Executive Summary: State-of-the-Art Review: Evaluation and Management of Pelvic Osteomyelitis in Stage IV Pressure Injuries: A Multidisciplinary Collaborative Approach.

Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.

Evaluation and Management of Pelvic Osteomyelitis in Stage IV Pressure Injuries: A Multidisciplinary Collaborative Approach.

Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.

The essential synergy of MD simulation and NMR in understanding amorphous drug forms.

Molecular dynamics (MD) simulations and chemical shifts from machine learning are used to predict 15N, 13C and 1H chemical shifts for the amorphous form of the drug irbesartan. The local environments are observed to be highly dynamic well below the glass transition, and averaging over the dynamics is essential to understanding the observed NMR shifts. Predicted linewidths are about 2 ppm narrower than observed experimentally, which is hypothesised to largely result from susceptibility effects. Previously observed differences in the 13C shifts associated with the two tetrazole tautomers can be rationalised in terms of differing conformational dynamics associated with the presence of an intramolecular interaction in one tautomer. 1H shifts associated with hydrogen bonding can also be rationalised in terms of differing average frequencies of transient hydrogen bonding interactions.

The 2023 report of the MJA-Lancet Countdown on health and climate change: sustainability needed in Australia's health care sector.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020, 2021 and 2022. It examines five broad domains: health hazards, exposures and impacts; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the sixth report of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Our results highlight the health and economic costs of inaction on health and climate change. A series of major flood events across the four eastern states of Australia in 2022 was the main contributor to insured losses from climate-related catastrophes of $7.168 billion - the highest amount on record. The floods also directly caused 23 deaths and resulted in the displacement of tens of thousands of people. High red meat and processed meat consumption and insufficient consumption of fruit and vegetables accounted for about half of the 87 166 diet-related deaths in Australia in 2021. Correction of this imbalance would both save lives and reduce the heavy carbon footprint associated with meat production. We find signs of progress on health and climate change. Importantly, the Australian Government released Australia's first National Health and Climate Strategy, and the Government of Western Australia is preparing a Health Sector Adaptation Plan. We also find increasing action on, and engagement with, health and climate change at a community level, with the number of electric vehicle sales almost doubling in 2022 compared with 2021, and with a 65% increase in coverage of health and climate change in the media in 2022 compared with 2021. Overall, the urgency of substantial enhancements in Australia's mitigation and adaptation responses to the enormous health and climate change challenge cannot be overstated. Australia's energy system, and its health care sector, currently emit an unreasonable and unjust proportion of greenhouse gases into the atmosphere. As the Lancet Countdown enters its second and most critical phase in the leadup to 2030, the depth and breadth of our assessment of health and climate change will be augmented to increasingly examine Australia in its regional context, and to better measure and track key issues in Australia such as mental health and Aboriginal and Torres Strait Islander health and wellbeing.

Modifications of surgical techniques in laparoscopic percutaneous extraperitoneal closure of inguinal ring for childhood inguinal hernia to achieve zero recurrence and zero subcutaneous stitch granuloma.

PURPOSE: To present our technical modifications of single incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of the internal inguinal ring (IIR) for pediatric inguinal hernia (PIH). METHODS: The prospectively collected data of all children diagnosed with PIH undergoing SILPEC at our center from 2016 to 2023 were reviewed and divided into two groups for result comparison: Group A: before and Group B: after the implementation of full modifications. Our modifications included using a nonabsorbable monofilament suture, creating a peritoneal thermal injury at the internal inguinal ring (IIR), employing a cannula to ensure the suture at the IIR ligates only the peritoneum, and double ligation of the IIR in selected cases. RESULTS: 1755 patients in group A and in group B (1 month to 14 years old) were enrolled. There were no significant differences regarding baseline patient characteristics between the two groups. At a median follow-up of 40 months, the rate of recurrent CIH and subcutaneous stitch granuloma (SSG) was 2.3% and 1.5% in group A vs. 0% and 0% in group B (p < 0.001). There were no hydroceles, no ascended or atrophic testis. CONCLUSIONS: Our SILPEC technical modifications can achieve zero recurrence and zero SSG for PIH.

Towards a home-grown rural health workforce: Evidence from Tasmania, Australia.

OBJECTIVE: To examine the association between place of origin and principal place of practice (PPP) of domestic Tasmanian health graduates who received end-to-end training with the University of Tasmania (UTAS). METHODS: The 2022 PPP for all UTAS domestic Tasmanian graduates from medicine, nursing, pharmacy, psychology, medical radiation science and paramedicine between 2011 and 2020 was identified using the online Australian Health Practitioner Regulation Agency (Ahpra) registration database. The graduate's place of origin (home address at the time of course application), together with their 2022 PPP, was described using the Modified Monash Model (MM) classification system of remoteness. Data were analysed using STATA. RESULTS: Over the 10-year period, 4079 domestic Tasmanians graduated from health courses at UTAS, of which 3850 (94.4%) were matched to an Australian PPP. In all, 78.3% of graduates were working in Tasmania, while the remainder (21.7%) were employed interstate. Of those with a Tasmanian PPP, 81.4% were working in a regional setting (MM2), while 77.6% of interstate employed graduates recorded a metropolitan (MM1) PPP. Rural place of origin (MM3-7) was associated with rural employment (MM3-7) in both Tasmania (OR, 37.08; 95% CI 29.01-47.39, p < 0.001), and on the Australian mainland (OR, 21.4; 95% CI 17.4-26.3, p < 0.001). CONCLUSIONS: Most domestic Tasmanian origin UTAS health graduates contribute to the state's health workforce after qualifying. Further research is needed to explore PPP over time and to understand why some graduates are motivated to seek employment on the Australian mainland and in particular, metropolitan cities.

Online large volume sample staking preconcentration and separation of enantiomeric GHRH analogs by capillary electrophoresis.

A capillary electrophoresis method is proposed to analyze the four most well-known growth hormone-releasing hormone (GHRH) analogs that are misused by athletes. Dimethyl-ß-cyclodextrin used as a chiral selector allowed, for the first time, the separation of those basic peptide analogs, including enantiopeptides (sermorelin and CJC-1293) that differ by the chirality of only one amino acid. To increase the method sensitivity, electrokinetic preconcentration methods have been investigated. The large volume sample stacking with polarity switching (PS-LVSS) method with an injected sample volume corresponding to 80% of the capillary one was found superior to the sweeping in terms of signal enhancement factor (SEF). Acid and organic solvent addition to the sample (0.1 mM phosphoric acid with 30% methanol) led to a twofold signal improvement, when compared to water as a matrix. We increased capillary dimensions to provide a signal enhancement through the injection of a larger sample volume. Finally, using a combination of the optimized PS-LVSS preconcentration with the chiral capillary zone electrophoresis (CZE), the GHRH analogs were separated and limits of detection between 75 and 200 ng/mL were reached. This method was successfully applied to urine after a desalting step. An optimized C18 SPE was used for that purpose in order to provide low sample conductivity (<130 µS/cm) and preserve the efficiency of LVSS preconcentration. SEF of 640 was obtained with desalted urine spiked with sermorelin by comparison to the CZE (without preconcentration) method.

Challenges of In Vitro Glycation when Producing Blood Materials for Hemoglobin A1C Immunoassays.

BACKGROUND: Blood materials are essential for quality control and assurance of hemoglobin A1C (HbA1C) measurements. This study presents an optimal condition for in vitro glycation to prepare blood materials for HbA1C with desired high HbA1C content and commutable with two immunoassays. METHODS: Washed erythrocytes were adjusted to a hematocrit (Hct) of 50 - 55% and glycated in vitro at 37°C for up to 120 hours with various concentrations of D-glucose in phosphate buffer saline to prepare blood materials for HbA1C. After glycation in each condition, glycation of blood material was inhibited and HbA1C level was monitored. The HbA1c in blood materials from in vitro glycation was compared in terms of stability and commutability with blood materials from other preparation methods. RESULTS: Incubation of erythrocytes with 400 mM D-glucose for 15 hours at 37°C resulted in a significant increase (p < 0.001) of HbA1c in blood materials by at least 40% with a remaining Hct between 38% to 42%. Hemoglobin A1C in blood materials was stable at 3.8 ± 0.8°C for 70 days and during transport for 3 days (temperature ranges from 8.1 to 23.5°C), after inhibition by glucose concentration solution. Hemoglobin A1C values in blood materials from in vitro glycation were commutable between enzymatic and turbidimetric immunoassay. CONCLUSIONS: An optimal condition for in vitro glycation by incubation of erythrocytes with 400 mM D-glucose for 15 hours at 37 °C was able to generate HbA1C material with intact erythrocytes that is sufficiently stable and commutable between enzymatic and turbidimetric immunoassay. Therefore, this condition is suitable for the preparation of blood material for HbA1C immunoassays.

Bowel seromuscular flaps used to repair pelvic defects in patients undergoing reoperative surgery.

BACKGROUND: Pedicled seromuscular bowel flaps may serve as an alternative for pelvic floor reconstruction when conventional omental and muscular flaps are not an option in patients undergoing reoperative abdominopelvic surgery. The aim of this study was to evaluate a unique series of bowel seromuscular flaps used to obliterate intrapelvic defects. METHODS: We conducted a retrospective study on all patients in a single tertiary care institutional database who had undergone pelvic reconstruction with a seromuscular bowel flap from January 2006 to December 2018. The primary outcomes measured were the 30-day morbidity and mortality rates. RESULTS: Twelve patients (6 men 6 women, median age 56.5 years [range 33-77 years]) underwent reoperative abdominopelvic surgery requiring the use of a native small or large seromuscular bowel flap to obliterate pelvic defects. The indications for surgery included chronic infections, fistulizing Crohn's disease, and cancer. In all cases, no residual omentum was available and rectus abdominis muscle flaps were not feasible due to prior operative scars. Thirty-day morbidity occurred in 5 patients (42%), and included urine leak from ureteral injury, anastomotic leak, acute kidney injury, and superficial surgical site infection. No flaps became ischemic or required removal in the postoperative setting. No mortality was recorded. CONCLUSIONS: Bowel seromuscular flaps are a feasible and safe alternative for covering pelvic defects in patients who are undergoing reoperative surgery without the option to use traditional omental and muscular flaps.

Laparoscopic percutaneous closure of patent processus vaginalis without hydrocelectomy for childhood primary hydrocele.

PURPOSE: To present our surgical technique and the outcome of single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of patent processus vaginalis (PPV) without hydrocelectomy for childhood primary hydrocele (CPH). METHODS: A prospective study was conducted on all cases of CPH treated with SILPEC at our center between June 2016 and December 2021. In our SILPEC procedure, PPV was closed extraperitoneally using a percutaneous needle with a wire lasso. No hydrocelectomy or fenestration of the hydrocele was performed. Percutaneous aspiration was performed when the hydrocele fluid could not be pushed back to the peritoneal cavity. RESULTS: 553 patients were enrolled, with a median age of 34 months (range from 22 months to 13 years). Ipsilateral PPV was present in all cases. There were no intraoperative complications and no conversion. At follow-up 6-72 months, recurrent hydrocele occurred in 0.36%, and subcutaneous stitch inflammatory reaction was noted in 0.7%. There was no case of testicular atrophy or iatrogenic cryptorchidism. Postoperative cosmesis was excellent as all patients were virtually scarless. CONCLUSIONS: Ipsilateral PPV was present in all cases of CPH in our series. Our technique of SILPEC of PPV without hydrocelectomy is feasible and safe, with excellent postoperative cosmesis in the management of CPH.

Reduction of recurrence by peritoneal thermal injury in laparoscopic percutaneous extraperitoneal closure of internal ring for inguinal hernia in children.

PURPOSE: To evaluate the impact of peritoneal thermal injury (PTI) in the reduction of recurrence incidence in laparoscopic percutaneous extra-peritoneal closure of internal ring (LPEC) for pediatric inguinal hernia (PIH) in children. METHODS: Medical records of patients undergoing LPEC for PIH at our center were reviewed and divided into 2 groups: Group A (period from June 2017 to December 2017)-without PTI and Group B (period from January 2018 to December 2018) with PTI. The surgical technique and the type of suture used for LPEC were the same for both groups. The outcomes of the two groups were analyzed and compared. RESULTS: 277 patients with 283 IHs in group A were compared to 376 patients with 389 IHs in group B. There were no significant differences between the two groups in terms of age, gender, uni- or bilateral hernia. At a median follow-up period of 48 months, there was no hydrocele, suture granuloma, testicular atrophy, or iatrogenic cryptorchidism in both groups. The recurrence rate in group A was 6.4%, significantly higher than 1.8% in group B (p = 0.002). CONCLUSIONS: Our study showed that PTI in LPEC for PIH is safe and associated with a significant reduction of recurrence incidence.

Laparoscopic versus open Kasai procedure for biliary atresia: long-term results of a randomized clinical trial.

PURPOSE: The role of the laparoscopic approach for the Kasai procedure in the management of biliary atresia is still controversial. The aim of this study is to compare the long-term results of the laparoscopic Kasai procedure (LKP) to the open Kasai procedure (OKP). METHODS: A randomized clinical trial was carried out from October 2009 to March 2017. Patients diagnosed with biliary atresia type III were randomized into 2 groups: one group underwent LKP and the other group-OKP. All the surgical procedures were performed by the same surgeon with the same technical principles. The long-term outcomes were compared between the two groups. RESULTS: 61 patients underwent LKP and 61 patients-OKP, with a median age at the surgery of 79.7 days. The two groups had no significant differences regarding the patients' baseline characteristics. At follow-up up to 142 months, the jaundice-free rate at the 6th postoperative month for LKP and OKP was 52.5% and 60.7%, respectively (p = 0.23). The 10-year cumulative survival after LKP tended to be inferior to OKP, respectively 44.3% vs. 58.9% (p = 0.09). CONCLUSIONS: In this study, the long-term results of LKP tended to be inferior compared to OKP although the differences were not significant.

Urban-rural disparities in acceptance of human papillomavirus vaccination among women in Can Tho, Vietnam.

Background: In Vietnam, cervical cancer is a significant public health concern for women. Unfortunately, despite the availability of the HPV vaccine, low vaccination rates persist. Objectives: This study investigates the discrepancy between urban and rural areas in the willingness to receive HPV vaccination with or without fees. Methods: A cross-sectional study was conducted on a sample of 648 women aged between 15 and 49, living in two urban and two rural Vietnamese districts of Can Tho, between May and December 2021. Results: The overall vaccination rate was 4%, with urban women having a higher rate of 4.9% compared to rural women at 3.1%. Among unvaccinated women, those from rural areas expressed a significantly higher desire to receive the free vaccine (91.4%) than urban women (84.4%). However, the intention to vaccinate declined when rural women and urban women were advised to pay the cost (63.4% and 57.1%, respectively). A strong correlation was found between a positive attitude and intention for vaccination, irrespective of its price or free availability. Education and access to information about the HPV vaccine were also identified as the most significant factors influencing the intention to vaccination among urban and rural women. Conclusion: The low HPV vaccination rates among women aged 15-49 living in both urban and rural regions of Vietnam are a notable public health concern. These outcomes emphasize the critical need for effective programs of vaccine laterization, as an introduction to the offer of affordable and accessible HPV vaccines for women in Can Tho, Vietnam.

Intersubband Polariton-Polariton Scattering in a Dispersive Microcavity.

The ultrafast scattering dynamics of intersubband polaritons in dispersive cavities embedding GaAs/AlGaAs quantum wells are studied directly within their band structure using a noncollinear pump-probe geometry with phase-stable midinfrared pulses. Selective excitation of the lower polariton at a frequency of ∼25 THz and at a finite in-plane momentum k_{‖} leads to the emergence of a narrowband maximum in the probe reflectivity at k_{‖}=0. A quantum mechanical model identifies the underlying microscopic process as stimulated coherent polariton-polariton scattering. These results mark an important milestone toward quantum control and bosonic lasing in custom-tailored polaritonic systems in the mid and far infrared.

Household-Contact Investigation for Detection of Tuberculosis in Vietnam.

BACKGROUND: Active case finding is a top priority for the global control of tuberculosis, but robust evidence for its effectiveness in high-prevalence settings is lacking. We sought to evaluate the effectiveness of household-contact investigation, as compared with standard, passive measures alone, in Vietnam. METHODS: We performed a cluster-randomized, controlled trial at clinics in 70 districts (local government areas with an average population of approximately 500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam. Health workers at each district clinic or hospital were assigned to perform either household-contact intervention plus standard passive case finding (intervention group) or passive case finding alone (control group). In the intervention districts, household contacts of patients with positive results for tuberculosis on sputum smear microscopy (smear-positive tuberculosis) were invited for clinical assessment and chest radiography at baseline and at 6, 12, and 24 months. The primary outcome was the cumulative incidence of registered cases of tuberculosis among household contacts of patients with tuberculosis during a 2-year period. RESULTS: In 70 selected districts, we enrolled 25,707 household contacts of 10,964 patients who had smear-positive pulmonary tuberculosis. In the 36 districts that were included in the intervention group, 180 of 10,069 contacts were registered as having tuberculosis (1788 cases per 100,000 population), as compared with 110 of 15,638 contacts (703 per 100,000) in the control group (relative risk of the primary outcome in the intervention group, 2.5; 95% confidence interval [CI], 2.0 to 3.2; P<0.001); the relative risk of smear-positive disease among household contacts in the intervention group was 6.4 (95% CI, 4.5 to 9.0; P<0.001). CONCLUSIONS: Household-contact investigation plus standard passive case finding was more effective than standard passive case finding alone for the detection of tuberculosis in a high-prevalence setting at 2 years. (Funded by the Australian National Health and Medical Research Council; ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044 .).

RDH10-mediated retinol metabolism and RARα-mediated retinoic acid signaling are required for submandibular salivary gland initiation.

In mammals, the epithelial tissues of major salivary glands generate saliva and drain it into the oral cavity. For submandibular salivary glands (SMGs), the epithelial tissues arise during embryogenesis from naïve oral ectoderm adjacent to the base of the tongue, which begins to thicken, express SOX9 and invaginate into underlying mesenchyme. The developmental mechanisms initiating salivary gland development remain unexplored. In this study, we show that retinoic acid (RA) signaling activity at the site of gland initiation is colocalized with expression of retinol metabolic genes Rdh10 and Aldh1a2 in the underlying SMG mesenchyme. Utilizing a novel ex vivo assay for SMG initiation developed for this study, we show that RDH10 and RA are required for salivary gland initiation. Moreover, we show that the requirement for RA in gland initiation involves canonical signaling through retinoic acid receptors (RAR). Finally, we show that RA signaling essential for gland initiation is transduced specifically through RARα, with no contribution from other RAR isoforms. This is the first study to identify a molecular signal regulating mammalian salivary gland initiation.

Cytotoxicity activities and chemical characteristics of exopolysaccharides and intracellular polysaccharides of Physarum polycephalum microplasmodia.

BACKGROUND: Microbial polysaccharides have been reported to possess remarkable bioactivities. Physarum polycephalum is a species of slime mold for which the microplasmodia are capable of rapid growth and can produce a significant amount of cell wall-less biomass. There has been a limited understanding of the polysaccharides produced by microplasmodia of slime molds, including P. polycephalum. Thus, the primary objectives of this research were first to chemically characterize the exopolysaccharides (EPS) and intracellular polysaccharides (IPS) of P. polycephalum microplasmodia and then to evaluate their cytotoxicity against several cancer cell lines. RESULTS: The yields of the crude EPS (4.43 ± 0.44 g/l) and partially purified (deproteinated) EPS (2.95 ± 0.85 g/l) were comparable (p > 0.05) with the respective crude IPS (3.46 ± 0.36 g/l) and partially purified IPS (2.45 ± 0.36 g/l). The average molecular weight of the EPS and IPS were 14,762 kDa and 1788 kDa. The major monomer of the EPS was galactose (80.22%), while that of the IPS was glucose (84.46%). Both crude and purified IPS samples showed significantly higher cytotoxicity toward Hela cells, especially the purified sample and none of the IPSs inhibited normal cells. Only 38.42 ± 2.84% Hela cells remained viable when treated with the partially purified IPS (1 mg/ml). However, although only 34.76 ± 6.58% MCF-7 cells were viable when exposed to the crude IPS, but the partially purified IPS displayed non-toxicity to MCF-7 cells. This suggested that the cytotoxicity toward MCF-7 would come from some component associated with the crude IPS sample (e.g. proteins, peptides or ion metals) and the purification process would have either completely removed or reduced amount of that component. Cell cycle analysis by flow cytometry suggested that the mechanism of the toxicity of the crude IPS toward MCF-7 and the partially purified IPS toward Hela cells was due to apoptosis. CONCLUSIONS: The EPS and IPS of P. polycephalum microplasmodia had different chemical properties including carbohydrate, protein and total sulfate group contents, monosaccharide composition and molecular weights, which led to different cytotoxicity activities. The crude and partially purified IPSs would be potential materials for further study relating to cancer treatment.

Trophic ecology of a Late Pleistocene early modern human from tropical Southeast Asia inferred from zinc isotopes.

Tam Pà Ling, a cave site in northeastern Laos, has yielded the earliest skeletal evidence of Homo sapiens in mainland Southeast Asia. The reliance of Pleistocene humans in rainforest settings on plant or animal resources is still largely unstudied, mainly due to poor collagen preservation in fossils from tropical environments precluding stable nitrogen isotope analysis, the classical trophic level proxy. However, isotopic ratios of zinc (Zn) in bioapatite constitute a promising proxy to infer trophic and dietary information from fossil vertebrates, even under adverse tropical taphonomic conditions. Here, we analyzed the zinc isotope composition (66Zn/64Zn expressed as δ66Zn value) in the enamel of two teeth of the Late Pleistocene (63-46 ka) H. sapiens individual (TPL1) from Tam Pà Ling, as well as 76 mammal teeth from the same site and the nearby Nam Lot cave. The human individual exhibits relatively low enamel δ66Zn values (+0.24‰) consistent with an omnivorous diet, suggesting a dietary reliance on both plant and animal matter. These findings offer direct evidence of the broad utilization of resources from tropical rainforests by one of the earliest known anatomically modern humans in Southeast Asia.

Capillary Electrophoresis-Mass Spectrometry at Trial by Metabo-Ring: Effective Electrophoretic Mobility for Reproducible and Robust Compound Annotation.

Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (µeff) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma, and urine samples spiked with the same metabolite mixture were used and distributed for analysis by all laboratories. The µeff was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning, and rinsing procedure, etc.) were left to the discretion of the contributing laboratories. The results revealed that the reproducibility of the µeff for 20 out of the 21 model compounds was below 3.1% vs 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the 13 laboratories. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics.

Revealing Intermolecular Hydrogen Bonding Structure and Dynamics in a Deep Eutectic Pharmaceutical by Magic-Angle Spinning NMR Spectroscopy.

Liquid forms of pharmaceuticals (ionic liquids and deep eutectic solvents) offer a number of potential advantages over solid-state drugs; a key question is the role of intermolecular hydrogen bonding interactions in enabling membrane transport. Characterization is challenging since high sample viscosities, typical of liquid pharmaceutical formulations, hamper the use of conventional solution NMR at ambient temperature. Here, we report the application of magic-angle spinning (MAS) NMR spectroscopy to the deep eutectic pharmaceutical, lidocaine ibuprofen. Using variable temperature MAS NMR, the neat system, at a fixed molar ratio, can be studied over a wide range of temperatures, characterized by changing mobility, using a single experimental setup. Specific intermolecular hydrogen bonding interactions are identified by two-dimensional 1H-1H NOESY and ROESY MAS NMR experiments. Hydrogen-bonding dynamics are quantitatively determined by following the chemical exchange process between the labile protons by means of line-width analysis of variable temperature 1H MAS NMR spectra.