Search

Studies the pharmacokinetics of baclofen, a GABA-B agonist, in pediatric patients with gastro-esophageal reflux. Drug dosage and administration; Body fluid concentration; Drug metabolism.

This paper introduces a novel approach for detecting the SARS-CoV-2 recombinant spike protein combining a label free electrochemical impedimetric immunosensor with the use of purified chicken IgY antibodies. The sensor employs three electrodes and is functionalized with an anti-S IgY antibody, ELISA and immunoblot assays confirmed the positive response of chicken immunized with SARS-CoV2 S antigen. The developed immunosensor is effective in detecting SARS-CoV-2 in nasopharyngeal clinical samples from suspected cases. The key advantage of this biosensor is its remarkable sensitivity, and its capability of detecting very low concentrations of the target analyte, with a detection limit of 5.65 pg/mL. This attribute makes it highly suitable for practical point-of-care (POC) applications, particularly in low analyte count clinical scenarios, without requiring amplification. Furthermore, the biosensor has a wide dynamic range of detection, spanning from 11.56 to 740 ng/mL, which makes it applicable for sample analysis in a typical clinical setting., (© 2024. The Author(s).)

Objectives: Abnormalities of gastric function in children with esophageal atresia (EA) could potentially contribute to gastrointestinal symptoms and reduced quality of life (QOL). Therefore, we aimed to determine the feasibility and clinical usefulness of gastric function testing in children with EA., Methods: The validated PedsQL Gastrointestinal Symptoms Questionnaire (PedsQL-GI) was completed to assess gastrointestinal symptoms and symptom-related QOL. Gastric emptying and gastric myoelectrical activity were studied using 13 C-gastric emptying octanoic acid breath test ( 13 C-GEBT) and surface electrogastrography (EGG). Correlations between 13 C-GEBT and EGG parameters and PedsQL-GI scores were investigated., Results: Fifteen patients (four males) were included (median age: 6 [3.0-8.5] years). Mean PedsQL-GI scores as reported by the children were comparable to the healthy population. However, parents reported a diminished QOL. Gastric function tests (gastric emptying and/or surface EGG) showed abnormalities in 12 patients (80%). Patients with abnormal slow waves showed abnormal gastric emptying coefficient more often. There was no significant association between 13 C-GEBT nor EGG results and PedsQL-GI scores., Conclusions: 13 C-GEBT and EGG can be used to evaluate gastric function in patients with EA. Abnormal gastric function tests were present in 80% of our cohort. However, abnormal gastric function did not significantly correlate with reported gastrointestinal symptom-related QOL., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The objectives of this study were to evaluate the stress distribution and risk of fracture of a non-vital immature maxillary central incisor subjected to various clinical procedures using finite element analysis (FEA). A three-dimensional model of an immature central incisor was developed, from which six main models were designed: untreated immature tooth (C), standard apical plug (AP), resin composite (RC), glass-fibre post (GFP), regeneration procedure (RET), and regeneration with induced root maturation (RRM). Mineral trioxide aggregate (MTA) or Biodentine ® were used as an apical or coronal plug. All models simulated masticatory forces in a quasi-static approach with an oblique force of 240 Newton at a 120° to the longitudinal tooth axis. The maximum principal stress, maximum shear stress, risk of fracture, and the strengthening percentage were evaluated. The mean maximum principal stress values were highest in model C [90.3 MPa (SD = 4.4)] and lowest in the GFP models treated with either MTA and Biodentine ® ; 64.1 (SD = 1.7) and 64.0 (SD = 1.6) MPa, respectively. Regarding the shear stress values, the dentine tooth structure in model C [14.4 MPa (SD = 0.8)] and GFP models [15.4 MPa (SD = 1.1)] reported significantly higher maximum shear stress values compared to other tested models (p < 0.001), while no significant differences were reported between the other models (p > 0.05). No significant differences between MTA and Biodentine ® regarding maximum principal stress and maximum shear stress values for each tested model (p > 0.05). A maximum strain value of 4.07E-03 and maximum displacement magnitude of 0.128 mm was recorded in model C. In terms of strengthening percentage, the GFP models were associated with the highest increase (22%). The use of a GFP improved the biomechanical performance and resulted in a lower risk of fracture of a non-vital immature maxillary central incisor in a FEA model., (© 2023. Springer Nature Limited.)

Background: It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered., Aim: To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer., Methods: BALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays., Results: When compared with non-treated controls, AOM/DSS mice receiving AAT therapy exhibited significantly longer colons, and less anal bleeding. Concurrently, AAT-treated mice had significantly fewer polyps, and lower numbers of large colon tumors. Immunohistochemical examinations of colon tissues showed significantly lower neutrophil counts, more granzyme B-positive but fewer MMP9 (gelatinase B)-positive cancer cells and lower numbers of apoptotic cells in mice receiving AAT therapy. The expression levels of IL4 were significantly higher while TNFA was slightly reduced in tumor tissues of AOM/DSS mice treated with AAT than in AOM/DSS mice., Conclusion: Human AAT is an acute phase protein with a broad-protease inhibitory and immunomodulatory activities used as a therapeutic for emphysema patients with inherited AAT deficiency. Our results are consistent with previous findings and support an idea that AAT alone and/or in combination with available anti-cancer therapies may represent a new personalized approach for patients with colitis-induced colon cancer., (© 2023. The Author(s).)

The GABA(B) receptor agonist baclofen is known to suppress the rate of spontaneous swallowing but not pharyngeal muscle contraction. The extent to which baclofen may alter volitional swallowing is not currently known. We investigated the effects of baclofen in healthy subjects, hypothesizing that baclofen exposure would alter volume-regulation and/or piecemeal deglutition behaviors during volitional swallowing attempts. Pharyngeal high-resolution manometry impedance (P-HRM-I) protocol was used to assess swallowing function of 22 healthy adult volunteers (median 29 years) who were investigated on two occasions, receiving 40 mg baclofen (oral) 1 h before study, or placebo (randomized). Standard swallow function variables recommended by the pharyngeal HRM Working Group were derived for 5 ml, 10 ml, and 20 ml volumes of thin and extremely thick liquid challenges. Multiple swallow behaviors, comprising two swallows <5 s apart, were characterized. The spontaneous swallow rate was also determined. Baclofen exposure had no overall significant effect on swallow variables. Upper esophageal sphincter pressure was weaker during exposure to baclofen, during both the pre-deglutitive and post-deglutitive phases of the swallow (p < 0.05 during thick liquid swallows). Piecemeal swallows, where the bolus is separated in two potions, were significantly more common during 20 ml boluses (p = 0.002). Baclofen decreased the frequency of piecemeal deglutition overall. Baclofen has limited to no effect on volitional swallowing measures, however, does reduce the likelihood of initiation of piecemeal deglutition to large volume challenges., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background/aims: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients., Methods: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR., Results: Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time ( P = 0.016), longest acid reflux episodes ( P = 0.024), and DeMeester scores ( P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time ( P = 0.014), higher DeMeester scores ( P = 0.019), higher total acid reflux events ( P = 0.037), and higher longest acid reflux episodes ( P = 0.006)., Conclusion: Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

The prevalence and anatomical features of C-Shaped Mandibular Second Molars (MSMs) are rarely studied in Jordanian sub-population. This study then took a part to evaluate the prevalence of C-shaped in MSMs using cone-beam computed tomography (CBCT) in the Jordanian sub-population. It used a cross-sectional design and three thousand scans collected over eight years between 2011 and 2019. The data were then reviewed for whether they were fully formed of MSMs. A total of 2037 cases that had 2845 MSMs were evaluated to identify C-shaped canals at coronal, middle, and apical sites. An oblique slicing module perpendicular to the long axis of MSMs was used to evaluate the teeth. The type and frequency of C-shaped canals, as well as the correlations between sex and side (right/left) and between sex and groove direction (buccal/lingual) were measured using the chi-square test on SPSS software at the significance level of 95%. A total of 342 teeth of 243 patients were C-shaped molars, which comprised 12% of the patient's teeth and 99 of them as a bilateral C-shaped canal with mean age of 40 years and sex ratio of 2:1 between female and male. With the limitations of this study, the lingual groove and type 3 were the most common properties of MSM. Besides, the Jordanian population mostly had C-shaped canals., (© 2022. The Author(s).)

Background: Cardiac Rehabilitation is an essential following major adverse cardiovascular events however there is no current data correlating rehab performance to long term outcomes., Hypothesis: Patient exercise performance during cardiac rehabilitation reliably predicts future cardiovascular events., Methods: We conducted a single-center study of 486 consecutive patients who participated in a CR program between January 2018 and August 2021. We assessed patient performance using a novel index, the CR-score, which integrated duration, speed of work, and workload conducted on each training device (TD). We used a binary recursive partition model to determine the optimal thresholds for cumulative CR score. We used Cox regression analysis to assess the mortality rate among patients who developed MACE ("study group") and those who did not ("control group")., Results: Among 486 eligible patients, 1-year MACE occurred in 27 (5.5%) patients and was more common in patients with prior cerebrovascular accident or transient ischemic attack (14.8% vs. 3.5%, p < .001). Age, gender, comorbidities, heart failure, and medical treatment did not significantly affect the outcome. The median cumulative CR score of the study group was significantly lower than the control group (595 ± 185.6 vs. 3500 ± 1104.7, p < .0001). A cumulative CR-score of ≥1132 correlated with the outcome (98.5% sensitivity, 99.6% specificity, 95% CI: 0.985-0.997, area 0.994, p < .0001). Patients older than 55 with a cumulative CR score of <1132 were at particularly high risk (OR: 7.4, 95% CI: 2.84-18.42) for 1-year MACE (log-rank p = .03)., Conclusion: Our proposed CR-score accurately identifies patients at high risk for 1-year MACE following the rehabilitation program. Multicenter validation is required., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Objective: To characterize esophageal motility and esophago-gastric junction (EGJ) function during feeding in neonatal intensive care unit (NICU) patients., Patients and Methods: High resolution manometry with impedance (HRIM) was used to investigate esophageal motility and EGJ function in patients admitted to the NICU. Twenty-eight preterm born infants with bronchopulmonary dysplasia (BPD), 12 born with isolated congenital diaphragmatic hernia (iCDH), and 10 with esophageal atresia (EA) were included. Thirteen healthy infants were included as controls. Esophageal motility and EGJ function were analyzed using objective esophageal bolus transport parameters., Results: Normal esophageal peristaltic wave patterns were observed in all investigated infants without EA. Nine of 10 patients with EA presented with abnormal esophageal motor wave patterns. A total of 224 nutritive swallows were analyzed (controls, n = 48; BPD, n = 96; iCDH, n = 60; EA, n = 20). Infants with BPD and iCDH had similar distal contractile strength (DCI) compared to healthy controls, while in patients with EA, DCI was significantly lower (Kruskal-Wallis test, p = 0.001). In most infants, EGJ relaxation after swallowing was unaffected. EGJ barrier function, in terms of EGJ-contractile integral, also appeared well-developed and did not differ significantly among patient groups., Conclusions: We conclude that esophageal motility studies using pressure-impedance analysis are feasible in young infants. Bolus transport mechanisms following nutritive swallows appeared well-established in all investigated infants with the exception of those with EA. EGJ relaxation was also functional after deglutition and EGJ function as an anti-reflux barrier appeared well-developed in all investigated NICU groups., Competing Interests: NR and TO hold a patent on AIMplot, the software used to analyze the pressure flow data. Swallow Gateway™ resource is provided and hosted by Flinders University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rayyan, Omari, Cossey, Allegaert and Rommel.)

Background/aims: Intrabolus pressures are important for esophageal bolus transport and may detect obstructed bolus flow. This study measured the effect esophageal outflow obstruction experimentally induce by a leg-lift protocol., Methods: Twenty-five gastroesophageal reflux disease patients referred for esophageal manometry and a normal motility diagnosis were included. Supine liquid swallows were tested. Leg-lift protocol generated esophageal outflow obstruction by increasing abdominal pressure. Esophageal pressure topography and intrabolus pressure metrics were calculated. These included, (1) mid-domain bolus distension pressure during esophageal emptying (DPE, mmHg) and (2) ramp pressure (mmHg/sec), generated by compression of the bolus between the peristaltic contraction and esophagogastric junction (EGJ)., Results: EGJ relaxation pressure was increased by leg-lift from 13 (11-17) to 19 (14-30) mmHg ( P < 0.005) and distal contractile integral also increased from 1077 (883-1349) to 1620 (1268-2072) mmHg∙cm∙sec ( P < 0.001) as a physiological response to obstruction. All bolus pressures were increased by leg lift; DPE increased from 17 (15-20) to 27 (19-32) mmHg ( P < 0.001), and ramp pressure increased from 3 (1-4) to 5 (2-9) mmHg/sec ( P < 0.05)., Conclusion: Measuring pressures within the intrabolus domain can quantify changes related to obstruction to outflow and may serve as adjunct measures for confirming a diagnosis EGJ outflow obstruction.

Background and study aims  Oropharyngeal dysphagia (OPD) is prevalent in patients with Parkinson's disease (PD). Upper esophageal sphincter (UES) dysfunction is an important pathophysiological factor for OPD in PD. The cricopharyngeus (CP) is the main component of UES. We assessed the preliminary efficacy of cricopharyngeal peroral endoscopic myotomy (C-POEM) as a treatment for dysphagia due to UES dysfunction in PD. Patients and methods  Consecutive dysphagic PD patients with UES dysfunction underwent C-POEM. Swallow metrics derived using high-resolution pharyngeal impedance manometry (HRPIM) including raised UES integrated relaxation pressure (IRP), raised hypopharyngeal intrabolus pressure (IBP), reduced UES opening caliber and relaxation time defined UES dysfunction. Sydney Swallow Questionnaire (SSQ) and Swallowing Quality of Life Questionnaire (SWAL-QOL) at before and 1 month after C-POEM measured symptomatic improvement in swallow function. HRPIM was repeated at 1-month follow-up. Results  C-POEM was performed without complications in all (n = 8) patients. At 1 month, there was an improvement in both the mean SSQ (from 621.5 to 341.8, mean difference -277.3, 95 %CI [-497.8, -56.7], P  = 0.02) and SWAL-QOL (from 54.9 to 68.3, mean difference 9.1, 95 %CI [0.7, 17.5], P  = 0.037) scores. Repeat HRPIM confirmed a decrease in both the mean UES IRP (13.7 mm Hg to 3.6 mm Hg, mean difference -10.1 mm Hg, 95 %CI [-16.3, -3.9], P  = 0.007) and the mean hypopharyngeal IBP (23.5 mm Hg to 10.4 mm Hg, mean difference -11.3 mm Hg, 95 %CI [-17.2, -5.4], P  = 0.003). Conclusions  In dysphagic PD patients with UES dysfunction, C-POEM is feasible and enhances UES relaxation and reduces sphincteric resistance to flow during the swallow, thereby improving dysphagia symptoms., Competing Interests: Competing interests Dr. Omari holds inventorship of the patent family that covers the analytical methods deployed to the swallowgateway.com website, which is owned and provided by Flinders University., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity., Aims: To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD., Methods: Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded., Results: We enrolled 105 patients, aged 21-64 years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05)., Conclusions: EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need., (© 2021 John Wiley & Sons Ltd.)