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Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

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Neural Regeneration Research 2024年第9期19卷 1861-1862页

作者： Robert Galinsky Laura Bennet alistair j.Gunn The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Obstetrics and Gynaecology Monash UniversityMelbourneVICAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal *** encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a *** cost of disability associated with preterm brain inj.ry continues to *** of this inj.ry,and disability,would significantly reduce this socioeconomic burden.

关键词： encephalopathy mortality hypoxic

The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling alistair j.mes Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna j.rdan Mathias j.rgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher j.seph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline

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Neural Regeneration Research 2021年第8期16卷 1490-1499页

作者： Morgan j.Schaeffer Leona Chan Philip A.barber Department of Clinical Neurosciences University of CalgaryCalgaryABCanada

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease(amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment.

关键词： amyloid arterial spin labeling cognitive decline dementia imaging magnetic resonance imaging positron emission tomography quantitative susceptibility mapping tau vascular disease white matter hyperintensities

Quality of life assessment in patients with chronic pancreatitis receiving antioxidant therapy

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World j.urnal of Gastroenterology 2010年第32期16卷 4066-4071页

作者： Nehal S Shah alistair j.Makin Aali j.Sheen Aj.th K Siriwardena Hepatobiliary Surgery Unit Manchester Royal InfirmaryManchester M13 9WLUnited Kingdom Department of Gastroenterology Manchester Royal InfirmaryManchester M13 9WLUnited Kingdom

AIM:To undertake a baseline study comparing quality of life(QoL) in patients with chronic pancreatitis(CP) on Antox to those with CP,matched for disease duration,who were not on this ***:CP was defined according to the Zurich *** eight consecutive patients with CP who were taking Antox(antioxidants) were compared with 69 consecutive control CP patients not on *** Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core questions 30 and Pancreatic Modification(28 questions) were used to assess *** of a total of 137 patients 28 in each group were matched for disease duration(within 12 mo).Median disease duration was 8(1-22) years in the Antox group and 7(1-23) years in the Non-Antox cohort(P = NS,Mann-Whitney U-test).Other parameters(age,gender,etiology,endocrine and exocrine insufficiency) were similar between ***:Median visual analogue pain score in the Antox group was 3(0-8) compared with 6(0-8) in the Non-Antox group(P < 0.01).Perceptions of cognitive,emotional,social,physical and role function were impaired in the Non-Antox group compared to Antox patients(P < 0.0001,P = 0.0007,P = 0.0032 and P < 0.005 and P < 0.001,respectively).Analgesics and opiate usage was significantly lower in the Antox group(P < 0.01).Overall physical health and global QoL was better in the Antox group(P < 0.0001,95% CI:1.5-3).CONCLUSION:Contemporary quality of life assessments show that after correction for disease duration and cigarette smoking,patients with CP taking antox had better scores than non-antox controls.

关键词： Chronic pancreatitis Antioxidants Quality of life Assessment Management

Anti-bat tiger moth sounds:Form and function

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Current Zoology 2010年第3期56卷 358-369页

作者： Aaron j.CORCORAN William E.CONNER j.sse R.barber Department of Biology Wake Forest University Department of Fish Wildlife and Conservation BiologyColorado State University

The night sky is the venue of an ancient acoustic battle between echolocating bats and their insect prey. Many tiger moths （Lepidoptera： Arctiidae） answer the attack calls of bats with a barrage of high frequency clicks. Some moth species use these clicks for acoustic aposematism and mimicry, and others for sonar j.mming, however, most of the work on these defensive functions has been done on individual moth species. We here analyze the diversity of structure in tiger moth sounds liom 26 spe- cies collected at three locations in North and South America. A principal components analysis of the anti-bat tiger moth sounds reveals that they vary markedly along three axes：（1） frequency, （2） duty cycle （sound production per unit time） and frequency modulation, and （3） modulation cycle （clicks produced during flexion and relaxation of the sound producing tymbal） structure. Tiger moth species appear to cluster into two distinct groups： one with low duty cycle and few clicks per modulation cycle that supports an acoustic aposematism function, and a second with high duty cycle and many clicks per modulation cycle that is con- sistent with a sonar j.mming function. This is the first evidence from a community-level analysis to support multiple functions for tiger moth sounds. We also provide evidence supporting an evolutionary history for the development of these strategies. Further- more, cross-correlation and spectrogram correlation measurements failed to support a ＂phantom echo＂ mechanism underlying sonar j.mming, and instead point towards echo interference [Current Zoology 56 （3）： 358-369, 2010].

关键词： Acoustic aposematism Sonar j.mming Arctiidae Cross-correlation Autocorrelation

Paleobiological significance of the j.mes Ross Basin

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Advances in Polar Science 2019年第3期30卷 186-198页

作者： j.alistair CRAME British Antarctic Survey High CrossMadingley RoadCambridge CB3 0ETUK

The extensive Late Mesozoic–Early Cenozoic sedimentary succession exposed within the j.mes Ross Basin,Antarctica has huge potential to enhance paleobiological investigations into both the marine and terrestrial fossil *** excess of 7 km in total thickness and spanning the Early Cretaceous(Aptian)–Late Eocene in age,it represents an invaluable high-latitude(~65°S)site for comparison with lower latitude,tropical ones in an essentially greenhouse *** Early Cretaceous(Aptian–Albian)sequence is deep-water but there are indications of shallowing to inner shelf depths in both the Turonian and Coniacian *** first prolific shallow-water marine fauna occurs in the Santonian–Campanian Santa Marta Formation and this is followed by repeated occurrences through the later Campanian,Maastrichtian,Danian and Middle Eocene(Lutetian).In this study an attempt has been made to compare these Antarctic faunas directly with the well-known ones of the same age from the US Gulf *** comparisons made for three time slices,Late Maastrichtian,Danian and Middle Eocene,indicate that the Antarctic is characterised by both low taxonomic diversity and high levels of *** j.mes Ross Basin is providing important evidence to indicate that the highest southern latitudes have always been characterised by a distinctive temperate biota,even on a pre-glacial *** roots of at least some elements of the modern Southern Ocean biota can be traced back to a Late Mesozoic–Early Cenozoic austral realm.

关键词： j.mes Ross Basin biostratigraphy molluscan faunas US Gulf Coast biodiversity patterns evolutionof temperate biotas

Challenges in developing therapeutic strategies for mild neonatal encephalopathy

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Neural Regeneration Research 2022年第2期17卷 277-282页

作者： Alice McDouall Guido Wassink Laura Bennet alistair j.Gunn j.anne O.Davidson Department of Physiology The University of AucklandAucklandNew Zealand

There is increasing evidence that infants with mild neonatal encephalopathy(NE) have significant risks of mortality, brain inj.ry and adverse neurodevelopmental outcomes. In the era of therapeutic hypothermia, infants need to be diagnosed within 6 hours of birth, corresponding with the window of opportunity for treatment of moderate to severe NE, compared to the retrospective grading over 2 to 3 days, typically with imaging and formal electroencephalographic assessment in the pre-hypothermia era. This shift in diagnosis may have increased the apparent prevalence of brain damage and poor neurological outcomes seen in infants with mild NE in the era of hypothermia. Abnormal short term outcomes observed in infants with mild NE include seizures, abnormal neurologic examination at discharge, abnormal brain magnetic resonance imaging and difficulty feeding. At 2 to 3 years of age, mild NE has been associated with an increased risk of autism, language and cognitive deficits. There are no approved treatment strategies for these infants as they were not included in the initial randomized controlled trials for therapeutic hypothermia. However, there is already therapeutic creep, with many centers treating infants with mild NE despite the limited evidence for its safety and efficacy. The optimal duration of treatment and therapeutic window of opportunity for effective treatment need to be specifically established for mild NE as the evolution of inj.ry is likely to be slower, based on preclinical data. Randomized controlled trials of therapeutic hypothermia for infants with mild NE are urgently required to establish the safety and efficacy of treatment. This review will examine the evidence for adverse outcomes after mild NE and dissect some of the challenges in developing therapeutic strategies for mild NE, before analyzing the evidence for therapeutic hypothermia and other strategies for treatment of these infants.

关键词： asphyxia electroencephalogram erythropoietin mild hypoxic ischemic encephalopathy neonatal encephalopathy neurological examination neuroprotection Sarnat score therapeutic hypothermia

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

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Neural Regeneration Research 2019年第10期14卷 1678-1683页

作者： Anthony Davies Guido Wassink Laura Bennet alistair j.Gunn j.anne O.Davidson Department of Physiology The University of Auckland

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and *** hypothermia significantly reduces death and maj.r disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and *** guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic *** clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong *** are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic *** studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of *** this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain inj.ry and neurological outcomes.

关键词： hypoxia-ischemia hypoxic-ischemic encephalopathy therapeutic hypothermia neuroprotection therapeutic strategies randomized controlled trials animal models fetal sheep piglets

A mechanochemical two for one:Mechanical activation of norborn-2-en-7-one releases carbon monoxide and switches on aggregation-induced emission

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Aggregate 2022年第2期3卷 1-2页

作者： Ross W.barber Maxwell j.Robb Division of Chemistry and Chemical Engineering California Institute of TechnologyPasadenaCaliforniaUSA

Mechanical forces are typically considered to be destructive in polymeric materials,leading to degradation via nonspecific chain ***,the emergence of the mechanophore hypothesis has enabled the design of polymers that... 详细信息

关键词： mechanophore polymer mechanochemistry molecular release