Graudelacruz2926
The increase in STAT1 and STAT2 did not result in any of the common consequences of increased IFN-I or STAT1 signaling in cancer. Knockdown of STAT1/2 did not affect the viability of the cells, but decreased PRL-3-induced glycolysis. Interestingly, glucose metabolism contributed to the activation of STAT1 and STAT2 and expression of IFN-I-stimulated genes in PRL-3-overexpressing cells. In summary, we describe a novel signaling circuit where the key IFN-I-activated transcription factors STAT1 and STAT2 are important drivers of the increase in glycolysis induced by PRL-3. Subsequently, increased glycolysis regulates the IFN-I-stimulated genes by augmenting the activation of STAT1/2.
Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion.
We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA.
We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA.
We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA.
While the role of high flow nasal cannulae (HFNC) in the management of respiratory failure continues to expand, few studies describe its use in acute hypercapnic respiratory failure.
In this retrospective study we assessed the safety and efficacy of HFNC for treatment of acute hypercapnic respiratory failure.
Admissions with acute hypercapnic respiratory failure to a thoracic medicine unit at a tertiary centre between January and August 2018 were included if treated with either HFNC or non-invasive ventilation (NIV). The primary outcome was post-treatment change in arterial pCO
. Demographics, comorbidities, length of stay, readmission rate and mortality were also collected.
64 patients were identified, comprising 69 presentations grouped according to initial treatment HFNC (n=24) or NIV (n=45). Patients in the NIV group had more severe blood gas derangement. In both groups, mean arterial pCO
improved significantly (-10 (95% CI -14 to -6) mmHg) from baseline with no evidence of a differential effect between groups. Six (25%) patients were transitioned from HFNC to NIV, of whom 3 had comorbid obesity and 2 had sleep disordered breathing. No significant differences in hospital length of stay, 30-day readmission rate or 90-day mortality were observed.
HFNC may be a reasonable initial treatment for patients with mild acute hypercapnic respiratory failure who do not have comorbid obesity or sleep disordered breathing. Prospective study may help identify clinical factors or phenotypes predictive of success with this treatment modality. This article is protected by copyright. All rights reserved.
HFNC may be a reasonable initial treatment for patients with mild acute hypercapnic respiratory failure who do not have comorbid obesity or sleep disordered breathing. Prospective study may help identify clinical factors or phenotypes predictive of success with this treatment modality. This article is protected by copyright. All rights reserved.Cold stimuli increase arterial stiffness, but it has not been explored whether arterial stiffness increases after swimming in cooler water. To investigate the effects of water temperature on changes in arterial stiffness after swimming, 13 men participated in three trials of 20-min swimming in 25 and 30°C water (S25 and S30, respectively) and sitting at poolside (CON) in random order. There were no significant differences between the S25 and S30 trials in mean swimming distance (719 vs. 722 m) and heart rate reserve during swimming (63% vs. 63%). Sublingual temperature was lower after swimming in 25°C water versus before swimming. Aortic pulse wave velocity (aortic PWV, an index of central arterial stiffness based on applanation tonometry) and brachial-ankle pulse wave velocity (baPWV, an index of systemic arterial stiffness based on air plethysmography) were higher 30 min after versus before swimming in 25°C water. Aortic PWV recovered to pre-swimming levels by 60 min after swimming in 25°C water, but baPWV was higher even at 60 min after swimming. PWVs did not change in the CON and S30 trials. Systemic vascular resistance based on Doppler ultrasonography did not change, but forearm vascular resistance based on strain-gauge plethysmography was higher 30 and 60 min after swimming in 25°C water. Heart rate was higher, but stroke volume was lower 30 min after swimming in 25°C water, resulting in no detectable change in cardiac output. In conclusion, arterial stiffness increases acutely after moderate-intensity swimming in cooler water.Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research.
Using plant-based extracts and their constituents has been suggested as an alternative tool to replace or integrate with the synthetic compounds used to manage insect pests. Here, we evaluated the potential of extracts obtained from Ficus carica Linn (Moraceae) branches and leaves against the Neotropical brown stink bug, Euschistus heros, one of the most prevalent insect pests in soybean fields. We further isolated and evaluated the toxicity of the extracts' major components against E. heros. Additionally, by using computational docking analysis and toxicological approaches, we assessed the physiological basis for the selectivity of these extracts against beneficial insects such as pollinator bees (i.e. Apis mellifera and the Neotropical stingless bee Partamona helleri), ladybeetles (Eriopis connexa and Coleomegilla maculata), and lacewings (Chrysoperla externa).
Our results demonstrate that branch (LC
=5.9 [4.7-7.1] mg mL
) and leaf (LC
=14.1 [12.5-15.4] mg mL
) extracts exhibited similar toxicity against E. heros. Our phytochemical analysis revealed psoralen and bergapten furanocoumarins as the major components of the extract. Based on our computational predictions, these molecules' differential abilities to physically interact with the acetylcholinesterases of E. heros and beneficial insects play relevant roles in their selectivity actions. The estimated LC
values of branch (30.0mg mL
) and leaf (30.0mg mL
) extracts killed less than 12% of the beneficial insects.
Overall, our findings revealed that furanocoumarin-rich extracts obtained from F. carica extracts have the potential to be used as alternative tools in the integrated management of stink bug pests.
Overall, our findings revealed that furanocoumarin-rich extracts obtained from F. carica extracts have the potential to be used as alternative tools in the integrated management of stink bug pests.
Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases.
58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID.
Of the 58 patients, 38 were male and 20 were female. Median age at transplantation tation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports.
Training in medicine is highly demanding and coincides with critical life tasks including relationship development, childbearing, and rearing. The rigid requirements of training programs risk precluding successful achievement of these extracurricular roles, forcing choices between work and other life commitments. Flexible employment structures that facilitate the development of high-quality physicians are needed.
The clinical department, trainees and senior administration designed flexible, part-time advanced training positions in rheumatology. We sought to deliver excellent training, supervision and support whilst ensuring safe, efficient clinical service delivery within existing systems and cultures. Barriers to implementation were actively identified. We rejected job share arrangements in favour of independent part time positions anchored to departmental education, clinical and trainee needs. The outcomes of these positions have been determined through regular trainee meetings, clinic activity and costs.
