In vivo mapping of a GPCR interactome using knockin mice.

With over 30% of current medications targeting this family of proteins, G-protein-coupled receptors (GPCRs) remain invaluable therapeutic targets. However, due to their unique physicochemical properties, their low abundance, and the lack of highly specific antibodies, GPCRs are still challenging to study in vivo. To overcome these limitations, we combined here transgenic mouse models and proteomic analyses in order to resolve the interactome of the δ-opioid receptor (DOPr) in its native in vivo environment. Given its analgesic properties and milder undesired effects than most clinically prescribed opioids, DOPr is a promising alternative therapeutic target for chronic pain management. However, the molecular and cellular mechanisms regulating its signaling and trafficking remain poorly characterized. We thus performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses on brain homogenates of our newly generated knockin mouse expressing a FLAG-tagged version of DOPr and revealed several endogenous DOPr interactors involved in protein folding, trafficking, and signal transduction. The interactions with a few identified partners such as VPS41, ARF6, Rabaptin-5, and Rab10 were validated. We report an approach to characterize in vivo interacting proteins of GPCRs, the largest family of membrane receptors with crucial implications in virtually all physiological systems.

Modulation of the gait pattern during split-belt locomotion after lateral spinal cord hemisection in adult cats.

Most previous studies investigated the recovery of locomotion in animals and people with incomplete spinal cord injury (SCI) during relatively simple tasks (e.g., walking in a straight line on a horizontal surface or a treadmill). We know less about the recovery of locomotion after incomplete SCI in left-right asymmetric conditions, such as turning or stepping along circular trajectories. To investigate this, we collected kinematic and electromyography data during split-belt locomotion at different left-right speed differences before and after a right thoracic lateral spinal cord hemisection in nine adult cats. After hemisection, although cats still performed split-belt locomotion, we observed several changes in the gait pattern compared with the intact state at early (1-2 wk) and late (7-8 wk) time points. Cats with larger lesions showed new coordination patterns between the fore- and hindlimbs, with the forelimbs taking more steps. Despite this change in fore-hind coordination, cats maintained consistent phasing between the fore- and hindlimbs. Adjustments in cycle and phase (stance and swing) durations between the slow and fast sides allowed animals to maintain 1:1 left-right coordination. Periods of triple support involving the right (ipsilesional) hindlimb decreased in favor of quad support and triple support involving the other limbs. Step and stride lengths decreased with concurrent changes in the right fore- and hindlimbs, possibly to avoid interference. The above adjustments in the gait pattern allowed cats to retain the ability to locomote in asymmetric conditions after incomplete SCI. We discuss potential plastic neuromechanical mechanisms involved in locomotor recovery in these conditions.NEW & NOTEWORTHY Everyday locomotion often involves left-right asymmetries, when turning, walking along circular paths, stepping on uneven terrains, etc. To show how incomplete spinal cord injury affects locomotor control in asymmetric conditions, we collected data before and after a thoracic lateral spinal hemisection on a split-belt treadmill with one side stepping faster than the other. We show that adjustments in kinematics and muscle activity allowed cats to retain the ability to perform asymmetric locomotion after hemisection.

Regulation of impulsive and aggressive behaviours by a novel lncRNA.

High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications. Elevated MAALIN in the dentate gyrus of impulsive-aggressive suicides was associated with lower MAOA expression. Viral overexpression of MAALIN in neuroprogenitor cells decreased MAOA expression while CRISPR-mediated knock out resulted in elevated MAOA expression. Using viral-mediated gene transfer, we confirmed that MAALIN in the hippocampus significantly decreases MAOA expression and exacerbates the expression of impulsive-aggressive behavioural traits in CD1 aggressive mice. Overall, our findings suggest that variations in DNA methylation mediate the differential expression of a novel lncRNA that acts on MAOA expression to regulate impulsive-aggressive behaviours.

Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence.

Cellular senescence is accompanied by dramatic changes in chromatin structure and gene expression. Using Saccharomyces cerevisiae mutants lacking telomerase (tlc1Δ) to model senescence, we found that with critical telomere shortening, the telomere-binding protein Rap1 (repressor activator protein 1) relocalizes to the upstream promoter regions of hundreds of new target genes. The set of new Rap1 targets at senescence (NRTS) is preferentially activated at senescence, and experimental manipulations of Rap1 levels indicate that it contributes directly to NRTS activation. A notable subset of NRTS includes the core histone-encoding genes; we found that Rap1 contributes to their repression and that histone protein levels decline at senescence. Rap1 and histones also display a target site-specific antagonism that leads to diminished nucleosome occupancy at the promoters of up-regulated NRTS. This antagonism apparently impacts the rate of senescence because underexpression of Rap1 or overexpression of the core histones delays senescence. Rap1 relocalization is not a simple consequence of lost telomere-binding sites, but rather depends on the Mec1 checkpoint kinase. Rap1 relocalization is thus a novel mechanism connecting DNA damage responses (DDRs) at telomeres to global changes in chromatin and gene expression while driving the pace of senescence.

Alleviating pain with delta opioid receptor agonists: evidence from experimental models.

The use of opioids for the relief of pain and headache disorders has been studied for years. Nowadays, particularly because of its ability to produce analgesia in various pain models, delta opioid receptor (DOPr) emerges as a promising target for the development of new pain therapies. Indeed, their potential to avoid the unwanted effects commonly observed with clinically used opioids acting at the mu opioid receptor (MOPr) suggests that DOPr agonists could be a therapeutic option. In this review, we discuss the use of opioids in the management of pain in addition to describing the evidence of the analgesic potency of DOPr agonists in animal models.

Evaluation and ranking of different interventions for pain relief during outpatient hysteroscopy: A systematic review and network meta-analysis.

AIM: To identify the highest-ranked pharmacological and nonpharmacological interventions for pain relief during outpatient hysteroscopy. METHODS: We conducted an online bibliographic search in different databases from inception till July 2019. We included randomized controlled trials assessing effect of pharmacological and nonpharmacological interventions on pain relief during outpatient hysteroscopy. Our main outcomes were pain scores at different endpoints of the procedure. We applied this network meta-analysis based on the frequentist approach using statistical package 'netmeta' (version 1.0-1) in R. RESULTS: The review included 39 randomized controlled trials (Women n = 3964). Misoprostol plus intracervical block anesthesia (mean difference [MD] = -3.32, 95% confidence interval [CI] [-6.06, -0.59]), misoprostol (MD = -1.92, 95% CI [-3.04, -0.81]) and IV analgesia (MD = -2.01, 95% CI [-3.27, -0.25]) were effective in reducing pain during the procedure compared to placebo. Ranking probability showed that misoprostol plus intracervical block anesthesia was the highest ranked pharmacological treatment for pain relief during the procedure (P score = 0.92) followed by misoprostol alone (P score = 0.78), and IV analgesia (P score = 0.76). Regarding nonpharmacological treatments, transcutaneous electrical nerve stimulation (TENS) showed a significant pain reduction compared to placebo (MD = -1.80, 95% CI [-3.31, -0.29]). TENS ranked as the best nonpharmacological treatment (P score = 0.80) followed by CO2 distention (P score = 0.65) and bladder distention (P score = 0.60). CONCLUSION: Combination of misoprostol plus local anesthesia appears to be the most effective pharmacological approach for pain reduction during and after outpatient hysteroscopy. Nonpharmacological approaches as TENS and bladder distention showed considerable efficacy but should be further investigated.

Delta opioid receptors recycle to the membrane after sorting to the degradation path.

Soon after internalization delta opioid receptors (DOPrs) are committed to the degradation path by G protein-coupled receptor (GPCR)-associated binding protein. Here we provide evidence that this classical post-endocytic itinerary may be rectified by downstream sorting decisions which allow DOPrs to regain to the membrane after having reached late endosomes (LE). The LE sorting mechanism involved ESCRT accessory protein Alix and the TIP47/Rab9 retrieval complex which supported translocation of the receptor to the TGN, from where it subsequently regained the cell membrane. Preventing DOPrs from completing this itinerary precipitated acute analgesic tolerance to the agonist DPDPE, supporting the relevance of this recycling path in maintaining the analgesic response by this receptor. Taken together, these findings reveal a post-endocytic itinerary where GPCRs that have been sorted for degradation can still recycle to the membrane.

Dithallium(III)-Containing 30-Tungsto-4-phosphate, [Tl2Na2(H2O)2(P2W15O56)2]16-: Synthesis, Structural Characterization, and Biological Studies.

Here we report on the synthesis and structural characterization of the dithallium(III)-containing 30-tungsto -4-phosphate [Tl2Na2(H2O)2{P2W15O56}2]16- (1) by a multitude of solid-state and solution techniques. Polyanion 1 comprises two octahedrally coordinated Tl3+ ions sandwiched between two trilacunary {P2W15} Wells-Dawson fragments and represents only the second structurally characterized, discrete thallium-containing polyoxometalate to date. The two outer positions of the central rhombus are occupied by sodium ions. The title polyanion is solution-stable as shown by 31P and 203/205Tl NMR. This was also supported by Tl NMR spectra simulations including several spin systems of isotopologues with half-spin nuclei (203Tl, 205Tl, 31P, 183W). 23Na NMR showed a time-averaged signal of the Na+ counter cations and the structurally bonded Na+ ions. 203/205Tl NMR spectra also showed a minor signal tentatively attributed to the trithallium-containing derivative [Tl3Na(H2O)2(P2W15O56)2]14-, which could also be identified in the solid state by single-crystal X-ray diffraction. The bioactivity of polyanion 1 was also tested against bacteria and Leishmania.

The Delta Opioid Receptor in Pain Control.

Nowadays, the delta opioid receptor (DOPr) represents a promising target for the treatment of chronic pain and emotional disorders. Despite the fact that they produce limited antinociceptive effects in healthy animals and in most acute pain models, DOPr agonists have shown efficacy in various chronic pain models. In this chapter, we review the progresses that have been made over the last decades in understanding the role played by DOPr in the control of pain. More specifically, the distribution of DOPr within the central nervous system and along pain pathways is presented. We also summarize the literature supporting a role for DOPr in acute, tonic, and chronic pain models, as well as the mechanisms regulating its activity under specific conditions. Finally, novel compounds that have make their way to clinical trials are discussed.

The bacteriophage-derived transcriptional regulator, LscR, activates the expression of levansucrase genes in Pseudomonas syringae.

Synthesis of the exopolysaccharide levan occurs in the bacterial blight pathogen of soybean, Pseudomonas syringae pv. glycinea PG4180, when this bacterium encounters moderate to high concentrations of sucrose inside its host plant. The process is mediated by the temperature-dependent expression and secretion of two levansucrases, LscB and LscC. Previous studies showed the importance of a prophage-associated promoter element in driving the expression of levansucrase genes. Herein, heterologous screening for transcriptional activators revealed that the prophage-borne transcriptional regulator, LscR, from P. syringae mediates expression of levansucrase. A lscR-deficient mutant was generated and exhibited a levan-negative phenotype when grown on a sucrose-rich medium. This phenotype was confirmed by zymographic analysis and Western blots which demonstrated absence of levansucrase in the supernatant and total cell lysates. Transcriptional analysis showed a down-regulation of expression levels of levansucrase and glycosyl hydrolase genes in the lscR-deficient mutant. Ultimately, a direct binding of LscR to the promoter region of levansucrase was demonstrated using electrophoretic mobility shift assays allowing to conclude that a bacteriophage-derived regulator dictates expression of bacterial genes involved in in planta fitness.

Synthesis, Structure, and Antibacterial Activity of a Thallium(III)-Containing Polyoxometalate, [Tl2{B-ß-SiW8O30(OH)}2]12.

We have synthesized and structurally characterized the first discrete thallium-containing polyoxometalate, [Tl2{B-ß-SiW8O30(OH)}2]12- (1). Polyanion 1 was characterized in the solid-state and shown to be solution-stable by 203/205Tl NMR, electrospray ionization mass spectrometry, and electrochemical studies. The antibacterial activity of 1 was also investigated.

Expression of extra-cellular levansucrase in Pseudomonas syringae is controlled by the in planta fitness-promoting metabolic repressor HexR.

BACKGROUND: Pseudomonas syringae pv. glycinea PG4180 causes bacterial blight on soybean plants and enters the leaf tissue through stomata or open wounds, where it encounters a sucrose-rich milieu. Sucrose is utilized by invading bacteria via the secreted enzyme, levansucrase (Lsc), liberating glucose and forming the polyfructan levan. P. syringae PG4180 possesses two functional lsc alleles transcribed at virulence-promoting low temperatures. RESULTS: We hypothesized that transcription of lsc is controlled by the hexose metabolism repressor, HexR, since potential HexR binding sites were identified upstream of both lsc genes. A hexR mutant of PG4180 was significantly growth-impaired when incubated with sucrose or glucose as sole carbon source, but exhibited wild type growth when arabinose was provided. Analyses of lsc expression resulted in higher transcript and protein levels in the hexR mutant as compared to the wild type. The hexR mutant's ability to multiply in planta was reduced. HexR did not seem to impact hrp gene expression as evidenced by the hexR mutant's unaltered hypersensitive response in tobacco and its unmodified protein secretion pattern as compared to the wild type under hrp-inducing conditions. CONCLUSIONS: Our data suggested a co-regulation of genes involved in extra-cellular sugar acquisition with those involved in intra-cellular energy-providing metabolic pathways in P. syringae.

TH1 cytokine response to HCV peptides in Egyptian health care workers: a pilot study.

Our objective was to elucidate the effects of different HCV peptides on TH1 cytokine synthesis (interleukin 2(IL2), gamma interferon (INFγ) and tumor necrosis factor α (TNF α)), in a proliferative response in a high risk population of HCV seronegative aviremic Egyptian healthcare workers (HCW). We studied the TH1 cytokine response to different HCV peptides among 47 HCW with and without evidence of HCV infection. Participants were classified according to the proliferation index (PI) in a CFSE proliferation assay as an indicator of previous exposure to HCV. Cytokines were analyzed using Luminex xMAP technology. Results showed that positive PI HCW produced a higher IL2 in response to all HCV peptides except NS4, a higher IFNγ response to NS3 and NS4 and no difference in TNFα response when compared to the negative PI HCWs. When compared to chronic HCV HCW, positive PI HCW showed no difference in the IL2 response, a higher IFNγ response to NS4 and NS5 HCV peptides and a higher TNFα response to all peptides. In conclusion the magnitude and type of cytokines produced in HCV infection is critical in determining the outcome of infection. NS4 & NS5 HCV peptides induce a protective TH1 response in positive PI HCW.

Prevalence of multiple forms of autoimmunity in Egyptian patients with Turner syndrome: relation to karyotype.

Our study aimed to investigate: the prevalence of autoantibodies related to organ-specific disease; the prevalence of some autoimmune diseases (AID) in Egyptian Turner syndrome (TS) patients; and the association of autoimmunity with patients' karyotypes. Eighty TS patients were subjected to history, auxological assessment and measurement of antithyroid peroxidase antibody (ATPOAb), antithyroglobulin antibody (ATGAb), anti-tissue transglutaminase IgA antibodies (ATTIgAAb), anti-glutamic acid decarboxylase-65 antibodies (GAD-65-Ab) and anti-adrenal cortex antibodies (AACAb). Of the 80 TS patients, 54 (67.5%) were seropositive for one or more autoantibodies. Thirty-five percent were positive for ATPOAb, 15% for ATGAb, 12.5% for ATTIgAAb, 3.75% for Anti-GAD-65Ab and 1.25% for AACAb. There was a non-significant association between the 45,X karyotype and overall prevalence of autoantibodies (p=0.20), while IsoXq was associated with increased prevalence of ATPOAb (p<0.01), ATGAb (p=0.01) and anti-GAD-65Ab (p=0.02). Thus, female TS patients face a high prevalence of autoimmunity and associated AID.

The nexus between indicators for sustainable transportation: a systematic literature review.

The relationship between indicators for sustainable transportation is a pressing issue that has argued the attention of policymakers, engineers, and academics. The transportation sector plays a crucial role in economic growth, while also having significant environmental consequences. This systematic literature review offers a comprehensive overview of the different research methodologies utilized to estimate the interrelationships between the transport sector, environmental degradation, and economic growth. Our study analyzed 977 citations sourced from Web of Science and SCOPUS, spanning the years 2010 to June 2022. The PRISMA methodology was employed for organizing and identifying articles. After a thorough evaluation, 52 published articles from 25 international journals were selected for further examination. Our findings show that researchers have used a variety of modeling approaches to shed light on this complex issue, with multivariate co-integration techniques, decomposition analysis, and the generalized method of moments being among the most widely used methods in recent years. This review provides perspectives to policymakers and decision-makers, enabling them to create effective energy and environmental strategies for a long-term, sustainable transportation future.

Emerging dysfunctions consequent to combined monoaminergic depletions in Parkinsonism.

The loss of dopamine (DA) neurons has been the pathophysiological focus of the devastating conditions of Parkinson's disease, but depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD. The present study aimed to investigate, in rats, the respective role of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) depletions on motor and non-motor behaviors and on subthalamic (STN) neuronal activity. We show that NA or DA depletion significantly decreased locomotor activity and enhanced the proportion of bursty and irregular STN neurons. Anxiety-like states required DA depletion plus the depletion of 5-HT or NA. Anhedonia and "depressive-like" behavior emerged only from the combined depletion of all three monoamines, an effect paralleled by an increase in the firing rate and the proportion of bursty and irregular STN neurons. Here, we provide evidence for the exacerbation of behavioral deficits when NA and/or 5-HT depletions are combined with DA depletion, bringing new insight into the combined roles of the three monoamines in PD.

Digital evaluation of Bolton's tooth size discrepancies among different malocclusions categories of Egyptian adolescent orthodontic population: A retrospective study.

OBJECTIVE: This retrospective investigation aimed to compare Bolton's ratios among different malocclusion groups of Egyptian adolescent orthodontic patients with original Bolton's standards. MATERIALS AND METHODS: Pre-treatment dental casts of 588 Egyptian subjects, 290 males and 298 females with mean age 16.7±2.2 years, were randomly selected and classified into 220 class I (108 males and 112 females), 230 class II (112 males and 118 females), and 138 class III (68 males and 70 females) groups. Mesiodistal widths from first molar to first molar were measured on 3-dimensionally scanned models via software and ratios were calculated. Two-way analysis of variance compared ratios as a function of skeletal classification and gender. Additionally, percentages of significant discrepancy outside 2 standard deviations (SDs) were calculated. RESULTS: The anterior mean ratio for the total sample were higher (79.4±4.7) and overall mean ratio was lower (90.1±5) than Bolton's standards. The differences between the obtained and standard values were statistically significant (P<0.001). However, there were no significant differences in either anterior ratio (P=0.637) or overall ratio (P=295) regarding gender. Class I cases showed the highest mean anterior ratio of 80±5.7 whereas class II and class III cases had the lowest ratio of 78.5±4.6 and 78.7±3.5, respectively. Concerning overall ratio, class III subjects had the highest ratio of 91.8±2.6 with no substantial distinction from class II cases (90.2±4.7) but was significantly different from class I cases that demonstrated the lowest ratio (89.7±5, P=0.020). High percentages of patients displayed clinically significant tooth size discrepancies (TSD), exceeding either above or below 2SD of Bolton's values, which were more marked in the anterior ratio. These were 25.2% and 7.4% for anterior ratio and 3.4% and 15.4% for overall ratio. CONCLUSIONS: Tooth size ratios of Egyptian orthodontic patients are generally different than the original Bolton's standards. Patients with class I and class III malocclusions had greater anterior and overall ratios than those with class II malocclusions with no considerable gender differences in either ratio.

Initial viral cycle threshold values in patients with COVID-19 and their clinical significance.

BACKGROUND: The connection between initial viral cycle threshold (Ct) values of the SARS-CoV-2 with symptoms and hospital course is not clearly studied. METHODS: This is a retrospective study of hospitalized COVID-19 patients from Jun 1st 2020 to March 30th, 2021 examining the relationship between initial viral cycle threshold (Ct) values of SARS-CoV-2 as obtained from nasopharyngeal samples. The clinical presentations and outcomes were analyzed in relation to the initial Ct values. RESULTS: The study included 202 hospitalized COVID-19 patients with a mean age (± SD) of 54.75 (± 15.93) and 123 (60.9%) males and 79 (39.1%) females. Of all the patients, the most frequent comorbidity was diabetes mellitus (95; 47%) and the most frequent symptoms were fever (148; 73.3%) and cough (141; 69.8%). There was no significant difference in relation to underlying conditions, clinical presentation, radiographic and laboratory data among those with low, medium and high Ct values. The mean Ct values showed no statistical change over the 10-month study period. CONCLUSIONS: Initial SARS-CoV-2 Ct values did not show any association with clinical symptoms and did not predict the need for mechanical intubation or death.

QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. METHODS: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). RESULTS: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test). CONCLUSION: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Value of intrauterine platelet-rich concentrates in patients with intrauterine adhesions after hysteroscopy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the value of intrauterine platelet-rich concentrates among patients with intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis. METHODS: Four different databases (PubMed, Cochrane Library, Scopus, and ISI web of science) were searched for the available studies from inception to November 2021. We selected randomized clinical trials (RCTs) that compared platelet-rich concentrates in the intervention group versus no injection of platelet-rich concentrates in the control group among women with intrauterine adhesions after operative hysteroscopy. Revman software was utilized for performing our meta-analysis. Our primary outcomes were the adhesion score and incidence of recurrence of severe intrauterine adhesions postoperatively. Our secondary outcomes were the clinical pregnancy rate, menstrual flow duration in days, and menstrual flow amount (number of pads). RESULTS: Five RCTs met our inclusion criteria with a total number of 329 patients. We found that platelet-rich concentrates were linked to a significant reduction in the postoperative adhesion score (MD = -1.00, 95% CI [-1.68, -0.32], p = 0.004). Moreover, there was a significant reduction in the incidence of severe IUAs recurrence among the platelet-rich concentrates group (7.6%) compared to the control group (23.4%) after hysteroscopy (p = 0.001). The clinical pregnancy rate was significantly increased among the platelet-rich concentrates group (37.1%) in comparison with the control group (20.7%) after hysteroscopic adhesiolysis (p = 0.008). There were significant improvements in the menstrual flow duration and amount among the platelet-rich concentrates group (p < 0.001). CONCLUSIONS: Intrauterine placement of platelet-rich concentrates is an effective method for the treatment of intrauterine adhesions after hysteroscopy.