'middle fossa arachnoid cysts') combined using Boolean operators, a systematic review of the PubMed and Cochrane CENTRAL was started on 1st February 2023, as per protocol (PROSPERO CRD42023394345); 65 records and then 46 reports were screened, 169 cases were pooled from the 19 recruited reports for the qualitative and quantitative syntheses, after methodological assessment (significantly excellent 57.9% quality) using the Joanna Briggs Institute critical appraisal tools. EVIDENCE SYNTHESIS: The male-to-female ratio was 2.4:1, with a weighted average-age of 11.25 years in the modal childhood (32.0%) age-group. Headaches (53/29.3%), seizures (30/16.6%) and macrocephaly (25/13.8%) were the commonest presentations. Right-sided (30/55.6%) and Galassi II (55/48.3%) and III (53/46.5%) lesions were common. Rigid (124/93.9%) endoscopes aided cysto-cisternostomy using mostly bipolar diathermy (31/43.7%) and ventriculostomy forceps (18/25.4%); creating one (22/18.3%), two (14/11.6%) or more (78/65.0%) stomas. Fenestration sites were specifically CNIII&ICA (32/25.8%), CNII&ICA (27/21.8%), CNIII&tentorium cerebelli (23/18.6%), CNIII&PCA (1/0.8%) and through the side of CNVI (1/0.8%) into the pre-pontine cistern. Good clinical and radiological outcomes were reported. CONCLUSIONS: Largely excellent-to-good quality, low-level evidence reported MCFACs presenting in childhood with headaches, seizures and macrocephaly. At least two fenestrations using bipolar-diathermy/forceps and balloon-catheter expansion were used for cysto-cisternostomy, with good outcomes.


Asunto(s)
Quistes Aracnoideos , Fosa Craneal Media , Neuroendoscopía , Humanos , Quistes Aracnoideos/cirugía , Neuroendoscopía/métodos , Fosa Craneal Media/cirugía , Masculino , Femenino , Niño , Resultado del Tratamiento
8.
Microsc Microanal ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973604

RESUMEN

Atom probe tomography (APT) has been utilized to investigate the microstructure of two model borosilicate glasses designed to understand the solubility limits of phosphorous pentoxide (P2O5). This component is found in certain high-level radioactive defence wastes destined for vitrification, where phase separation can potentially lead to a number of issues relating to the processing of the glass and its long-term chemical and structural stability. The development of suitable focused ion beam (FIB)-preparation routes and APT analysis conditions were initially determined for the model glasses, before examining their detailed microstructures. In a 3.0 mol% P2O5-doped glass, both visual inspection and sensitive statistical analysis of the APT data show homogeneous microstructures, while raising the content to 4.0 mol% initiates the formation of phosphorus-enriched nanoscale precipitates. This study confirms the expected inhomogeneities and phase separation of these glasses and offers routes to characterizing these at near-atomic scale resolution using APT.

9.
Alzheimers Dement ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39031528

RESUMEN

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38842372

RESUMEN

BACKGROUND: Exposure to hypoxia immediately challenges a variety of physiologic systems that limit exercise capacity. Under normoxia, caffeine (CAFF) increases ventilation and subsequent oxygenation of hemoglobin (SpO2) and skeletal muscle (SmO2). CAFF improves exercise performance at altitude. However, little attention has been given to submaximal exercise in hypoxia, particularly regarding low CAFF consumers and female participants. The aim of this study was to determine the effect of CAFF on pulmonary, metabolic, and perceptual variables in response to submaximal running in hypoxia in low CAFF consuming males and females. METHODS: In a double blinded, counterbalanced design, 14 (6 females) individuals (24.1±5.1 years; VO2max: 40.6±5.6 mL × kg-1 × min-1; 20.8±8.0% body fat), who habitually consumed ≤150 mg/day of CAFF performed treadmill running at workloads of 25%, 40%, 60%, and 75% of sea level VO2max in normobaric hypoxia (FIO2=0.15) on two separate occasions: 1) 60 minutes after 6 mg/kg of CAFF; or 2) placebo. RESULTS: CAFF had no effect on any variable measured. Specifically, VE (condition: P=0.12; interaction: P=0.19), VT (condition: P=0.16; interaction: P=0.57), and Ve:VO2 (condition: P=0.07; interaction: P=0.69) were similar between groups. Further, CAFF had no effect on relative VO2 (condition: P=0.84; interaction: P=0.95), HR (condition: P=0.28; interaction: P=0.35), SmO2 (condition: P=0.66; interaction: P=0.82), or SpO2 (condition: P=0.16; interaction: P=0.97). Finally, rating of perceived exertion (RPE; P=0.92) and acute mountain sickness scores (P=0.29) were similar across conditions. CONCLUSIONS: These data demonstrate that CAFF provides no physiologic advantage to submaximal exercise in acute, normobaric hypoxia with low CAFF consuming males and females.

11.
Acta Med Philipp ; 58(1): 42-50, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939853

RESUMEN

Objectives: Perception about Physical and Rehabilitation Medicine provides information about awareness on identifying disabilities and managing their impact on activities of daily living; however, misconceptions about the field continue to exist among both students and physicians. This study aims to describe the perceptions of clinical clerks and interns towards the practice and role of Rehabilitation Medicine in management of patients. Methods: This is a descriptive cross-sectional study. Students from the Learning Unit 6 and 7 of UP College of Medicine answered adapted online survey forms from a previous study and participated in online focus group discussions. Qualitative data were used to infer the perception of medical students towards the specialty. The effect of the respondent's profile, background and affiliation on their knowledge, attitudes and perceptions were analyzed using One-Way ANOVA (α = 0.05). Qualitative data were analyzed using thematic analysis. Results: Learning Unit 6 and 7 students were found to have a perceived broad level of knowledge with regards the specialty. The students associated the specialty with focus on holistic care, quality of life, interdisciplinary collaboration, and diversity of cases managed. No statistically significant differences were found between the perception among: 1) Learning Unit 6 and 7, 2) those with or without a previous encounter with the specialty, 3) allied medical and non-allied medical undergraduate courses in terms of: a) confidence in the knowledge (p = 0.489), b) familiarity with conditions managed (p = 0.93) and c) interest towards the specialty (p = 0.693). The Organ System Integrated (OSI) curriculum, which promotes horizontal and vertical integration of concepts, provided a wide understanding of the basic concepts related to physiatry. The students' responses suggest a positive attitude towards Physical and Rehabilitation Medicine, as measured in their level of interest about knowing more regarding the specialty. Most common perceptions were that the specialty was multidisciplinary and holistic. However, the respondents' perceptions regarding the roles of the Rehabilitation team were limited. Conclusion: Learning unit level 6 and 7 students had a broad understanding of the practice and scope of the Physical and Rehabilitation Medicine specialty. Future researches can include other medical students in all year levels, including Learning Units 3, 4 and 5 of UPCM, to observe the development of their perceptions about the specialty throughout medical school.

12.
Acta Med Philipp ; 58(1): 79-83, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939850

RESUMEN

Looking along the physiological and physical changes in aging, in the light of a major burn, co-morbidities, surgical intervention and precaution, a geriatric burn patient requires a delicate balance of ideal burn care and rehabilitation to achieve functional independence. A 70-year-old patient, with 30% total body surface area flame burn injury, underwent bilateral partial calcanectomy secondary to calcaneus osteomyelitis, and Meek micrograft technique for burn injury on bilateral lower extremities, is presented in this case report. In order to ensure good graft take, her knees were immobilized causing bilateral soft tissue contractures. Subsequently, upon initiation of ambulation, gait abnormalities observed include absence of heel off and toe off, with heel walking. The patient was admitted for intensive inpatient rehabilitation, where significant improvement in the knee range of motion and ambulation were achieved. The patient was eventually discharged ambulatory with walker. Despite expected complications, rehabilitation management proved to be beneficial in improving function and ambulation in geriatric burn patient.

14.
Environ Pollut ; 357: 124439, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942279

RESUMEN

Emerging pollutants, such as pharmaceuticals and microplastics have become a pressing concern due to their widespread presence and potential impacts on ecological systems. To assess the ecosystem-level effects of these pollutants within a multi-stressor context, we simulated real-world conditions by exposing a near-natural multi-trophic aquatic food web to a gradient of environmentally relevant concentrations of fluoxetine and microplastics in large mesocosms over a period of more than three months. We measured the biomass and abundance of different trophic groups, as well as ecological functions such as nutrient availability and decomposition rate. To explore the mechanisms underlying potential community and ecosystem-level effects, we also performed behavioral assays focusing on locomotion parameters as a response variable in three species: Daphnia magna (zooplankton prey), Chaoborus flavicans larvae (invertebrate pelagic predator of zooplankton) and Asellus aquaticus (benthic macroinvertebrate), using water from the mesocosms. Our mesocosm results demonstrate that presence of microplastics governs the response in phytoplankton biomass, with a weak non-monotonic dose-response relationship due to the interaction between microplastics and fluoxetine. However, exposure to fluoxetine evoked a strong non-monotonic dose-response in zooplankton abundance and microbial decomposition rate of plant material. In the behavioral assays, the locomotion of zooplankton prey D. magna showed a similar non-monotonic response primarily induced by fluoxetine. Its predator C. flavicans, however, showed a significant non-monotonic response governed by both microplastics and fluoxetine. The behavior of the decomposer A. aquaticus significantly decreased at higher fluoxetine concentrations, potentially leading to reduced decomposition rates near the sediment. Our study demonstrates that effects observed upon short-term exposure result in more pronounced ecosystem-level effects following chronic exposure.

15.
bioRxiv ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38853984

RESUMEN

Metabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter coordinates metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial metabolic pathways has remained unexplored. Here, we investigate the metabolic consequences of uniporter loss- and gain-of-function, and identify a key transcriptional regulator that mediates these effects. Using gene expression profiling and proteomic, we find that loss of uniporter function increases the expression of proteins in the branched-chain amino acid (BCAA) catabolism pathway. Activity is further augmented through phosphorylation of the enzyme that catalyzes this pathway's committed step. Conversely, in the liver cancer fibrolamellar carcinoma (FLC)-which we demonstrate to have high mitochondrial calcium levels- expression of BCAA catabolism enzymes is suppressed. We also observe uniporter-dependent suppression of the transcription factor KLF15, a master regulator of liver metabolic gene expression, including those involved in BCAA catabolism. Notably, loss of uniporter activity upregulates KLF15, along with its transcriptional target ornithine transcarbamylase (OTC), a component of the urea cycle, suggesting that uniporter hyperactivation may contribute to the hyperammonemia observed in FLC patients. Collectively, we establish that FLC has increased mitochondrial calcium levels, and identify an important role for mitochondrial calcium signaling in metabolic adaptation through the transcriptional regulation of metabolism.

17.
Neurosurg Focus ; 56(6): E7, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38823058

RESUMEN

OBJECTIVE: This study presents the results of an evaluation of the effectiveness of percutaneous thermal radiofrequency (RF) ablation of spinal nerve roots to reduce spasticity and improve motor function in children with cerebral palsy (CP). METHODS: A retrospective analysis was conducted on the surgical treatment outcomes of 26 pediatric patients with severe CP (Gross Motor Function Classification System levels IV-V). The assessment protocol included muscle tone assessment using the modified Ashworth scale (MAS), evaluation of passive and active range of motion, gait video recording, and locomotor status evaluation using the Gross Motor Function Measure (GMFM)-88 scale. Thermal RF rhizotomy (ablation of spinal nerve roots) was performed on all patients at the L2-S1 levels at 70°C for 90 seconds. The statistical data analysis was conducted using the t-test and Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. RESULTS: Before the operation, the average level of spasticity in the lower-limb muscles of all patients was 3.0 ± 0.2 according to the MAS. In the early postoperative period, the spasticity level in all examined muscle groups significantly decreased to a mean of 1.14 ± 0.15 (p < 0.001). In the long-term postoperative period, the spasticity level in the examined muscle groups averaged 1.49 ± 0.17 points on the MAS (p < 0.001 compared to baseline, p = 0.0416 compared to the early postoperative period). Despite the marked reduction of spasticity in the lower limbs, no significant change in locomotor status according to the GMFM-88 scale was observed in the selected category of patients. In the long-term period, during the control examination of patients, the GMFM-88 level increased on average by 3.6% ± 1.4% (from 22.2% ± 3.1% to 25.8% ± 3.6%). CONCLUSIONS: The findings of this study offer preliminary yet compelling evidence that RF ablation of spinal nerve roots can lead to a significant and enduring decrease in muscle tone among children with severe spastic CP. Further studies and longer-term data of the impact on functionality and quality of life of patients with CP after spinal root RF ablation are needed.


Asunto(s)
Parálisis Cerebral , Rizotomía , Raíces Nerviosas Espinales , Humanos , Parálisis Cerebral/cirugía , Rizotomía/métodos , Raíces Nerviosas Espinales/cirugía , Masculino , Femenino , Niño , Estudios Retrospectivos , Preescolar , Resultado del Tratamiento , Espasticidad Muscular/cirugía , Adolescente , Vértebras Lumbares/cirugía , Ablación por Radiofrecuencia/métodos
18.
Sci Adv ; 10(25): eadi0707, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38905351

RESUMEN

Ras is a small GTPase that is central to important functional decisions in diverse cell types. An important aspect of Ras signaling is its ability to exhibit bimodal or switch-like activity. We describe the total reconstitution of a receptor-mediated Ras activation-deactivation reaction catalyzed by SOS and p120-RasGAP on supported lipid membrane microarrays. The results reveal a bimodal Ras activation response, which is not a result of deterministic bistability but is rather driven by the distinct processivity of the Ras activator, SOS. Furthermore, the bimodal response is controlled by the condensation state of the scaffold protein, LAT, to which SOS is recruited. Processivity-driven bimodality leads to stochastic bursts of Ras activation even under strongly deactivating conditions. This behavior contrasts deterministic bistability and may be more resistant to pharmacological inhibition.


Asunto(s)
Transducción de Señal , Proteínas ras , Proteínas ras/metabolismo , Proteínas Son Of Sevenless/metabolismo , Humanos
19.
J Vasc Interv Radiol ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901491

RESUMEN

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31-71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil-to-n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5-20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RF ablation is an option to treat patients with PLE.

20.
AIMS Microbiol ; 10(2): 273-287, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919722

RESUMEN

Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for Mycobacterium tuberculosis (Mtb) and drug resistance using line probe assay (LPA) and Mycobacterium growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at P < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.

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