Total Flavonoids of Aurantii Fructus Immaturus Regulate miR-5100 to Improve Constipation by Targeting Fzd2 to Alleviate Calcium Balance and Autophagy in Interstitial Cells of Cajal.

Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network.

Pedagogical practices and civic knowledge and engagement in Latin America: Multilevel analysis using ICCS data.

This study explored the relationship between pedagogical practices and the civic knowledge and engagement of students from five Latin American and Caribbean countries, using a multilevel analysis of the 2016 International Civic and Citizenship Education Study (ICCS). The results reveal the complex interplay of educational, sociodemographic, and attitudinal factors in shaping the civic knowledge and engagement of students. Extracurricular civic engagement showed a negative correlation with student civic knowledge and engagement as measured by the ICCS cognitive test. However, civic learning in school positively related to cognitive abilities, emphasizing the importance of integrating civic learning into the curriculum. Interestingly, students' educational aspirations emerged as a significant factor shaping their civic engagement, suggesting a strategy to foster high educational aspirations to enhance cognitive performance. Additionally, gender dynamics were evident in civic education, with girls consistently outperforming boys in all participating countries. The correlation between home literacy resources and test scores illuminated the significant role of home environments in academic achievement. Lastly, students' attitudes towards political participation had a notable connection to civic knowledge outcomes, presenting an exciting avenue for future research. Collectively, these findings underscore the need for a comprehensive approach to civic education and further research to refine effective strategies.

Diagnostic challenges of hypoganglionosis based on immunohistochemical method.

Background: Hypoganglionosis resembles Hirschsprung's disease as in both diseases, patients may present with severe constipation or pseudo-obstruction. To date, diagnosis of hypoganglionosis is still difficult to be established due to lack of international consensus regarding diagnostic criteria. This study aims to evaluate the use of immunohistochemistry to provide objective support for our initial subjective impression of hypoganglionosis as well as to describe the morphological features of this study. Methods: This is a cross-sectional study. Three resected intestinal samples from patients with hypoganglionosis at Kyushu University Hospital, Fukuoka, Japan were included in this study. One healthy intestinal sample was used as control. All specimens were immunohistochemically stained with anti-S-100 protein, anti-α-smooth muscle actin (α-SMA), and anti-c-kit protein antibodies. Results: (I) S-100 immunostaining: hypoplasia of the myenteric ganglia and marked reduction of intramuscular nerve fibers were observed in several segments of the intestine. (II) α-SMA immunostaining: the pattern of the muscular layers was almost normal in all segments; however, some areas showed hypotrophy of the circular muscle (CM) layers and hypertrophy of the longitudinal muscle (LM) layers. (III) C-kit immunostaining: a decreased in the number of interstitial cells of Cajal (ICCs) was observed in almost all segments of the resected intestine, even around the myenteric plexus. Conclusions: Each segment of intestine in hypoganglionosis had different numbers of ICCs, sizes, and distributions of ganglions, as well as patterns of musculature, which may range from severely abnormal to nearly normal. Further investigations regarding the definition, etiology, diagnosis, and treatment of this disease should be performed to improve the prognosis of this disease.

Laxative effect of Wenyang Yiqi Decoction on loperamide-induced astriction model mice.

Background: Although a common disease, astriction is difficult to treat and severely affects quality of life. Wenyang Yiqi Decoction (WYD) is a kind of traditional Chinese medicine (TCM) that is used to treat astriction; however, the mechanism remains unclear. Therefore, this work assessed the laxative effect of WYD on loperamide-induced astriction (LIA) model mice. Methods: We replicated a constipation model in mice and detected changes in fecal parameters such as feces quantity and water content, intestinal transit function, and histopathological changes in the constipated mice. After five days of WYD intervention, mouse tissues were taken out for detection. We also measured the levels of gastrin (Gas), substance P (SP), acetylcholinesterase (AChE), and vasoactive intestinal peptide (VIP) in the mice's serum. Additionally, we used quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to detect c-Kit and stem cell factor (SCF), and examined the effects of WYD on the tight junction (TJ) proteins occludin (Ocln), zonula occludens-1 (ZO-1), and claudin-1 (Cldn-1) in the mice's intestines. Results: Through histopathological changes, we observed less destruction of epithelial cells and greater integrity of goblet and epithelial cells in WYD-treated mice than in mice in the loperamide group. qRT-PCR and western blot analysis of c-Kit and SCF showed that WYD could boost the levels of c-Kit and SCF. The qRT-PCR and immunohistochemical (IHC) analyses of enteral tight occludin (Ocln), occludenas-1 (ZO-1), and cldin-1 (Cldn-1) showed that WYD could boost the level of ZO-1 and decrease the level of Cldn-1. The study also investigated the effect of WYD treatment on the enteral barrier function of astriction model mice and found that the TJ proteins (ZO-1, Cldn-1) in the colon of the astriction model mice had significant changes compared to the normal group, and WYD intervention was found to increase the expression of ZO-1, and decrease the expression of Cldn-1. Conclusions: WYD alleviates LIA by regulating enteral hormones, boosting the number of interstitial cells of Cajal (ICCs), or adjusting enteral block action.

Can Ingoing Contact Chains and other cattle movement network metrics help predict herd-level bovine tuberculosis in Irish cattle herds?

We used logistic regression to investigate whether the risk of an Irish cattle herd undergoing a bovine tuberculosis (bTB) breakdown increased with the size of the Ingoing Contact Chain (ICC) of previous herd to herd cattle movements, in a sequence up to eight moves back from the most recent, direct, movement into the herd. We further examined whether taking into account the bTB test history of each herd in the chain would improve model fit. We found that measures of cattle movements directly into the herd were risk factors for subsequent bTB restrictions, and the number of herds that animals were coming from was the most important of these. However, in contrast to a previous study in Great Britain, the ICC herd count at steps more remote than direct movements into the herd did not result in better fitting models than restricting the count to direct movements. Restricting the ICC counts to herds which had previously or would in the future test positive for bTB resulted in improved model fits, but this was not the case if only the previous test status was considered. This suggests that in many cases bTB infected animals are moving out of herds before being identified through testing, and that risk-based trading approaches should not rely solely on the previous test history of source herds as a proxy for future risk. Model fit was also improved by the inclusion of variables measuring bTB history of the herd, bTB in neighbouring herds, herd size, herd type, the movement network measures "in strength" and "betweenness", altitude, modelled badger abundance and county. Rainfall was not a good predictor. The most influential measures of bTB in nearby herds (a proxy for neighbourhood infection) were the proportion of herds with a history of bTB whose centroids were within 6 km, or whose boundaries were within 4 km, of the index herd. As well as informing national control and surveillance measures, our models can be used to identify areas where bTB rates are anomalously high, to prompt further investigation in these areas.

Detecting Illegal Intercountry Trade of Mercury Using Discrepancies in Mirrored Trade Data.

The ongoing international movement to phase out mercury, mainly led by the Minamata Convention on Mercury, raises concerns about illegal intercountry trade, including smuggling. This study aims to detect the existence of illegal intercountry mercury trade under the social mercury phase-out movement, focusing on discrepancies in each country's trade statistics. To analyze the trends by year and country for discrepancies in intercountry mercury trade, an intraclass correlation coefficient (ICC) was applied to the mirrored exports and imports from trade statistics of each country provided by the UN Comtrade. The year-based ICC analysis identified a tendency to reduce the detection of discrepancies in the reported mirrored exports and imports for mercury at the intercountry level under the recent mercury phase-out movement. Through an ICC analysis focusing on exporting and importing countries, the validity of the ICC analysis was verified as a way to detect illegal intercountry trade of mercury. Our analyses detecting the illegal trade of related countries contribute to the effectiveness evaluation and custom capacity building required in the Minamata Convention by offering a data-driven method to enable the effective detection of illegal mercury trade.

METTL3 contributes to slow transit constipation by regulating miR-30b-5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase-like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC). MATERIAL AND METHOD: The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid-induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR-30b-5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss-of-function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR-30b-5p with PIK3R2. RESULTS: The results showed that the METTL3, DGCR8, miR-30b-5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid-induced ICCs. Silencing of METTL3 and miR-30b-5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid-induced ICCs. Moreover, overexpression of miR-30b-5p reversed the cytoprotection of METTL3 knockdown in glutamic acid-induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid-induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid-induced ICCs significantly accelerated the maturation of pri-miR-30b-5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC. CONCLUSIONS: Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid-induced ICCs by interacting with the DGCR8 and successively modulating the miR-30b-5p/PIK3R2 axis in an m6A-dependent manner, and METTL3 may be a potential therapeutic target for STC.

A 15-year retrospective review of urodynamic studies in children at Red Cross War Memorial Children's Hospital, Cape town, South Africa.

BACKGROUND: Despite the undeniable diagnostic benefits of urodynamic studies (UDS), their adoption into clinical practice in Africa has been slow. This study aimed to review the use of invasive UDS in children at a tertiary paediatric hospital in South Africa. METHODS: A retrospective analysis of 1108 UDS was conducted. Patient demographic characteristics, primary diagnosis, indication and urodynamic outcomes were reviewed. Presence of urodynamic high-risk features were documented, and a comparison was made between the first study and follow-up study. RESULTS: This study revealed increasing trends in the use of UDS from 2015. Referrals were from Urology (37.7%), Spinal defects clinic (34.4%), Nephrology (20.8%) and other departments (7.0%). The most common reason for referral was review of medical treatment (36.5%). Spinal dysraphism (58.3%) accounted for the majority of conditions seen. Majority (59.1%) of the patients were receiving more than one type of bladder treatment at the time of their first study, with clean intermittent catheterisation (46.5%) being the most common form of bladder management. 97.5% of studies were performed using transurethral bladder catheterization. Urodynamic diagnosis was neurogenic in 74.0%, anatomical (12.2%), functional (8.8%) and normal (5.0%). There was statistically significant improvement in bladder compliance, detrusor leak point pressure and detrusor sphincter dyssynergia between the first study and a subsequent study following therapeutic intervention. CONCLUSIONS: The unique ability of UDS to demonstrate changes in detrusor pressures, which is a common reason for therapy failure, makes UDS an invaluable tool in the diagnosis and management of children with lower urinary tract dysfunction.

Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice.

Systemic delivery of adeno-associated virus (AAV) vectors transduces the enteric nervous system. However, less is known on the mapping and morphological and neurochemical characterization in the adult mouse colon. We used AAV9-CAG-GFP (AAV9) and AAV-PHP.S-hSyn1-tdTomato farnesylated (PHP.S-tdTf) to investigate the segmental distribution, morphologies and neurochemical coding of the transduction. The vectors were retro-orbitally injected in male and female adult mice, and 3 weeks later, the colon was prepared for microcopy with or without immunohistochemistry for neuronal and non-neuronal markers. In contrast to the distributions in neonatal and juvenile rodents, the AAV transduction in neurons and/or nerve fibers was the highest in the proximal colon, decreased gradually in the transverse, and was sparse in the distal colon without difference between sexes. In the proximal colon, the AAV9-transduced myenteric neurons were unevenly distributed. The majority of enteric neurons did not have AAV9 expression in their processes, except those with big soma with or without variously shaped dendrites, and a long axon. Immunolabeling demonstrated that about 31% neurons were transduced by AAV9, and the transduction was in 50, 28, and 31% of cholinergic, nitrergic, and calbindin-positive myenteric neurons, respectively. The nerve fiber markers, calcitonin gene-related peptide alpha, tyrosine hydroxylase or vasoactive intestinal polypeptide co-localized with AAV9 or PHP.S-tdTf in the mucosa, and rarely in the myenteric plexus. Unexpectedly, AAV9 expression appeared also in a few c-Kit immunoreactive cells among the heavily populated interstitial cells of Cajal (ICC). In the distal colon, the AAV transduction appeared in a few nerve fibers mostly the interganglionic strands. Other types of AAV9 and AAV-PHP vectors induced a similar colonic segmental difference which is not colon specific since neurons were transduced in the small intestine and gastric antrum, while little in the gastric corpus and none in the lower esophagus. Conclusion: These findings demonstrate that in adult mice colon that there is a rostro-caudal decrease in the transduction of systemic delivery of AAV9 and its variants independent of sex. The characterization of AAV transduction in the proximal colon in cholinergic and nitrergic myenteric neurons along with a few ICC suggests implications in circuitries regulating motility.

Validity and reliability of the movement assessment battery second edition test in children with and without motor impairment: A prospective cohort study.

Background: Examining the reliability and validity of the second edition movement assessment battery test (MABC-2) in children with and without motor impairment. Materials and methods: In this prospective cohort study, the MABC-2 test and developmental coordination disorder questionnaire 2007 (DCDQ'07) were completed by children and their parents. By using 95% confidence intervals, minimal detectable change (MDC95) was calculated, and concurrent validity was investigated. By applying the MABC-2 test as a reference standard (cut-off fifth centile), sensitivity and specificity were examined. Results: 273 children (mean age: 6.3 ± 2.3 years; 70% male) with and without motor impairment completed the investigation. For test-retest reliability, intra-class correlation coefficients (ICCs) was >0.89 for the MABC-2 test. The MDC95 value for the motor skill test was 5.76. There was a significant correlation between the MABC-2 test and DCDQ'07 (r = 0.60, P < 0.001) and the Go/No-Go test (r = 0.50, P < 0.001). Overall, the sensitivity was very high (90%), the specificity was low (46%), and positive and negative predictive values were high (69% and 81%, respectively). Conclusion: The MABC-2 test can be considered a valid and reliable motor skill assessment tool for children with and without motor impairment.

Frequencies of glycosylphosphatidylinositol (GPI)-deficient cells using high-sensitivity flow cytometry as per the 2018 ICCS/ESCCA consensus guideline in patients with hematologic malignancy, aplastic anemia, or cytopenia.

OBJECTIVES: We examined the frequencies and sizes of glycosylphosphatidylinositol (GPI)-deficient cells as per the International Clinical Cytometry Society/European Society for Clinical Cell Analysis (ICCS/ESCCA) consensus guidelines for the high-sensitivity detection of GPI-deficient cells. METHODS: In 2018, the ICCS/ESCCA guidelines for the high-sensitivity detection of GPI-deficient cells were published. We evaluated frequencies and sizes of GPI-deficient red blood cells (RBCs), neutrophils, and monocytes as determined using the ICCS/ESCCA guidelines and Clinical and Laboratory Standards Institute (CLSI) guidelines in patients with a hematologic malignancy, aplastic anemia, or cytopenia. RESULTS: A total of 106 (38.7%) patients exhibited GPI deficiency in at least one blood cell lineage. GPI-deficient cells of one or more lineages were found in 62.7% of patients with a hematologic malignancy, 51.1% of patients with aplastic anemia, and 23.4% of patients with cytopenia. GPI-deficient monocytes were most frequently detected in all three groups. By population size, GPI-deficient clones (>1%) in monocytes were mostly detected in patients with a hematologic malignancy or aplastic anemia. Rare cells with GPI deficiency (<0.1%) in monocytes were most common among patients with cytopenia. CONCLUSION: High-sensitive flow cytometry analysis including monocytes may be necessary for patients with a hematologic disorder.

Adolescents' Political Socialization at School, Citizenship Self-efficacy, and Expected Electoral Participation.

Adolescents' political socialization is crucial for their future political participation. Little research has examined this relationship and the importance of citizenship self-efficacy in an Asian context. This study focused on the effectiveness of Korean adolescents' political socialization and self-efficacy on their expected electoral participation. Data from Korean 8th graders participating in the 2016 International Civic and Citizenship Education Study were examined (N = 2601; Mage = 14.02; 46% female). Political socialization included open classroom discussion, active learning strategies, and formal citizenship education. The result showed that citizenship self-efficacy is the most important predictor for Korean adolescents' future engagement, but open classroom discussion is not significant. It indicates that citizenship education needs to consider countries' social and cultural contexts.

Colonic Motility Is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice.

BACKGROUND & AIMS: Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. METHODS: We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT2B receptor (HTR2B) antagonist or agonist. RESULTS: Colonic transit was delayed in males with diabetes, although colonic Tph1+ cell density and 5-HT levels were increased. Colonic transit was not further reduced in diabetic mice by EC cell depletion. The HTR2B protein, predominantly expressed by colonic ICCs, was markedly decreased in the colonic muscles of males and ovariectomized females with diabetes. Ca2+ activity in colonic ICCs was decreased in diabetic males. Treatment with an HTR2B antagonist impaired CMMCs and colonic motility in healthy males, whereas treatment with an HTR2B agonist improved CMMCs and colonic motility in males with diabetes. Colonic transit in ovariectomized females with diabetes was also improved significantly by the HTR2B agonist treatment. CONCLUSIONS: Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.

Measuring Nanoscale Distances by Structured Illumination Microscopy and Image Cross-Correlation Spectroscopy (SIM-ICCS).

Since the introduction of super-resolution microscopy, there has been growing interest in quantifying the nanoscale spatial distributions of fluorescent probes to better understand cellular processes and their interactions. One way to check if distributions are correlated or not is to perform colocalization analysis of multi-color acquisitions. Among all the possible methods available to study and quantify the colocalization between multicolor images, there is image cross-correlation spectroscopy (ICCS). The main advantage of ICCS, in comparison with other co-localization techniques, is that it does not require pre-segmentation of the sample into single objects. Here we show that the combination of structured illumination microscopy (SIM) with ICCS (SIM-ICCS) is a simple approach to quantify colocalization and measure nanoscale distances from multi-color SIM images. We validate the SIM-ICCS analysis on SIM images of optical nanorulers, DNA-origami-based model samples containing fluorophores of different colors at a distance of 80 nm. The SIM-ICCS analysis is compared with an object-based analysis performed on the same samples. Finally, we show that SIM-ICCS can be used to quantify the nanoscale spatial distribution of functional nuclear sites in fixed cells.

Electroacupuncture accelerates the delayed intestinal transit in POI by suppressing M1 like muscularis macrophages and IL6 secretion.

BACKGROUND: Electroacupuncture (EA) at ST-36 could accelerate the delayed gastrointestinal (GI) motility in many GI motility dysfunction models, but the definite effect and mechanisms are unclear. In this study, we intended to investigate the effects of EA on intestinal manipulation (IM) mice model and involved mechanisms. METHODS: Male C57BL/6 mice were randomized into five groups: normal control, intestinal manipulation (IM), IM with sham EA (SEA), IM with high-frequency EA (HEA), and IM with low-frequency EA (LEA). The GI transit was evaluated. The infiltration of muscularis macrophages (MMφ) and its phenotype were analyzed with flow cytometry. Magnetic-activated cell sorting was applied to isolate MMφ, and the relationship between the MMφ and interstitial cells of Cajal (ICCs) was further investigated. RESULTS: (1) Compared with the IM group, HEA and LEA attenuated the delayed intestinal transit. (2) Both the HEA and LEA obviously reduced the MMφ and suppressed the M1 activation of the MMφ in the ileum. (3) EA restored the disrupted ICC networks through inhibiting the release of IL6 by the MMφ. CONCLUSION: (1) Electroacupuncture at acupoint ST-36 could accelerate the delayed intestinal transit in the IM murine model by restoring the ICC networks. (2) EA protected the ICCs through reducing the MMφ, inhibiting its M1 polarization and its IL6 secretion.

Examining measurement equivalency within the Latin American module of the International Civic Competence Study 2009.

The International Civic and Citizenship Education Study (ICCS) studies are intercontinental studies on the civic education of youth from Asia, Europe, and Latin America. Before we engage in comparative studies on youth from different world regions, we must first establish the equivalency of the scales and items within the databases. The purpose of this study was to examine the level of differential functioning on the Attitudes Towards Neighborhood Diversity 10-item scale in the Latin American module within the ICCS 2009 database for youth from Colombia, Guatemala, and Chile. We first examined the unidimensionality of the scale within each country by assessing configural invariance. Of countries that demonstrated at least adequate fit for configural invariance, we proceeded to examine differential functioning at the item and scale levels. Findings demonstrated that configural invariance held for Chile and Guatemala only. While differential functioning was present on nine of the 10 items between Chile and Guatemala, in all cases the amounts were negligible. There was no differential functioning on the overall scale. Whilst equivalency holds for certain countries on certain scales, in other cases it did not. Thus scholars may consider scale refinement methods before making comparative analyses.

[Elimination disorders - ICD-11 classification and definitions]. / Ausscheidungsstörungen ­ Klassifikation und Definition nach ICD-11.

Elimination disorders - ICD-11 classification and definitions Abstract. Elimination disorders are common in children and are can be divided into three main groups: nocturnal enuresis, daytime urinary incontinence, and encopresis or fecal incontinence. There are also many subgroups that can be diagnosed exactly. This review critically presents the definitions and the classification suggestions of the ICD-11. It compares the definitions of enuresis according to ICD-11 with those of nocturnal enuresis and daytime urinary incontinence of the ICCS. It also contrasts encopresis according to ICD-11 with functional constipation and nonretentive fecal incontinence by the Rome-IV criteria. It becomes apparent that the ICD-11 does not reflect current research findings; that it does not render specific diagnoses, which are prerequisites for effective treatment; and that it is not exact enough for research. In conclusion, the ICCS and Rome-IV definitions are the preferred classification systems in clinical practice and research.

Mapping community, social, and economic risks to investigate the association with school violence and bullying in Italy.

BACKGROUND: School violence and bullying are a pandemic issue. The academic literature underlined the need to investigate social-contextual risk factors. The United Nations called for more comprehensive and disaggregated data to inform prevention strategies. OBJECTIVE: The present study comprises a set of secondary analyses on Italian data from the International Civic and Citizenship Study 2016. We adopted an innovative 'bottom-up' approach to identify the level of disaggregation for national data. The researchers focused on community, social, and economic risk indicators at school-level, and investigated whether it was possible to aggregate schools in different classes, depending on their risk profile. PARTICIPANTS AND SETTINGS: Analyses were implemented on a nationally representative sample of 170 Principals of lower secondary schools, 2,527 teachers and 3,766 students at grade 8. METHODS AND ANALYSES: A Latent Class Analyses was conducted on risk indicators and four classes of risk were identified: No Risk, Community Risk, Socio-economic Risk, Multi-Risk (entropy = .786). No significant differences were found across classes in relation to urban/rural location, school size, and geographical macro-partition. On the contrary, significant differences emerged when considering teachers' perception of bullying, social problem, and students' behavior at school. Furthermore significant differences were found for the quality of relationship with teachers as reported by students. CONCLUSIONS: Results a) suggested a potential gradient of increasing risk moving across the classes; b) provided a contribution to address the gap in the investigation of contextual factors and bullying; c) offered a new lens to tailor interventions to prevent school violence and bullying.

Metastasis-associated protein 1 (MTA1) regulates the catecholamine production homeostasis via transcriptional repression of aromatic l-amino acid decarboxylase (Aadc) in the interstitial cells of Cajal of mouse prostate.

Based on the lately identified role for the interstitial cells of Cajal (ICCs) of mouse prostate in catecholamine production, as well as the well-established role for the master coregulator metastasis-associated protein 1 (MTA1) in inflammation, we probed into the functional link between aberrant MTA1 expression and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using both a MTA1-/- mouse model of experimental autoimmune prostatitis (EAP) and an in vitro chronic prostatitis model in cultured murine ICCs. EAP-induced MTA1 expression was enriched in ICCs of mouse prostate. EAP resulted in a higher increase in the pelvic pain response in MTA1-/- mice compared to WT mice. Consistently, the ICCs from MTA1-/- mice produced higher levels of catecholamines upon induction of in vitro chronic prostatitis. Mechanistically, MTA1 could directly suppress the transcription of Aadc, a rate-limiting enzyme during catecholamine synthesis, in a HDAC2-depdendent manner. Importantly, treatment with AADC inhibitor NSD-1015 significantly ameliorated EAP-elicited pain response and catecholamine overactivity in MTA1-/- mice. Taken together, our findings reveal an inherent regulatory role of the MTA1/AADC pathway in the maintenance of catecholamine production homeostasis in prostate ICCs, and also point to a potential use of HDAC inhibitors and/or AADC inhibitors to treat CP/CPPS.