KMT2D regulates activation, localization, and integrin expression by T-cells.

Individuals with Kabuki syndrome present with immunodeficiency; however, how pathogenic variants in the gene encoding the histone-modifying enzyme lysine methyltransferase 2D (KMT2D) lead to immune alterations remain poorly understood. Following up on our prior report of KMT2D-altered integrin expression in B-cells, we performed targeted analyses of KMT2D's influence on integrin expression in T-cells throughout development (thymocytes through peripheral T-cells) in murine cells with constitutive- and conditional-targeted Kmt2d deletion. Using high-throughput RNA-sequencing and flow cytometry, we reveal decreased expression (both at the transcriptional and translational levels) of a cluster of leukocyte-specific integrins, which perturb aspects of T-cell activation, maturation, adhesion/localization, and effector function. H3K4me3 ChIP-PCR suggests that these evolutionary similar integrins are under direct control of KMT2D. KMT2D loss also alters multiple downstream programming/signaling pathways, including integrin-based localization, which can influence T-cell populations. We further demonstrated that KMT2D deficiency is associated with the accumulation of murine CD8+ single-positive (SP) thymocytes and shifts in both human and murine peripheral T-cell populations, including the reduction of the CD4+ recent thymic emigrant (RTE) population. Together, these data show that the targeted loss of Kmt2d in the T-cell lineage recapitulates several distinct features of Kabuki syndrome-associated immune deficiency and implicates epigenetic mechanisms in the regulation of integrin signaling.

Müllerian Agenesis in a patient with Rubinstein-Taybi Syndrome: A Case Series and Review of the Overlapping Developmental Biologic Pathways.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multi-system neurodevelopmental condition caused by deficiency of CREBBP (16p13.3) or EP300 (22q13.2). Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is defined as congenital agenesis of the uterus, cervix, and upper vagina without a definite genetic cause. INDEX CASE AND CASE SERIES: We present a 14-year-old female with RSTS type 1 (CREBBP, c.4395-2A>C) and MRKH, the first documented in the literature. Following presentation to Gynecology for anticipatory guidance regarding future menstrual suppression and follow-up of previously diagnosed labial adhesions, exam under anesthesia revealed a single urogenital opening with cystoscopy demonstrating a normal urethra and bladder. Laboratory evaluation was consistent with peripubertal female gonadotropins and estradiol, 46,XX karyotype, and normal microarray, and a pelvic MRI confirmed Müllerian agenesis. Given this case, we assessed our cohort of females with RSTS and found that 4 of 12 individuals also had Müllerian anomalies. CONCLUSION: Gynecologic evaluation should be a part of medical care for females with RSTS, particularly in individuals with delayed menarche or abnormal menstrual history, on the basis of the observed association between RSTS and Müllerian anomalies in this case series. Although several candidate genes and copy number variants are associated with MRKH, no candidate genes in close proximity to the 16p13.3 region have been identified to explain both RSTS and MRKH in the index patient. Due to the regulatory nature of CREBBP during embryonic development, we theorize that CREBBP may play a role in the migration of Müllerian structures during embryogenesis.

Unequivocal Identification of Spin-Triplet and Spin-Singlet Superconductors with Upper Critical Field and Flux Quantization.

Spin-triplet superconductors play central roles in Majorana physics and quantum computing but are difficult to identify. We show the methods of kink-point upper critical field and flux quantization in superconducting rings can unequivocally identify spin-singlet, spin-triplet in centrosymmetric superconductors, and singlet-triplet admixture in noncentrosymmetric superconductors, as realized in γ-BiPd, ß-Bi_{2}Pd, and α-BiPd, respectively. Our findings are essential for identifying triplet superconductors and exploring their quantum properties.

Early Measures of TBI Severity Poorly Predict Later Individual Impairment in a Rat Fluid Percussion Model.

BACKGROUND: Multiple measures of injury severity are suggested as common data elements in preclinical traumatic brain injury (TBI) research. The robustness of these measures in characterizing injury severity is unclear. In particular, it is not known how reliably they predict individual outcomes after experimental TBI. METHODS: We assessed several commonly used measures of initial injury severity for their ability to predict chronic cognitive outcomes in a rat lateral fluid percussion (LFPI) model of TBI. At the time of injury, we assessed reflex righting time, neurologic severity scores, and 24 h weight loss. Sixty days after LFPI, we evaluated working memory using a spontaneous alternation T-maze task. RESULTS: We found that righting time and weight loss had no correlation to chronic T-maze performance, while neurologic severity score correlated weakly. DISCUSSION: Taken together, our results indicate that commonly used early measures of injury severity do not robustly predict longer-term outcomes. This finding parallels the uncertainty in predicting individual outcomes in TBI clinical populations.

Behavioral and neuropsychiatric challenges across the lifespan in individuals with Rubinstein-Taybi syndrome.

Introduction: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by developmental and intellectual disability, broadening of thumbs and halluces, and characteristic facial features. Pathogenic variants in CREBBP lead to RSTS type 1 (RSTS1) and in EP300 lead to RSTS type 2 (RSTS2). Individuals with RSTS can demonstrate a variety of behavioral and neuropsychiatric challenges, including anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression. Behavioral challenges are consistently reported as one of the primary factors impacting quality of life. Despite the high prevalence and morbidity of behavioral and neuropsychiatric features of RSTS, a paucity of data exists regarding its natural history. Methods: To better understand the neurocognitive and behavioral challenges faced by individuals with RSTS, 71 caregivers of individuals with RSTS, ranging in age from one to 61 years, completed four questionnaires measuring obsessive compulsive disorder (OCD)-like symptoms, anxiety, challenging behaviors, and adaptive behavior and living skills. Results: Results revealed a high prevalence of neuropsychiatric and behavioral challenges across ages. We found specific challenging behaviors were worse in school age individuals. Scaled adaptive behavior and living skill scores differed across ages with an increased gap between typically developing peers becoming more apparent at older ages. Between types, individuals with RSTS2 had better adaptive behavior and living skills and less stereotypic behaviors but higher social phobia than individuals with RSTS1. Further, female individuals with RSTS1 appear to have increased hyperactivity. However, both groups had impairments in adaptive functioning compared to typically developing peers. Discussion: Our findings support and expand previous reports of a high prevalence of neuropsychiatric and behavioral challenges in individuals with RSTS. However, we are the first to report differences between types of RSTS. Further, age-related differences were seen with higher challenging behaviors within school-age individuals, which may improve over time, and lower adaptive behavioral skills compared to normative scales. Anticipation of these potential differential challenges across age is vital for proactive management for individuals with RSTS. Our study underscores the importance of enacting neuropsychiatric and behavioral screening earlier in childhood so appropriate management can be implemented. However, further longitudinal studies in larger cohorts are needed to understand better how behavioral and neuropsychiatric characteristics of RSTS evolve over the lifespan and differentially affect subpopulation groups.

[Clinical application value of modified Lee grading system to evaluate the degree of foraminal stenosis in patients with intervertebral foraminal lumbar disc herniation].

Objective: To investigate the clinical application value of the modified Lee grading system (abbreviated as the modified system) in evaluating the degree of intervertebral foraminal stenosis(IFS) in patients with foraminal lumbar disc herniations(FLDH). Methods: MRI data of 83 patients with FLDH-IFS (34 patients in the operation group and 49 patients in the conservative group) in Yantai Affiliated Hospital of Binzhou Medical University and Yantai Yantaishan Hospital from March 2018 to February 2021 were retrospectively collected. There were 43 males and 40 females, ranged from 34 to 82 years old, with an average of (61±10) years. MRI images of selected patients were independently evaluated and recorded by two radiologists in a blind method, using both the Lee grading system (abbreviated as Lee system) and the modified system, respectively and each method was evaluated twice. The difference between the evaluation level of the two systems, and the agreement of observer assessments of the two systems were compared, and the correlation between the evaluation level of the two grading systems and the clinical treatment modalities was analyzed. Results: The percentage of nongrade 3 (grade 0-2) patients with effective conservative treatment according to the two grading systems was 94.6 % (139/147) and 64.2 % (170/265), respectively. The percentage of grade 3 patients requiring surgical treatment according to the two grading systems was 69.2 % (128/185) and 61.2 % (41/67), respectively. There was a statistically significant difference between the evaluation levels of the modified system and the Lee system (Z=-5.16, P=0.001). In the Lee system, the intra-observer observation consistency Kappa values of the two radiologists were 0.735 and 0.542, respectively, which were highly and moderately consistent; and the inter-observer observation consistency Kappa values were 0.426-0.521, which were moderate consistency. In the modified system, the intra-observer consistency Kappa values of the two radiologists were 0.900 and 0.921, respectively, and the consistency was almost completely consistent; and the inter-observer consistency Kappa values were 0.783-0.861, which were highly consistent or almost completely consistent. Lee system and clinical treatment modalities was correlative (rs=0.39,P<0.001), and modified system and clinical treatment modalities was correlative (rs=0.61,P<0.001). Conclusion: According to FLDH-IFS, the modified system can comprehensively and accurately grade, with high reliability and reproducibility. The evaluation level has a more significant correlation with clinical treatment modalities.

[Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis].

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.

Comparison of the outer membrane proteomes between clinical carbapenem-resistant and -susceptible Acinetobacter baumannii.

BACKGROUND AND AIM: Carbapenem resistance has become a major obstacle in combating Acinetobacter baumannii infections. Although enzymatic degradation by ß-lactamases is the pivotal mechanism of carbapenem resistance, porin deficiency has also been implicated in the mechanism. In this study, outer membrane proteins (OMPs) pattern of a clinical multidrug-resistant A. baumannii isolate were analysed in order to attain a deeper understanding of carbapenem-resistance strategies. METHODS: OMPs extracts, respectively, separated from carbapenem-resistant and -susceptible clinical A. baumannii isolates were compared using two-dimensional polyacrylamide gel electrophoresis. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). RESULTS: Twenty-three differently expressed proteins were identified between the resistant and susceptible isolates. Among them, six were annotated convincingly as OMPs in UniProt database. CarO was found absent from the resistant isolate and the expression levels of Omp33-36 and Omp25 were significantly lower than that in the susceptible counterpart. Strikingly, a LysM domain/BON superfamily protein, which has been linked to carbapenem resistance in Klebsiella pneumoniae, was found underexpressed by tenfold in the resistant isolate. CONCLUSION: Our study verified some porins which have been proven to play an important role in bacterial resistance against carbapenems. Underexpression of the LysM domain/BON superfamily protein may indicate its possible engagement in bacterial drug resistance, but its actual role requires more investigation.

[Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing].

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Leftover Opioid Analgesics and Disposal Following Ambulatory Pediatric Surgeries in the Context of a Restrictive Opioid-Prescribing Policy.

BACKGROUND: Opioid analgesics are commonly prescribed for postoperative analgesia following pediatric surgery and often result in leftover opioid analgesics in the home. To reduce the volume of leftover opioids and overall community opioid burden, the State of Tennessee enacted a policy to reduce initial opioid prescribing to a 3-day supply for most acute pain incidents. We aimed to evaluate the extent of leftover opioid analgesics following pediatric ambulatory surgeries in the context of a state-mandated restrictive opioid-prescribing policy. We also aimed to evaluate opioid disposal rates, methods of disposal, and reasons for nondisposal. METHODS: Study personnel contacted the parents of 300 pediatric patients discharged with an opioid prescription following pediatric ambulatory surgery. Parents completed a retrospective telephone survey regarding opioid use and disposal. Data from the survey were combined with data from the medical record to evaluate proportion of opioid doses prescribed that were left over. RESULTS: The final analyzable sample of 185 patients (62% response rate) were prescribed a median of 12 opioid doses (interquartile range [IQR], 12-18), consumed 2 opioid doses (IQR, 0-4), and had 10 opioid doses left over (IQR, 7-13). Over 90% (n = 170 of 185) of parents reported they had leftover opioid analgesics, with 83% of prescribed doses left over. A significant proportion (29%, n = 54 of 185) of parents administered no prescribed opioids after surgery. Less than half (42%, n = 71 of 170) of parents disposed of the leftover opioid medication, most commonly by flushing down the toilet, pouring down the sink, or throwing in the garbage. Parents retaining leftover opioids (53%, n = 90 of 170) were most likely to keep them in an unlocked location (68%, n = 61 of 90). Parents described forgetfulness and worry that their child will experience pain in the future as primary reasons for not disposing of the leftover opioid medication. CONCLUSIONS: Despite Tennessee's policy aimed at reducing leftover opioids, a significant proportion of prescribed opioids were left over following pediatric ambulatory surgeries. A majority of parents did not engage in safe opioid disposal practices. Given the safety risks related to leftover opioids in the home, further interventions to improve disposal rates and tailor opioid prescribing are warranted after pediatric surgery.

[Value of heart rate-blood pressure product of multiplication for identifying compensated shock in children].

Objective: To estimate the predictive value of heart rate (HR)-blood pressure (BP) products of multiplication for compensated shock in children. Methods: The study population consisted of 99 children with shock who had lactate measured before receiving vasopressor agents in Department of Critical Care Medicine of Children's Hospital, Capital Institute of Pediatrics from October 2015 to March 2021. The clinical data including the HR, BP, HR to BP ratio, HR-BP product and lactate at admission and after the correction of shock, as well as the 28-day mortality were collected. According to the outcome at the 28th day, the patients were divided into survival group and non-survival group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test. Pearson correlation analysis was used to analyze the correlations between lactate and HR, BP, HR to BP ratio and HR-BP product, respectively. Receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive values of HR, BP, HR to BP ratio and HR-BP product for lactate greater than 2 mmol/L. Results: In these 99 children, 49 were males, and the median age was 3.8 (0.7-6.0) years. The most common type of shock was septic shock (61 cases, 62%), followed by cardiogenic shock (12 cases, 12%), hemorrhagic shock (12 cases, 12%), Kawasaki disease shock syndrome (8 cases, 8%) and anaphylactic shock (6 cases, 6%). Sixty-six patients (67%) survived, and 33 patients (33%) died. ROC curve showed that the area under curves (AUC) of lactate (optimal cutoff value 3.15 mmol/L, sensitivity 96.0%, specificity 54.4%, P<0.01) and HR to systolic blood pressure ratio (HR/SBP) (optimal cutoff value 2.0 times/(min·mmHg), sensitivity 62.5%, specificity 69.0%, P = 0.03) for predicting adverse outcome were 0.769 and 0.649, respectively. There were significant correlations between lactate and HR to diastolic blood pressure (DBP) ratio, HR to mean blood pressure (MBP) ratio, SBP, HR/SBP, MBP, DBP and HR (r= 0.476, 0.452, -0.444, 0.425,-0.410, -0.364, 0.177, all P<0.01), while no significant correlation was found between lactate and the products of HR and BP(all P>0.05). HR/SBP performed better than the other six parameters for predicting lactate>2 mmol/L, with the AUC of 0.872 and the optimal cutoff value of 1.4 bpm/mmHg (sensitivity 92.1%, specificity 70.9%, P<0.01). When MBP was greater than or equal to 65 mmHg, MBP × HR, DBP × HR, SBP × HR, HR, HR/SBP, HR/MBP and HR/DBP were significantly correlated with lactate (r= 0.706, 0.705, 0.669, 0.626, 0.555, 0.502, 0.446, all P<0.01). And MBP × HR performed better for predicting lactate>2 mmol/L than the other six parameters, with the AUC of 0.974 and the optimal cutoff value of 9446 bpm × mmHg (sensitivity 100.0%, specificity 90.9%, P<0.01). Conclusions: The product of HR and BP, especially the MBP × HR, shows higher predictive values for abnormally elevated lactate in children with compensated shock than the HR/SBP does. It is worth recommending for early identification of compensated shock in children.

[Clinical characteristics of children infected with different subtypes/genotypes of human respiratory syncytial virus in Beijing from 2009 to 2017].

Objective: To explore the different clinical characteristics of children infected with different subtype/genotype of human respiratory syncytial virus (HRSV) in Beijing. Methods: Respiratory specimens for positive HRSV were randomly collected from children with acute respiratory tract infection (ARTI) in the epidemic season of HRSV from November of each year to January of the next year during 2009 and 2017. G genes of HRSV were amplified and sequenced for subtyping and genotyping by bioinformatics analysis. Clinical data were collected and analyzed. Results: Out of 590 children, 376 (63.7%) with subtype A, and 214 (36.3) with subtype B. The annual dominant subtypes of HRSV from 2009 to 2017 were B-A-A-B-AB-A-A-B-A, respectively, whilst a total of 10 genotypes were detected with 95.8% assigned to genotype ON1 and NA1 of subtype A, and genotype BA9 of subtype B. Children infected with subtype B (96 cases, 44.9%) were more likely aged 0-3 month old than those with subtype A (118 cases, 31.4%) (P=0.001), and more likely to be admitted to Intensive Care Unit(ICU) ((124 cases, 57.9%) than those with subtype A (172 cases, 45.7%)) (P=0.005). Statistical significance were shown among children infected with genotype ON1, NA1 or BA9, in the possibility of infection in children aged 0-3 month (P=0.003), proportion of admission into ICU (P=0.007), length of stay in hospital (P=0.001), and clinical outcome (P=0.001), respectively. Conclusion: Children infected with different subtype or genotype of HRSV have different clinical characteristics, which stresses the important role of the monitoring HRSV subtypes and genotypes among children.

Rapid and accurate diagnosis of brain abscess caused by Nocardia asiatica with a combination of Ziehl-Neelsen staining and metagenomics next-generation sequencing.

BACKGROUND AND PURPOSE: Early and accurate diagnosis is vital in cerebral nocardiosis, a very rare and infectious disease associated with a high mortality rate. Herein, we report a case that a patient with brain abscess was swiftly diagnosed and successfully treated. METHODS: We report a case of a 61-year-old woman with a brain abscess caused by Nocardia asiatica, diagnosed by a combination of Ziehl-Neelsen staining and metagenomics next-generation sequencing (mNGS). RESULTS: A 61-year-old woman with left breast cancer resection, diabetes mellitus and a 7-month discontinuous cough and fever was admitted to our hospital. On the third day of hospitalization, she experienced a sudden loss of consciousness and was diagnosed with a brain abscess and a pathological change in cerebral mass on brain magnetic resonance imaging (MRI). Due to the failure of culturing any microorganisms from the pup, the dissected sample from the patient with Ziehl-Neelsen staining tested positive for acid-fast bacilli and was subjected to mNGS. The pathogen was identified as N. asiatica and the patient was treated accordingly with linezolid and trimethoprim-sulfamethoxazole until complete recovery was confirmed by the follow-up cerebral MRI. CONCLUSIONS: This is the first case report of a brain abscess caused by N. asiatica being swiftly diagnosed by a combination of Ziehl-Neelsen staining and mNGS. This rapid diagnosis allowed us to successfully treat this rare infection.

"My Body Hates Me": A Qualitative Analysis of the Experience of Functional Nausea in Adolescent Girls and Their Mothers.

Nausea is a somatic sensation typically associated with the need to vomit in order to remove a toxin from the body. When nausea occurs in the absence of a specific structural cause or toxin, it is classified as a functional gastrointestinal disorder (FGID). Functional nausea was newly recognized in 2016 as a FGID in children and little is known about its prevalence, course or patient experiences. Nausea co-occurring with functional abdominal pain in childhood has been associated with long-term risk for anxiety and ongoing somatic symptoms into young adulthood. However, few studies have focused uniquely on the experience and impact of nausea on youth. The present study aimed to qualitatively understand the experiences of adolescent girls with functional nausea and their parents. Five mother-daughter dyads were recruited from a specialized pediatric gastroenterology clinic focused on nausea and completed semi-structured interviews. Interviews were transcribed and coded using interpretive phenomenological analysis (IPA). Four main themes emerged: nausea interference, body frustration, misunderstanding of symptoms, and maternal helplessness and guilt. These themes were similar to prior studies on the experiences of youth with chronic pain but also indicated unique challenges due to nausea, such as significant food restriction and subsequent weight loss.

Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial.

Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). Before and after the intervention, participants underwent separate laboratory sessions to assess responses to evoked heat pain after receiving saline placebo or intravenous naloxone (opioid antagonist) in a double-blinded, crossover fashion. Chronic pain intensity and interference were assessed before and after the intervention. Endogenous opioid analgesia was indexed by naloxone-placebo condition differences in evoked pain responses (blockade effects). Relative to controls, exercise participants reported significantly greater pre-post intervention decreases in chronic pain intensity and interference (Ps < 0.04) and larger reductions in placebo condition evoked pain responsiveness (McGill Pain Questionnaire-Short Form [MPQ]-Total). At the group level, EO analgesia (MPQ-Total blockade effects) increased significantly pre-post intervention only among female exercisers (P = 0.03). Dose-response effects were suggested by a significant positive association in the exercise group between exercise intensity (based on meeting heart rate targets) and EO increases (MPQ-Present Pain Intensity; P = 0.04). Enhanced EO analgesia (MPQ-Total) was associated with a significantly greater improvement in average chronic pain intensity (P = 0.009). Aerobic exercise training in the absence of other interventions appears effective for CLBP management. Aerobic exercise-related enhancements in endogenous pain inhibition, in part EO-related, likely contribute to these benefits.

[Chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy].

Objective: To investigate chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy. Methods: A total of 831 tissue samples of spontaneous abortion in early pregnancy were collected from June 2015 to August 2018 in the First Affiliated Hospital of Nanjing Medical University. Chromosomal copy number was analyzed by next generation sequencing (NGS). The relationships between chromosome abnormality and maternal age, in vitro fertilization-embryo transfer (IVF-ET) pregnancy, number of previous spontaneous abortions, history of live birth were analyzed by statistical methods. Results: Among 831 tissue samples of spontaneous abortion in early pregnancy, 461 (55.5%, 461/831) were found to have chromosome abnormalities. Maternal age (OR=1.107, 95%CI: 1.070- 1.145) and history of live birth (OR=1.909, 95%CI: 1.182-3.083) were the positive correlative factors of chromosome abnormality. Times of previous spontaneous abortion (OR=0.807, 95%CI: 0.702-0.928) and IVF-ET pregnancy (OR=0.554, 95%CI: 0.404-0.760) were the negative correlative factors of chromosome abnormality. Conclusions: Chromosome abnormality is an important cause of spontaneous abortion in early pregnancy. The rate of chromosome abnormality increases with the increase of maternal age and the history of live birth, and decreases with the increase of number of previous spontaneous abortion and IVF-ET pregnancy.

Absence of Evidence of Electrical Switching of the Antiferromagnetic Néel Vector.

Much theoretical and experimental attention has been focused on the electrical switching of the antiferromagnetic (AFM) Néel vector via spin-orbit torque. Measurements employing multiterminal patterned structures of Pt/AFM show recurring signals of the supposedly planar Hall effect and magnetoresistance, implying AFM switching. We show in this Letter that similar signals have been observed in structures with and without the AFM layer, and of an even larger magnitude using different metals and substrates. These may not be the conclusive evidence of spin-orbit torque switching of AFM, but the thermal artifacts of patterned metal structure on substrate. Large current densities in the metallic devices, beyond the Ohmic regime, can generate unintended anisotropic thermal gradients and voltages. AFM switching requires unequivocal detection of the AFM Néel vector before and after SOT switching.

MiR-32-5p regulates the proliferation and metastasis of cervical cancer cells by targeting HOXB8.

OBJECTIVE: To investigate the effects of miR-32-5p on the biological behaviors of cervical cancer (CCa), the relevant mechanism was studied in CCa cell lines (HeLa) in vitro. PATIENTS AND METHODS: The expression level of miR-32-5p was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TargetScan, miRDB, microRNA databases and Luciferase method were conducted to predict and validate the target gene of miR-32-5p; the effects of miR-32-5p on cell proliferation, clone formation, invasion and migration capacity were analyzed in vitro study. RESULTS: We found miR-32-5p to be significantly inhibited in CCa tissues and cells. Bioinformatics approach together with Luciferase method screened Homeobox B8 (HOXB8) as a downstream regulatory target of miR-32-5p. Besides, HOXB8 was incredibly high expression in CCa tissues and cells. After transfection in HeLa cells by miR-32-5p mimics, HOXB8 expression was indicated to be negatively correlated with miR-32-5p both in qRT-PCR and Western blot (WB) assays. The subsequent experiments showed that decreased expression of HOXB8 resulting from up-regulation of miR-32-5p could weaken the cell proliferation, clone formation, invasion and migration ability of HeLa cells. CONCLUSIONS: MiR-32-5p could inhibit the cellular malignant behavior through regulating the expression of HOXB8 in HeLa cells. We provide a new clue for the study of molecular mechanisms of CCa. MiR-32-5p/HOXB8 axis might serve as potential target for the clinical diagnosis and treatment of CCa.

Competitive interaction on dual-species biofilm formation by spoilage bacteria, Shewanella baltica and Pseudomonas fluorescens.

AIMS: This study aims to characterize the biofilm produced by mono- and dual-species of Shewanella baltica and Pseudomonas fluorescens as fish spoilers at the different incubation temperature, and to elucidate the interactive behaviour of dual-species biofilm development. METHODS AND RESULTS: The mono- and dual-species biofilm formation and adhesion characteristics of S. baltica and P. fluorescens were evaluated by using crystal violet staining, scanning electron microscopy and confocal laser scanning microscopy. Results showed that P. fluorescens had significantly higher biofilm biomass and polysaccharides production than S. baltica, and two isolates reached the maximum biofilm biomass during the early stationary phase. Lower biomass and polysaccharides in dual-species biofilms were observed compared to mono-species of P. fluorescens. Meanwhile, S. baltica and P. fluorescens formed fragile and viscous pellicles with different spatial architectures respectively. In dual-species pellicle few large microcolonies were dominated by P. fluorescens. Compared to mono-species of PF07, adherent cell population and biofilm thickness at the developing phase significantly decreased, and biofilm-forming cycle prolonged in the dual-species biofilms. Biofilm formation and adhesion of mono- and dual-species at 4 or 15°C were significantly higher than at 30°C during the same phase. The culture supernatant extracts of the two spoilage strains greatly inhibited biofilm development to each other. CONCLUSIONS: Shewanella baltica and P. fluorescens had different biofilm and pellicle characteristics, and the inhibitory development on dual-species biofilm was associated with the competitive interaction by the two psychrotrophic spoilage bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to a better understanding of interactive behaviour of multispecies biofilm communities by psychrotrophic spoilage bacteria at low temperature, which could contribute to further control contamination of spoilage organism during the preservation and processing of aquatic products.