PYLORIC IMPEDANCE PLANIMETRY DURING ENDOSCOPIC PER-ORAL PYLOROMYOTOMY (POP) GUIDES MYOTOMY EXTENT.

BACKGROUND: Per-oral pyloromyotomy (POP), also known as gastric per-oral pyloromyotomy (G-POEM), is the first-line endoscopic intervention for medically refractory gastroparesis. We sought to assess the value of pyloric impedance planimetry using functional luminal imaging probe (FLIP) during POP. METHODS: Patients undergoing POP were retrospectively reviewed from October 2019-February 2024. FLIP measurements, symptoms measured by the gastroparesis cardinal symptom index (GCSI), and gastric emptying scintigraphy (GES) were evaluated before and after POP. RESULTS: Thirty-five patients (29 (82.9%) female, 51.3 (38.4, 60.9) years old, BMI 29.26 (25.46, 32.56kg/m2) underwent POP. Twenty-three patients had pre- and post-POP FLIP measurements. Median pyloric diameter increased from 14.4 (12, 16) to 16 (14.8, 18) mm (S=116.5, p<0.0001). Median distensibility index (DI) increased from 4.85 (3.38, 6) to 8.45 (5.25, 11) mm2/mmHg (S=112, p<0.0001). Management changed based on FLIP values for 5 patients (21.7%) prompting additional myotomy. At 18 (12.8, 47.8) days post-procedure, median GCSI score decreased from 3.33/5 (2.56, 4.12) preoperatively to 2/5 (1, 2.89) postoperatively (S=-193, p<0.001). At 136 (114, 277) day follow-, improvement in GCSI score persisted with a median score of 2.44/5 (1.44, 3.67) (S=-61, p=0.021). Median retention at 4hours on GES decreased from 29% (16.5, 52) to 19.5% (5.75, 35.3) at 97 (88, 130) days post-procedure (S=-108, p=0.0038). There was 75% improvement and 40% normalization of objective gastric emptying (n=26). Greater increase in diameter after pyloromyotomy correlated to a greater decrease in four-hour gastric retention (r=-0.4886, p=0.021). CONCLUSION: POP with FLIP resulted in clinical and radiographic improvement in patients with gastroparesis. FLIP measurements guided myotomy extent, changing management in 21.7% of patients and were correlated with gastric emptying, demonstrating its distinct utility in treatment of gastroparesis.

Patient-Reported Outcome Measures for Pelvic Organ Prolapse: A Systematic Review Using the COnsensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Checklist.

BACKGROUND: Patient-reported outcome measures (PROMs) are recommended to measure the impact of a health condition or intervention effectiveness as they aim to capture what is most meaningful to patients. Several PROMs are used to evaluate pelvic organ prolapse (POP)-related domains, yet the measurement properties of these instruments have not been fully explored with a rigorous analysis of the methodological quality and quality of evidence. OBJECTIVE: To conduct a systematic review reporting on the measurement properties of PROMs used for the assessment of POP-related domains in accordance with the COSMIN guidelines. SEARCH STRATEGY: Five databases were searched from inception to December 2023. SELECTION CRITERIA: Studies were eligible if they involved (1) at least one group of female adults diagnosed with or presenting with symptoms of POP; (2) a self-reported outcome measure (PROMs, questionnaires) to evaluate POP-related domains; and (3) at least one measurement property. DATA COLLECTION AND ANALYSIS: Methodological quality and measurement quality were assessed using the COSMIN risk of bias (ROB) checklist and the COSMIN criteria for good measurement properties. MAIN RESULTS: A total of 13 PROMs were included. The BIPOP had the lowest ROB for Content Validity. The POP-SS was the only PROM with sufficient evidence of adequate construct validity and responsiveness to be used in both surgical and conservative management settings. CONCLUSION: This original work identified a gap in evidence regarding the measurement qualities of identified PROMs used in the POP population.

Mussel watch program in the Sea of Japan: Persistent organic pollutants in bivalves of the family Mytilidae.

In this study current data on the content of POPs in soft tissues of bivalvia species from the Mytilidae family are presented. The highest concentrations of both OCPs and PCBs were found in Amur Bay. The lowest levels were recorded for Bolshoy Pelis Island. Temporal trends of pollutant concentrations showed a decrease from 1996 to 2022. Nevertheless, in 2017 and 2022, we recorded substantial concentrations of less persistent, lower chlorinated PCB congeners that characterized a recent entry of pollutants into the water body. When comparing the obtained data with the results of studies conducted in the countries of the Asia-Pacific region, it was found that the levels of DDT and its metabolites and PCBs in mollusks of the coastal waters of the Sea of Japan were lower than in other countries of the region, however, relatively high pollution of Peter the Great Bay with HCH isomers was noted.

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.

INTRODUCTION: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential. METHOD: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 µM. The derivative 5h, with an IC50 of 13.60 ± 2.51 µM, emerged as the most potent inhibitor. RESULTS: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results. CONCLUSION: All findings underscored the potential of synthesized derivatives for drug development.

Impact of automated pop-up alerts on simultaneous prescriptions of antimicrobial agents and metal cations.

BACKGROUND: Antimicrobial agents (AMAs) are essential for treating infections. A part of AMAs chelate with metal cations (MCs), reducing their blood concentrations. That drug-drug interaction could lead to a reduction of therapeutic efficacy and the emergence of drug-resistant bacteria. However, prescriptions ordering concomitant intake (co-intake) of AMAs and MCs are frequently seen in clinical settings. A method for preventing such prescriptions is urgently needed. METHODS: We implemented pop-up alerts in the hospital's ordering and pharmacy dispensation support system to notify the prescriptions ordering co-intake of AMAs and MCs for physicians and pharmacists, respectively. To assess the effectiveness of the pop-up alerts, we investigated the number of prescriptions ordering co-intake of AMAs and MCs and the number of pharmacist inquiries to prevent co-intake of AMAs and MCs before and after the implementation of pop-up alerts. RESULTS: Before the implementation of pop-up alerts, 84.5% of prescriptions containing AMA and MCs ordered co-intake of AMAs and MCs. Implementing pop-up alerts time-dependently reduced the proportion of prescriptions ordering co-intake of AMAs and MCs to 43.8% and 29.5% one year and two years later, respectively. The reduction of tetracycline-containing prescriptions was mainly significant. Before the implementation of pop-up alerts, the proportion of prescriptions in which pharmacists prevented co-intake of AMAs and MCs was 3.4%. Implementing pop-up alerts time-dependently increased proportions of such prescriptions to 20.9% and 28.2% one year and two years later. CONCLUSION: Implementing pop-up alerts reduced prescriptions ordering co-intake of AMAs and MCs and accelerated pharmacists to prevent co-intake of AMAs and MCs. The implementation of dual pop-up alerts in the hospital's ordering and pharmacy dispensation support system could help prevent co-intake of AMAs and MCs.

Urge Symptoms after Vaginal Uterosacral Plication in Urinary Incontinence Patients without Proximal Urethral Mobility: A Prospective Study.

INTRODUCTION: The primary objective of this study was to evaluate the impact of vaginal uterosacral plication on urge symptoms and quality of life in a cohort of patients with uterosacral ligament insufficiency and urge symptoms. METHODS: A total of 40 female patients were included in the study, and their posterior fornix was supported with gauze to simulate the surgical procedure. Uterosacral plication was applied to patients who experienced a decrease in urinary incontinence, nocturia, a sense of urgency, and a decrease in urge urinary incontinence symptoms or complete recovery. Images of the bladder, bladder neck, urethra, and symphysis pubis were obtained preoperatively and 1 year postoperatively. POP-Q staging was also performed, and patients completed the Overactive Bladder Evaluation Form (OAB-V8) and the Incontinence Impact Questionnaire Short Form (ICIQ-SF). RESULTS: Results from the OAB-V8 questionnaire showed that postoperative nocturia scores improved by 72.1% compared to preoperative scores, and the need to urinate at night and waking up scores improved by 68.3%. The mean bladder neck thickness and the mean detrusor thickness were significantly decreased from 10 to 9.2 (p < 0.0001) and from 8.7 to 6.4 (p < 0.0001), respectively. The ICIQ-SF questionnaire scores showed a 68.4% improvement in urinary incontinence affecting daily life after the operation. CONCLUSION: This study adds to the clinical evidence that uterosacral ligament support improves symptoms of overactive bladder syndromes, including urgency and nocturia. The use of pelvic floor ultrasound and the apical tamponade test is important in patient selection for the correct indication.

Dioxin concentrations and congener distribution in biomass ash from small to large scale biomass combustion plants.

Biomass plays a pivotal role in global energy production, with a significant share allocated for industrial heat and power generation. The combustion of biomass generates biomass ash, which is widely utilized as a fertiliser. However, concerns arise regarding the presence of dioxins in biomass ash, which may limit its continued use. Dioxins are toxic compounds listed under the Stockholm Convention due to their persistence and detrimental effects on human health and the environment. This study investigates the dioxin content in biomass ashes produced in various combustion plants with a capacity of 1-50MWth in Estonia, where biomass is widely used for heating and power production. The research encompassed samples from nine biomass combustion plants with varying technical parameters considering both bottom and fly ash. Dioxin concentrations were determined for 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like PCBs (PCBs). The results indicate that dioxin TEQ content in all samples was well below the European Union's (EU) POP Regulation limit of 5 µg TEQ/kg, with most values being at least tenfold lower. However, some samples failed to meet the EU Fertilising Products Regulation's threshold of 20 ng TEQ/kg. Notably, fly ash exhibited higher dioxin concentrations than bottom ash. While PCBs were in significant concentrations, PCDDs dominated the overall dioxin TEQ content. This study provides essential insights into the dioxin content in biomass ash and its correlation with current EU regulatory limits. It also highlights the complex distribution of dioxin congeners, particularly PCBs, within biomass ash, emphasizing the continued research's importance.

Engineering Lipid-Based Pop-up Conductive Interfaces with PEDOT:PSS and Light-Responsive Azopolymer Films.

Significant challenges have emerged in the development of biomimetic electronic interfaces capable of dynamic interaction with living organisms and biological systems, including neurons, muscles, and sensory organs. Yet, there remains a need for interfaces that can function on demand, facilitating communication and biorecognition with living cells in bioelectronic systems. In this study, the design and engineering of a responsive and conductive material with cell-instructive properties, allowing for the modification of its topography through light irradiation, resulting in the formation of "pop-up structures", is presented. A deformable substrate, composed of a bilayer comprising a light-responsive, azobenzene-containing polymer, pDR1m, and a conductive polymer, PEDOT:PSS, is fabricated and characterized. Moreover, the successful formation of supported lipid bilayers (SLBs) and the maintenance of integrity while deforming the pDR1m/PEDOT:PSS films represent promising advancements for future applications in responsive bioelectronics and neuroelectronic interfaces.

The effect of therapeutic and deterrent messages on Internet users attempting to access 'barely legal' pornography.

Online child sexual abuse material (CSAM) is a growing problem. Prevention charities, such as Stop It Now! UK, use online messaging to dissuade users from viewing CSAM and to encourage them to consider anonymous therapeutic interventions. This experiment used a honeypot website that purported to contain barely legal pornography, which we treated as a proxy for CSAM. We examined whether warnings would dissuade males (18-30 years) from visiting the website. Participants (n = 474) who attempted to access the site were randomly allocated to one of four conditions. The control group went straight to the landing page (control; n = 100). The experimental groups encountered different warning messages: deterrence-themed with an image (D3; n = 117); therapeutic-themed (T1; n = 120); and therapeutic-themed with an image (T3; n = 137). We measured the click through to the site. Three quarters of the control group attempted to enter the pornography site, compared with 35 % to 47 % of the experimental groups. All messages were effective: D3 (odds ratio [OR] = 5.02), T1 (OR = 4.06) and T2 (OR = 3.05). Images did not enhance warning effectiveness. We argue that therapeutic and deterrent warnings are useful for CSAM-prevention.

Corrigendum: Impact of background music on reading comprehension: influence of lyrics language and study habits.

[This corrects the article DOI: 10.3389/fpsyg.2024.1363562.].

[Effects of thunder-fire moxibustion on balance function and musculoskeletal metabolism in female patients of primary osteoporosis with low muscle mass].

OBJECTIVE: To observe the effects of thunder-fire moxibustion on the balance function and musculoskeletal metabolism in female patients of primary osteoporosis (POP) with low muscle mass. METHODS: Sixty female patients of POP with low muscle mass were randomly divided into an observation group (30 cases, 5 cases dropped out) and a control group (30 cases, 2 cases dropped out). The patients in the control group were treated with oral administration of Caltrate D (1.5 g calcium carbonate + 125 IU vitamin D3), one tablet per day for 12 weeks. In addition to the control treatment, the patients in the observation group were treated with thunder-fire moxibustion at Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Ganshu (BL 18), Shenshu (BL 23), and Dachangshu (BL 25), 30 min per acupoint, once every other day, three times a week, for 12 weeks. Balance function indexes (95% confidence ellipse area of the center of pressure [COP], total displacement, average speed), lumbar pain visual analogue scale (VAS), serum muscle metabolism factors (myostatin [MSTN], peroxisome proliferator-activated receptor γ coactivator-1α [PGC-1α]) and bone metabolism factors (aminoterminal propeptide typeⅠ procollagen [PINP], C-terminal telopeptide of typeⅠcollagen [CTX-Ⅰ]) were compared before and after treatment in both groups. RESULTS: Compared before treatment, the 95% confidence ellipse area of COP, total displacement, and average speed in the observation group were decreased after treatment (P<0.01), and the above indexes in the observation group were lower than those in the control group (P<0.05). Compared before treatment, the VAS scores in both groups were decreased after treatment (P<0.01), the score in the observation group was lower than that in the control group (P<0.01). Compared before treatment, the serum levels of MSTN, PINP and CTX-Ⅰ in the observation group were reduced after treatment (P<0.01), while the serum level of PGC-1α was increased (P<0.01). The control group showed a decrease in serum level of MSTN (P<0.05). The observation group had lower serum levels of MSTN and PINP (P<0.05) and higher serum level of PGC-1α (P<0.01) compared to the control group. CONCLUSION: The thunder-fire moxibustion can effectively relieve lumbar pain, improve balance function, and regulate musculoskeletal metabolism in female patients of POP with low muscle mass.

Robotic versus Mini-Laparoscopic Colposacropexy to Treat Pelvic Organ Prolapse: A Retrospective Observational Cohort Study and a Medicolegal Perspective.

Background: POP (pelvic organ prolapse) involves the descent of one or more pelvic organs downwards with or without protrusion from the vaginal opening, caused by the relaxation and weakening of ligaments, connective tissue, and pelvic muscles. Such an outcome negatively impacts the quality of life. The gold standard procedure for repairing apical compartment prolapse is colposacropexy (CS) to secure the anterior and posterior walls of the vagina to the anterior longitudinal sacral ligament, located anteriorly to the sacral promontory, using a mesh. Several surgical approaches are feasible. Laparotomic or minimally invasive methods, including laparoscopic or robotic ones, can restore the horizontal axis of the vagina and typically involve concomitant hysterectomy. Methods: This study is based on 80 patients who underwent CS at Palermo's Ospedali Riuniti Villa Sofia-Cervello from 2019 to 2023. Women aged 35-85 at the time of surgery were divided into two groups: 40 patients underwent mini-laparoscopic surgery, and 40 patients underwent robotic surgery. The following parameters were accounted for: demographic data (initials of name and surname, age), preoperative clinical diagnosis, date of surgery, surgical procedure performed, estimated intraoperative blood loss, duration of surgical intervention, length of hospital stay, postoperative pain assessed at 24 h using the VAS scale, and any complications occurring in the postoperative period. Mini-laparoscopic CS (Minilap) and robotic CS (Rob) were then compared in terms of outcomes. Results: In the Minilap group, 11 patients out of 40 had a preoperative diagnosis of vaginal vault prolapse. The average age in this group was 61.6. Five of these patients had isolated cystocele, while the rest presented vaginal stump prolapse linked to cystocele, rectocele, or both. The remaining 29 patients in the Minilap group had a preoperative diagnosis of uterovaginal prolapse, also associated with cystocele, rectocele, or both, or isolated in nine cases. In the Rob group (average age: 60.1), 13 patients were diagnosed with vaginal prolapse (isolated or associated with cystocele), while the remaining 27 had a diagnosis of uterovaginal prolapse. In the Minilap group, the average procedure duration was 123.3 min, shorter than the Rob group (160.1 min). Conclusions: The data collected throughout this prospective study point to the mini-laparoscopic approach as being preferable over the robotic one in terms of surgical procedure length, intraoperative blood loss, postoperative pain, and aesthetic outcome. Hospital stay duration and post operative complication rates were similar for both groups. The innovative and ever-progressing nature of such procedures calls for novel standards prioritizing patient care as well as medicolegal viability.

The benefits of ablation using TactiFlex compared with TactiCath in an ex vivo model: a face-to-face experimental comparison study.

BACKGROUND: TactiFlex is a next-generation catheter that is being used increasingly in ablation-treatment strategies. The purpose of this study was to investigate the differences in ablation lesions when the ablation power, time, and perfusion flow are varied with TactiFlex and TactiCath catheters. METHODS: The TactiFlex and TactiCath catheters were contacted perpendicularly/obliquely/parallel to the swine myocardium at varying powers (30, 40, and 50 W), time points (10, 15, 20, 25, 30, and 40 s), and forces (5, 10, 15, 20, and 30 g); the depth, width, and area of each lesion were measured, and the number of steam pops that occurred was counted. RESULTS: A total of 672 (336 lesions for each catheter) radiofrequency (RF) energy applications were delivered and 648 lesions were analyzed, excluding steam pops. The surface area and volume increased significantly with an increasing contact force for the TactiCath. The TactiCath lesions were significantly deeper than those for TactiFlex in most groups with the same power and seconds. The surface area was significantly larger when the catheters were contacted obliquely/parallel to the myocardium than perpendicularly using TactiCath, whereas the difference was less significant in the case of TactiFlex. In a 10-g contact force ablation experiment, TactiFlex did not cause pops, but TactiCath caused pops in 9.8% of cases. CONCLUSION: The TactiFlex lesions were shallower than those of TactiCath. However, TactiFlex catheters reduced the steam pops during RF applications. Those data should help clinicians understand the characteristics of the catheters and develop adequate strategies.

The effect of a spinal thrust manipulation's audible pop on brain wave activity: a quasi-experimental repeated measure design.

Introduction: High velocity thrust manipulation is commonly used when managing joint dysfunctions. Often, these thrust maneuvers will elicit an audible pop. It has been unclear what conclusively causes this audible sound and its clinical meaningfulness. This study sought to identify the effect of the audible pop on brainwave activity directly following a prone T7 thrust manipulation in asymptomatic/healthy subjects. Methods: This was a quasi-experimental repeated measure study design in which 57 subjects completed the study protocol. Brain wave activity was measured with the Emotiv EPOC+, which collects data with a frequency of 128 HZ and has 14 electrodes. Testing was performed in a controlled environment with minimal electrical interference (as measured with a Gauss meter), temperature variance, lighting variance, sound pollution, and other variable changes that could have influenced or interfered with pure EEG data acquisition. After accommodation each subject underwent a prone T7 posterior-anterior thrust manipulation. Immediately after the thrust manipulation the brainwave activity was measured for 10 seconds. Results: The non-audible group (N = 20) consisted of 55% males, and the audible group (N = 37) consisted of 43% males. The non-audible group EEG data revealed a significant change in brain wave activity under some of the electrodes in the frontal, parietal, and the occipital lobes. In the audible group, there was a significant change in brain wave activity under all electrodes in the frontal lobes, the parietal lobe, and the occipital lobes but not the temporal lobes. Conclusion: The audible sounds caused by a thoracic high velocity thrust manipulation did not affect the activity in the audible centers in the temporal brain region. The results support the hypothesis that thrust manipulation with or without audible sound results in a generalized relaxation immediately following the manipulation. The absence of a significant difference in brainwave activity in the frontal lobe in this study might indicate that the audible pop does not produce a "placebo" mechanism.

Prevalence and risk factors of pelvic organ prolapse among women in Sidama region, Ethiopia: A community-based survey.

BACKGROUND: Pelvic organ prolapse is a descent of the vaginal compartments and the surrounding organ due to loss of support of the vaginal tissue. It has a significant psychological, physical, and social impact that affects women's quality of life. However, its true prevalence is unknown due to the variability in the methods used to diagnose the disorder. OBJECTIVES: This study aimed to determine the prevalence of pelvic organ prolapse and its associated risk factors among women in Sidama region, Ethiopia. STUDY DESIGN: A community-based cross-sectional survey was conducted in the Dale-Wonsho Health and Demographic Surveillance Site, Sidama region, from March to October 2023. METHODS: A multi-stage stratified cluster sampling was used to select a sample of 816 women. Anatomical prolapse was diagnosed based on the standardized pelvic organ prolapse quantification method, and symptomatic prolapse was assessed by patient-reported symptoms. A complex survey-based modified Poisson regression was used to assess the risk factors associated with prolapse. RESULTS: A total of 815 participated in the interview, and 779 (95.6%) underwent pelvic examination to assess for prolapse status. Anatomical prolapse (Stages II-IV) was observed in 241 (30.9%; 95% confidence interval = 24-38.7) of the participants. The prevalence of symptomatic pelvic organ prolapse was 78.5% (95% confidence interval = 69.1-85.7) among women with anatomical prolapse (189/241). This prevalence falls to 24.27% (95% confidence interval = 19.98-29.16) for the total sample population. Higher frequency of childbirth, prolonged heavy lifting activities, and prolonged labor increased the likelihood of developing anatomical prolapse. Childbirth at an early age and prolonged heavy lifting activities were significantly associated with symptomatic prolapse. CONCLUSION: Anatomical prolapse and symptomatic prolapse are high in the study area. Parity, prolonged heavy lifting, prolonged labor, and early age childbirth were associated with pelvic organ prolapse. Community-based education and interventions that focus on the modification of risk factors are needed.

A study on pelvic organ prolapse confirmed through physical examination and symptoms of prolapse assessed among women in Sidama region of EthiopiaWhy was the study done? Pelvic organ prolapse occurs when one or more vaginal compartments and their surrounding organs drop from their normal position. Imagine the pelvic floor as a supportive sling made of muscles, ligaments, and tissues. These structures usually hold organs, such as vagina, bladder, uterus, and rectum in place. However, when the pelvic floor weakens due to factors, such as pregnancy, childbirth, or menopause, these organs bulge. Symptoms may include feeling a tissue bulge near the vaginal opening, pelvic pressure, lower back pain, urinary changes, and even difficulty keeping in a tampon. However, evidence about how common the problem is in the Sidama region is limited. This may hinder the need for efforts to be taken in identifying and treating the disorder. What did the researchers do? The research team assessed the symptoms of prolapse by asking women through house-to-house visits invited them to the nearby health facility and conducted pelvic examination to confirm the presence of prolapse. Women's characteristics that can be related to prolapse were also assessed through interview. What did the researchers find? A total of 815 women participated in interviews on prolapse symptoms, and 779 underwent pelvic examination. Among those examined, one in three women (241/779) has a physically confirmed prolapse. Among the confirmed prolapses, 189 women reported symptom of prolapse. Women who have birth many times, who work on prolonged heavy lifting activities, and who have a history of labor that lasted more than 24 h have a high chance to develop prolapse. Similarly, those who gave birth before the age of 18 years and those engaged in prolonged heavy lifting activities have higher chance of developing prolapse symptoms. What do the findings mean? The findings showed that prolapse is common in the Sidama region of Ethiopia and that it needs attention of stakeholders.

Development and testing of an efficient micropollutant monitoring strategy across a large watershed.

In recent decades, extensive monitoring programmes have been conducted at the national, international, and project levels with the objective of expanding our understanding of the contamination of surface waters with micropollutants, which are often referred to as hazardous substances (HS). It has been demonstrated that HS enter surface waters via a number of pathways, including groundwater, atmospheric deposition, soil erosion, and urban systems. Given the ever-growing list of substances and the high resource demand associated with laboratory analysis, it is common practice to quantify the listed pathways based on emission factors derived from temporally and spatially constrained monitoring programmes. The derivation calculations are subject to high uncertainties, and substantial knowledge gaps remain regarding the relative importance of the unique pathways, territories, and periods. This publication presents a monitoring method designed to quantify the unique emission pathways of HS in large geographical areas characterized by differences in land use, population, and economic development. The method will be tested for a wide range of HS (ubiquitous organic and inorganic pollutants, pesticides, pharmaceuticals) throughout small sub-catchments located on tributaries. The results of the test application demonstrate a high diversity of both emission loads and instream concentrations throughout different regions for numerous substances. Riverine concentrations are found to be highly dependent on the flow status. Soil concentration levels of polycyclic aromatic hydrocarbons (PAH) and perfluoroalkyl substances (PFAS) are found to be in proportion, whereas that of potentially toxic elements (PTE) in a reverse relationship with economic development. In many instances, concentration levels are also contingent upon land use. The findings of this study reinforce the necessity for the implementation of harmonised and concerted HS monitoring programmes, which should encompass a diverse range of substances, emission sources, pathways and geographical areas. This is essential for the reliable development of emission factors.

Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors.

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC50 value of 16.47 ± 0.54 µM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug development.

Harmonizing Between Chemical Functionality and Surface Area of Porous Organic Polymeric Nanotraps for Tuning Carbon Dioxide Capture.

The energy sector has demonstrated significant enthusiasm for investigating post-combustion CO2 capture, storage, and separation. However, the practical application of current porous adsorbents is impeded by challenges related to cost competitiveness, stability, and scalability. Intregation of heteroatoms in the porous organic polymers (POPs) dispense it more susceptible for CO2 adsorption to attenuate green house gases. In this regard, two hydroxy rich hypercrosslinked POPs, namely Ph/Tt-POP have been developed by one-pot condensation polymerization using a facile synthetic strategy. The high surface areas of both the Ph/Tt-POP (1057 and 893 m2g-1, respectively), and the heteroatom functionality in the POP framework instigated us to explore our material for CO2 adsorption study. The CO2 uptake capacities in Ph/Tt-POP are found to be 2.45 and 2.2 mmol g-1, at 273 K respectively. Further, in-situ static 13C NMR experiment shows that CO2 molecules in Tt-POP appear to be less mobile than those in Ph-POP which probably due to the presence of triazine functional groups along with high abundant -OH groups in the Tt-POP framework. An in-depth study of the CO2 adsorption mechanism by density functional theory (DFT) calculations also shows that CO2 adsorption at the cages formed by two benzyl rings represents the most stable interaction and CO2 molecule is more favorably adsorbed on the Ph-POP with the more negative interaction energies values compared to that of Tt-POP. Further, Non-covalent interaction (NCI) plot reveals that CO2 molecules adsorb more on the Ph-POP than Tt-POP, which can be explain by hydrogen bond formation in case of Tt-POP repeating units turning aside CO2 molecule to interact with the Ph component. Overall, our present study reflects the comprising effects of surface area of the solid adsorbents as well as their functionality can be beneficial for developing efficient hypercrosslinked porous polymers as solid CO2 adsorbent.