Surgical options in suprastomal collapse-induced severe airway obstruction.

PURPOSE: A single institutions experience with various surgical options in the treatment of severe suprastomal collapse (SSC). METHODS: The study included 18 tracheostomized children with SSC treated between January 2012 and December 2018. Data included: patient demography, initial airway lesions, comorbidities, indication and age at tracheostomy, prior airway surgery, stomal demography, type of surgery, postoperative management, complications and treatment outcomes. RESULTS: Four techniques were used to correct SSC. The surgical choice was dependent on stoma demography and associated airway lesions. Excision was done in eight patients and rib cartilage augmentation in five. Three patients had single stage tracheal resection and anastomosis. Two patients received stomal rigidification and temporary placement of Montgomery T tube. Three patients with anterior rib graft augmentation required additional lateral tracheal wall rigidification. Three patients (two with cartilage augmentation, and one with stomal rigidification) developed minimal granulation tissue in the postoperative period. Complete SSC resolution was seen in all except two patients who had a partial response to the treatment. All patients were successful decannulated and are currently asymptomatic. CONCLUSION: Decannulation failures may be due to severe suprastomal collapse that could be either unique or associated with obstructing laryngotracheal lesions. Therefore, it is essential to select the most appropriate surgical treatment to obtain overall favorable outcomes.

Decoding supraglottic stenosis.

OBJECTIVE: Supraglottic stenosis (SPGS) is a rare condition and little is known about its optimal management. Its etiologies are varied and depend on the age group. Here, we review our institution's series of patients and propose treatment strategies for SPGS. METHODS: SPGS patients between 2013 and 2019 were retrospectively reviewed. We recorded their demography, clinical data and endoscopy. The patients were treated with either an endoscopic, open or a combined approach. Subsequently, we reviewed photo and video documents, medical sheets and long-term follow-up charts. RESULTS: The report includes 14 children having a mean age of 5.7 years (range 2 months-13 years). Seven children had undergone prior supraglottoplasty for laryngomalacia, three children had blunt neck trauma and four had iatrogenic plus post-intubation etiology. Five children received endoscopic treatment and are currently symptom free. Four patients received a combined repair with satisfactory results. Five children received an open repair, four of which are decannulated and feed orally without aspiration. Most children in this group required additional endoscopic interventions. CONCLUSION: Post supraglottoplasty stenosis can be treated optimally by an endoscopic approach. More severe supraglottic cicatrical sequelae with posterior glottic involvement may require a combined endoscopic and open approach. Transglottic stenoses with severe grades of multi-level stenoses require an extended cricotracheal resection.

A de novo missense mutation in SLC12A5 found in a compound heterozygote patient with epilepsy of infancy with migrating focal seizures.

Epilepsy of infancy with migrating focal seizures (EIMFS) is an infantile epileptic encephalopathy characterized by refractory seizures, severe psychomotor delay, and multiple moving epileptic discharges. The genetic etiology of EIMFS is relatively homogeneous with the majority of causative mutations found in KCNT1. Currently, gene panel or whole-exome sequencing is used for testing. To verify the pathogenicity of a variant, co-segregation of the variant and the disorder in a pedigree is important; hence, de novo mutations that are judged to be deleterious may be considered pathogenic because the patients are isolated. In contrast, in cases from non-consanguineous families, genes that cause disorders in a recessive manner should remain as potential candidates. Herein, we performed gene panel sequencing of a patient with EIMFS from a non-consanguineous family, and found a compound heterozygous constellation consisting of a maternally inherited p.Ser399Leu and a de novo p.Arg880Leu in SLC12A5, which encodes the neuronal KCC2 cotransporter. These unique mutations show gene variants that act in a recessive manner may be pathogenic for patients from non-consanguineous families.

Electric-Field Induced Activation of Dark Excitonic States in Carbon Nanotubes.

Electrical activation of optical transitions to parity-forbidden dark excitonic states in individual carbon nanotubes is reported. We examine electric-field effects on various excitonic states by simultaneously measuring photocurrent and photoluminescence. As the applied field increases, we observe an emergence of new absorption peaks in the excitation spectra. From the diameter dependence of the energy separation between the new peaks and the ground state of E11 excitons, we attribute the peaks to the dark excited states which became optically active due to the applied field. Field-induced exciton dissociation can explain the photocurrent threshold field, and the edge of the E11 continuum states has been identified by extrapolating to zero threshold.

Gate-Tunable Atomically Thin Lateral MoS2 Schottky Junction Patterned by Electron Beam.

Among atomically thin two-dimensional (2D) materials, molybdenum disulfide (MoS2) is attracting considerable attention because of its direct bandgap in the 2H-semiconducting phase. On the other hand, a 1T-metallic phase has been revealed, bringing complementary application. Recently, thanks to top-down fabrication using electron beam (EB) irradiation techniques, in-plane 1T-metal/2H-semiconductor lateral (Schottky) MoS2 junctions were demonstrated, opening a path toward the co-integration of active and passive two-dimensional devices. Here, we report the first transport measurements evidencing the formation of a MoS2 Schottky barrier (SB) junction with barrier height of 0.13-0.18 eV created at the interface between EB-irradiated (1T)/nonirradiated (2H) regions. Our experimental findings, supported by state-of-the-art simulation, reveal unique device fingerprint of SB-based field-effect transistors made from atom-thin 1T layers.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein for patients with chronic hepatitis B and C: a comparative study.

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F4 in the two groups were 2.83 COI in patients with hepatitis B and 5.03 COI in patients with hepatitis C (P=.0046). The median WFA+ -M2BP values in F3 or more in the two groups were 1.79 COI in patients with hepatitis B and 3.79 COI in patients with hepatitis C (P<.0001). The median WFA+ -M2BP values in F2 or more in the two groups were 1.49 COI in the hepatitis B cohort and 3.19 COI in the hepatitis C group (P<.0001). Among five liver fibrosis markers, WFA+ -M2BP had the highest correlation coefficient (rs =.629) in terms of correlation with the degree of fibrosis in the patients with hepatitis C and had the second highest rs value (.415) in the hepatitis B group. Although WFA+ -M2BP could be a useful indicator of liver fibrosis, WFA+ -M2BP levels in the two groups significantly differed even in the same degree of fibrosis. Individual cut-off values in each aetiology for the degree of fibrosis should be determined.

Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly.

OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively. The weights of body, brain and uterus and the contents of protein and myelin galactolipids including galactosylceramide and sulfatide were measured. RESULTS: Memory impairment and depression-like behaviors in OVX rats were recovered to the levels of sham-operated rats by RJ administration. Increased body weight and decreased uterine weight in OVX rats were recovered to the levels of sham-operated rats by 17ß-estradiol (E2) administration but not by RJ administration. In contrast, brain weight was slightly increased by RJ administration but not by E2 administration. The contents of protein and myelin galactolipids were higher in the brains of RJ-administered OVX rats than in the brains of E2-administered OVX rats. CONCLUSION: The results suggest that RJ has a beneficial effect on neurological symptoms of a menopausal disorder.

Immunocytochemical staining for stratifin and OCIAD2 in bronchial washing specimens increases sensitivity for diagnosis of lung cancer.

OBJECTIVE: Brushing or washing cytology taken at bronchoscopy is a standard diagnostic procedure for lung cancer. The present study evaluated the sensitivity of immunocytochemical diagnosis of lung cancer using bronchial washing materials. METHODS: We collected bronchial washing samples taken at bronchoscopy between July 2012 and July 2013 at Tsukuba University Hospital and studied 106 cases that were finally diagnosed as lung cancer. We collected exfoliated cells using a thin-layer advanced cytology assay system (TACAS(™)) and performed cytological diagnosis using Papanicolaou staining. As controls, we randomly selected 30 tumour-negative cases from among samples collected during the same period. Using these materials, we also examined the expression of stratifin (14-3-3 sigma) (n = 92) and OCIAD2 ovarian immunoreactive antigen domain 2) (n = 106) by immunocytochemistry, as these are considered to be broad spectrum immune markers for lung adenocarcinoma including early invasive lung adenocarcinoma. RESULTS: Using Papanicolaou staining, 52 out of 106 lung cancers (49.1%) were diagnosed as positive. However, positivity was increased to 63.0% by immunocytochemistry using anti-stratifin or anti-OCIAD2 antibodies. Biopsies were taken in 103/106 cases and cancer was diagnosed in 60/103, (58.3%). The sensitivity of stratifin or OCIAD2 was significantly higher than that of Papanicolaou staining (P = 0.027), but immunocytochemistry detected false-positive cells in 3/30 cases (10%) for stratifin and 2/30 cases (7%) for OCIAD2. CONCLUSION: Immunocytochemical staining for stratifin and OCIAD2 improved diagnostic sensitivity for lung cancers but diagnostic specificity was lower than that for cytology alone. The immunostains carried up to a 10% risk of a false-positive result and therefore positive staining must be confirmed by morphological evidence of malignancy.

Spontaneous exciton dissociation in carbon nanotubes.

Simultaneous photoluminescence and photocurrent measurements on individual single-walled carbon nanotubes reveal spontaneous dissociation of excitons into free electron-hole pairs. The correlation of luminescence intensity and photocurrent shows that a significant fraction of excitons are dissociating before recombination. Furthermore, the combination of optical and electrical signals also allows for extraction of the absorption cross section and the oscillator strength. Our observations explain the reasons why photoconductivity measurements in single-walled carbon nanotubes are straightforward despite the large exciton binding energies.

Segregation of a QTL cluster for home-cage activity using a new mapping method based on regression analysis of congenic mouse strains.

Recent genetic studies have shown that genetic loci with significant effects in whole-genome quantitative trait loci (QTL) analyses were lost or weakened in congenic strains. Characterisation of the genetic basis of this attenuated QTL effect is important to our understanding of the genetic mechanisms of complex traits. We previously found that a consomic strain, B6-Chr6C(MSM), which carries chromosome 6 of a wild-derived strain MSM/Ms on the genetic background of C57BL/6J, exhibited lower home-cage activity than C57BL/6J. In the present study, we conducted a composite interval QTL analysis using the F2 mice derived from a cross between C57BL/6J and B6-Chr6C(MSM). We found one QTL peak that spans 17.6 Mbp of chromosome 6. A subconsomic strain that covers the entire QTL region also showed lower home-cage activity at the same level as the consomic strain. We developed 15 congenic strains, each of which carries a shorter MSM/Ms-derived chromosomal segment from the subconsomic strain. Given that the results of home-cage activity tests on the congenic strains cannot be explained by a simple single-gene model, we applied regression analysis to segregate the multiple genetic loci. The results revealed three loci (loci 1-3) that have the effect of reducing home-cage activity and one locus (locus 4) that increases activity. We also found that the combination of loci 3 and 4 cancels out the effects of the congenic strains, which indicates the existence of a genetic mechanism related to the loss of QTLs.

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice.

AIMS/HYPOTHESIS: Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the process. METHODS: Diabetes was induced in wild-type (WT) and Tlr4 knockout (KO) mice by intraperitoneal injection of streptozotocin (STZ). At 2 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Functional and histological analyses were carried out 6 weeks later. RESULTS: Compared with treatment with STZ or HFD alone, treatment of WT mice with both STZ and HFD markedly aggravated nephropathy, as indicated by an increase in albuminuria, mesangial expansion, infiltration of macrophages and upregulation of pro-inflammatory and extracellular-matrix-associated gene expression in glomeruli. In Tlr4 KO mice, the addition of an HFD to STZ had almost no effects on the variables measured. Production of protein S100 calcium binding protein A8 (calgranulin A; S100A8), a potent ligand for TLR4, was observed in abundance in macrophages infiltrating STZ-HFD WT glomeruli and in glomeruli of diabetic nephropathy patients. High-glucose and fatty acid treatment synergistically upregulated S100a8 gene expression in macrophages from WT mice, but not from KO mice. As putative downstream targets of TLR4, phosphorylation of interferon regulatory factor 3 (IRF3) was enhanced in kidneys of WT mice co-treated with STZ and HFD. CONCLUSIONS/INTERPRETATION: Activation of S100A8/TLR4 signalling was elucidated in an animal model of diabetic glomerular injury accompanied with hyperlipidaemia, which may provide novel therapeutic targets in progressive diabetic nephropathy.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Treatment outcomes in patients with laryngotracheal lesions and compromised airway during and prior to the coronovirus disease 2019 pandemic: a tertiary institution's experience.

OBJECTIVE: This study aimed to compare treatment outcomes in patients with laryngeal and tracheal stenosis treated during and prior to the coronavirus disease 2019 pandemic period. METHOD: Patients treated for laryngotracheal lesions with impending airway compromise during the active pandemic period were matched with those treated for similar lesions in the preceding years in a monocentric tertiary hospital setting. RESULTS: During the pandemic period of 55 days, 31 patients underwent 47 procedures. Seven patients (2 children, 5 adults) had open airway surgery, and one had an operation-specific complication. Twenty-four patients (10 children, 14 adults) underwent 40 endoscopic interventions without any complications. Operation specific results during and prior to the pandemic were comparable. CONCLUSION: The management strategy in patients with laryngotracheal lesions and impending airway compromise should not be altered during periods of risk from coronavirus disease 2019. Avoiding a tracheostomy by performing primary corrective surgery or proceeding with a definitive decannulation would be beneficial in these patients to reduce the risk of contagion.

A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.

We have prepared an mAb specific for a human cell surface component (termed anti-Fas mAb). Anti-Fas shows cell-killing activity that is indistinguishable from the cytolytic activity of TNF. Fas antigen was characterized by western blotting, indicating that Fas antigen is a cell surface protein with a molecular weight of 200,000, which is different from the molecular weight of TNF-R. Fas antigen, however, is co-downregulated with the TNF-R when cells sensitive to the cytolytic activity of TNF are incubated with either TNF or anti-Fas. In contrast, Fas antigen on cells insensitive to TNF is not co-downregulated with the TNF-R. We suggest that the cell-killing activity of TNF is mediated by Fas antigen associated with the TNF-R.

Relationship between chronic kidney disease and silent cerebral infarction in patients with Type 2 diabetes.

AIMS: Silent cerebral infarction (SCI) is an independent risk factor for future symptomatic stroke. Although the prevalence of SCI is closely related to kidney function in non-diabetic individuals, evidence is lacking whether albuminuria and/or reduced estimated glomerular filtration rate (eGFR) independently increase the risk of SCI in diabetic patients. We therefore examined the relationships between albuminuria, eGFR and SCI in patients with Type 2 diabetes mellitus (T2DM). METHODS: We studied 786 T2DM patients with an eGFR > or = 15 ml/min 1.73/m(2), including 337 women and 449 men [mean (+/- sd), age 65 +/- 11 years]. All patients underwent cranial magnetic resonance imaging (MRI) to detect SCI. GFR was estimated using the modified three-variable equation for Japanese subjects. Albuminuria was defined as a first morning urinary albumin-to-creatinine ratio (ACR) > or = 30 mg/g. RESULTS: SCI was detected in 415 (52.8%) of the subjects. The prevalence of SCI was significantly associated with both elevated ACR and decreased eGFR in univariate analysis. In multivariate logistic regression analysis, urinary ACR remained independently associated with SCI after adjusting for conventional cardiovascular risk factors [odds ratio (OR) of urinary ACR per logarithmical value: 1.89, 95% confidence interval (CI) = 1.41-2.51, P < 0.001]; however, eGFR was no longer significantly associated with SCI (OR per ml/min 1.73/m(2) = 0.99, 95% CI = 0.98-1.00, P = 0.095). CONCLUSION: In conclusion, albuminuria but not decreased eGFR may be an independent predictor of prevalent SCI in patients with T2DM.

Direct detection of circular polarized light in helical 1D perovskite-based photodiode.

Detection of circularly polarized light (CPL) has a high potential for development of various optical technologies. Conventional photodetectors require optical polarizers on the device to detect polarized light, and this causes substantial losses of sensitivity and resolution in light detection. Here, we report direct CPL detection by a photodiode using a helical one-dimensional (1D) structure of lead halide perovskites composed of naphthylethylamine-based chiral organic cations. The 1D structure with face-sharing (PbI6)4- octahedral chains whose helicity is largely affected by chiral cations shows intense circular dichroism (CD) signals over 3000 mdeg at 395 nm with the highly anisotropy factor (g CD) of 0.04. This high CD enables photocurrent detection with effective discrimination between left-handed and right-handed CPLs. The CPL detector based on this 1D perovskite achieved the highest polarization discrimination ratio of 25.4, which largely surpasses the direct detecting CPL devices (<4) using chiral plasmonic metamaterials and organic materials.

Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes.

BACKGROUND: House dust mites produce serine and cysteine proteases. Mite-derived proteases have been suggested to be involved in the pathogenesis of allergies; however, whether mite-derived serine protease activity can stimulate keratinocytes remains unknown. METHODS: We examined the activation of primary human keratinocytes by serine protease-rich extract of whole mite culture and compared with that by recombinant group 1 allergens (rDer f 1 and rDer p 1), which exclusively exhibit cysteine protease activity. RESULTS: Protease activity of whole mite culture extract (WCE), rDer f 1 and rDer p 1 induced the release of IL-8 and granulocyte-macrophage colony-stimulating factor. Protease activity of WCEs induced a significant upregulation of their mRNA expression but rDer f 1 had much less effect. Protease activity of the WCE stimulated intracellular Ca(2+) mobilization but rDer f 1 and rDer p 1 did not. The mobilization induced by agonists for the human protease-activated receptor (PAR)-2, an agonist peptide or trypsin, was diminished by pre-incubation of keratinocytes with WCE. rDer f 1 inefficiently cleaved a synthetic N-terminal peptide of PAR-2 at different sites from trypsin, but the resultant peptides did not stimulate the release of interleukin-8. CONCLUSIONS: The results suggest that mite-derived serine protease activity may contribute to the pathogenesis of atopic dermatitis by activating keratinocytes via PAR-2 activation but cysteine protease activity of Der f 1 and Der p 1 acts via another mechanism.

Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.

Interleukin-3 (IL-3) binds to its receptor with high and low affinities, induces tyrosine phosphorylation, and promotes the proliferation and differentiation of hematopoietic cells. A binding component of the IL-3 receptor was cloned. Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM]. No consensus sequence for a tyrosine kinase was present in the cytoplasmic domain. Thus, additional components are required for a functional high affinity IL-3 receptor. A sequence comparison of the IL-3 receptor with other cytokine receptors (erythropoietin, IL-4, IL-6, and the beta chain IL-2 receptor) revealed a common motif of a distinct receptor gene family.