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2.
Intensive Care Med ; 50(4): 539-547, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38478027

RESUMEN

PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.


Asunto(s)
Antibacterianos , Sepsis , Adulto , Niño , Humanos , Antibacterianos/uso terapéutico , Teorema de Bayes , Enfermedad Crítica/terapia , Unidades de Cuidado Intensivo Pediátrico , Estudios Prospectivos , Sepsis/tratamiento farmacológico , Programas Informáticos
3.
Nanoscale Horiz ; 9(5): 718-730, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38533801

RESUMEN

Chemical synthesis typically yields the most thermodynamically stable ordered arrangement, a principle also governing surface synthesis on an atomically level two-dimensional (2D) surface, fostering the creation of structured 2D formations. The linear connection arising from energetically stable chemical bonding precludes the generation of a 2D random network comprised of one-dimensional (1D) convoluted stripes through on-surface synthesis. Nonetheless, we underscored that on-surface synthesis possesses the capability not solely to fashion a 2D ordered linear network but also to fabricate a winding 2D network employing a precursor with a soft ring and intermediate state bonding within the Ullmann reaction. Here, on-surface synthesis was exhibited on Cu(111) employing a 2D self-assembled monolayer array of 4,4',5,5'-tetrabromodibenzo[18]crown-6 ether (BrCR) precursors. These precursors were purposefully structured, with a crown ether ring at the core and Br atoms positioned at the head and tail ends, facilitating preferential connections along the elongated axis to foster a 1D stripe configuration. We illustrate how adjustments in the quantities of the intermediate state, serving as a primary linkage, can yield a labyrinthine, convoluted winding 2D network of stripes. The progression of growth, underlying mechanisms, and electronic structures were scrutinized using an ultrahigh vacuum low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) setup combined with density functional theory (DFT) calculations. This experimental evidence opens a novel functionality in leveraging on-surface synthesis for the formation of a 2D random network. This discovery holds promise as a pioneering constituent in the construction of a ring host supramolecule, augmenting its capability to ensnare guest atoms, molecules, or ions.

4.
Nano Lett ; 24(4): 1309-1315, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38258741

RESUMEN

Electrically percolating nanowire networks are among the most promising candidates for next-generation transparent electrodes. Scientific interest in these materials stems from their intrinsic current distribution heterogeneity, leading to phenomena like percolating pathway rerouting and localized self-heating, which can cause irreversible damage. Without an experimental technique to resolve the current distribution and an underpinning nonlinear percolation model, one relies on empirical rules and safety factors to engineer materials. We introduce Bose-Einstein condensate microscopy to address the longstanding problem of imaging active current flow in 2D materials. We report on performance improvement of this technique whereby observation of dynamic redistribution of current pathways becomes feasible. We show how this, combined with existing thermal imaging methods, eliminates the need for assumptions between electrical and thermal properties. This will enable testing and modeling individual junction behavior and hot-spot formation. Investigating both reversible and irreversible mechanisms will contribute to improved performance and reliability of devices.

5.
Microbiol Spectr ; 12(2): e0306523, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38193658

RESUMEN

We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g., Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8-16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use.IMPORTANCESepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods.


Asunto(s)
Secuenciación de Nanoporos , Sepsis , Humanos , Cultivo de Sangre/métodos , Pruebas de Sensibilidad Microbiana , Sepsis/microbiología , Antibacterianos , Cuidados Críticos
6.
BMJ Open ; 13(12): e078175, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38101825

RESUMEN

INTRODUCTION: Few clinical trials have investigated physiotherapy interventions to treat hypoxaemia following abdominal surgery. The objective of this study is to determine the feasibility and safety of conducting a clinical trial of physiotherapist-led non-invasive ventilation (NIV). METHODS AND ANALYSIS: This single-centre, 50-patient, parallel-group, assessor blinded, pilot feasibility randomised controlled trial with concealed allocation will enrol spontaneously ventilating adults with hypoxaemia within 72 hours of major abdominal surgery. Participants will receive either (1) usual care physiotherapy of a single education session (talk), daily walking of 10-15 min (walk) and four sessions of coached deep breathing and coughing (breathe) or (2) usual care physiotherapy plus four 30 min sessions of physiotherapist-led NIV delivered over 2 postoperative days. Primary feasibility and safety outcome measures are; number of eligible patients recruited per week, total time of NIV treatment delivered, acceptability of treatments to patients and clinicians and incidence of adverse events. Secondary feasibility outcomes include measures of recruitment and treatment adherence. Exploratory outcome measures include change in respiratory parameters, postoperative pulmonary complications, length of hospital stay, health-related quality of life, postoperative activity levels and mortality. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the relevant institution. Results will be published to inform future research. TRIAL REGISTRATION NUMBER: ACTRN12622000839707.


Asunto(s)
Ventilación no Invasiva , Fisioterapeutas , Adulto , Humanos , Ventilación no Invasiva/métodos , Calidad de Vida , Estudios de Factibilidad , Proyectos Piloto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Hipoxia/etiología , Hipoxia/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
N Engl J Med ; 389(25): 2341-2354, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-37888913

RESUMEN

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).


Asunto(s)
COVID-19 , Enfermedad Crítica , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Simvastatina , Humanos , Teorema de Bayes , COVID-19/mortalidad , COVID-19/terapia , Tratamiento Farmacológico de COVID-19 , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Mortalidad Hospitalaria , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Simvastatina/uso terapéutico , Resultado del Tratamiento
8.
Sensors (Basel) ; 23(10)2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430534

RESUMEN

Nanostructured tungsten disulfide (WS2) is one of the most promising candidates for being used as active nanomaterial in chemiresistive gas sensors, as it responds to hydrogen gas at room temperature. This study analyzes the hydrogen sensing mechanism of a nanostructured WS2 layer using near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) and density functional theory (DFT). The W 4f and S 2p NAP-XPS spectra suggest that hydrogen makes physisorption on the WS2 active surface at room temperature and chemisorption on tungsten atoms at temperatures above 150 °C. DFT calculations show that a hydrogen molecule physically adsorbs on the defect-free WS2 monolayer, while it splits and makes chemical bonds with the nearest tungsten atoms on the sulfur point defect. The hydrogen adsorption on the sulfur defect causes a large charge transfer from the WS2 monolayer to the adsorbed hydrogen. In addition, it decreases the intensity of the in-gap state, which is generated by the sulfur point defect. Furthermore, the calculations explain the increase in the resistance of the gas sensor when hydrogen interacts with the WS2 active layer.

9.
Phys Chem Chem Phys ; 25(17): 12322-12330, 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37083208

RESUMEN

High-throughput photofragmentation studies of thymine and guanine were performed at 257 and 343 nm and for a wide range of ionisation laser intensities. Combining a continuous laser-based thermal desorption source with femtosecond multiphoton ionisation using a 50 kHz repetition rate laser allowed us to produce detailed 2D maps of fragmentation as a function of incident laser intensity. The fragmentation was distinctly soft, the parent ions being at least an order of magnitude more abundant than fragment ions. For thymine there was a single dominant fragmentation channel, which involves consecutive HNCO and CO losses. In contrast, for guanine there were several competing ones, the most probable channel corresponding to CH2N2 loss through opening of the pyrimidine ring. The dependence of parent ion abundance on the ionisation laser intensity showed that at 257 nm the ionisation of thymine is a 1 + 1 resonance enhanced process through its open-shell singlet state.

10.
Rev Sci Instrum ; 94(3): 037101, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37012808

RESUMEN

The paper under discussion promises a spin- and angle-resolved inverse-photoemission (IPE) setup, where the spin-polarization direction of the electron beam used for excitation "can be tuned to any preferred direction" while "preserving the parallel beam condition." We support the idea to improve IPE setups by introducing a three-dimensional spin-polarization rotator, but we put the presented results to the test by comparing them with the literature results obtained by existing setups. Based on this comparison, we conclude that the presented proof-of-principle experiments miss the target in several aspects. Most importantly, the key experiment of tuning the spin-polarization direction under otherwise allegedly identical experimental conditions causes changes in the IPE spectra that are in conflict with existing experimental results and basic quantum-mechanical considerations. We propose experimental test measurements to identify and overcome the shortcomings.

11.
Spinal Cord ; 61(6): 330-337, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36932257

RESUMEN

STUDY DESIGN: A prospective cohort of patients with acute tetraplegia. OBJECTIVES: This study aimed to determine the feasibility of using mouthpiece ventilation (MPV) in the intensive care unit (ICU) for patients who are extubated after suffering an acute cervical spinal cord injury (CSCI). SETTING: ICU, Princess Alexandra Hospital, Brisbane Australia. METHODS: New admissions to ICU in the 14 months between April 2017 and June 2018 with a CSCI who underwent intubation were assessed for inclusion. MPV was provided to consenting participants (who were deemed likely to be able to maintain ventilation on their own) at the time of extubation and was utilised in addition to standard care while participants were awake. MPV settings, usage, and support hours to educate and facilitate MPV were collected. Feedback from participants and clinical staff was gathered throughout the study. Pre- and post-extubation measures of forced vital capacity (FVC), the frequency of endotracheal suction of sputum, and gas exchange using ventilation-perfusion ratios were recorded along with the incidence of reintubation. RESULTS: Fourteen participated in utilising MPV with 16 episodes of extubation. The average time per participant to have MPV titrated and bedside data collected was 178 minutes. Data from 16 episodes of extubation have been included. Three of the 14 participants failed initial extubation. Feedback from participants and clinicians has been positive and constructive, enabling MPV settings to be adapted to the person with acute CSCI during this pilot study. CONCLUSION: MPV is feasible to use post-extubation for people with CSCI in ICU. Pressure control mode MPV was deemed the most suitable for newly extubated acute CSCI patients. Intensive clinical support is required initially to provide education prior to MPV, and at the time of extubation for both patient and treating clinicians. Both report it to be a useful adjunct to ICU treatment.


Asunto(s)
Traumatismos de la Médula Espinal , Desconexión del Ventilador , Humanos , Estudios Prospectivos , Extubación Traqueal , Estudios de Factibilidad , Proyectos Piloto , Traumatismos de la Médula Espinal/complicaciones , Respiración Artificial , Unidades de Cuidados Intensivos , Cuadriplejía/etiología
12.
Anaesth Intensive Care ; 50(6): 430-446, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35722809

RESUMEN

The Australian and New Zealand College of Anaesthetists (ANZCA) recently reviewed and updated the guideline on equipment to manage a difficult airway. An ANZCA-established document development group, which included representatives from the Australasian College for Emergency Medicine and the College of Intensive Care Medicine of Australia and New Zealand, performed the review, which is based on expert consensus, an extensive literature review, and bi-nationwide consultation. The guideline (PG56(A) 2021, https://www.anzca.edu.au/getattachment/02fe1a4c-14f0-4ad1-8337-c281d26bfa17/PS56-Guideline-on-equipment-to-manage-difficult-airways) is accompanied by a detailed background paper (PG56(A)BP 2021, https://www.anzca.edu.au/getattachment/9ef4cd97-2f02-47fe-a63a-9f74fa7c68ac/PG56(A)BP-Guideline-on-equipment-to-manage-difficult-airways-Background-Paper), from which the current recommendations are reproduced on behalf of, and with the permission of, ANZCA. The updated 2021 guideline replaces the 2012 version and aims to provide an updated, objective, informed, transparent, and evidence-based review of equipment to manage difficult airways.


Asunto(s)
Anestesistas , Cuidados Críticos , Humanos , Nueva Zelanda , Australia , Universidades
13.
J Phys Chem Lett ; 13(26): 6110-6116, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35759344

RESUMEN

Many sophisticated approaches for analyzing properties of chiral matter have been developed in recent years. But in general, the available chiroptical methods are limited to either solvated or small gaseous molecules. Studying the chirality of large biopolymers in the gas phase, including aspects of the secondary structure, becomes accessible by combining the electrospray ionization technique with chiroptical detection protocols. Here, laser-induced photodetachment from gramicidin anions, a peptide consisting of 15 amino acids has been investigated. The angular distribution of photoelectrons is demonstrated to be sensitive to the substitution of protons by cesium ions, which is accompanied by a conformational change. The photoelectron circular dichroism (PECD) is -0.5% for bare gramicidin, whereas gramicidin with several Cs+ ions attached exhibits a PECD of +0.5%. The results are complemented and supported by ion mobility studies. The presented approach offers the prospect of studying chirality and the secondary structure of various biopolymers.


Asunto(s)
Gramicidina , Protones , Aniones , Dicroismo Circular , Gases/química , Gramicidina/química , Iones
14.
Am J Respir Crit Care Med ; 206(7): 874-882, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35608484

RESUMEN

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Adulto , Australia , Glucemia , Enfermedad Crítica/terapia , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hipoglucemia/complicaciones , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico
15.
Sci Rep ; 11(1): 22412, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34789806

RESUMEN

Recent developments in performance and practicality of optically-pumped magnetometers (OPMs) have enabled new capabilities in non-invasive brain function mapping through magnetoencephalography. In particular, the lack of cryogenic operating conditions allows for more flexible placement of sensor heads closer to the brain, leading to improved spatial resolution and source localisation capabilities. Through recording visually evoked brain fields (VEFs), we demonstrate that the closer sensor proximity can be exploited to improve temporal resolution. We use OPMs, and superconducting quantum interference devices (SQUIDs) for reference, to measure brain responses to flash and pattern reversal stimuli. We find highly reproducible signals with consistency across multiple participants, stimulus paradigms and sensor modalities. The temporal resolution advantage of OPMs is manifest in a twofold improvement, compared to SQUIDs. The capability for improved spatio-temporal signal tracing is illustrated by simultaneous vector recordings of VEFs in the primary and associative visual cortex, where a time lag on the order of 10-20 ms is consistently found. This paves the way for further spatio-temporal studies of neurophysiological signal tracking in visual stimulus processing, and other brain responses, with potentially far-reaching consequences for time-critical mapping of functionality in healthy and pathological brains.

16.
Ann Card Anaesth ; 24(4): 441-446, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34747751

RESUMEN

Context and Aims: To describe current fluid and vasopressor practices after cardiac surgery in Australia and New Zealand cardiothoracic intensive care units (ICU). Design and Setting: This web-based survey was conducted in cardiothoracic ICUs in Australia and New Zealand. Methods: Intensivists, cardiac surgeons, and anesthetists were contacted to complete the online survey that asked questions regarding first and second choice fluids and vasopressors and the tools and factors that influenced these choices. Results: There were 96 respondents including 51 intensivists, 27 anesthetists, and 18 cardiac surgeons. Balanced crystalloids were the most preferred fluids (70%) followed by 4% albumin (18%) overall and among intensivists and anesthetists; however, cardiac surgeons (41%) preferred 4% albumin as their first choice. The most preferred second choice was 4% albumin (74%). Among vasopressors, noradrenaline was the preferred first choice (93%) and vasopressin the preferred second choice (80%). 53% initiated blood transfusion at a hemoglobin threshold of 70 g/L. Clinical acumen and mean arterial pressure were the most commonly used modalities in determining the need for fluids. Conclusions: There is practice variation in preference for fluids used in cardiac surgical patients in Australia and New Zealand; however, balanced crystalloids and 4% albumin were the most popular choices. In contrast, there is broad agreement with the use of noradrenaline and vasopressin as first and second-line vasopressors. These data will inform the design of future studies that aim to investigate hemodynamic management post cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Fluidoterapia , Humanos , Unidades de Cuidados Intensivos , Encuestas y Cuestionarios , Vasoconstrictores/uso terapéutico
17.
Intensive Care Med ; 47(11): 1248-1257, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34609547

RESUMEN

PURPOSE: To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis. METHODS: We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ - 3 mEq/L at 48 h. RESULTS: Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48 h, mean fluid administration was 6798 ± 4850 ml vs 6574 ± 3123 ml, median anion gap 6 mEq/L (IQR 5-7) vs 7 mEq/L (IQR 5-7) and median blood ketones 0.3 mmol/L (IQR 0.1-0.5) vs 0.3 (IQR 0.1-0.5) in the PL and SC groups. DKA resolution at 48 h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73-21.16, p = 0.111). At 24 h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68-10.72, p = 0.002). The median ICU and hospital lengths of stay were 49 h (IQR 23-72) vs 55 h (IQR 41-80) and 81 h (IQR 58-137) vs 98 h (IQR 65-195) in the PL and SC groups. CONCLUSION: Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.


Asunto(s)
Cetoacidosis Diabética , Adulto , Estudios Cruzados , Cetoacidosis Diabética/tratamiento farmacológico , Fluidoterapia , Humanos , Solución Salina , Cloruro de Sodio/uso terapéutico
18.
Nano Lett ; 21(18): 7534-7541, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34472869

RESUMEN

In this study, an electrostatically induced quantum confinement structure, so-called quantum point contact, has been realized in a p-type trilayer tungsten diselenide-based van der Waals heterostructure with modified van der Waals contact method with degenerately doped transition metal dichalcogenide crystals. Clear quantized conductance and pinch-off state through the one-dimensional confinement were observed by dual-gating of split gate electrodes and top gate. Conductance plateaus were observed at a step of e2/h in addition to quarter plateaus such as 0.25 × 2e2/h at a finite bias voltage condition indicating the signature of intrinsic spin-polarized quantum point contact.

19.
Cells ; 10(7)2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-34202258

RESUMEN

Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs' adipogenic differentiation potential. Treatment with baricitinib, a JAK-STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation.


Asunto(s)
Lamina Tipo A/metabolismo , Progeria/patología , Piel/patología , Células Madre/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Adipogénesis/efectos de los fármacos , Adolescente , Animales , Azetidinas/farmacología , Compuestos de Boro , Diferenciación Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Niño , Preescolar , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Interleucina-8/metabolismo , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Masculino , Ratones , PPAR gamma/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Purinas/farmacología , Pirazoles/farmacología , Células Madre/efectos de los fármacos , Sulfonamidas/farmacología
20.
Phys Rev E ; 103(6): L061301, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34271727

RESUMEN

Volume integrals over the radial pair-distribution function, so-called Kirkwood-Buff integrals (KBIs), play a central role in the theory of solutions by linking structural with thermodynamic information. The simplest example is the compressibility equation, a fundamental relation in statistical mechanics of fluids. Until now, KBI theory could not be applied to crystals because the integrals strongly diverge when computed in the standard way. We solve the divergence problem and generalize KBI theory to crystalline matter by using the recently proposed finite-volume theory. For crystals with harmonic interaction, we derive an analytic expression for the peak shape of the pair-distribution function at finite temperature. From this we demonstrate that the compressibility equation holds exactly in harmonic crystals.

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