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To evaluate one-stage thyroid cartilage laryngotracheal reconstruction in children less than one year of age with congenital subglottic stenosis.
Methods
Congenital subglottic stenosis children less than one year old who underwent one-stage thyroid cartilage laryngotracheal reconstruction between 2016 and 2020 in our department were retrospectively reviewed. Their clinical characteristics, treatments and prognoses were assessed.
Results
Eleven congenital subglottic stenosis children (6–11 months) were included: seven with Myer–Cotton grade II, and four with Myer–Cotton grade III. Their tracheal diameters were corrected to normal size using thyroid cartilage, and they were intubated under sedation for two weeks after surgery. Moreover, all of them received anti-infection and anti-reflux therapies during hospitalisation. No breathing difficulty, aspiration, hoarseness or laryngitis was observed during the follow-up period (10–30 months), and their growth and development were age appropriate.
Conclusion
The one-stage thyroid cartilage laryngotracheal reconstruction is a good treatment option for congenital subglottic stenosis children less than one year old with Myer–Cotton grade II–III.
OBJECTIVES/GOALS: RETgene fusions in sarcoma are rare and their impact on pathogenicity is unknown. Malignant peripheral nerve sheath tumors (MPNST) are a deadly, genomically heterogenous soft tissue sarcoma rarely harboring targetable aberrations. We present a case of a CCDC6-RET fusion MPNST sensitive to RET-inhibitor therapy in a xenograft model. METHODS/STUDY POPULATION: Lung tumor tissue was obtained per an approved collection protocol from a 21yo male patient with a spontaneous MPNST harboring an inactivating mutation in NF-1 and a CCDC6-RET gene fusion detected by a commercially available sequencing panel (Signatera). To confirm pathogenicity of the RET fusion, fresh tumor tissue was engrafted into immunocompromised NSG mice in the anterior and posterior flanks, harvested at ~10 weeks, and re-transplanted into bilateral flanks. When tumor diameters reached 0.5-1cm (~4 weeks), mice were randomized into 3 groups (n=6/group) and treated with either vehicle (V) (PBS), the RET-specific inhibitor selpercatinib (S) (20mg/kg twice daily), or the multi-kinase inhibitor cabozantinib (C) (30mg/kg daily) by oral gavage. Mice were monitored weekly for weight and tumor size. RESULTS/ANTICIPATED RESULTS: 92% (33/36) of implanted tumors were evaluable for treatment response. Pre-treatment tumor volumes (mm3) across all three groups were similar (mean/Std Dev – V: 230/111, S: 271/132, C: 230/123). At day 7, tumor growth was significantly inhibited by S and C versus V (ANOVA p < 0.001, post-hoc Tukey’s V vs S p= 0.0178, V vs C p< 0.0001, S vs C p= 0.0005). V-treated tumors increased in volume by 60% while S reduced tumor volume by ~80% and C reduced tumor volume by ~20%. S and C treatments were tolerated well. and S improved survival with 100% of mice alive at day 63 vs 0% in V and C groups. 6 of the 12 implanted tumors treated with S, 50% increased in size after ~6-weeks following a >90% initial tumor reduction in tumor volume. Follow-on molecular studies in S-resistant tumors are ongoing. DISCUSSION/SIGNIFICANCE: Targetable genomic changes in MPNST, especially in RET, are infrequent and often considered stochastic. Our findings suggest that precision medicine approaches pairing genomic sequencing and in vivotesting of target gene pathogenicity may guide treatment planning and novel discovery for rare, difficult to treat sarcomas.
Initial microbial colonization plays an important role in neonatal gut health. However, studies on gut microbial composition at birth are challenging, due to the limited access to accurate sampling. Here, we characterized the jejunal and ileal bacterial composition (epimural and luminal) of neonatal calves within 30 minutes after birth, and compared it with maternal (birth canal and rectum) and birth environments. RNA-based quantification along with amplicon sequencing revealed the colonization of active, dense (1.1–9.4 × 108 16S rRNA copy/g of sample), and diverse bacteria in the calf small intestine at birth. Pseudomonadaceae and Propionibacteriaceae dominated epimural communities, while Propionibacteriaceae, Prevotellaceae, Ruminococcaceae, and Lachnospiraceae dominated luminal communities. The composition of calf gut bacteria at birth was significantly different from maternal bacteria, especially for beneficial bifidobacteria. The bacterial communities of calf body habitats were similar to those of the birth environment, which was again divergent from gut microbiota. This study suggests an establishment of small intestinal-specific microbiota from birth, which is considerably deviated from maternal microbiota. In corollary, we further propose that small intestinal microbiota colonization could be mainly modulated by host selection.
The efficient separation of hexane isomers from the light naphtha fraction is a significant challenge in the petrochemical industry. 5A zeolite adsorbent is used commercially to sieve alkane isomers. In this study, 5A zeolites were synthesized using a low-cost natural clay mineral precursor, i.e. palygorskite (PAL), with the addition of crystallization directing agent (CDA). By varying the mass ratio of CDA/deionized water, 5A zeolites were obtained as CDA-5%, CDA-7.5%, and CDA-10%. All products were submicron particles with an average particle size of 400–800 nm. A sieving test of CDA-induced 5A zeolites was carried out on hexane adsorbates including n-hexane (nHEX), 2-methylpentane (2MP), and 3-methylpentane (3MP). According to vapor-phase batch adsorption experiments, a significant equilibrium amount (0.149 g/g) of nHEX and only 0.0321 g/g 2MP and 0.0416 g/g 3MP were adsorbed on the 5A zeolite product with CDA-5%. The dynamic adsorption performance of 5A zeolite (CDA-5%) was evaluated by breakthrough curves of binary mixtures of nHEX/2MP and nHEX/3MP. Palygorskite 5A (PAL 5A) zeolite achieved maximum dynamic adsorption capacities of nHEX (0.16 g/g in both cases) at 200°C and 1.2 MPa total pressure. This work provided an economic alternative for the synthesis of 5A zeolites using natural clay minerals instead of chemical raw materials.
Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).
Participants and Methods:
Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.
Results:
Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.
Conclusions:
Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.
Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear.
Methods
One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed.
Results
Cognitive impairment (global cognition, verbal memory, language, visual–spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS.
Conclusions
Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.
Depressive symptoms, functional impairment, and decreased quality of life (QOL) are three important domains of major depressive disorder (MDD). However, the possible causal relationship between these factors has yet to be elucidated. Moreover, it is not known whether certain symptoms of MDD are more impairing than others. The network approach is a promising solution to these shortfalls.
Methods
The baseline data of a multicenter prospective project conducted in 11 governances of China were analyzed. In total, 1385 patients with MDD were included. Depressive symptoms, functioning disability, and QOL were evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17), the Sheehan Disability Scale (SDS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). The network was estimated through the graphical Least Absolute Shrinkage and Selection Operator (LASSO) technique in combination with the directed acyclic graph.
Results
Three centrality metrics of the graphical LASSO showed that social life dysfunction, QOL, and late insomnia exhibited the highest strength centrality. The network accuracy and stability were estimated to be robust and stable. The Bayesian network indicated that some depressive symptoms were directly associated with QOL, while other depressive symptoms showed an indirect association with QOL mediated by impaired function. Depressed mood was positioned at the highest level in the model and predicted the activation of functional impairment and anxiety.
Conclusions
Functional disability mediated the relationship between depressive symptoms and QOL. Family functionality and suicidal symptoms were directly related to QOL. Depressed mood played the predominant role in activating both anxiety symptom and functional impairment.
Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case–control study of 260 AMD cases and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95 % confidence interval (CI) of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs (95 % CI) were 0·30 (0·10, 0·88) for lutein and 0·28 (0·11, 0·74) for β-cryptoxanthin. The associations for other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD. ORs (95% CIs) comparing extreme categories were 0·42 (0·20, 0·88) for spinach and 0·52 (95% CI: 0·27, 0·98) for egg. Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0·23; 95% CI: 0·08, 0·71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
For each recollement of triangulated categories, there is an epivalence between the middle category and the comma category associated with a triangle functor from the category on the right to the category on the left. For a morphic enhancement of a triangulated category $\mathcal {T}$, there are three explicit ideals of the enhancing category, whose corresponding factor categories are all equivalent to the module category over $\mathcal {T}$. Examples related to inflation categories and weighted projective lines are discussed.
We present here the first study on the stability of plane Poiseuille flow when the fluid is stratified in density perpendicularly to the plane of horizontal shear. Using laboratory experiments, linear stability analyses and direct numerical simulations, we describe the appearance of an instability that results from a resonance of internal gravity waves and Tollmien–Schlichting waves carried by the flow. This instability takes the form of long meanders confined in thin horizontal layers stacked along the vertical axis.
Prior research in the behavioral sciences has demonstrated that reminders can be an effective tool for encouraging health-related behavior changes. This article extends that literature by reporting the outcome of a randomized controlled trial of mailed vaccination reminders. In addition to making a substantive contribution regarding the efficacy of mailed reminders, this article also makes a methodological contribution: it illustrates how researchers can study the causal impact of an intervention even when a pure parallel trial is not possible. In this study, the Louisiana Department of Health sent postcard reminders regarding four recommended vaccinations (influenza, tetanus, shingles and pneumonia) to 208,867 senior residents of Louisiana. We used block randomization and a stepped wedge design to assess the efficacy of the intervention. Individuals were blocked by their prior vaccine record and randomized to receive the postcard in one of four consecutive months (October–January). The reminder postcard had an overall positive effect on vaccination rates. The statistically significant and substantively small increase in overall vaccination rates was driven by participants who received the postcard reminder early in the intervention period.
This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.
This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
Methods
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
Results
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
Conclusions
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
A greater understanding of the rumen microbiota and its function may help find new strategies to improve feed efficiency in cattle. This study aimed to investigate whether the cattle breed affects specific ruminal taxonomic microbial groups and functions associated with feed conversion ratio (FCR), using two genetically related Angus breeds as a model. Total RNA was extracted from 24 rumen content samples collected from purebred Black and Red Angus bulls fed the same forage diet and then subjected to metatranscriptomic analysis. Multivariate discriminant analysis (sparse partial least square discriminant analysis (sPLS-DA)) and analysis of composition of microbiomes were conducted to identify microbial signatures characterizing Black and Red Angus cattle. Our analyses revealed relationships among bacterial signatures, host breeds and FCR. Although Black and Red Angus are genetically similar, sPLS-DA detected 25 bacterial species and 10 functions that differentiated the rumen microbial signatures between those two breeds. In Black Angus, we identified bacterial taxa Chitinophaga pinensis, Clostridium stercorarium and microbial functions with large and small subunits ribosomal proteins L16 and S7 exhibiting a higher abundance in the rumen microbiome. In Red Angus, nonetheless, we identified the poorly characterized bacterial taxon Oscillibacter valericigenes with a higher abundance and pathways related to carbohydrate metabolism. Analysis of composition of microbiomes revealed that C. pinensis and C. stercorarium exhibited a higher abundance in Black Angus compared to Red Angus associated with FCR, suggesting that these bacterial species may play a key role in the feed conversion efficiency of forage-fed bulls. This study highlights how the discovery of signatures of bacterial taxa and their functions can be used to harness the full potential of the rumen microbiome in Angus cattle.
To revise an abbreviated version of the Silhouettes subtest of the Visual Object and Space Perception (VOSP) battery in order to recognize mild cognitive impairment (MCI) and determine the optimal cutoffs to differentiate among cognitively normal controls (NC), MCI, and Alzheimer’s Disease (AD) in the Chinese elderly.
Design:
A cross-sectional validation study.
Setting:
Huashan Hospital, Shanghai, China.
Subjects:
A total of 591 participants: Individuals with MCI (n = 211), AD (n = 139) and NC (n = 241) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.
Methods:
Baseline neuropsychological battery (including VOSP) scores were collected from firsthand data. An abbreviated version of silhouettes test (Silhouettes-A) was revised from the original English version more suitable for the elderly, including eight silhouettes of animals and seven silhouettes of inanimate objects, with a score ranging from 0 to 15.
Results:
Silhouettes-A was an effective test to screen MCI in the Chinese elderly with good sensitivity and specificity, similar to the Montreal cognitive assessment and superior to other single tests reflecting language, spatial, or executive function. However, it had no advantage in distinguishing MCI from AD. The corresponding optimal cutoff scores of Silhouettes-A were 10 for screening MCI and 8 for AD.
Conclusion:
Silhouettes-A is a quick, simple, sensitive, and dependable cognitive test to distinguish among NC, MCI, and AD patients.
The links between low socioeconomic status and poor health are well established, yet despite adversity, some individuals with low socioeconomic status appear to avoid these negative consequences through adaptive coping. Previous research found a set of strategies, called shift-and-persist (shifting the self to stressors while persisting by finding meaning), to be particularly adaptive for individuals with low socioeconomic status, who typically face more uncontrollable stressors. This study tested (a) whether perceived social status, similar to objective socioeconomic status, would moderate the link between shift-and-persist and health, and (b) whether a specific uncontrollable stressor, unfair treatment, would similarly moderate the health correlates of shift-and-persist. A sample of 308 youth (Meanage = 13.0, range 8–17), physician diagnosed with asthma, completed measures of shift-and-persist, unfair treatment, asthma control, and quality of life in the lab, and 2 weeks of daily diaries about their asthma symptoms. Parents reported on perceived family social status. Results indicated that shift-and-persist was associated with better asthma profiles, only among youth from families with lower (vs. higher) parent-reported perceived social status. Shift-and-persist was also associated with better asthma profiles, only among youth who experienced more (vs. less) unfair treatment. These findings suggest that the adaptive values of coping strategies for youth with asthma depend on the family's perceived social status and on the stressor experienced.
Geochronological, elemental and isotopic data of the Dashizhuzi granites and lamprophyre dykes from the eastern Hebei – western Liaoning on the northern North China Craton (NCC) provide an insight into the nature of their magma sources and subcontinental lithospheric mantle. The Dashizhuzi granites have an emplacement age of 226 Ma. They have enriched lithospheric mantle type 1 (EM1-like) Sr–Nd isotopic compositions, and have distinctive features of high Na2O and Sr and low Y with high Sr/Y and (La/Yb)N ratios. These characteristics show that the Dashizhuzi granites originated directly from melting of mafic lower crust composed of pre-existing ancient crustal and enriched mantle-derived juvenile crustal materials at normal continental crustal depth of 33–40 km. The lamprophyre dykes are dated at 167 Ma, and can be divided into two groups. The Group 1 dykes have variable Sr–Nd isotopic compositions and mid-ocean-ridge basalt (MORB-) like Th/U, Ba/Th and Ce/Pb ratios, whereas the Group 2 dykes have enriched Sr–Nd isotopic compositions and notable high Co, Cr, MgO and low Al2O3 characteristics. These distinctive features suggest that the Group 1 dykes were derived from a relatively fertile lithospheric mantle source (garnet-facies amphibole-bearing lherzolite) which has experienced variable degrees of asthenospheric mantle-derived melt–peridotite interaction prior to melting. However, the Group 2 dykes were derived from an ancient garnet-facies phlogopite and/or amphibole-bearing lherzolite lithospheric mantle. Thinning of the Early Mesozoic lithospheric mantle beneath the northern NCC is dominantly through melt–peridotite interaction and thermo-mechanical erosion prior to Middle Jurassic time. The chemical compositions have been modified at the bottom of the lithospheric mantle through melt–peridotite interaction processes.
In this paper, we propose an integral equation approach for pricing an American-style Parisian up-and-out call option under the Black–Scholes framework. The main difficulty of pricing this option lies in the determination of its optimal exercise price, which is a three-dimensional surface, instead of a two-dimensional (2-D) curve as is the case for a “one-touch” barrier option. In our approach, we first reduce the 3-D pricing problem to a 2-D one by using the “moving window” technique developed by Zhu and Chen (2013, Pricing Parisian and Parasian options analytically. Journal of Economic Dynamics and Control, 37(4): 875-896), then apply the Fourier sine transform to the 2-D problem to obtain two coupled integral equations in terms of two unknown quantities: the option price at the asset barrier and the optimal exercise price. Once the integral equations are solved numerically by using an iterative procedure, the calculation of the option price and the hedging parameters is straightforward from their integral representations. Our approach is validated by a comparison between our results and those of the trusted finite difference method. Numerical results are also provided to show some interesting features of the prices of American-style Parisian up-and-out call options and the behaviour of the associated optimal exercise boundaries.