Titration Studies Research Articles

1046 Severe hypoventilation in a child with rapid onset weight gain

Abstract Introduction Pediatric sleep-related hypoventilation is a clinical pattern in which ventilatory insufficiency occurs in the setting of either severe OSA (obstructive hypoventilation) or obesity hypoventilation (sleep related hypoventilation). We are reporting a case describing the management of overlapping obstructive hypoventilation due to uncontrolled severe OSA and pediatric obesity hypoventilation syndrome. Report of case(s) The patient is a full term African American 5 y/o male with past medical history of obesity and prediabetes who was referred to discuss sleep related problems after rapid onset of weight gain.He gained 76 lbs over 8-month period; during this time his aunt noticed apneic events with the development of loud snoring.Initial workup was negative for abnormal findings,MRI w/w/o was unremarkable and TSH, cortisol, GH, IGF-1 and prolactin were all within normal limits. X-ray bone age study showed skeletal age appropriate for patient's chronologic age.Upper airway exam showed severe tonsillar hypertrophy 3+ with Mallampati class 4.The diagnostic PSG demonstrated the presence of 12 obstructive, 151 central, and 61 mixed apneas.There were 214 hypopneas resulting in an Apnea\Hypopnea Index of 60.5 events per hour.Mean oxygen saturation was 91.3%.The lowest oxygen saturation during sleep was 64.0%.Time spent ≤88% oxygen saturation was 119.7 minutes (26.2%). End tidal CO2 range was between 50-100 mmHg for 30% of study.The titration study revealed that the optimal treatment modality was BiPAP ST. Conclusion This case focuses on a five-year-old male who experienced rapid onset weight gain and presented with snoring, excessive daytime sleepiness and apneic events and was found to have profound hypoventilation with hypopnea predominant severe obstructive sleep apnea.The initial differential diagnosis of pediatric sleep-related hypoventilation includes ROHHAD, congenital central hypoventilation syndrome, primary central sleep apnea and obesity hypoventilation syndrome.The most common cause of hypoventilation during sleep in children remains OSA.The stepwise approach to management in such a case includes tonsillectomy with adenoidectomy,along with use of BiPAP. After the T&A the patient should have repeat PSG with capnography, if hypercarbia persists on post procedure PSG, he will need to continue BiPAP therapy with appropriate weight loss program. Early recognition evaluation, and treatment of obstructive sleep apnea in the pediatric population is imperative to prevent long-term consequences. Support (if any)

1023 A Case of Stridor in the Sleep Clinic

Abstract Introduction Multisystem atrophy (MSA) is a neurological degenerative progressive disease affecting multiple systems. These patients are frequently seen in the sleep clinic at specialty centers by sleep neurologists for co-management of sleep disordered breathing and nocturnal respiratory issues. Stridor is a life-threatening condition seen in these patients and requires emergent action. We present a case of MSA with worsening stridor that was missed in the era of virtual telemedicine. Report of case(s) A 53-year-old female with a history of obstructive sleep apnea (OSA) on BiPAP S and multiple system atrophy with parkinsonian subtype presented virtually to sleep clinic for follow up evaluation of her sleep disordered breathing. Six months prior to her visit she was noted to have bilateral vocal fold hypomobility without stridor. At that time, she had a residual apnea-hypopnea index (AHI) of 1.4 with BiPAP-S 16/13 cm H2O and no nocturnal stridor. She was wheelchair bound. She had routine follow up visits with various providers however these were telemedicine visits with her husband doing most of the talking due to weakness. Over the next 5 months she had worsening fatigue and was using BiPAP S during the day intermittently and was referred to the sleep medicine clinic for consideration of supplemental oxygen at night. A repeat overnight oximetry revealed residual oxygen desaturation index (ODI) of 2.5/hr while on BiPAP S. Repeat pulmonary function testing was ordered and patient was recommended to return for immediate in person follow up. When seen in person, patient was noted to have significant stridor which had been ongoing and worsening over last few months including being appreciated while on PAP therapy. Emergent same-day ENT consultation was arranged by sleep providers. Posterior cordectomy was performed shortly thereafter. The patient was scheduled for an AVAPS titration study. Conclusion In cases with progressive neuromuscular disease, stridor may be missed during virtual appointments for a variety of reasons including technical difficulties, or the virtual medium not being sensitive enough to convey stridor. This case highlights the importance of having a high index of suspicion for stridor and impending respiratory failure requiring emergent intervention in patients with neuromuscular disease. Support (if any)

Factors Associated with the Underestimation of Manual CPAP Titration Pressure.

During the SARS-CoV-2 pandemic, the use of in-laboratory positive airway pressure (PAP) titration studies was not routinely suggested. PAP pressure prediction calculations are emerging as alternative methods for the treatment of these patients. The underestimation of PAP titration pressure usually leads to unsatisfactory results for PAP therapy. This study aimed to evaluate the factors associated with the underestimation of PAP titration pressure when using PAP pressure prediction equations. Estimated PAP pressure formulas based on body mass index (BMI) and apnea-hypopnea index (AHI) were chosen to validate the accuracy of equations in the successful prediction of titration pressure. Among 341 adult patients diagnosed with obstructive sleep apnea (OSA) by overnight polysomnography (PSG) and who received overnight PAP titration in order to select a successful pressure, the mean age of the total subjects was 55.4 years old and 78.9% of patients were male. The average BMI and AHI scores were 27.1 ± 4.8 and 37 ± 21.7, respectively. After multivariate stepwise regression analysis, the odds ratio of participants with a pretitration AHI was 1.017 (95% CI: 1.005-1.030). Only the severity of OSA was significantly different between the underestimated group and the adequately assessed group. In conclusion, a high AHI, but not BMI, is associated with an underestimated CPAP titration pressure in adult patients with OSA.

Synthesis, crystal structure, DNA binding, molecular docking, DFT, Hirshfeld surface analysis, and cytotoxicity of copper (II) complex with malonamide and 2,9-dimethyl-1,10-phenanthroline

A new copper (II) complex, [Cu(dmp)(malon)(H2O)](NO3)2 where malon = malonamide and dmp = 2,9-dimethyl-1,10-phenanthroline, has been synthesized and characterized by elemental analysis, FT-IR, UV–Visible and single crystal XRD techniques. The complex was crystallized in a monoclinic system with space group P21/n. Single-crystal XRD studies have established that the copper (II) complex cation has a distorted square-pyramidal geometry, with Jahn-teller distortion occurring in the CuN2O3 core. The DFT/UB3LYP/LANL2DZ level of theory was used to optimize the structure of the present complex. The essential interactions within the crystal structure that lead to molecular packing were identified using Hirshfeld surface analysis. UV–Visible absorption titration, fluorescence, cyclic voltammetry, and viscometric titration studies were used to study the interactions of the present complex with calf thymus DNA (CT-DNA) and propose a partial intercalation binding mechanism. The complex demonstrated strong cytotoxic effects against the human hepatocellular carcinoma cell line (HepG2), and it was discovered to have effective antibacterial and antifungal properties. The efficient binding of the copper (II) complex was observed from molecular docking analysis.

Pediatric outpatient non-invasive ventilation program: Reflections on the first experience from the Middle East.

Long-term noninvasive ventilation (NIV) is being progressively used in children. The current guidelines recommend NIV initiation in the hospital during overnight polysomnography (PSG) titration study. Due to the logistic, socioeconomic, and financial difficulties including bed availability, an outpatient program for NIV initiation and patients/parents counseling to prevent delay and provide cost-effective care has been commissioned. Hence, this study reports on the clinical outcome of our program as it represents the first reported experience from the middle east. A retrospective review of electronic medical charts was conducted for all patients with PSG-confirmed sleep-related breathing disorders (SRBD) who were evaluated and treated in the NIV clinic in the pediatric pulmonary clinic at Sidra Medicine from January 2020 to November 2021. Patients' data included demographics, PSG results, and NIV clinic records. The results show that twenty-eight patients (17 male, 11 female) were included during the study period. The patients' median age at NIV initiation was 11±5.17 years. The median BMI was 32.72±15.91 kg/m2. The most common diagnosis was morbid obesity in 9 (32%) of the patients. The identified SRBD based on the diagnostic PSG were obstructive sleep apnea in 21 patients, hypoventilation in 3 patients, mixed apnea in 3 patients, and central apnea in 1 patient. The median total Apnea-Hypopnea Index (AHI) was 12.7 (0.7-153.9) events per hour. The main reason for the initial NIV clinic visit was NIV initiation in 19 patients. Upon follow-up, six patients were successfully weaned off NIV support by the treating pulmonologist. Five patients refused to use NIV at home. Fifteen out of the remaining seventeen patients used NIV ≥ 4 hours per night (subjective adherence: 88%). Twelve patients used the NIV for ≥ 24 nights per month (70.6%). All parents reported that the clinic experience was beneficial and helped them to be more comfortable with applying the NIV machine at home. In conclusion, pediatric NIV outpatient programs are achievable and beneficial, especially in developing countries. Pediatric NIV clinics managed by a specialized and experienced team play important role in the initiation and follow-up of NIV support. They provide alternative pathways for the care of pediatric patients, education, and support of their families, and decrease the load on intensive care and sleep laboratory units. Studies about cost-effectiveness are needed to evaluate the impact of implementing outpatient NIV programs on sleep laboratories and hospital admission rates.

Design, Synthesis and Evaluation of a Series of Zinc(II) Complexes of Anthracene-Affixed Multifunctional Organic Assembly as Potential Antibacterial and Antibiofilm Agents against Methicillin-Resistant Staphylococcus aureus

A novel class of zinc(II)-based metal complexes, i.e., [Zn2(acdp)(μ-Cl)]·2H2O (1), [Zn2(acdp)(μ-NO3)]·2H2O (2), and [Zn2(acdp)(μ-O2CCF3)]·2H2O (3) (Cl- = chloride; NO3- = nitrate; CF3CO2- = trifluoroacetate) of anthracene-affixed multifunctional organic assembly, H3acdp (H3acdp = N,N'-bis[anthracene-2-ylmethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), have emerged as promising antibacterial and antibiofilm agents in the domain of medicinal chemistry. Accordingly, complexes 1-3 were synthesized by utilizing H3acdp in combination with ZnCl2, Zn(NO3)2·6H2O, and Zn(CF3CO2)2·H2O respectively, in the presence of NaOH at ambient temperature. The complexation between H3acdp and Zn2+ was delineated by a combined approach of spectrophotometric and spectrofluorometric titration studies. The stoichiometry of acdp3-/Zn2+ in all three complexes is observed to be 1:2, as confirmed by spectrophotometric/spectrofluorometric titration data. Elemental analysis (C, H, N, Zn), molar conductance, FTIR, UV-vis, and thermoanalytical (TGA/DTA) data were effectively used to characterize these complexes. Besides, the structures of 1-3 were established by density functional theory (DFT) calculation using B3LYP/6-311G, specifying a self-assembled compact geometry with average Zn···Zn separation of 3.4629 Å. All three zinc complexes exhibited significantly high antibacterial and antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA BAA1717). However, complex 1 showed a more recognizable activity than 2 and 3, with minimum inhibitory concentration (MIC) values of 200, 350, and 450 μg/mL, respectively. The antimicrobial activity was tested by employing the minimum inhibitory concentration (MIC) and time-kill assay. The crystal violet (CV) assay and microscopic study were performed to examine the antibiofilm activity. As observed, complexes 1-3 had an effect on the production of extracellular polymeric substance (EPS), biofilm cell-viability, and other virulence factors such as staphyloxanthin and hemolysin production, autoaggregation ability, and microbial cell-surface hydrophobicity. Reactive oxygen species (ROS) generated due to inhibition of staphyloxanthin production in response to 1-3 were also analyzed. Moreover, complexes 1-3 showed an ability to damage the bacterial cell membrane due to accumulation of ROS resulting in DNA leakage. In addition, complexes 1-3 displayed a synergistic/additive activity with a commercially available antibiotic drug, vancomycin, with enhanced antibacterial activity. On the whole, our investigation disclosed that complex 1 could be a promising drug lead and attract much attention to medicinal chemists compared to 2 and 3 from therapeutic aspects.

0973 HGNS Sensing Lead Damage After 3D Mammogram Requiring HGNS IPG and Lead Re-Implantation

Abstract Introduction Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness, nocturnal hypoxemia, and daytime fatigue. Standard therapy is with positive airway pressure (PAP) therapy. If this is unsuccessful or poorly tolerated, a hypoglossal nerve stimulator (HGNS) can be surgically implanted for treatment. The goal of HGNS treatment is to advance the tongue with each respiration during sleep to relieve oropharyngeal obstruction causing OSA. This therapy has been shown to be efficacious and well tolerated for moderate to severe sleep apnea with a low complication rate. Report of case(s) A 61 year-old female with history of obesity and severe OSA presented to the sleep clinic with complaint of excessive daytime sleepiness and persistently elevated apnea-hypopnea index (AHI) of 42 events/hour despite adequate usage of CPAP therapy. She underwent an HGNS placement for treatment. Following HGNS activation she used it nightly and three months after implantation underwent an HGNS titration study which was successful (AHI 5.7) and the patient was started on optimal treatment settings with resulting resolution of OSA symptoms. After a period of successful device usage, she presented for follow up and reported complaints of excessive fatigue and sleepiness that was sudden. She attributed these changes to a 3D mammography study she underwent for breast cancer surveillance. Repeat home sleep apnea testing showed sudden worsening of her AHI to 50.6. During a thorough investigation of her device, HGNS sensing waveforms indicated possible sensing lead fracture. The patient was taken to the operating room for implanted pulse generator removal and replacement with new sensing and stimulation leads. Intra-operatively, it was noted that the distal sensing lead had several tears of the polyurethane insulation near the hub of the sensor. Following successful re-implantation sensing returned to normal and she has continued HGNS treatment. Conclusion We present a case of an unusual complication of HGNS sensing lead damage following a 3D mammography study. This led to surgical exploration with removal of a torn sensing lead and re-implantation of the HGNS generator and leads. Attention should be brought to patients and providers in the future regarding this rare, but potentially serious complication. Support (if any)

PO-02-058 USING A NOVEL IN VITRO HUMAN BLOOD LOOP MODEL TO EXPLAIN SCAR TISSUE FORMATION A PHYSICIAN MAY ENCOUNTER IN EXTRACTING CORONARY SINUS LEADS

The Medtronic Attain Stability Model 4798 (ASQ) coronary sinus (CS) lead was designed with an active fixation helix for precise placement and extractability. We sought to understand extractability of ASQ as compared to a lead with 1. favorable extractability such as Medtronic Attain Performa Model 4598, and 2. the Medtronic Star Fix® in which considerable fibrotic tissue growth involves the expanded fixation lobes, making the extraction process very challenging. Typically, animal models are used to understand lead fibrotic tissue growth, however, such studies are of limited value. In this study, we used a novel in vitro human blood loop model to evaluate flow profiles and coagulation response which has shown to be a surrogate to fibrotic tissue growth and scar formation. This model allows for improved control and accelerated test conditions in comparison to animal models. To assess thrombus formation as an early indicator of long-term scar development in three Medtronic CS leads and the impact of CS vein fixation design. In this blood donor study, leads were placed inside a closed loop system representing the average CS diameter. Loops were primed with freshly drawn heparinized human blood, donated via an IRB approved Medtronic blood donor program. Heparin concentration was chosen from prior titration studies to prevent clotting in the loop alone. Experiments were run for five hours at 37°C under continuous flow conditions comparable with known CS flow rates. Change in flow rate over time was measured. Post blood exposure, leads were subjected to histological evaluation. On histologic evaluation the Star Fix® (n=6) showed mean thrombus coverage of 70.8±28% compared to minimal thrombus coverage of 3±1.5% on ASQ (n=6) and 3±1.7% on Performa (n=3) (p < 0.05) (Image 1). At a constant pump speed, the 95th percentile of flow rate drop was 165mL/min with Star Fix® implants compared to only 13mL/min drop with ASQ and 9mL/min with Performa. This novel model demonstrates how lead design can impact flow profiles and subsequent thrombus formation as a surrogate to vascular scar formation. The ASQ has minimal thrombus formation and is comparable to Attain Performa. In contrast, Star Fix® with expanded fixation lobes has considerable flow disruption and thrombus formation consistent with the clinical findings of significant scar formation that can result in a challenging extraction procedure.

0988 Vagal Nerve Stimulation and OSA

Abstract Introduction We present a case of obstructive sleep apnea (OSA) worsened by implantation of a vagal nerve stimulator (VNS). A 22-year-old M with PMH of autism and refractory epilepsy s/p VNS implantation was diagnosed with moderate OSA. His parents noted that his sleep-disordered breathing worsened after VNS implantation. He was started on APAP 4-12 cm H2O. Review of adherence data revealed an elevated residual apnea-hypopnea index (AHI) despite nightly usage. PAP titration study was obtained with improvement of AHI on 16 cm H2O. Despite consequent use of determined pressure settings, residual AHI remained elevated. In consultation with the patient’s neurologist, VNS settings were gradually down titrated. Residual AHI improved and remained low as CPAP settings were subsequently weaned. Report of case(s) The vagus nerve is part of the parasympathetic nervous system. Afferent fibers project to cortical regions involved in seizure activity. Vagal nerve activation leads to desynchrony, thereby decreasing seizure activity.3 VNS, an adjunctive non-pharmacologic treatment of refractory epilepsy, consists of a generator with multiple adjustable settings and a lead connected to the left vagus nerve.1 VNS activation, in conjuction with medical therapy, can lead to decreased seizures. However, VNS may cause complications such as vocal cord dysfunction, laryngeal spasm, and dyspnea.2 In this case, VNS was noted to cause OSA due to increased airway obstruction, though the pathophysiological mechanism behind this has not been clearly delineated. 3 Conclusion Based on current evidence of precipitation or worsening OSA with VNS activation, screening and diagnostic testing for OSA in patients under evaluation for VNS placement should be considered. A multidisciplinary approach between Sleep Medicine and Neurology in conjunction with patient goals can lead to a balanced optimization of both epilepsy and OSA management via adjustments of VNS settings, anti-epileptics, and CPAP. Support (if any) 1. VNS therapy epilepsy. Epilepsy Foundation. https://www.epilepsy.com/sites/default/files/atoms/files/516VNS_VNS_FINAL.pdf. December 20, 2022. 2. Ebben MR, Sethi NK, Conte M, Pollak CP, Labar D. Vagus nerve stimulation, sleep apnea, and CPAP titration. J ClinSleepMed. 2008 Oct 15;4(5):471-3. PMID: 18853706. 3. Parhizgar F, Nugent K, Raj R. Obstructive sleep apnea and respiratory complications associated with vagus nerve stimulators. J ClinSleepMed. 2011 Aug 15;7(4):401-7. doi: 10.5664/JCSM.1204. PMID: 21897779.

Dynamic Metalloporphyrin-Based [2]Rotaxane Molecular Shuttles Stimulated by Neutral Lewis Base and Anion Coordination.

A series of dynamic metalloporphyrin [2]rotaxane molecular shuttles comprising of bis-functionalised Zn(II) porphyrin axle and pyridyl functionalised macrocycle components are prepared in high yield via active metal template synthetic methodology. Extensive variable temperature 1 H NMR and quantitative UV-Vis spectroscopic titration studies demonstrate dynamic macrocycle translocation is governed by an inter-component co-ordination interaction between the macrocycle pyridyl and axle Zn(II) metalloporphyrin, which serves to bias a 'resting state' co-conformation. The dynamic shuttling behaviour of the interlocked structures is dramatically inhibited by the addition of a neutral Lewis base such as pyridine, but can also be tuned via post-synthetic rotaxane demetallation of the porphyrin axle core to give free-base, or upon subsequent metallation, Ni(II) [2]rotaxane analogues. Importantly, the Lewis acidic Zn(II) porphyrin axle component is also capable of coordinating anions which induces mechanical bond shuttling behaviour resulting in a novel optical sensing response.

Investigation on the Anticancer and Antibacterial Mechanism of Thiazoline/Imidazoline Derived Palladium(II) Complexes.

Biological activities of a series of palladium(II) complexes (M1-M9) bearing N∩N, N∩S, and N∩O chelating ligands are reported. The palladium complexes were tested for their cytotoxic properties against human cervical cancer (HeLa) cells and antibacterial activity against Gm+ve and Gm-ve bacteria. Among the palladium complexes studied (M1-M9), the complex M5, M8, and M9 were found to be more effective in inhibiting the proliferation of HeLa cells. Hence, these complexes were further investigated for their potential role in cellular damage and apoptosis. DCFDA staining, Rhodamine 123 staining and DNA cleavage assay revealed that complex M5, M8 and M9 induced apoptotic cell death in HeLa cells through ROS generation, DNA damage and mitochondrial depolarization. Computational and titration studies also indicated strong electrostatic interaction with DNA groove. Most of the complexes exhibited good antibacterial activity against both Gm+ve and Gm-ve bacteria. The antibacterial activity of the compounds could not be correlated with their anticancer activity indicating a differential mechanism at their effective concentrations. The detailed study on the antibacterial mechanism of the most potent complex M7 revealed that it exerted its antibacterial activity by inhibiting the function of FtsZ and perturbing the localization of the Z-ring at the mid cell.

Heated humidified high flow nasal cannula therapy in children with obstructive sleep apnea: A randomized cross-over trial

Objective/backgroundModerate-to-severe obstructive sleep apnea (OSA) is highly prevalent in children with obesity and/or underlying medical complexity. The first line of therapy, adenotonsillectomy (AT), does not cure OSA in more than 50% of these children. Consequently, continuous positive airway pressure (CPAP) is the main therapeutic option but adherence is often poor. A potential alternative which may be associated with greater adherence is heated high-flow nasal cannula (HFNC) therapy; however, its efficacy in children with OSA has not been systematically investigated.The study aimed to compare the efficacy of HFNC with CPAP to treat moderate-to-severe OSA with the primary outcome measuring the change from baseline in the mean obstructive apnea/hypopnea index (OAHI). Participants/methodsThis was a single-blinded randomized, two period crossover trial conducted from March 2019 to December 2021 at a Canadian pediatric quaternary care hospital. Children aged 2–18 years with obesity and medical complexity diagnosed with moderate-to-severe OSA via overnight polysomnography and recommended CPAP therapy were included in the study. Following diagnostic polysomnography, each participant completed two further sleep studies; a HFNC titration study and a CPAP titration study (9 received HFNC first, and 9 received CPAP first) in a random 1:1 allocation order. ResultsEighteen participants with a mean ± SD age of 11.9 ± 3.8 years and OAHI 23.1 ± 21.7 events/hour completed the study. The mean [95% CI] reductions in OAHI (-19.8[-29.2, -10.5] vs. -18.8 [-28.2, -9.4] events/hour, p = 0.9), nadir oxygen saturation (7.1[2.2, 11.9] vs. 8.4[3.5, 13.2], p = 0.8), oxygen desaturation index (-11.6[-21.0, -2.3] vs. -16.0[-25.3, -6.6], p = 0.5) and sleep efficiency (3.5[-4.8, 11.8] vs. 9.2[0.9, 15.5], p = 0.2) with HFNC and CPAP therapy were comparable between conditions. ConclusionHFNC and CPAP therapy yield similar reductions in polysomnography quantified measures of OSA severity among children with obesity and medical complexities. Trial registrationNCT05354401 ClinicalTrials.gov.

Synthesis and Study of Crown Ether-Appended Tetraplatinum(II) Macrocylic Chemosensors for Cation Detection

Two new functionalized platinum(II) rectangles, Pt1 and Pt2, were designed and synthesized from phenanthro crown ether- and biphenyl polyether-bridged bicarboxylate ligands, respectively. The fluorescence titration study of rectangles Pt1 and Pt2 with alkali- and alkaline-earth-metal cations indicated that Pt1 can selectively recognize Na+, while Pt2 has selective binding ability for Mg2+. These selectivity findings suggest that the comparative size and conformational nature of the polyether receptor cavity have a crucial influence on the cation selection.

Oxidized pectin modified by sulfonic acid groups as a bio-derived solid acid for the synthesis of 1-amidoalkyl-2-naphthols

The widespread use of homogeneous acids faces enormous environmental problems due to their corrosive nature and recovery issues. On the other hand, developing heterogeneous catalysts with high acid content and benign nature is challenging. Thus, pectin was selected as a cost-effective and eco-friendly support material for preparing a solid acid with high Brønsted acidity. Therefore, pectin was first oxidized by NaIO4 to produce oxidized pectin (OPec) with aldehyde groups as additional sites to effectively anchor melamine (Mel) and chlorosulfonic acid (SA). After oxidation, the dialdehyde content (Ac) was found to be 53.2%. Then, the as-produced OPec-Mel-SA was compared with the catalyst based on non-oxidized pectin (Pec-Mel-SA) to ensure the positive effect of oxidation on the catalytic activity and morphology. Field emission scanning electron microscopy (FESEM) images revealed that OPec-Mel-SA is more ordered with fewer aggregated particles relative to Pec-Mel-SA. The results of energy dispersive X-Ray analysis (EDX) indicated a higher sulfur content for OPec-Mel-SA than Pec-Mel-SA. Moreover, BET (Brunauer-Emmet-Teller) analysis showed a higher SBET and pore volume for OPec-Mel-SA. The higher acidity of OPec-Mel-SA over Pec-Mel-SA nanoparticles was confirmed by titration and Hammet acidity function (H0) studies using H2SO4 as a benchmark. Accordingly, the OPec-Mel-SA nanoparticles presented a higher catalytic activity compared to Pec-Mel-SA for the three-component synthesis of 1-amidoalkyl-2-naphthols from aldehyde, 2-naphthol, and benzamide, under solvent-free conditions. As a bio-inspired and metal-free heterogeneous solid acid, the OPec-Mel-SA nanoparticles were reusable and highly stable for at least five runs.

N-aryl-4-amino-1,8-naphthalimide Tröger's bases-based internal charge transfer (ICT) fluorescence ‘turn-on’ chemosensors for volatile organic amines

The design of reliable sensor systems for quick sensing and monitoring the trace concentrations of volatile organic compounds (VOCs) has been a topical area of research in recent years due to their serious menace to living systems and environmental hazardousness. In this article, we report two unique ‘cleft-shaped’ N-aryl-4-amino-1,8-naphthalimide derived Tröger's bases (TBNap-Ph and TBNap-Es) as efficient, fast fluorescence sensors for discriminative sensing of volatile organic amines (VOAs). The fluorescence titration studies using TBNap-Ph and TBNap-Es demonstrated discriminative fluorescence sensing responses for VOAs with high selectivity for benzylamine detection. The initial emission intensity of TBNap-Ph and TBNap-Es was enhanced drastically upon the addition of benzylamine. However, similar titration studies using other VOAs such as n-propylamine, n-butylamine, diethylamine, isopropylamine, 3-dimethylamino-1-propylamine, triethylamine, and ethanolamine elicited poor to negligible changes in the fluorescence emission intensity. The selective ‘turn-on’ fluorescence sensing of benzylamine was also reflected by sharp color changes and these sensors can be used to detect benzylamine at the parts-per-millions (ppm) level of sensitivity. Furthermore, the experimentally observed discriminative fluorescence sensing property of TBNap-Ph and TBNap-Es towards VOAs was supported by computational calculations.

Sleep medicine practices in pediatric patients during the COVID-19 pandemic

Objectives: The COVID-19 pandemic required precautions for infection control in sleep centers. Our aim was to assess the impact of the COVID-19 pandemic on sleep medicine practices. Methods: Data of patients undergoing polysomnography and positive airway pressure titration studies prior to (2019) and during the pandemic (2020) were analyzed. In addition, the effect of taking appropriate precautions and performing SARS-CoV-2 polymerase chain reaction testing on the safety of sleep medicine practices was investigated. Results: The median age of the patients who underwent sleep studies (polysomnography + positive airway pressure titration studies) in 2019 was 7 (2.5-11.5) years (164 male, 147 female), whilst it was 9 (4-12) years (127 male, 84 female) in 2020. During the outbreak, the frequency of sleep studies increased from 3% (311 tests/10068 total number of outpatient visits in 2019) to 3.7% (211 tests/5666 in 2020). In contrast, the frequency of positive airway pressure titration studies declined from 31.8% (99 positive airway pressure titration studies/311 sleep studies) to 21.8% (46 positive airway pressure titration studies/211 sleep studies) in 2020 compared to 2019. Down syndrome was found to be the most common indication both in 2019 (20.9% of all tests) and 2020 (13.7%). Conclusions: Polysomnographies were performed at a high rate despite the pandemic. However, positive airway pressure titration studies were avoided except for urgent indications because of the potential for aerosolization. In this study, it was shown that sleep studies can be performed safely when necessary precautions are taken.

Molecular Influences on the Quantification of Lewis Acidity with Phosphine Oxide Probes.

Gutmann-Beckett-type measurements with phosphine oxide probes can be used to estimate effective Lewis acidity with 31P nuclear magnetic resonance spectroscopy, but the influence of the molecular structure of a given probe on the quantification of Lewis acidity remains poorly documented in experimental work. Here, a quantitative comparison of triethyl (E), trioctyl (O), and triphenyl (P) phosphine oxides as molecular probes of Lewis acidity has been carried out via titration studies in MeCN with a test set of six mono- and divalent metal triflate salts. In comparison to E, the bulkier O displays a similar range of chemical shift values and binding affinities for the various test metal ions. Spectral linewidths and speciation properties vary for individual cation-to-probe ratios, however, confirming probe-specific properties that can impact the data quality. Importantly, P displays a consistently narrower dynamic range than both E and O, illustrating how electronic changes at phosphorus can influence the NMR response. Comparative parametrizations of the effective Lewis acidities of a broader range of metal ions, including the trivalent rare earth ions Y3+, Lu3+, and Sc3+ as well as the uranyl ion (UO22+), can be understood in light of these results, providing insight into the fundamental chemical processes underlying the useful approach of single-point measurements for quantification of effective Lewis acidity. Together with a study of counteranion effects reported here, these data clarify the diverse ensemble of factors that can influence the measurement of Lewis acid/base interactions.

The counterion-mediated controllable coacervation of nano-ions with polyelectrolytes

Nano-ions can complex with polyelectrolytes for coacervates with hierarchical structures; however, the rational design of functional coacervations is still rare due to the poor understanding of their structure–property relationship from their complex interaction. Herein, 1 nm anionic metal oxide clusters, PW12O403-, with well-defined, mono-disperse structures are applied to complex with cationic polyelectrolyte and the system shows tunable coacervation via the alternation of counterions (H+ and Na+) of PW12O403-. Suggested from Fourier transform infrared spectroscopy (FT-IR) and isothermal titration studies, the interaction between PW12O403- and cationic polyelectrolytes can be modulated by the bridging effect of counterions via hydrogen bonding or ion–dipole interaction to carbonyl groups of polyelectrolytes. The condensed structures of the complexed coacervates are explored by small angle X-ray and neutron scattering techniques, respectively. The coacervate with H+ as counterions shows both crystallized and discrete PW12O403- clusters, with a loose polymer-cluster network in comparison to the system of Na+ which shows a dense packing structure with aggregated nano-ions filling the meshes of polyelectrolyte networks. The bridging effect of counterions helps understand the super-chaotropic effect observed in nano-ion system and provides avenues for the design of metal oxide cluster-based functional coacervates.

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3-4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further.

A reversible and selective chromogenic thiazole tagged chemosensor for Hg2+in aqueous medium: Crystal structure, theoretical investigations and real sample analysis

A novel thiazole tagged Schiff base chemosensor, (E)-N'-((2-aminothiazol-5-yl)methylene)-2-hydroxybenzohydrazide (ATH) has been synthesized in excellent yield by a simple one pot method and characterized by single crystal X-ray diffraction and spectroscopic techniques. The sensing ability of ATH was determined for detection of Hg2+ ions in the presence of different metal ions in aqueous medium. It behaves as an extremely selective and sensitive chromogenic sensor for naked-eye detection of Hg2+ ions with a colour change from colourless to yellow due to ligand to metal charge transfer. Remarkably, the binding constant (Ka) and limit of detection (LOD) for ATHHg2+ complex were found as 1.75 × 104M −1 and 8.85 × 10−7 M, respectively. The Job's plot indicated that the stoichiometric ratio of ATH to Hg2+ is 1:1. The binding mechanism was established based on FT-IR, 1H NMR titration, mass spectrometry and density functional theory studies. The chemosensor exhibited an excellent colorimetric property in 7.0–12.0 pH range. The chemosensor was found to be reversible and reusable in the presence of CN− ions with logic gate behaviour. Further, the chemosensor was utilized to sense Hg2+ ions in tap and Ganga river water samples.