LD Group Research Articles

Cross-disorder comparison of sensory reactivity, pain, gastro-intestinal symptoms and obsessive-compulsive symptoms in adolescents and young adults with autism and other neurodevelopmental disorders

There is considerable evidence of the relationship among sensory reactivity, abdominal pain, and gastrointestinal symptoms in individuals with Autism Spectrum Disorder (ASD). Furthermore, these events are linked to the gut-microbiota-brain axis via the enteric nervous system. However, few studies have compared autism with other neurodevelopmental disorders in terms of sensory reactivity, pain, or gastrointestinal symptoms. Consequently, this study aimed to analyze the differences in sensory reactivity, pain, and gastrointestinal symptoms between adolescents and young adults with ASD and other neurodevelopmental and neurotypical disorders. Differences in sensory reactivity, pain, gastrointestinal symptoms, and obsessive-compulsive symptoms between a group of individuals with ASD level I (n = 37), Attention Deficit Hyperactivity Disorder or ADHD (n = 15), Learning Difficulties or LD (n = 23), and a control or neurotypical group (n = 76) were analyzed. Higher levels of sensory hyperreactivity were found in individuals with ASD than in the other clinical (ADHD and LD) and neurotypical groups. Sensory hyporeactivity was greater in individuals with ASD as well as in individuals with ADHD than that in the neurotypical group. Higher levels of pain were found in the ADHD group than in the ASD or neurotypical group. Gastrointestinal symptoms of the abdominal type were more severe in the ASD group than in the ADHD, and LD groups, whereas dyspepsia was more severe in the ADHD group. The results indicate a sensory and gastrointestinal profile in individuals with ASD and ADHD. Future studies should increase the number of participants for each neurodevelopmental disorder and perform a more comprehensive analysis of the gut microbiota-brain axis.

3D EVALUATION OF MICROGAPS AT THE IMPLANT-ABUTMENT CONNECTION BEFORE AND AFTER THERMODYNAMIC CYCLING.

To analyze the microgap changes between hybrid-abutment crowns made of two materials and three internal taper connec9on implants with different connection designs before and after thermodynamic loading. A total of 30 implants-10 each of Straumann Bone Level Implant-RC (STR); GC AADVA Implant (AAD); and Astra-Tech OsseoSpeed EV (AST)-were included in this laboratory study. Each implant had an internal taper connection, but their designs were slightly different. Five hybrid-abutment crowns were fabricated using a lithium disilicate ceramic (LD), and five were fabricated using polymethylmethacrylate (PMMA) with CAD/CAM technologies for each implant system, providing six sample groups STR-LD, AAD-LD, AST-LD, STR-PMMA, AAD-PMMA, and ASTPMMA. The microgap volume was measured using micro-CT images obtained before and after thermodynamic loading equivalent to 4 months of clinical use. Student t test, one-way ANOVA, and Tukey test were used for comparisons. The greatest microgap volume increase was recorded (3.405% ± 1.567%) in the AST-LD group, and the lowest increase (0.45% ± 0.373%) was in the STR-PMMA group. A statistically significant difference in microgap increase was not detected among PMMA and LD groups: for STR-LD/STR-PMMA (t test: P = .273); for AAD-LD/AAD-PMMA (t test: P = .374); and for AST-LD/AST-PMMA (t test: P = .268). However, the difference in the microgap increase between the different implant systems was statistically significant. The microgap between hybrid-abutment crowns and implants increased after short-term thermodynamic cycling. Hybrid-abutment crowns with different elastic modulus showed similar microgap increase. The geometric shape of the connection influenced the microgap increase.

523 - Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a phase 2b trial (STREAM-AD)

Abstract Introduction/Background Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing). Objectives To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD. Methods STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to <75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD], n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388). Results Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of –32.1% (95% CI: –43.9, –20.3; P<0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, –27.3 (95% CI: –39.1, –15.6; P<0.0001); 125 mg, –22.2 (95% CI: –34.0, –10.4; P=0.0002); and 62.5 mg, –30.2 (95% CI: –41.9, –18.5; P<0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P<0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS ≥4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified. Conclusions In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups.

Chishao (Paeoniae Radix Rubra) alleviates intra-hepatic cholestasis by modulating NTCP in rats.

Background: Cholestasis is a common pathological manifestation dominated by accumulation of potentially toxic biliary compounds. Na+-taurocholate cotransporting polypeptide (NTCP) plays a critical role in protection from cholestasis and can be targeted therapeutically. Chishao (Paeoniae Radix Rubra) is a clinically efficacious agent for treating cholestasis, but the underlying mechanism has not been fully clarified. Objective: To evaluate the effects of Chishao on the expression of NTCP in rats with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. Methods: Chishao extracts were obtained by water decoction. Cholestasis model induced by ANIT in rats were established. Thirty rats were divided into five groups: control group (C), ANIT model group (M), 10g/kg Chishao group (LD), 20g/kg Chishao group (MD) and 40g/kg Chishao group (HD). The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP) and total bile acid (TBA) were detected. The mRNA and protein expression of NTCP, multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) were detected by reverse transcription qPCR and Western blotting respectively. To assess the effects of Chishao on NTCP, MRP2 and BSEP localized at the membrane of hepatocytes, an in vitro experiment involving primary hepatocytes was conducted via the utilization of laser scanning confocal microscopy. Results: The extracts of Chishao significantly improved serum ALT, AST, ALP, TB, DB and TBA (p < 0.05), especially ALP in the HD group (p < 0.01). The histological pathological findings were also reversed in LD, MD and HD groups. The mRNA level of MRP2 was significantly downregulated after treatment with ANIT, whereas it was reversed in MD and HD groups (p < 0.05). The mRNA expression of NTCP was significantly downregulated after ANIT treatment, but dramatically upregulated in the HD group. The expressions of BSEP and MRP2 were similar, but that of NTCP decreased after ANIT treatment, which was reversed significantly by Chishao extracts in a dose-dependent manner. The expression of NTCP in hepatocytes from rats increased dose-dependently after Chishao treatment in vitro. Conclusion: Chishao extracts can improve the serum and histological performances of intra-hepatic cholestasis caused by ANIT, probably by working on transport proteins in liver cell membranes.

A preliminary report comparing the effect of Asafoetida with oral contraceptive on polycystic ovarian syndrome in a double-blind randomized trial.

Polycystic ovarian syndrome (PCOS) is the most common cause of infertility and endocrine disorders in women of childbearing age. In Persian medicine, Ferula assafoetida L. (Asafoetida) was recommended for treating PCOS. The present study was conducted to compare the effect of Asafoetida with oral contraceptive tablets on PCOS patients. Patients with PCOS (n=30) were enrolled in a double-blind randomized clinical trial. On Day 5 of the menstrual cycle, patients received two periods of 21-day treatment, with 7 days rest between the two treatments. On a daily basis, half of the patients (n=15) received Asafoetida (1 g), and the rest received low dose oral contraceptive (LD; one tablet). Menstrual status, anthropometric characteristics, hematology and biochemistry parameters, ovarian ultrasound examination and hirsutism were evaluated prior to the initiation of the experiment and 14 days after the end of treatment. The occurrence of menstrual cycles and pregnancy was assessed eight months after the end of treatment. The incidence of pregnancy was greater in patients who received Asafoetida compared to those who received LD (p=0.019). The time intervals between menstrual cycles became shorter in both groups (p<0.05). The occurrence of regular menstrual cycles remained longer in the Asafoetida compared to the LD group (p=0.001). Concentrations of triglycerides, cholesterol, HDL and LDL were significantly increased after treating with LD (p<0.05). In PCOS patients, the occurrence of regular menstrual cycles and the incidence of pregnancy were improved following treatment with Asafoetida. This medicament could be considered a safe treatment for patients with PCOS.

Integrative analysis of metabolome and transcriptome provides new insights into functional components of Lilii Bulbus

ObjectiveLilium brownii var. viridulum (LB) and L. lancifolium (LL) are the main sources of medicinal lily (Lilii Bulbus, Baihe in Chinese) in China. However, the functional components of these two species responsible for the treatment efficacy are yet not clear. In order to explore the therapeutic material basis of Lilii Bulbus, we selected L. davidii var. willmottiae (LD) only used for food as the control group to analyze the differences between LD and the other two (LB and LL). MethodsMetabolome and transcriptome were carried out to investigate the differences of active components in LD vs LB and LD vs LL. Data of metabolome and transcriptome was analysed using various analysis methods, such as principal component analysis (PCA), hierarchical cluster analysis (HCA), and so on. Differentially expressed genes (DEGs) were enriched through KEGG and GO enrichment analysis. ResultsThe PCA and HCA of the metabolome indicated the metabolites were clearly separated and varied greatly in LL and LB contrasted with LD. There were 318 significantly differential metabolites (SDMs) in LD vs LB group and 298 SDMs in LD vs LL group. Compared with LD group, the significant up-regulation of steroidal saponins and steroidal alkaloids were detected both in LB and LL groups, especially in LB group. The HCA of transcriptome indicated that there was significant difference in LB vs LD group, while the difference between LL and LD varied slightly. Additionally, 47 540 DEGs in LD vs LB group and 18 958 DEGs in LD vs LL group were identified. Notably, CYP450s involving in the biosynthesis of steroidal saponins and steroidal alkaloids were detected, and comparing with LD, CYP724, CYP710A, and CYP734A1 in LB and CYP90B in LL were all up-regulated. ConclusionThis study suggested that steroidal saponins and steroidal alkaloids maybe the representative functional components of Lilii Bulbus, which can provide new insights for Lilii Bulbus used in the research and development of classic famous formula.

Duration of osteoporosis treatment to reduce the risk of subsequent osteoporotic fracture and all-cause mortality in elderly hip fracture patients in a Korean real-world study

SummaryThis study aimed to evaluate the association between treatment duration of osteoporosis medications and clinical outcomes of patients with hip fracture. We found that the risk of subsequent osteoporotic fractures and all-cause mortality showed a decreasing trend as the treatment duration of osteoporosis medications increased.PurposeTo assess the risk of subsequent osteoporotic fracture (SOF) and all-cause mortality (ACM) in elderly patients with hip fracture in South Korea and to evaluate the potential reduction in the risk of SOF and ACM with varying durations of osteoporosis treatment.MethodsNewly diagnosed patients with hip fracture (age ≥ 60 years) who initiated osteoporosis medication within 3 months after the hip fracture from 2003–2014 were identified from the National Health Insurance Service-Senior cohort. The risk of SOF and ACM was estimated after the 1-year exposure-measurement period. Adjusted hazard ratios (aHRs) were calculated for treatment duration of osteoporosis medications categorized as short-term treatment (ST, < 3 months), early discontinuation (ED, ≥ 3– < 6 months), late discontinuation (LD, ≥ 6– < 12 months), and treatment continuation (TC, ≥ 12 months).ResultsA total of 4,421 patients were included in the analysis. The 3-year cumulative incidence of SOF was 22.4%, 22.0%, 23.9%, and 21.6%, and that of 3-year ACM was 29.8%, 27.0%, 19.7%, and 18.9% in the ST, ED, LD, and TC groups, respectively. Compared with the ST group, the risk of SOF showed a decreasing trend in the TC group (aHR [95% CI], 0.77 [0.58–1.00]). The risk of ACM was significantly reduced in the LD (aHR 0.68 [0.57–0.82]) and TC (aHR 0.65 [0.50–0.84]) groups.ConclusionThese findings underscore the importance of early and continuous osteoporosis treatment for elderly patients with hip fracture to improve health outcomes. The benefits of long-term osteoporosis treatment should be discussed in clinical practice to improve overall health outcomes.

Comparison of Analgesic Efficacy of Levobupivacaine with or without Dexamethasone in Lower Abdominal Surgeries under Subarachnoid Block: A Pilot Randomised Controlled Trial

Introduction: Subarachnoid Block (SAB) is a commonly used technique for lower abdominal surgery. Dexamethasone has been proven effective as an additive when used with bupivacaine. However, there has been no study comparing the analgesic efficacy of dexamethasone with levobupivacaine under SAB. Aim: To compare the analgesic efficacy of levobupivacaine with or without dexamethasone in patients scheduled for lower abdominal surgeries. Materials and Methods: A pilot randomised doubleblind controlled trial was undertaken in the Department of Anaesthesiology, University College of Medical Sciences Guru Tagh Bahudur (UCMS-GTB) Hospital, New Delhi, India on 60 patients with Americian Soceity of Anaesthesiolgy (ASA) grade I or II, aged 18-65 years, undergoing lower abdominal surgeries under SAB from January 2021 to August 2022. In Group LS, 12.5 mg of 0.5% isobaric levobupivacaine (2.5 mL) with normal saline (1 mL) was administered, and in Group LD, 12.5 mg of 0.5% isobaric levobupivacaine (2.5 mL) with 4 mg dexamethasone (1 mL) was given. Patients were assessed for sensory and motor block, haemodynamic parameters, pain score, and side-effects. Unpaired t-tests/Mann-Whitney U tests were used to determine significance. A p-value of less than 0.05 was considered significant. Results: The two groups were comparable in terms of demographic profile. The age in the LS group was 37.80±9.98 years, and in the LD group, it was 38.63±12.37 years. The maleto-female ratio in the LS and LD groups was 17:13 and 21:9, respectively. The weight range in both groups was between 50 to 67 kg. The Basal Metabolic Index (BMI) was 22.40±2.43 kg/ m2 and 21.70±2.21 kg/m2 in the LD and LS groups, respectively. All these parameters, including height, had a p-value of more than 0.005, except for the duration of analgesia. The duration of effective analgesia was also longer in the LD group (247.00±36.69 min) than in the LS group (138.50±22.52 min) with a p-value of &lt;0.001. The time of onset of sensory block was 9.13±2.98 minutes in the LD group and 10.30±3.06 minutes in the LS group, which was statistically insignificant. Conclusion: Authors concluded addition of 4 mg (1 mL) of dexamethasone to 2.5 mL of 0.5% isobaric levobupivacaine provides a clinically longer duration of effective analgesia with early onset and better quality of sensory and motor block than 2.5 mL of 0.5% isobaric levobupivacaine alone. Therefore, 4 mg of dexamethasone with 2.5 mL of 0.5% isobaric levobupivacaine is recommended for lower abdominal surgeries under SAB.

Factors Affecting Success Rates in Endoscopic Repair of CSF Rhinorrhea.

Our aim in this study is to assess the effect of factors such as age, etiology, defect size, application of lumbar drainage and surgical technique on Cerebrospinal Fluid (CSF) fistula repair success rates. The Electronic Medical Records (EMR) system of our clinic was retrospectively reviewed for cases that were operated between 2006 and 2020 for CSF fistula originating from anterior skull base with endoscopic transnasal technique. A total of 35 patients were included in the study. Patients were grouped according to the number of layers used in repair (two, three or four-layered reconstruction) and defect size (smaller than 5 mm, 5 to 10 mm and larger than 10mm), etiology, location of the defect and application of lumbar drainage as LD (+) and LD (-). Complications and CSF leak recurrence were compared between groups. Recurrence rates in patients who had 2 layered reconstructions were significantly higher compared to patients who had 3 or 4 layered reconstructions (p=0.049). The recurrence rate in LD (+) group (41.7%) was significantly lower compared to LD (-) group (4.3%) (p=0.012). There were no significant difference in recurrence rates between groups in terms of age, defect size, defect location and etiology. In endoscopic transnasal repair of anterior skull base-derived bos fistulas, planning the reconstruction at least 3 times and applying lumbar CSF drainage increases the success rates.

Effects and mechanisms of Salvia miltiorrhiza Bunge extract on myocardial cell apoptosis in rat heart failure model.

This work aimed to investigate the effects of Tanshinone IIA (Tan IIA) on myocardial cell (MC) apoptosis in a rat model of heart failure (HF). Tan IIA was extracted from Salvia miltiorrhiza Bunge (SMB) using an ethanol reflux method. Fifty rats were randomly divided into five groups: sham (no treatment), mod (HF model establishment), low dose (LD: 0.1 mL/kg Tan IIA), medium dose (MD: 0.3 mL/kg Tan IIA), and high dose (HD: 0.5 mL/kg Tan IIA), with 10 rats in each group. The effects of different doses of Tan IIA on cardiac function, MC apoptosis, and the levels of proteins associated with the PI3K/Akt/mTOR signaling pathway were compared. Mod group showed a significant decrease in systolic arterial pressure, mean arterial pressure, heart rate, left ventricular systolic pressure, left ventricular ejection fraction, left ventricular fractional shortening, and the levels of p-PI3K, p-Akt, and p-mTOR proteins versus sham group (p < 0.05). Additionally, the left ventricular end-diastolic diameter (LVIDd), end-systolic diameter, diastolic pressure, and MC apoptosis were significantly increased (p < 0.05). LD, MD, and HD groups exhibited significant improvements across various indicators of cardiac function and MC apoptosis versus mod group (p < 0.05). Tan IIA may improve cardiac function and inhibit MC apoptosis in rats with HF by modulating the PI3K/Akt/mTOR signaling pathway.

Comparison of levobupivacaine with dexamethasone versus levobupivacaine for ultrasound-guided transversus abdominis plane block in lower abdominal surgeries in a tertiary care hospital in Chengalpattu district – A randomized control trial

Introduction: Transversus abdominis plane (TAP) block is a regional technique for analgesia of the anterolateral abdominal wall. Ultrasound guidance is now considered the gold standard in TAP blocks. It involves the injection of a local anesthetic solution into a plane between the internal oblique muscle and transversus abdominis muscle. Since the thoracolumbar nerves originating from the T6 to L1 spinal roots run into this plane and supply sensory nerves to the anterolateral abdominal wall, the local anesthetic spread in this plane can block the neural afferents and provide analgesia to the anterolateral abdominal wall. Levobupivacaine is a local anesthetic from the amino amide class of medications. Adjuvants are drugs when added along with local anesthetics have a synergistic action to improve the duration and quality of analgesia. Objectives: The objective of this study was to study the effectiveness of ultrasound-guided transversus abdominis plane block using levobupivacaine with dexamethasone in terms of hemodynamic stability and duration of postoperative analgesia and pain scores (visual analog scale [VAS]), time of requirement of rescue analgesics among patients who have undergone lower abdominal surgeries. Methods: This is a double-blinded randomized control trial. This study was conducted among 60 patients who have undergone lower abdominal surgeries in a tertiary care hospital. Postsurgery, intraoperatively prior shifting out the patient, two groups received transversus abdominis plane block, one received 28 ml of 0.25% levobupivacaine with 2 ml of normal saline and another group received 28 ml of 0.25% levobupivacaine with 2 ml (8 mg) dexamethasone. Duration of postoperative analgesia and the efficacy between the two groups were compared with hemodynamic parameters and VAS score. Results: The study groups were not significantly different in terms of demographic data or the American Society of Anesthesiologists Grading. The mean onset of breakthrough pain was significantly higher in the L group. The time of requirement of rescue analgesics was also significantly shorter in the L group compared to the LD group. The VAS pain score was significantly lower in the Group LD as compared to the L group. Conclusion: Hence, it was noticed that dexamethasone when added to levobupivacaine had better hemodynamic stability in terms of blood pressure, heart rate, saturation, respiratory rate, and mean arterial pressure. The requirement of rescue analgesics was also reduced in this group and the time of breakthrough pain was also prolonged. This group had significantly lower pain scores.

Assessment of Micro-Gap in Hybrid Abutment-Crowns Fabricated with Different Materials

Objective: The aim of this in vitro study is to evaluate the micro-gap changes in three dimensions after thermodynamic loading between hybrid abutment crowns made of different materials and implants with internal conical connection.&#x0D; Methods: A total of 10 morse cone connection implants (Straumann Bone Level Implant, Institut Straumann AG, Basel, Switzerland) were used. In this study, two study groups were formed using lithium disilicate glass-ceramic (LD) and polymethyl methacrylate (PMMA) in hybrid abutment-crown production (n=5). Hybrid abutment-crowns were fabricated by CAD/CAM system. Hybrid abutment crowns were designed and manufactured digitally. A 4-month of clinical cycle was applied to the samples in the chewing simulator. The micro-gap at the implant- abutment interface was visualized with micro-CT before and after thermodynamic loading. Micro-gap change was determined using these obtained images. For comparisons, independent t-test was used.&#x0D; Results: When comparing the micro-gap volumes before and after aging, no significant difference was observed between the LD and PMMA groups. The micro-gap increase after loading was 0.68 ±0.209 in the LD group and 0.45 ±0.373 in the PMMA group. Although the increase was higher in the LD group, there is no statistically significant difference between two groups.&#x0D; Conclusion: he micro-gap in the interface of implants and hybrid abutment crowns increased after aging. Hybrid abutment-crown material affected the micro-gap increase, but it was not statistically significant.

Trokanterik femur kırıklarında lateral dekübit pozisyonu ve traksiyon masasının intramedüller çivilemeye etkisinin karşılaştırılması

Purpose: The objective of this study is to evaluate the influence of patient positioning on intraoperative outcomes, specifically intraoperative time, fracture reduction, and implant location, in individuals with trochanteric femur fractures undergoing intramedullary nailing. The study compares two patient positions: the lateral decubitus position (LDP group) and the utilization of a traction table (TT group).&#x0D; Materials and Methods: A total of 82 patients with trochanteric femur fractures, who underwent surgery were included. The patients were divided into LDP and TT groups. Various parameters, including age, gender, fracture details, setup time, operation time, anesthesia time, fluoroscopy time, tip-apex distance (TAD), collodiaphyseal angle (CDA), reduction quality, and implant position, were analyzed.&#x0D; Result: Surgical time in the LD group was 33.90 ± 6.05 minutes, whereas in the TT group, it was 33.00 ± 6.64 minutes. Anesthesia time was 50.55 ± 7.46 minutes in the LD group and 55.26 ± 12.49 minutes in the TT group. Fluoroscopy time in the LD group was 45.20 ± 7.18 seconds, while in the TT group, it was 46.23 ± 4.50 seconds. Lateral decubitus position resulted in shorter setup and anesthesia times compared to the traction table. &#x0D; Conclusion: Intramedullary nailing in the lateral decubitus position is a viable and practical choice for fracture reduction, with the potential to decrease morbidity and mortality rates especially in elderly patients.

Patient Outcomes after Initial High Dose Versus Low Dose Romiplostim for Inpatient Management of Immune Thrombocytopenia

Introduction: Romiplostim is a thrombopoietin receptor agonist approved by the US FDA for chronic immune thrombocytopenia (ITP) in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The recommended dose is 1 mcg/kg/week subcutaneously, escalated weekly by increments of 1 mcg/kg to achieve and maintain a platelet count of 50 x 10 9 /L g ( Kuter et al 2021). It has been postulated that starting at the maximum recommended dose of 10 mcg/kg/week in patients with severe bleeding may swiftly increase platelets and minimize bleeding ( Roumier et al 2021). However, this approach may also increase the risk of major thrombotic events (TE). It is unclear if the more aggressive dosing strategy results in more rapid, robust responses and a tolerable safety profile compared to the FDA approved approach. Methods: This retrospective chart review included adult patients who initiated romiplostim while admitted for ITP at a Mayo Clinic Enterprise site from May 2018 to May 2022. Outcomes included rate of TE at 30 days and 90 days and time to first TE in patients receiving initial romiplostim doses of &amp;lt; 5 mcg/kg (low dose, LD) and &amp;gt; 5 mcg/kg (high dose, HD), median time to platelet response (defined as platelets &amp;gt; 30 x10 9/L and &amp;gt; 50 x10 9/L on 2 separate checks) in LD vs HD, and cost to the institution comparing LD to HD. Outcomes were summarized using descriptive statistics. Statistical analysis was done using BlueSky. Fischer's exact test and chi-squared were performed for categorical data, and Wilcoxon rank sum test were done for continuous variables. Results: Forty-five patients met eligibility criteria: 33 (73%) received initial romiplostim doses &amp;lt; 5 mcg/kg and 12 (27%) received doses &amp;gt; 5 mcg/kg. The majority of patients (43/45 (96%)) presented with platelets &amp;lt; 50 x 10 9/L. The median age was 65 years (68 in LD vs 57 HD). There were 24 (73%) males in the LD group vs five (42%) in the HD group. At baseline, 64% (n = 21) of LD patients and 75% (n = 9) of HD patients presented with bleeding. Major bleeding (defined by 2019 ASH ITP guidelines) was present in 21% (n= 7) vs 17% (n = 2) of patients, LD versus HD, respectively ( Neunert et al 2019). The overall incidence of TE in this study was 24% (n = 11): LD 5 (15%) and HD 6 (50%) (p = 0.044) at 90 days. Median days to TE was 21 days, 12 days in LD group (range 5-21) vs 24.5 days (range 14-58) in HD group (p = 0.067). TE included deep vein thrombosis (DVT, n = 6), DVT with pulmonary embolism (n = 1), portal vein thrombus (n = 1), multiple brain infarcts (n = 1), splenic vein thrombus (n = 1), and left atrial appendage thrombus (n = 1). The median platelet count at the time of TE was 304 x 10 9/L, 415 x 10 9/L (range 58-900) in the LD group vs 323 x 10 8/L (range 33-1427) in the HD group (p = 0.79). Thirty-two (71%) out of 45 patients had a response to romiplostim: 22 in the LD group (71%) vs 10 (83.3%) in the HD group (p = 0.698). Of the patients that responded, the median time to response was 6 days in the LD group vs 11.5 days in the HD group (p = 0.09) The median dose at time of initial response was 2 mcg/kg in the LD group and 6 mcg/kg in the HD group. Wholesale Acquisition Cost (WAC) was used to determine the cost per dose, rounded to the nearest vial size. The average WAC for the initial dose in LD patients was $1806.80 compared to $6061.79 in HD patients. Conclusion:There was a significantly increased incidence of thrombosis in patients admitted with ITP that received initial romiplostim doses &amp;gt; 5 mcg/kg, with no differences in the time to platelet response. Careful consideration of risks versus benefits should be given prior to initiating romiplostim at doses higher than recommended doses.

Effects of the Fibrous Root of Polygonatum cyrtonema Hua on Growth Performance, Meat Quality, Immunity, Antioxidant Capacity, and Intestinal Morphology of White-Feathered Broilers.

This study was designed to evaluate the effects of different doses of the fibrous roots of Polygonatum cyrtonema Hua on the growth performance, slaughter parameters, meat quality, immune function, cytokines, antioxidant capacity, and intestinal morphology of white-feathered broilers. Also, the mechanism to improve immune functions of broilers was explored through network pharmacology and molecular docking technology. A total of 360 AA-white-feathered broilers were randomly divided into six groups (not separated by sex), with six repetitions per group (n = 10). The groups were as follows: basal diet (CON group), basal diet supplemented with 300 mg/kg aureomycin (ANT group), basal diet supplemented with 2%, 3%, and 4% fibrous root raw powder (LD, MD, and HD group), or basal diet supplemented with 3% fibrous root processed powder (PR group), in a 42-day experiment. The dietary inclusion of P. cyrtonema fibrous roots increased slaughter performance (p < 0.05), reduced the fat rate (p < 0.05), improved intestinal morphology (p < 0.05), and improved the immune organ index to varying degrees. It also significantly improved pH reduction, drip loss, and pressure loss of breast muscle and leg muscle (p < 0.05). Furthermore, it significantly improved immune and antioxidant functions including decreased MDA content of serum (p < 0.01), increased GSH-Px content (p < 0.01), IgG, IgA, and C4 contents (p < 0.05), and increased expression of IL-2 and IFN-γ (p < 0.01). Additionally, the mechanism by which fibrous roots improve immune function in broilers was explored using network pharmacology and molecular docking technology. Network pharmacology and molecular docking revealed that flavonoids such as baicalein, 4',5-Dihydroxyflavone, 5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, and 5,7-dihydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-6,8-dimethyl-chroman-4-one were key components that enhanced immune function through the MAPK1 and other key targets involved in regulating the MAPK signaling pathway. From the findings, it can be concluded that incorporating P. cyrtonema Hua fibrous root as a natural feed supplement and growth promoter in broiler diets had a positive impact on bird health and performance.

Do ADHD and SLD children differ in executive functions and behavioural problems? A comparative study

AbstractIt is well‐known that children with attention‐deficit/hyperactivity disorder (ADHD) and specific learning disorder (SLD) often exhibit behavioural and emotional problems. However, little is known about how these problems compare between the two groups of children. This study sought to fill this gap in knowledge by comparing the executive functions and behavioural–emotional problems of children with ADHD, SLD and typically developing children. For this study, 94 children were recruited through purposeful sampling (ADHD = 23, SLD = 30 and TD = 41). All participants were screened based on WISC‐IV. Subsequently, participants were administered executive functions and behavioural problems questionnaires. The analysis of the data using MANOVA and Scheffe post hoc pairwise shows that children with ADHD and SLD had significantly higher scores on measures of executive function impairment than typically developing children. Our study revealed that children in the ADHD group scored significantly higher in social problems, aggressive behaviours, AD/HD problems, ODD, conduct problems and externalizing problems sub‐tests. Conversely, the LD group demonstrated higher scores in the anxiety problems sub‐test. Furthermore, Our study demonstrated that children in the ADHD group scored significantly higher in the following sub‐tests: metacognition, inhibit, shift, bri, shift and emotion control. In contrast, the LD group exhibited higher scores in the initiate sub‐test. In addition, the two groups of children with disorders also exhibited more behavioural–emotional problems than typically developing children. These findings suggest that ADHD and SLD are associated with impaired executive function and increased behavioural–emotional problems. These findings have implications for the assessment and treatment of these disorders.

75 Can the Children’s Communication Checklist Differentiate Between Children with High Functioning Autism, ADHD, and Academically-Based Learning Disabilities?

Objective:The Children’s Communication Checklist-Second Edition (CCC-2) is a rating scale designed to assess domains of communication skills with emphasis on pragmatics (Bishop, 2006). The CCC comprises 10 subtests addressing various aspects of oral communication skills: Speech, Syntax, Semantics, Coherence, Initiation, Scripted Language, Context, Nonverbal Communication, Social Relations, and Interests. In a study conducted on the original CCC, Geurts et al. (2004) found that when compared to normal controls, pragmatic difficulties occurred in children with either high functioning autism (HFA) or ADHD. Since the initial version of the CCC, no study has examined whether the revised version can differentiate children with HFA, ADHD, and LD, the purpose of the present study. Focus was on derived factors of the structure/content of language and the pragmatics of language.Participants and Methods:Forty-one participants grouped according to diagnosis were drawn from two archival data pools, one adapted from a previous study conducted by Casey and Scott (2016) and the other from a set of anonymized patients from a neuropsychological clinic. Fourteen participants met clinical criteria for autism (Mage = 11.95), 12 participants met criteria for ADHD without co-morbid disorders (Mage = 9.5), and 15 participants met criteria for a learning disability involving reading, writing, math, or some combination (Mage = 10.13). Group-specific descriptive statistics were computed for the participants’ age, full scale intelligence quotient (IQ), and General Communication Composite (GCC). Two factor scores were computed, one composed of the subtests that constitute the structure/content aspects of language (Speech, Syntax, Semantics, and Coherence) and one composed of the pragmatic aspects of language (Initiation, Nonverbal Communication, Social Relations, and Interests), an area of particular weakness in HFA. Independent samples ANOVAs were conducted on both factor scores to determine whether the CCC-2 could differentiate the three groups. Post-hoc comparisons were planned for the subtests comprising the factor(s) that differentiated the groups.Results:Participants in the ADHD (M = 9.45, SD = 2.45) group were significantly younger than those in the HFA group (M = 11.95, SD = 2.24) and LD group (M = 10.13, SD = 2.58), the latter two not differing significantly. The groups did not differ significantly on IQ, nor on the structure/content factor. On the pragmatic factor, the LD group (M = 10.18, SD = 9.91) had significantly higher scores than the ADHD group (M = 7.79, SD = 6.54), which in turn, had significantly higher scores than the HFA group (M = 5.48, SD = 8.26), F(2, 38) = 17.81, p &lt; .01. Within this composite, the same pattern was shown on Nonverbal Communication, F(2, 38) = 9.29, p &lt; .01, and Interests, F(2, 38) = 17.81, p &lt; .01.Conclusions:Compared to children with an academically-based learning disability, children with ADHD and HFA demonstrated pragmatic difficulties on the CCC-2. Although there was overlap between the pragmatic language characteristics of children with ADHD and children with HFA, the CCC-2 demonstrated utility in distinguishing the two disorders on certain aspects of communication skills, suggesting that it is a useful tool in differential diagnosis.

Phenethylamine Is a Potential Density Stress Pheromone in Turbot (Scophthalmus maximus)

Pheromones play a vital role in regulating fish behavior, including reproduction, aggregation, hazard recognition and food location. To gain a better understanding of chemical communication in fish produced by density changes, this study analyzed the metabolites released by turbot (Scophthalmus maximus) under different stocking densities. The experiment was conducted at low (LD: 3.01 kg/m2), medium (MD: 6.62 kg/m2) and high (HD: 10.84 kg/m2) densities for 15 days. High-throughput non-targeted metabolomics (LC-MS/MS) was used to identify variations in metabolites released into the aquatic environment by turbot at different densities. Results showed that 29 and 47 metabolites were significantly upregulated in the MD and HD groups, respectively, compared with the LD group. Among them, hexadecanedioic acid, xanthine, phenethylamine, proline and styrene were significantly upregulated in the MD vs. LD, HD vs. MD and HD vs. LD. The VIP diagram of OPLS-DA alignment showed that phenethylamine was the most important metabolite shared by MD vs. LD, HD vs. MD and HD vs. LD. Key gene changes in the GH/IGF-1 signaling pathway, HPI axis of turbot were studied using qRT-PCR for density treatment. The results demonstrated that the expression of GH, GHR and IGF-1 was significantly lower, while the expression of CRH and ACTH was higher in the HD group. Additionally, plasma levels of cortisol, glucose, triglycerides and T3 were also highest in the HD group compared with the LD and MD groups. Phenylethylamine concentration was positively correlated with the HPI axis and negatively correlated with the GH/IGF-1 signaling pathway. To investigate the impact of phenethylamine accumulation on turbot, an acute treatment experiment with phenethylamine was set up. Its concentration in the aquatic environment was set at 0 (CON), 10−7 (LP) and 10−5 (HP) mol/L via exogenous addition, and turbot were exposed to these environments for 2 days. There was a high degree of concordance between the GH/IGF-1 signaling pathway (GH, GHR, IGF-1), HPI axis (CRH, ACTH) and plasma physiological changes (cortisol, glucose, triglycerides, T3) in the phenethylamine-treated group and the density-treated group. Therefore, accumulation of phenethylamine with increasing stocking density may be a potential cause of density stress. Phenylethylamine has a dose-dependent and trace effect as a pheromone.

Three-dimensional finite element stress analysis of surface-mounted inlays in repairing pulp-penetrating non-carious cervical lesion of maxillary first premolar.

This study aimed to explore the stress distribution of surface-mounted inlays with two ceramic materials and different strategies for fiber post-restoration on pulp-penetrating non-carious cervical lesion in a maxillary first premolar to provide minimally invasive and reasonable restorative methods. The cone beam computed tomography data of the standard right upper first premolar were selected. Healthy control (HC) and defective control (DC) finite element models were established. Then, eight experimental models were established according to two different ceramic materials (IPS e.max CAD [LD] and Lava Ultimate [LU]) and different locations of fiber post (without fiber post [NP], fiber post in buccal root canal [B], fiber post in palatal root canal [P], fiber post in both root canals [BP]), namely, LDNP, LDB, LDP, LDBP, LUNP, LUB, LUP, and LUBP. Axial load F1 and lateral load F2 were applied. Maximum principal stress and displacement of the buccal tip were investigated using finite element analysis software. Then, the percentage change of the following indicators in each experimental group was analyzed: stress of defective tip with group DC, stress of enamel and dentine, and displacement of buccal tips with group HC. It was considered similar when the percentage change was less than 5%. LD and LU groups could effectively reduce the stress of the defective tip, but the decreasing amplitude in the former was greater than that of the latter. For the stress of surface-mounted inlays and resin adhesive layer, LD groups were higher than LU groups, and no significant difference in stress peak was found among different experimental groups in the same material. In addition, fiber posts in double root canals could significantly reduce buccal tip displacement. For pulp-penetrating non-carious cervical lesions, the restorative strategy of surface-mounted inlays could be applied. Compared with Lava Ultimate, IPS e.max CAD could better protect the defective tip tooth. Furthermore, fiber posts in double root canals could decrease overall deformation and increase the retention of surface-mounted inlays.

Dietary supplementation with Dendrobium officinale leaves improves growth, antioxidant status, immune function, and gut health in broilers.

The Dendrobium officinale leaves (DOL) is an underutilized by-product with a large biomass, which have been shown to exhibit immunomodulatory and antioxidant functions. The purpose of this research was to investigate the effects of DOL on broiler growth performance, antioxidant status, immune function, and gut health. One hundred and ninety-two 1-day-old chicks were selected and divided into 4 groups at random, 6 replicates for each group and 8 in each. Chicks were given a basal diet supplemented with different amounts of DOL: 0% (control group, NC), 1% (LD), 5% (MD), or 10% (HD). During the feeding trial (70 days), broiler body weight, feed intake, and residual feeding were recorded. On d 70, 12 broilers from each group were sampled for serum antioxidant and immune indexes measurement, intestinal morphological analysis, as well as 16S rRNA sequencing of cecal contents and short-chain fatty acid (SCFA) determination. In comparison to the NC group, the LD group had greater final body weight and average daily gain, and a lower feed conversion ratio (p < 0.05, d 1 to 70). However, in MD group, no significant change of growth performance occurred (p > 0.05). Furthermore, DOL supplementation significantly improved the levels of serum total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and catalase, but reduced the level of malondialdehyde (p < 0.05). Higher serum immunoglobulin A (IgA) content and lower cytokine interleukin-2 (IL-2) and IL-6 contents were observed in DOL-fed broilers than in control chickens (p <0.05). Compared to the NC group, duodenal villus height (VH) and villus height-to-crypt depth (VH:CD) ratio were considerably higher in three DOL supplementation groups (p < 0.05). Further, 16S rRNA sequencing analysis revealed that DOL increased the diversity and the relative abundance of cecal bacteria, particularly helpful microbes like Faecalibacterium, Lactobacillus, and Oscillospira, which improved the production of SCFA in cecal content. According to Spearman correlation analysis, the increased butyric acid and acetic acid concentrations were positively related to serum antioxidant enzyme activities (T-AOC and GSH-Px) and immunoglobulin M (IgM) level (p < 0.05). Overall, the current study demonstrated that supplementing the dies with DOL in appropriate doses could enhance growth performance, antioxidant capacity, and immune response, as well as gut health by promoting intestinal integrity and modulating the cecal microbiota in broilers. Our research may serve as a preliminary foundation for the future development and application of DOL as feed additive in broiler chicken diets.