We performed exome sequencing for mutation discovery of an ENU (N-ethyl-N-nitrosourea)-derived mouse model characterized by significant elevated plasma alkaline phosphatase (ALP) activities in female ...and male mutant mice, originally named BAP014 (bone screen alkaline phosphatase #14). We identified a novel loss-of-function mutation within the Fam46a (family with sequence similarity 46, member A) gene (NM_001160378.1:c.469G>T, NP_001153850.1:p.Glu157*). Heterozygous mice of this mouse line (renamed Fam46a ᴱ¹⁵⁷*ᴹʰᵈᵃ) had significantly high ALP activities and apparently no other differences in morphology compared to wild-type mice. In contrast, homozygous Fam46a ᴱ¹⁵⁷*ᴹʰᵈᵃ mice showed severe morphological and skeletal abnormalities including short stature along with limb, rib, pelvis, and skull deformities with minimal trabecular bone and reduced cortical bone thickness in long bones. ALP activities of homozygous mutants were almost two-fold higher than in heterozygous mice. Fam46a is weakly expressed in most adult and embryonic tissues with a strong expression in mineralized tissues as calvaria and femur. The FAM46A protein is computationally predicted as a new member of the superfamily of nucleotidyltransferase fold proteins, but little is known about its function. Fam46a ᴱ¹⁵⁷*ᴹʰᵈᵃ mice are the first mouse model for a mutation within the Fam46a gene.
Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), also termed Hashimoto’s encephalopathy (HE), is a rare immune-mediated disorder and is also affecting children and ...adolescents. It is characterized by altered mental status, seizures, and cognitive dysfunction. Therapeutic options include steroid treatment and prognosis range from complete recovery, a relapsing course to long-term cognitive sequelae. We describe a previously healthy 13-year-old girl presenting to the emergency room with coma and refractory status epilepticus. Generalized tonic-clonic seizures persisted after pre-hospital infusion of antiepileptic medication. She was found to have highly elevated levels of thyroid-stimulating hormone and anti-thyroid peroxidase antibodies not only in blood but also in cerebrospinal fluid while showing negative results for traumatic, infectious, metabolic, toxic, neoplastic, or other known specific autoimmune diseases. Cranial neuroimaging revealed no abnormality. A diagnosis of SREAT was established, and the patient improved rapidly on corticosteroids and levothyroxine therapy. However, 3 months after the discontinuation of steroid treatment, the girl relapsed. The current literature regarding SREAT is reviewed and summarized.
Conclusion
: In children with SREAT, early diagnosis and treatment with corticosteroids is crucial and can lead to rapid clinical improvement. Clinicians should be aware of this uncommon but treatable condition, especially in female adolescents with unexplained seizures or an encephalopathic state.
Electrical impedance tomography (EIT) is a low-cost, noninvasive and radiation free medical imaging modality for monitoring ventilation distribution in the lung. Although such information could be ...invaluable in preventing ventilator-induced lung injury in mechanically ventilated patients, clinical application of EIT is hindered by difficulties in interpreting the resulting images. One source of this difficulty is the frequent use of simple shapes which do not correspond to the anatomy to reconstruct EIT images. The mismatch between the true body shape and the one used for reconstruction is known to introduce errors, which to date have not been properly characterized. In the present study we, therefore, seek to 1) characterize and quantify the errors resulting from a reconstruction shape mismatch for a number of popular EIT reconstruction algorithms and 2) develop recommendations on the tolerated amount of mismatch for each algorithm. Using real and simulated data, we analyze the performance of four EIT reconstruction algorithms under different degrees of shape mismatch. Results suggest that while slight shape mismatch is well tolerated by all algorithms, using a circular shape severely degrades their performance.
In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious ...virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children's stool for more than 4 weeks.
Breathing moves volumes of electrically insulating air into and out of the lungs, producing conductivity changes which can be seen by electrical impedance tomography (EIT). It has thus been apparent, ...since the early days of EIT research, that imaging of ventilation could become a key clinical application of EIT. In this paper, we review the current state and future prospects for lung EIT, by a synthesis of the presentations of the authors at the 'special lung sessions' of the annual biomedical EIT conferences in 2009-2011. We argue that lung EIT research has arrived at an important transition. It is now clear that valid and reproducible physiological information is available from EIT lung images. We must now ask the question: How can these data be used to help improve patient outcomes? To answer this question, we develop a classification of possible clinical scenarios in which EIT could play an important role, and we identify clinical and experimental research programmes and engineering developments required to turn EIT into a clinically useful tool for lung monitoring.
To provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and ...inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension.
Prospective interventional trial.
Two PICUs.
Eight children with early acute respiratory distress syndrome (< 72 hr).
On 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient's safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1.
Lung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by -9.1% (95% CI, -13.7 to -4.4;
< 0.001) during titration. Collapse was changed by -9.9% (95% CI, -15.3 to -4.5;
< 0.001), while overdistension did not increase significantly (0.8%; 95% CI, -2.9 to 4.5;
= 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6-2.2;
= 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI -0.3 to 3.0,
= 0.026; Pao
: 17.6 mm Hg, 95% CI 7.8-27.5,
= 0.0039; and Pao
/Fio
ratio: 55.2 mm Hg, 95% CI 27.3-83.2,
< 0.001, all values are change in pre vs post).
Electrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.
O-mannosylation is an important protein modification in eukaryotes that is initiated by an evolutionarily conserved family of protein O-mannosyltransferases. The first mammalian protein ...O-mannosyltransferase gene described was the human POMT1. Mutations in the hPOMT1 gene are responsible for Walker-Warburg syndrome (WWS), a severe recessive congenital muscular dystrophy associated with defects in neuronal migration that produce complex brain and eye abnormalities. During embryogenesis, the murine Pomt1 gene is prominently expressed in the neural tube, the developing eye, and the mesenchyme. These sites of expression correlate with those in which the main tissue alterations are observed in WWS patients. We have inactivated a Pomt1 allele by gene targeting in embryonic stem cells and produced chimeras transmitting the defect allele to offspring. Although heterozygous mice were viable and fertile, the total absence of Pomt1-/- pups in the progeny of heterozygous intercrosses indicated that this genotype is embryonic lethal. An analysis of the mutant phenotype revealed that homozygous Pomt1-/- mice suffer developmental arrest around embryonic day (E) 7.5 and die between E7.5 and E9.5. The Pomt1-/- embryos present defects in the formation of Reichert's membrane, the first basement membrane to form in the embryo. The failure of this membrane to form appears to be the result of abnormal glycosylation and maturation of dystroglycan that may impair recruitment of laminin, a structural component required for the formation of Reichert's membrane in rodents. The targeted disruption of mPomt1 represents an example of an engineered deletion of a known glycosyltransferase involved in O-mannosyl glycan synthesis.
To investigate the electrical activity of the diaphragm during extubation readiness testing.
Prospective observational trial.
A 29-bed medical-surgical pediatric intensive care unit.
Mechanically ...ventilated children between 1 month and 18 yrs of age.
Twenty patients underwent a standardized extubation readiness test using a minimal pressure support ventilation strategy. A size-appropriate multiple-array esophageal electrode (electrical diaphragmatic activity catheter), which doubled as a feeding tube, was inserted. The electrical diaphragmatic activity, ventilatory parameters, and spirometry measurements were recorded with the Servo-i ventilator (Maquet, Solna, Sweden). Measurements were obtained before the extubation readiness test and 1 hr into the extubation readiness test.
During extubation readiness testing, the ratio of tidal volume to delta electrical diaphragmatic activity was significantly lower in those patients who passed the extubation readiness test compared to those who failed the extubation readiness test (extubation readiness test, pass: 24.8 ± 20.9 mL/μV vs. extubation readiness test, fail: 67.2 ± 27 mL/μV, respectively; p = .02). Delta electrical diaphragmatic activity correlated significantly with neuromuscular drive assessed by airway opening pressure at 0.1 secs (before extubation readiness test: r = .591, p < .001; during extubation readiness test: r = .682, p < .001). Eight out of 20 patients had ventilator dys-synchrony identified with electrical diaphragmatic activity during extubation readiness testing.
Patients who generate higher diaphragmatic activity in relation to tidal volume may have better preserved diaphragmatic function and a better chance of passing the extubation readiness test as opposed to patients who generate lower diaphragmatic activity in relation to tidal volume, indicating diaphragmatic weakness. Electrical activity of the diaphragm also may be a useful adjunct to assess neuromuscular drive in ventilated children.
Contradictory behavior of microvascular retinal endothelial cells (REC) - a reliable in vitro model to study retinal diseases - have recently been reported which might result from cultivating the ...cells in standard DMEM not optimized for this cell type. Therefore, we studied DMEM's effects on phenotype and behavior of immortalized bovine REC. Cells were cultivated in endothelial cell growth medium (ECGM) until a confluent monolayer was reached and then further kept for 1–4 days in ECGM, DMEM, or mixes thereof all supplemented with 5% fetal bovine serum, endothelial cell growth supplement, 90 μg/ml heparin, and 100 nM hydrocortisone. Within hours of cultivation in DMEM, the cell index – measured to assess the cell layer's barrier function - dropped to ~5% of the initial value and only slowly recovered, not only accompanied by stronger expression of HSP70 mRNA and secretion of interleukin-6, but also by lower expressions of tight junction proteins claudin-5, claudin-1 or of the marker of cell type conversion caveolin-1. Altered subcellular localizations of EC-typic claudin-5, vascular endothelial cadherin and von Willebrand factor were also observed. Taken together, all experiments with (retinal) EC cultivated in common DMEM need to be interpreted very cautiously and should at least include phenotypic validation.
Endothelial cells; Retinal endothelial cells; Cell culture medium; Cell type conversion; Phenotype; Paracellular flow; Barrier dysfunction; Transcellular transport; Cell index measurements; DMEM; ECGM-MV.
OBJECTIVE:Respiratory inductance plethysmography (RIP) and electrical impedance tomography (EIT) are two monitoring techniques that have been used to assess lung volume noninvasively.
METHODS:RIP ...uses two elastic bands around the chest and abdomen to assess global changes in lung volume. In animal models, RIP has been shown to detect changes in lung mechanics during high-frequency oscillatory ventilation and has the potential to quantify lung volumes noninvasively. EIT measures regional impedance changes with 16 electrodes around the patient’s chest, each of them injecting and receiving small currents. Impedance changes have been correlated with volume changes in animal models and in humans. In a recent animal model, EIT was shown to be capable of tracking lung volume changes during high-frequency oscillatory ventilation.
CONCLUSION:The promise of monitoring techniques such as RIP and EIT is that they will guide lung protective ventilation strategies and allow the clinician to optimize lung recruitment, maintain an open lung, and limit overdistension. EIT is the only bedside method that allows repeated, noninvasive measurements of regional lung volumes. In the future, it will be important to standardize the definitions of alveolar recruitment and ultimately demonstrate the superiority of EIT-guided ventilator management in providing lung protective ventilation.
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