Background: Home care support is beneficial for children needing mechanical ventilation, when clinically stable.
Methods: A retrospective analysis was carried out of the long‐term home ventilation ...management of a pediatric population with chronic respiratory failure composed of 20 ventilator‐dependent children categorized according to age, diagnosis and ventilation support. Age groups consisted of 10% under 1 year, 30% between 2 and 5 years, 30% between 6 and 12 years, and 30% older than 12 years. Diagnostic categories included myopathic disorder, n = 5; congenital central hypoventilation syndrome, n = 6; chest wall disorder, n = 5; cystic fibrosis, n = 1; pulmonary hypertension, n = 1; and diaphragmatic paralysis, n = 2.
Results: Sixty‐five percent were ventilated using non‐invasive mode (NIMV): eight with nasal mask, five with full‐face mask, and two children in NIMV also used negative pressure mode; 35% were ventilated using tracheostomy, one of them also used a diaphragmatic pacer. Seventy percent needed nocturnal ventilatory support, (20% 12–18 h, 10% full‐day). A total of 18 children were included in the home care and follow‐up program. Two children died: one because of worsening of his chronic disease and one because of septic shock.
Conclusion: Although home care ventilation is not yet widely diffused, it represents a valid alternative to long hospitalization for children with stable chronic respiratory failure.
To report the successful management of end-stage hypercapnic respiratory failure through the association of noninvasive mechanical ventilation and a novel automated device (Decapsmart) of low-flow ...veno-venous extracorporeal CO2 removal.
Case report.
Pediatric intensive care unit at a tertiary care children's hospital.
A pediatric patient affected by bronchiolitis obliterans with refractory hypercapnic respiratory failure. The patient received successful lung transplantation after respiratory support with noninvasive mechanical ventilation and a novel automated device of low-flow veno-venous extracorporeal CO2 removal.
Treatment of end-stage hypercapnic respiratory failure with the association of noninvasive ventilation and low-flow veno-venous extracorporeal CO2 removal as a bridge to lung transplantation.
Respiratory support controlling hypercapnia, limiting volutrauma, barotraumas, and preventing the incidence of ventilator-associated pneumonia/lung colonization.
Noninvasive mechanical ventilation and Decapsmart have proven efficacious in managing refractory hypercapnic respiratory failure in a pediatric patient awaiting lung transplantation.
Original Article OTTONELLO, GIANCARLO; FERRARI, ILARIA; PIRRODDI, INES MARIA GRAZIA ...
Pediatrics international,
12/2007, Letnik:
49, Številka:
6
Journal Article
Recenzirano
Home care support is beneficial for children needing mechanical ventilation, when clinically stable. A retrospective analysis was carried out of the long-term home ventilation management of a ...pediatric population with chronic respiratory failure composed of 20 ventilator-dependent children categorized according to age, diagnosis and ventilation support. Age groups consisted of 10% under 1 year, 30% between 2 and 5 years, 30% between 6 and 12 years, and 30% older than 12 years. Diagnostic categories included myopathic disorder, n = 5; congenital central hypoventilation syndrome, n = 6; chest wall disorder, n = 5; cystic fibrosis, n = 1; pulmonary hypertension, n = 1; and diaphragmatic paralysis, n = 2. Sixty-five percent were ventilated using non-invasive mode (NIMV): eight with nasal mask, five with full-face mask, and two children in NIMV also used negative pressure mode; 35% were ventilated using tracheostomy, one of them also used a diaphragmatic pacer. Seventy percent needed nocturnal ventilatory support, (20% 12-18 h, 10% full-day). A total of 18 children were included in the home care and follow-up program. Two children died: one because of worsening of his chronic disease and one because of septic shock. Although home care ventilation is not yet widely diffused, it represents a valid alternative to long hospitalization for children with stable chronic respiratory failure. PUBLICATION ABSTRACT
Targeting the translation machinery in cancer Bhat, Mamatha; Robichaud, Nathaniel; Hulea, Laura ...
Nature reviews. Drug discover/Nature reviews. Drug discovery,
04/2015, Letnik:
14, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Dysregulation of mRNA translation is a frequent feature of neoplasia. Many oncogenes and tumour suppressors affect the translation machinery, making aberrant translation a widespread characteristic ...of tumour cells, independent of the genetic make-up of the cancer. Therefore, therapeutic agents that target components of the protein synthesis apparatus hold promise as novel anticancer drugs that can overcome intra-tumour heterogeneity. In this Review, we discuss the role of translation in cancer, with a particular focus on the eIF4F (eukaryotic translation initiation factor 4F) complex, and provide an overview of recent efforts aiming to 'translate' these results to the clinic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. ...Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1). Potent active-site mTOR inhibitors engender mitochondrial hyperfusion due to the diminished translation of MTFP1, which is mediated by translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Uncoupling MTFP1 levels from the mTORC1/4E-BP pathway upon mTOR inhibition blocks the hyperfusion response and leads to apoptosis by converting mTOR inhibitor action from cytostatic to cytotoxic. These data provide direct evidence for cell survival upon mTOR inhibition through mitochondrial hyperfusion employing MTFP1 as a critical effector of mTORC1 to govern cell fate decisions.
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•The mTORC1/4E-BPs/MTFP1/DRP1 axis controls mitochondrial dynamics•Active-site mTOR inhibitors induce mitochondrial hyperfusion and branching•mTORC1 regulates MTFP1 translation and mitochondrial recruitment of DRP1 via 4E-BPs•Uncoupling MTFP1 levels from the mTORC1 axis upon mTOR inhibition leads to apoptosis
Morita et al. show that mTORC1 signaling controls mitochondrial dynamics to govern cell fate decisions. mTORC1 inhibition by asTORi treatment leads to mitochondrial branching and hyperfusion through 4E-BP-dependent suppression of MTFP1 mRNA translation.
To evaluate, characterise and compare the extent of tissue shrinkage induced from three different commercial microwave ablation devices, and to elucidate the mechanism behind the distinctive ...performances obtained.
Microwave ablation (N = 152) was conducted with three different commercial devices on cubes of ex vivo liver (10-40 ± 2 mm/side) embedded in agar phantoms. 50-60 W was applied for 1-10 min duration. Pre- and post-ablation dimensions of the samples, as well as the extent of carbonisation and coagulation were measured and correlated. ANOVA was performed to evaluate statistical significance.
For all devices, logarithmic correlations with time were observed for both tissue shrinkage (R
= 0.84-1.00) and induced carbonisation (R
= 0.73-0.99) radially to the antenna axis. Along the longitudinal axis of the antenna, for two of the devices shrinkage did not appreciably change with time (p > 0.05), yet carbonisation increased linearly (R
= 0.57-0.94). For the third fully internally-cooled device, both carbonisation and shrinkage showed logarithmic trends (R
= 0.85-0.98 and R
= 0.78-0.94, respectively) based upon delayed carbonisation appearing only 5 min into ablation and onward. For all devices, non-uniform shrinkage was noted within the coagulated area increasing from the boundary of the ablated area (14%) to the limit of carbonisation (39%) in a linear fashion (R
= 0.88) Conclusions: Microwave ablation device construction can alter the extent of post-ablation coagulation and tissue shrinkage. Given that tissue shrinkage in the coagulated area shows non-uniform behaviour, observed differences can be attributed in part to the applicator cooling system that alters the ablation temperature profile.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the risk factors for early graft detachment in Descemet membrane endothelial keratoplasty (DMEK).
Case-control study.
Participants: A total of 173 donor corneas and 173 eyes of the ...patients following DMEK or DMEK in combination with phacoemulsification and intraocular lens implantation were included. Intervention: Pre-stripped DMEK grafts were transplanted using pull-through technique. At the end of surgery, the anterior chamber was filled with air, which was removed 3 hours later only if pupillary block was suspected. Rebubbling was performed in all cases with graft detachment, independently of its extension, as documented by means of anterior segment optical coherence tomography. The donor characteristics were collected from the eye bank database and matched with the recipient database. Main Outcome Measures: Donor and recipient characteristics affecting graft detachment using univariate and multivariate analysis.
The combination of DMEK with cataract removal and IOL implantation (odds ratio OR = 5.31, 95% confidence interval CI 2.03-13.86, P < .002) and air fill of ≤75% of anterior chamber height at 2-3 hours postoperatively (OR = 2.66, 95% CI 1.12-6.34, P = .027) were found to be independent risk factors for postoperative graft detachment.
Cataract removal at the time of DMEK is a risk factor for early graft detachment and therefore sequential surgery may be preferred over combined surgery in an attempt at minimizing rebubbling. Air level in the anterior chamber should be monitored and maintained above 75% in the early hours following surgery.
Repeat associated non-AUG (RAN) translation is found in a growing number of microsatellite expansion diseases, but the mechanisms remain unclear. We show that RAN translation is highly regulated by ...the double-stranded RNA-dependent protein kinase (PKR). In cells, structured CAG, CCUG, CAGG, and G₄C₂ expansion RNAs activate PKR, which leads to increased levels of multiple RAN proteins. Blocking PKR using PKR-K296R, the TAR RNA binding protein or PKR-KO cells, reduces RAN protein levels. p-PKR is elevated in C9orf72 ALS/FTD human and mouse brains, and inhibiting PKR in C9orf72 BAC transgenic mice using AAV-PKR-K296R or the Food and Drug Administration (FDA)-approved drug metformin, decreases RAN proteins, and improves behavior and pathology. In summary, targeting PKR, including by use of metformin, is a promising therapeutic approach for C9orf72 ALS/FTD and other expansion diseases.
Purpose: The aim of this study was to develop a predictive model of the shrinkage of liver tissues in microwave ablation.
Methods: Thirty-seven cuboid specimens of ex vivo bovine liver of size ...ranging from 2 cm to 8 cm were heated exploiting different techniques: 1) using a microwave oven (2.45 GHz) operated at 420 W, 500 W and 700 W for 8 to 20 min, achieving complete carbonisation of the specimens, 2) using a radiofrequency ablation apparatus (450 kHz) operated at 70 W for a time ranging from 6 to 7.5 min obtaining white coagulation of the specimens, and 3) using a microwave (2.45 GHz) ablation apparatus operated at 60 W for 10 min. Measurements of specimen dimensions, carbonised and coagulated regions were performed using a ruler with an accuracy of 1 mm. Based on the results of the first two experiments a predictive model for the contraction of liver tissue from microwave ablation was constructed and compared to the result of the third experiment.
Results: For carbonised tissue, a linear contraction of 31 ± 6% was obtained independently of the heating source, power and operation time. Radiofrequency experiments determined that the average percentage linear contraction of white coagulated tissue was 12 ± 5%. The average accuracy of our model was determined to be 3 mm (5%).
Conclusions: The proposed model allows the prediction of the shrinkage of liver tissues upon microwave ablation given the extension of the carbonised and coagulated zones. This may be useful in helping to predict whether sufficient tissue volume is ablated in clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder engendered by transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Given the ...early onset of behavioral and molecular changes, it is imperative to know the optimal timing for therapeutic intervention. Case reports documented benefits of metformin treatment in FXS children between 2 and 14 y old. In this study, we administered metformin from birth to Fmr1−/y mice which corrected up-regulated mitogen-2 activated protein kinase/extracellular signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 signaling pathways and specific synaptic mRNA-binding targets of FMRP. Metformin rescued increased number of calls in ultrasonic vocalization and repetitive behavior in Fmr1−/y mice. Our findings demonstrate that in mice, early-in-life metformin intervention is effective in treating FXS pathophysiology.
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