Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.

Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive Sleep Apnea.

RATIONALE: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown. OBJECTIVES: To characterize phenotypes of ventilatory control that are associated with the presence of OSA in preterm-born children during early childhood. METHODS: Preterm- and term-born children without comorbid conditions were enrolled. They were categorized into an OSA group and a non-OSA group on the basis of polysomnography. MEASUREMENTS AND MAIN RESULTS: Loop gain, controller gain, and plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and blood gas response to a change in ventilation, respectively, were estimated from spontaneous sighs identified during polysomnography. Cardiorespiratory coupling, a measure of brainstem maturation, was estimated by measuring the interval between inspiration and the preceding electrocardiogram R-wave. Cluster analysis was performed to develop phenotypes based on controller gain, plant gain, cardiorespiratory coupling, and gestational age. The study included 92 children, 63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48% OSA). Three phenotypes of ventilatory control were derived with risks for OSA being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a stepwise decrease in controller gain and an increase in plant gain from clusters 1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling and gestational age than clusters 2 and 3. No difference in loop gain was found between clusters. CONCLUSIONS: The risk for OSA could be stratified according to controller gain, plant gain, cardiorespiratory coupling, and gestational age. These findings could guide personalized care for children at risk for OSA.

The Relationship Between Body Mass Index and Fatty Infiltration in the Shoulder Musculature.

OBJECTIVE: Fatty infiltration in the rotator cuff muscles has been well studied in the setting of rotator cuff tendon tears to help predict outcomes of surgical repair. Fatty infiltration in the rotator cuff has also been independently correlated to the variables of age and sex. The purpose of our study was to determine if there is a relationship between body mass index and fatty infiltration in patients with no imaging evidence of rotator cuff tendinosis or tear. METHODS: Radiology reports of all magnetic resonance imaging examinations of the shoulder were searched over a 2-year period. Studies with imaging findings of rotator cuff tendinosis, partial tear, or full thickness tear were excluded from the study, resulting in a total of 143 patients with normal rotator cuffs who were included in the study. These studies were reviewed by consensus by 2 fellowship-trained musculoskeletal radiologists who used the Goutallier 5-stage scoring system to grade the supraspinatus, infraspinatus, subscapularis, teres minor, teres major, and deltoid muscles. RESULTS: Sex was shown not to be significantly associated with fatty infiltration with the exception of the deltoid muscle, which showed a statistically significant increase in fatty infiltration associated with female sex (P = 0.038). Age was shown to be a statistically significant predictor of fatty infiltration for all 6 muscles (P < 0.05). Body mass index was shown to be a statistically significant predictor of fatty infiltration for all of the evaluated shoulder musculature (P < 0.05) with the exception of the teres minor. CONCLUSIONS: Our results suggest that increased body mass index is associated with increased fatty infiltration in the supraspinatus, infraspinatus, subscapularis, teres major, and deltoid muscles. This relationship could help guide the decisions of orthopedic surgeons when considering rotator cuff repair.

Cross-species single-cell spatial transcriptomic atlases of the cerebellar cortex.

The molecular and cellular organization of the primate cerebellum remains poorly characterized. We obtained single-cell spatial transcriptomic atlases of macaque, marmoset, and mouse cerebella and identified primate-specific cell subtypes, including Purkinje cells and molecular-layer interneurons, that show different expression of the glutamate ionotropic receptor Delta type subunit 2 (GRID2) gene. Distinct gene expression profiles were found in anterior, posterior, and vestibular regions in all species, whereas region-selective gene expression was predominantly observed in the granular layer of primates and in the Purkinje layer of mice. Gene expression gradients in the cerebellar cortex matched well with functional connectivity gradients revealed with awake functional magnetic resonance imaging, with more lobule-specific differences between primates and mice than between two primate species. These comprehensive atlases and comparative analyses provide the basis for understanding cerebellar evolution and function.

Solving the spectral gap problem with a four-mirror bow-tie cavity in waveguide free-electron laser oscillators.

The generation of intense coherent radiation pulses in the far-infrared and terahertz regimes is of considerable interest to the free-electron laser (FEL) radiation user community. At long wavelengths, the diffraction effect can be quite severe, therefore, an optical waveguide is required to confine the radiation field. However, it will also bring about some new phenomena, and the most noteworthy one is the spectral gap phenomenon: at some particular wavelengths, regardless of electron beam adjustments, the coupling efficiency and output power of waveguide FEL oscillators drop significantly. Such spectral gap has an adverse effect on experimental results since numerous experiments require continuous spectral scanning. In this paper, we propose to utilize a bow-tie cavity instead of conventional cavities to the waveguide FEL to solve the spectral gap problem. The simulation was carried out based on the parameters of FELiChEM, a newly built user facility in China. Numerical simulation code OPC combining with modified GENESIS is used to enable the modelling, for the first time, of a bow-tie cavity based FEL in the far-infrared wavelength regime. The simulation results indicate that this novel structure can effectively eliminate the spectral gaps and substantially enhance long-wavelength laser performance.

The Effect of Serum ß-Human Chorionic Gonadotropin on Pregnancy Complications and Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis.

Background: The relationship among elevated serum ß-human chorionic gonadotropin (ß-hCG), the incidence of pregnancy complications, and adverse pregnancy outcomes has been controversial. Differences in study design, subject bias due to demographic characteristics, and differences in local medical levels could contribute to inconsistent results. Methods: Literature searches were performed in PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science Digital Library (CSDL) databases. Inclusion criteria were as follows: (1) research subjects were singleton pregnant women; (2) the study is identified as cohort study; (3) the subjects were assigned to the high ß-hCG group and control group according to whether the exposure factors increased ß-hCG in the second trimester; (4) the observed outcomes include at least pregnancy-induced hypertension (PIH), diabetes (gestational diabetes mellitus, GMD), preterm delivery (PD), and intrauterine growth restriction (IUGR); and (5) the odds ratio (OR) and 95% confidence interval (CI) of exposure factors are calculated based on literature dataset. To determine the risk bias of selected literatures, Newcastle-Ottawa scale was applied. The chi-square test was further used for heterogeneity analysis. If heterogeneity was identified, subgroup analyses were then performed for source investigation. Results: A total of 13 literatures were included and analyzed, including 67,355 pregnant women and 5980 pregnant women assigned to the high ß-HCG group and 61,375 pregnant women to the control group. The incidence of PIH in the high ß-HCG group was higher than that in the control group (OR = 2.11, 95% CI [1.90, 2.35], Z = 13.85, P < 0.00001). There was no heterogeneity among literatures (χ 2 = 8.53, P = 0.38, I 2 = 6%), and thus there is no identified publication bias (P > 0.05). The incidence of preterm birth in the high ß-HCG group was higher than that in the control group (OR = 2.11, 95% CI [1.90, 2.35], Z = 13.85, P < 0.00001). The analysis suggested no heterogeneity among included literatures (χ 2 = 11.78, P = 0.11, I 2 = 41%) and no publication bias (P > 0.05). Higher incidence of abortion was observed in the high ß-HCG group compared with the control group (OR = 2.80, 95% CI [1.92, 4.09], Z = 5.32, P < 0.00001). There was no heterogeneity among literatures (χ 2 = 3.43, P = 0.33, I 2 = 13%) and no publication bias (P > 0.05). The incidence of gestational diabetes was higher in the high ß-HCG group than in the control group (OR = 2.15, 95% CI [1.05, 4.40], Z = 2.09, P = 0.04). Heterogeneity was identified among literatures (χ 2 = 47.01, P < 0.00001, I 2 = 87%). Sensitivity analysis showed that the results were not robust, and there was no publication bias (P > 0.05). Compared with control, the incidence of IGUR was higher in the high ß-HCG group (OR = 2.70, 95% CI [1.75, 4.19], Z = 4.45, P < 0.0001) with no heterogeneity among literatures (χ 2 = 3.92, P = 0.14, I 2 = 49%) and no publication bias (P > 0.05). Conclusion: High levels of ß-hCG during pregnancy in singleton women are associated with a high incidence of pregnancy complications and adverse pregnancy outcomes. Pregnant women with high levels of ß-hCG should be monitored more closely, followed up, and given timely medical interventions to reduce the incidence of pregnancy complications and adverse outcomes.

Expression Analysis of Molecular Chaperones Hsp70 and Hsp90 on Development and Metabolism of Different Organs and Testis in Cattle (Cattle-yak and Yak).

Hsp70 and Hsp90 play an important role in testis development and spermatogenesis regulation, but the exact connection between Hsp70 and Hsp90 and metabolic stress in cattle is unclear. Here, we focused on the male cattle−yak and yak, investigated the expression and localization of Hsp70 and Hsp90 in their tissues, and explored the influence of these factors on development and metabolism. In our study, a total of 54 cattle (24 cattle−yaks and 30 yaks; aged 1 day to 10 years) were examined. The Hsp90 mRNA of the cattle−yak was first cloned and compared with that of the yak, and variation in the amino acid sequence was found, which led to differences in protein spatial structure. Using real-time quantitative PCR (RT-qPCR) and Western blot (WB) techniques, we investigated whether the expression of Hsp70 and Hsp90 mRNA and protein are different in the cattle−yak and yak. We found a disparity in Hsp70 and Hsp90 mRNA and protein expression in different non-reproductive organs and in testicular tissues at different stages of development, while high expression was observed in the testes of both juveniles and adults. Moreover, it was intriguing to observe that Hsp70 expression was significantly high in the yak, whereas Hsp90 was high in the cattle−yak (p < 0.01). We also examined the location of Hsp70 and Hsp90 in the testis by immunohistochemical (IHC) and immunofluorescence (IF) techniques, and the results showed that Hsp70 and Hsp90 were positive in the epithelial cells, spermatogenic cells, and mesenchymal cells. In summary, our study proved that Hsp70 and Hsp90 expressions were different in different tissues (kidney, heart, cerebellum, liver, lung, spleen, and testis), and Hsp90 expression was high in the testis of the cattle−yak, suggesting that dysplasia of the cattle−yak may correlate with an over-metabolism of Hsp90.

An intein-split transactivator for intersectional neural imaging and optogenetic manipulation.

The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of common effectors and insufficient gene expression. Here, we utilized the protein-splicing technique mediated by intervening sequences (intein) and devised an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in multiple-feature defined cell types in mice. We validated the specificity and sufficiency of IBIST to control fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions. The IBIST-based Ca2+ imaging showed that the IBIST can intersect five features and that hippocampal neurons tune differently to distinct emotional stimuli depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and controls common effectors to effectively regulate gene expression, monitor and manipulate neural activities.

TCF7L1 Genetic Variants Are Associated with the Susceptibility to Cervical Cancer in a Chinese Population.

BACKGROUND: Cervical cancer (CC) is the second most common tumor in women worldwide. Studies have been accepted that genetic variations play an important role in the development of CC. The aim of this study was to evaluate the impact of TCF7L1 variants on CC risk. METHODS: 508 patients of cervical cancer and 497 healthy subjects were recruited to determine the impact of TCF7L1 polymorphisms on CC susceptibility. The associations were investigated by computing odds ratios (ORs) and 95% confidence intervals. The effect of SNP-SNP interactions on CC risk was explored by multifactor dimensionality reduction analysis. RESULTS: Our study showed that rs11904127 (OR 0.79, p = 0.010) and rs62162674 (OR 0.82, p = 0.044) of TCF7L1 significantly decreased cervical cancer risk. Stratified analysis indicated that rs11904127 and rs62162674 present decreased susceptibility to CC in age > 51 years (OR 0.74, p = 0.019; OR 0.72, p = 0.014, respectively). Haplotype analyses revealed that Grs2366264Trs11689667Crs62162674 has a lower risk to cervical cancer (OR = 0.43, p = 0.018). Besides, there is strong interaction of rs11904127 and rs2366264. CONCLUSION: Rs11904127 and rs62162674 in TCF7L1 are related to cervical cancer. We suggest that these variants can be used as prognostic markers for judging the susceptibility to cervical cancer.

Evaluation of Risk Scores to Predict Pediatric Severe Asthma Exacerbations.

BACKGROUND: Asthma exacerbations commonly lead to unplanned health care utilization and are costly. Early identification of children at increased risk of asthma exacerbations would allow a proactive management approach. OBJECTIVE: We evaluated common asthma risk factors to predict the probability of exacerbation for individual children aged 0-21 years using data from the electronic medical record (EMR). METHODS: We analyzed longitudinal EMR data for over 3000 participants with asthma seen at Cincinnati Children's Hospital Medical Center over a 7-year period. The study population was divided into 3 age groups: 0-4, 5-11, and 12-21 years. Each age group was divided into a derivation cohort and a validation cohort, which were used to build a risk score model. We predicted risk of exacerbation in the next 12 months, validated the scores by risk stratum, and developed a clinical tool to determine the risk level based on this model. RESULTS: Risk model results were confirmed with validation cohorts by calendar year and age groups. Race, allergic sensitization, and smoke exposure were each important risk factors in the 0-4 age group. Abnormal spirometry and obesity were more sensitive predictors of exacerbation in children >12 years. For each age group, a higher expanded score was associated with a higher predicted probability of an asthma exacerbation in the subsequent year. CONCLUSION: This asthma exacerbation prediction model, and the associated clinical tool, may assist clinicians in identifying children at high risk for exacerbation that may benefit from more aggressive management and targeted risk mitigation.

The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS. METHODS: Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study. RESULTS: This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals. CONCLUSION: The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease. ETHICS AND DISSEMINATION: In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics. OSF REGISTRATION DOI: 10.17605/OSF.IO/8GW9M.

Sleep manifestations, sleep architecture in children with Eosinophilic esophagitis presenting to a sleep clinic.

STUDY OBJECTIVES: To describe sleep manifestations, polysomnographic (PSG) findings, and specific sleep disorders in children with Eosinophilic Esophagitis (EoE). METHODS: This retrospective study included children with EoE who were referred to sleep clinics. Clinical manifestations, PSG variables, and diagnosis of sleep disorders were analyzed. Sleep architecture of patients with EoE was compared to control subjects. RESULTS: In sum, 81 children with EoE met the criteria for entry into the analysis with a mean age of 10.1 ± 4.4 years. Of those, 46 children (57%) presented in the sleep clinic with active EoE symptoms, while 35 (43%) children did not have active EoE symptoms at presentation. Several sleep complaints were common in children with EoE, including snoring (62, 76.5%), restless sleep (54, 66.6%), legs jerking or leg discomfort (35, 43.2%) and daytime sleepiness (47, 58.0%). Comparing sleep architecture with controls, children with EoE had significantly higher NREM2 (P= < 0.001), lower NREM3 (P= < 0.001), lower rapid eye movement (REM) (P = 0.017), increased periodic leg movements (PLM) index (P= < 0.001) and increased arousal index (P = 0.007). There were no significant differences in the sleep efficiency between the EoE and control subjects. Common sleep diagnoses included obstructive sleep apnea (OSA, 30, 37.0%) and periodic limb movements disorder (PLMD, 20, 24.6%). Of note, we found a much higher percentage of PLMD in active EoE compared to inactive EoE (P = 0.004). CONCLUSIONS: Children with EoE have frequent sleep complaints and several sleep disorders identified from the sleep study, including sleep-disordered breathing and PLMD. Analysis of sleep architecture demonstrates significant sleep fragmentation as evidenced by decreased slow-wave sleep and REM sleep and increased arousal index.

Deciphering the transcriptional regulatory networks that control size, color, and oil content in Brassica rapa seeds.

BACKGROUND: Brassica rapa is an important oilseed and vegetable crop species and is the A subgenome donor of two important oilseed Brassica crops, Brassica napus and Brassica juncea. Although seed size (SZ), seed color (SC), and oil content (OC) substantially affect seed yield and quality, the mechanisms regulating these traits in Brassica crops remain unclear. RESULTS: We collected seeds from a pair of B. rapa accessions with significantly different SZ, SC, and OC at seven seed developmental stages (every 7 days from 7 to 49 days after pollination), and identified 28,954 differentially expressed genes (DEGs) from seven pairwise comparisons between accessions at each developmental stage. K-means clustering identified a group of cell cycle-related genes closely connected to variation in SZ of B. rapa. A weighted correlation analysis using the WGCNA package in R revealed two important co-expression modules comprising genes whose expression was positively correlated with SZ increase and negatively correlated with seed yellowness, respectively. Upregulated expression of cell cycle-related genes in one module was important for the G2/M cell cycle transition, and the transcription factor Bra.A05TSO1 seemed to positively stimulate the expression of two CYCB1;2 genes to promote seed development. In the second module, a conserved complex regulated by the transcription factor TT8 appear to determine SC through downregulation of TT8 and its target genes TT3, TT18, and ANR. In the third module, WRI1 and FUS3 were conserved to increase the seed OC, and Bra.A03GRF5 was revealed as a key transcription factor on lipid biosynthesis. Further, upregulation of genes involved in triacylglycerol biosynthesis and storage in the seed oil body may increase OC. We further validated the accuracy of the transcriptome data by quantitative real-time PCR of 15 DEGs. Finally, we used our results to construct detailed models to clarify the regulatory mechanisms underlying variations in SZ, SC, and OC in B. rapa. CONCLUSIONS: This study provides insight into the regulatory mechanisms underlying the variations of SZ, SC, and OC in plants based on transcriptome comparison. The findings hold great promise for improving seed yield, quality and OC through genetic engineering of critical genes in future molecular breeding.

Age-related changes in the morphology and the distribution of IgA and IgG in the pharyngeal tonsils of yaks (Bos grunniens).

To evaluate age-related changes in the morphology as well as the expression and localization of IgA and IgG in yak pharyngeal tonsils, 20 healthy yaks were divided into four age groups [newborn (1-7 days old), juvenile (5-7 months old), adult (3-6 years old) and old (7-10 years old)]. Morphologic characteristics were observed by histological techniques. The expression and localization of IgA and IgG in pharyngeal tonsils were detected by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The results showed that the epithelium of the pharyngeal tonsils included nonreticular epithelium with an intact basement membrane and reticular epithelium with a discontinuous basement membrane and nonepithelial cell infiltration. In newborn yaks, only primary lymphoid follicles were observed in pharyngeal tonsils. In other age groups, both primary and secondary lymphoid follicles were observed, but some of the lymphoid follicles in the old yaks were degenerated. The number of lymphoid follicles increased from the newborn to the adult group and peaked in the adult group, but the number decreased in the old group. In addition, the age-related trends of IgA and IgG protein expression were similar to those of the number of lymphoid follicles. The concentration of IgG was significantly higher than that of IgA in all age groups. Both IgA and IgG antibody secreting cells (ASCs) were distributed in the subepithelial region of the nonreticular epithelium, the reticular epithelium, the lymphoid follicles, the interfollicular areas and in between the salivary glands. The densities of IgA and IgG ASCs in pharyngeal tonsils were similar to the expression trend of both proteins in each age group. The results indicate that the morphology and amount of lymphoid follicles in yak pharyngeal tonsils vary with age. Pharyngeal tonsils produce more IgG than IgA, indicating that IgG could be significant component of mucosal immune responses in yaks.

Clinical presentation, diagnosis and polysomnographic findings in children with migraine referred to sleep clinics.

OBJECTIVE: An association between migraine and sleep disturbances in children was reported, yet limited clinical data exist. The current study addresses the clinical presentation, polysomnographic (PSG) characteristics, and comorbid sleep diagnoses of children with migraine referred to the sleep clinic. PATIENTS: A retrospective review was performed of headache center patients evaluated by the sleep center between 2007 and 2017. Children ≤18 years old, diagnosed with migraine headache, and who had PSG within one year of evaluation in the headache clinic, were included. PSG findings, as well as demographics, were compared to a group of controls aged 5-14 years-old. RESULTS: In sum, 185 children with a diagnosis of migraine were included: 39% males, 75% Caucasian, mean age 13.5 ± 3.4, and 57% obese. Additionally, 180 children were included in the control group. The common presenting sleep symptoms were snoring (66%), sleep onset and sleep maintenance problems (25%), and excessive daytime sleepiness (20%). For the sleep diagnosis, 40% had obstructive sleep apnea (OSA), 27% had insomnia, 15% had periodic limb movement disorder (PLMD), and 6% had a central disorder of hypersomnolence. In terms of sleep architecture, children with migraine had significantly higher NREM 2 (p < 0.001) and a lower percentage of NREM3 (p < 0.001) compared to controls after adjustment for demographics and the presence of sleep-disordered breathing. CONCLUSIONS: Children referred to the sleep clinic who also had migraine, experience various types of sleep complaints. OSA, insomnia, and PLMD were relatively common in this population. Changes in sleep architecture, specifically increased NREM2 and decreased slow wave sleep compared to the control group, were also observed.

Yak (Bos grunniens) Tonsils: Morphological Description and Expression of IgA and IgG.

This study aimed to describe the morphology, expression of IgA and IgG in adult yak tonsils. The 12 clinically healthy yak tonsils [3- to 6-year old, n = 12] were examined for morphology using light, and transmission electron microscopes. Expression of IgA and IgG was measured by qRT-PCR, ELISA, and immunohistochemistry. The results showed that the palatine tonsil, the tonsil of the soft palate, and the lingual tonsil were oropharyngeal tonsils. The stratified squamous epithelia covering them had a thick underlying layer of connective tissue and their crypts were heavily infiltrated by lymphocytes. The pharyngeal tonsil and the tubal tonsil were nasopharyngeal tonsils. The epithelia of them was predominantly pseudostratified columnar ciliary epithelium, which were loosely arranged with a number of desmosomes or intermediate junctions variably connecting them. The expression levels of IgA and IgG mRNA and protein from high to low was in the pharyngeal tonsil, palatine tonsil, tonsil of the soft palate, lingual tonsil, and tubal tonsil, respectively. Interestingly, the expression of IgG was very significantly higher than that of IgA in yak tonsils (P < 0.01). Both the IgA and IgG ASCs were distributed in the subepithelial areas of the non-reticular crypt epithelium, especially areas of pseudostratified columnar ciliary epithelium, the reticular crypt epithelium, lymphoid follicles, interfollicular areas, and with some of the positive cells aggregating around the glands. The results indicated that the tonsils were not only typical secondary lymphoid organs but also lymphoepithelial structures. IgG could be a significant component of mucosal immune responses in yak tonsils. Anat Rec, 302:999-1009, 2019. © 2018 Wiley Periodicals, Inc.

The effect of adenotonsillectomy on ventilatory control in children with obstructive sleep apnea.

STUDY OBJECTIVES: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in children and the effect of adenotonsillectomy are unknown. We aimed to examine the difference in ventilatory control between children with OSA and those without OSA. We also examined the effect of adenotonsillectomy on parameters of ventilatory control. METHODS: Healthy children with OSA and matched controls were recruited. Polysomnography was performed before adenotonsillectomy in the OSA group and 6 months postoperatively. Controls underwent the same assessment at the two time points. Loop gain (LG), controller gain (CG), and plant gain (PG), which reflect the stability of ventilatory control, chemoreceptor sensitivity and the pulmonary control of blood gas in response to a change in ventilation, respectively, were estimated from polysomnographic tracings which included spontaneous sighs and tracings with tidal breathing. A linear mixed model was used to examine the changes of the ventilatory control parameters from baseline to 6 months. RESULTS: Ninety-nine children aged 7-13 were recruited to the study. Fifty-three with OSA and 46 controls. At baseline, compared with controls, children with OSA had higher PG and lower CG. LG did not differ between groups. Six months following adenotonsillectomy, there was a significant decrease in PG in the OSA group, while no change observed in the control group. CONCLUSIONS: The study demonstrates that the pulmonary control of blood gas homeostasis is disturbed in children with OSA and it normalizes following adenotonsillectomy.

Phenotype of ventilatory control in children with moderate to severe persistent asthma and obstructive sleep apnea.

STUDY OBJECTIVES: To examine the role of ventilatory control in asthmatic children with obstructive sleep apnea (OSA) and the relationships between measures of ventilatory control, OSA severity, and pulmonary function. METHODS: Five- to 18-year-old children with persistent asthma and nightly snoring were enrolled in the study. Children had physical examination, pulmonary function test, and polysomnography. Loop and controller gains were derived from 5 min segments which included a sigh during nonrapid eye movement sleep by applying a mathematical model that quantifies ventilatory control from the ensuing responses to the sighs. Plant gain was derived from 5 min segments of spontaneous breathing (i.e. without sighs). Nonparametric statistical tests were used for group comparisons. Cluster analysis was performed using Bayesian profile regression. RESULTS: One hundred thirty-four children were included in the study, 77 with and 57 without OSA. Plant gain was higher in children with OSA than in those without OSA (p = 0.002). A negative correlation was observed between plant gain and forced expiratory volume in 1 second (p = 0.048) and the ratio of f forced expiratory volume to forced vital capacity (p = 0.02). Plant gain correlated positively with severity of OSA. Cluster analysis demonstrated that children with more severe OSA and abnormal lung function had higher plant gain and a lower controller gain compared with the rest of the population. CONCLUSIONS: Children with OSA and persistent asthma with abnormal lung function have phenotypic characteristics which consist of diminished capacity of the lungs to maintain blood gas homeostasis reflected by an increase in plant gain and decreased chemoreceptor sensitivity.

Sleep Disorders and Their Management in Children With Ehlers-Danlos Syndrome Referred to Sleep Clinics.

STUDY OBJECTIVES: The nature of sleep disorders in children with Ehlers-Danlos syndrome (EDS) is unknown. We aimed to describe the type, the management, and the short-term outcome of sleep disorders in children with EDS referred to sleep clinics. METHODS: This is a retrospective review of medical records and polysomnography tests of children with EDS younger than 18 years who were referred to the sleep clinic. Demographic information and medical history were collected, and polysomnography tests were reviewed. Questionnaires completed during previous clinic visits, including the Pediatrics Sleep Questionnaire (PSQ), Epworth Sleepiness Scale (ESS), and Pediatric Quality of Life Inventory (PedsQL), were also evaluated. RESULTS: Sixty-five patients with EDS-hypermobility type were included. The mean age was 13.15 ± 3.9 years. There were 68% of patients who were female, and 91% of patients were Caucasian. The mean follow-up period was 1.14 ± 1.55 years. Common sleep diagnoses included insomnia (n = 14, 22%), obstructive sleep apnea (OSA) (n = 17, 26%), periodic limb movement disorder (PLMD) (n = 11, 17%), and hypersomnia (n = 10, 15%). In addition, 65% required pharmacologic treatment and 29% were referred to behavioral sleep medicine. For OSA, two patients required continuous positive airway pressure. A significant improvement was observed in the PSQ, ESS, and PedsQL scores during follow-up visits after treatment (n = 34; P = .0004, 0.03, and 0.01, respectively). CONCLUSIONS: There is a high prevalence of sleep disorders, including OSA, insomnia, PLMD, and hypersomnia in children with EDS referred to sleep clinics. Specific management can improve quality of life and questionnaire scores of this patient population. Our study emphasizes the importance of screening for sleep disorders in children with EDS.

Age-related changes in the morphology and the distribution of IgA and IgG in the palatine tonsils of yaks (Bos grunniens).

This study aimed to describe the age-related morphological changes and the distribution of IgA and IgG antibody-secreting cells (ASCs) in yaks. The palatine tonsils of twenty clinically healthy yaks, viz. newborn juvenile, adult and aged, were studied using histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). The results showed that the palatine tonsils found in two tonsillar sinus were elongated kidney-shaped structures. Some external crypts and internal crypts were present. The palatine tonsils were partially enclosed by a connective tissue capsule and had trabeculae extending into the organ. Within these encapsulated organs, mucous glands were seen very obviously. Each crypt was highly branched and lined with stratified squamous non-keratinized epithelium. Several nonepithelial cells infiltrated between the epithelial cells, forming patches of reticular epithelium or lymphoepithelium. In newborn yaks, the lymphoid follicles were not observed. In other groups, the lymphoid follicles consisted of primary lymphoid follicles and secondary lymphoid follicles. Both IgA and IgG ASCs were distributed in the interfollicular areas, lymphoid follicles, the subepithelial areas of the non-reticular crypt epithelium, and the reticular crypt epithelium, with a few positive cells aggregated around the gland. The density of the two ASCs and the expression of the two proteins gradually increased from newborn to adult and reached a peak at adult age; they then decreased with age. However, the density of the IgG ASCs and the expression of IgG protein was significantly higher than that of IgA in all groups (P<0.01). The results indicated that the palatine tonsils were not only lymphoepithelial structures but also typical secondary lymphoid organs. IgG could be a significant component of mucosal immune responses in the palatine tonsils of yaks.