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1.
Microbiol Spectr ; 11(6): e0356223, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37971233

ABSTRACT

IMPORTANCE: Compared with the phyllosphere, bacteria inhabiting bark surfaces are inadequately understood. Based on a preliminary pilot study, our work suggests that microbial populations vary across tree bark surfaces and may differ in relation to surrounding land use. Initial results suggest that stemflow, the water that flows along the bark surface, actively moves bacterial communities across a tree. These preliminary findings underscore the need for further study of niche microbial populations to determine whether there are connections between the biodiversity of microbiomes inhabiting corticular surfaces, land use, and hydrology.


Subject(s)
Plant Bark , Trees , Pilot Projects , Trees/microbiology , Biodiversity , Bacteria/genetics
2.
QJM ; 116(2): 115-119, 2023 Feb 24.
Article in English | MEDLINE | ID: mdl-35169852

ABSTRACT

BACKGROUND: Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity. AIM: There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021. We aim to describe this outbreak and provide detail on two cases in which isotonitazene was quantified in serum samples. METHODS: Serum samples were available for comprehensive toxicological analysis for two presentations. Written consent was obtained and the samples were analysed through a Thermo XRS ultrahigh-performance liquid chromatography system, interfaced to a Thermo Q Exactive high-resolution accurate mass spectrometer, operating in heated positive ion electrospray mode. Acquired data were processed using Toxfinder software (Thermo) against a regularly updated in-house database. RESULTS: There was an increase in acute opioid presentations to our emergency department from a median of 10 per month to 36 in August 2021. Twenty were treated with naloxone, and 23 were admitted to the hospital for observation and treatment. Serum sample analysis from two patients with acute opioid toxicity responsive to naloxone detected the presence of isotonitazene (0.18 and 0.81 ng/ml). CONCLUSION: We report a cluster of acute opioid toxicity presentations to our Emergency Department with detection of isotonitazene in two cases. Analytical screening is important in determining the presence of novel psychoactive substances (NPS) and to help inform the public health of the implications of NPS use, particularly during clusters of acute recreational drug toxicity presentations.


Subject(s)
Illicit Drugs , Opiate Overdose , Humans , Analgesics, Opioid , Naloxone , Emergency Service, Hospital
3.
Clin Toxicol (Phila) ; 60(10): 1094-1098, 2022 10.
Article in English | MEDLINE | ID: mdl-35943421

ABSTRACT

OBJECTIVE: Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. METHODS: Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. RESULTS: By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). CONCLUSIONS: ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.


Subject(s)
Cannabinoid Receptor Agonists , Crack Cocaine , Adult , Male , Humans , Adolescent , Young Adult , Middle Aged , Heroin , Pregabalin , Emergency Service, Hospital , England/epidemiology , Hallucinations , Benzodiazepines , Seizures
5.
J West Afr Coll Surg ; 10(3): 1-7, 2020.
Article in English | MEDLINE | ID: mdl-35720954

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic affected the delivery of surgical care and services. This review article aims to appraise the impact of COVID-19 on surgical care. The authors discuss the literature on surgery and COVID-19 under the following themes: emergency case triaging, elective surgery triaging, operating on a COVID-19-positive patient, surgical smoke, management of scarce resources, and restarting elective surgery. Most of the large surgical societies recommended and most surgical departments all over the world implemented the cancellation of elective surgeries, while emergency surgeries proceeded as usual. Elective surgeries were triaged taking into consideration the COVID-19 infection rate in the locality, availability of resources, and the need for intensive care unit beds and ventilators. A COVID-19-positive patient should not be denied surgery if indicated, and the recommended precautions and use of personal protective equipment should be adhered to. The generation of surgical smoke occurs in both laparoscopic and open surgeries, and it has not been shown to contain this novel virus. Smoke generation should be minimized and laid down guidelines followed. Laparoscopic surgery seems to have an advantage over open surgery in this regard. In resuming elective surgeries, the local infection rates, bed occupancy rate, and availability of resources should be taken into cognizance. We should learn from this pandemic so as to be prepared for future occurrences, which is a significant possibility.


La pandémie de maladie à virus Corona 2019 (COVID-19) a affecté la prestation de soins et de services chirurgicaux. Cet examen dans notre article vise à évaluer l'impact des Covid-19 sur la chirurgie des soins. Les auteurs discutent de la littérature sur la chirurgie et Covid-19 sous les thèmes suivants: cas urgence triaging, la chirurgie élective triant, opérant sur un patient positif Covid-19, la fumée chirurgicale, la gestion des ressources rares et le redémarrage de la chirurgie élective. La plupart des grandes sociétés chirurgicales recommandaient, et la plupart des services de chirurgie du monde entier ont mis en oeuvre l'annulation des chirurgies électives tandis que les chirurgies d'urgence se déroulaient comme d'habitude. Sur électifs Guéries ont été triés en prenant en considération la Covid -19 taux d'infection dans la localité, la disponibilité des ressources et la nécessité d'I intensive C sont Unit (USI) lits et des ventilateurs. Un Covid -19 patients positif ne doit pas se voir refuser la chirurgie si cela est indiqué, et les précautions recommandées et l'utilisation d'Équipement de protection PERSONNEL LES (EPP) doivent être respectées. La génération de fumée chirurgicale se produit à la fois en chirurgie la périscopique et en chirurgie ouverte et il n'a pas été démontré qu'elle contenait ce nouveau virus. La production de fumée doit être réduite au minimum et des directives établies doivent être suivies. La chirurgie laparoscopie semble avoir un avantage sur la chirurgie ouverte dans ce domaine. En résumant les chirurgies électives, t- il des taux d'infection locale, le taux d'occupation des lits et la disponibilité des ressources devraient être prises en connaissance. Nous devons tirer les leçons de cette pandémie pour nous préparer à de futures occurrences, ce qui est une possibilité importante.

6.
Gen Comp Endocrinol ; 288: 113372, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31866306

ABSTRACT

Reproduction is energetically expensive and investing in this life history trait is likely accompanied by significant changes in physiological activity. Investment strategy necessary for achieving reproductive success in reptiles can vary with reproductive form and pattern, potentiating different consequences for competing fitness-related traits such as those key to survival. The goal of this study was to assess if and how energetic state (i.e., energy metabolites) and self-maintenance (i.e., immunocompetence) are hormonally modulated across reproductive contexts in an oviparous, parthenogenetic lizard, the Colorado Checkered Whiptail Aspidoscelis neotesselata. Here blood plasma samples were collected from lizards within the US Army Fort Carson Military Installation near Colorado Springs, CO, USA, during seasons of reproductive activity (i.e., June) and inactivity (i.e., August). Measures of reproductive (i.e., estradiol) and energy-mobilizing (i.e., corticosterone) hormones, energy metabolites (i.e., glucose, triglycerides, and free glycerol), and innate immunity (i.e., bactericidal ability) were compared by season and reproductive stage. Levels of energy metabolites and bactericidal ability were compared to levels of E2 and CORT. Bactericidal ability was also compared to levels of energy metabolites. Corticosterone and glucose levels were lower during the reproductive season while triglyceride levels and bactericidal ability were higher, but both estradiol and free glycerol levels did not differ between seasons. Throughout vitellogenesis, corticosterone and glucose levels as well as bactericidal ability did not differ, but estradiol levels were higher during early and mid-stage and both triglyceride and free glycerol levels were lower during gravidity. Corticosterone levels were negatively associated with circulating triglycerides and bactericidal ability, but were not related to glucose nor free glycerol levels. Estradiol levels were positively associated with free glycerol levels and bactericidal ability, but were not related to glucose nor triglyceride levels. Finally, bactericidal ability was negatively associated with glucose, but positively associated with triglycerides. Differences in energetic state and immunocompetence are thus reflected by shifts in hormone secretion across reproductive investment. These findings provide partial support for the hypothesis that energetic state is differentially regulated by steroid hormones to afford reproduction, potentially at the cost of future survival.


Subject(s)
Energy Metabolism/physiology , Gonadal Steroid Hormones/metabolism , Immunocompetence/physiology , Lizards/physiology , Reproduction/physiology , Animals , Corticosterone/blood , Estradiol/blood , Female , Lizards/metabolism , Male , Oviparity/physiology , Parthenogenesis/physiology , Seasons , Vitellogenesis/physiology
7.
Sci Total Environ ; 691: 631-643, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31325863

ABSTRACT

Contaminants in the marine environment are widespread, but ship-based sampling routines are much narrower. We evaluated the utility of seabirds, highly-mobile marine predators, as broad samplers of contaminants throughout three tropical ocean regions. Our aim was to fill a knowledge gap in the distributions of, and processes that contribute to, tropical marine contaminants; and explore how species-specific foraging ecologies could inform or bias our understanding of contaminant distributions. Mercury and persistent organic pollutant (POPs) concentrations were measured in adults of five seabird species from four colonies in the central Pacific (Laysan and Tern Islands, Hawaii; Palmyra Atoll) and the eastern Caribbean (Barbuda). Blood-based total mercury (THg) and 89 POPs were measured in two seabird families: surface-foraging frigatebirds (Fregata spp.) and plunge-diving boobies (Sula spp.). Overall, largescale contaminant differences between colonies were more informative of contaminant distributions than inter-specific foraging ecology. Model selection results indicated that proximity to human populations was the best predictor of THg and POPs. Regional differences in contaminants were distinct: Barbudan Magnificent Frigatebirds had more compounds (n=52/89 POP detected) and higher concentrations (geometric mean THg=0.97µgg-1; mean ΣPOP53=26.6ngmL-1) than the remote colonies (34-42/89 POP detected; range of THg geometric means=0.33-0.93µgg-1; range of mean ΣPOP53:7.3-17.0ngmL-1) and had the most recently-synthesized POPs. Moderate differences in foraging ecologies were somewhat informative of inter-specific differences in contaminant types and concentrations between nearshore and offshore foragers. Across species, contaminant concentrations were higher in frigatebirds (THg=0.87µgg-1; ΣPOP53=17.5ngmL-1) compared to boobies (THg=0.48µgg-1; ΣPOP53=9.8). Ocean currents and contaminants' physiochemical properties provided additional insight into the scales of spatial and temporal contaminant exposure. Seabirds are excellent, broad samplers with which we can understand contaminant distributions in the marine environment. This is especially important for tropical remote regions that are under-sampled.


Subject(s)
Birds/metabolism , Environmental Monitoring , Environmental Pollutants/metabolism , Environmental Pollution/statistics & numerical data , Animals , Environmental Pollutants/analysis , Mercury/analysis
8.
Soft Matter ; 14(42): 8570-8579, 2018 Oct 31.
Article in English | MEDLINE | ID: mdl-30320333

ABSTRACT

Recent studies of colloidal systems with a short-range attraction and long-range repulsion (SALR) have been demonstrated to have a generalized phase diagram with multiple liquid states defined by their structures. In this paper, we identify the different liquid states of previous experimentally studied lysozyme samples within this proposed generalized state diagram and explore the dynamic properties of each liquid state. We show that most lysozyme samples studied here and previously at low and intermediate concentrations are dispersed fluids while a few high concentration samples are randomly percolated liquids. In the dispersed fluid region, the short-time diffusion coefficient measured by neutron spin echo agrees well with the long time diffusion coefficient estimated with the solution viscosity. This dynamic feature is maintained even for some samples in the random percolated region. However, the short-time and long-time diffusion coefficients of random percolated fluids deviate at larger concentration and attraction strength. At high enough concentrations, the mean square displacement can be as slow as those of many glassy colloidal systems at time scales near the characteristic diffusion time even though these lysozyme samples remain in liquid states at the long-time limit. We thus identify the region in the generalized phase diagram where these equilibrium states with extremely slow local dynamics exist relative to bulk percolation and kinetic arrest (gel and glassy) transitions.

9.
Eur Radiol ; 28(11): 4717-4724, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29808426

ABSTRACT

OBJECTIVES: To assess patterns of parenchymal tissue on mammography in women with dense breasts and to determine how this varies with age and affects recall to assessment and cancer diagnosis. METHOD: Breast density data was obtained in women attending routine mammographic screening from April 2013 to March 2015 using automated breast density assessment software. Women with the densest breasts were selected for visual interpretation of parenchymal pattern (PP). One hundred non-assessed women, aged 50, 55, 60, 65 and 69-71 years (total = 500), provided controls. Cases included women recalled for assessment (mastectomy or implants excluded) (total = 280). Mammograms reviewed by ten readers and PP classified as: (1) very smooth; (2) mainly smooth; (3) mixed; (4) mainly nodular; (5) very nodular. The ratio of women in each category at each age and screening outcomes were compared by Pearson's chi-squared test. RESULTS: Reader agreement for scoring PP was good (intraclass correlation = 0.6302). Proportions of women in each PP category were similar at all ages for controls (p = 0.147) and cases (p = 0.657). The ratio of PP categories did not vary significantly with age in those who underwent biopsy (p = 0.484). Thirty-four cancers were diagnosed. There was a significant correlation between a diagnosis of cancer and nodular PP compared to not nodular PP (p = 0.043). CONCLUSIONS: The ratio of smooth to nodular pattern in women with the densest breasts did not vary with age. The PP of the breast tissue did not affect likelihood of recall to assessment or biopsy. There was a significant relationship between a nodular parenchymal pattern and diagnosis of cancer. KEY POINTS: • This paper shows that there is good agreement between mammogram readers when classifying mammographic PP on a five-point scale from very smooth to very nodular. • In non-assessed women with the densest breasts, there is no significant change in the proportions of smooth to nodular patterns with increasing age. • The likelihood of recall for further assessment or biopsy at assessment is not related to PP in women with highest breast density. • When recalled for further assessment, significantly more women are diagnosed with cancer in the group with nodular PP on mammography when compared with smooth and mixed patterns.


Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer/methods , Magnetic Resonance Imaging/methods , Mammography/methods , Mass Screening , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Adult , Biomarkers, Tumor/metabolism , Biopsy , Breast Density , Breast Neoplasms/epidemiology , Breast Neoplasms/metabolism , Disease-Free Survival , Female , Humans , Middle Aged , Netherlands/epidemiology , Survival Rate/trends
11.
J Am Chem Soc ; 138(34): 10794-7, 2016 08 31.
Article in English | MEDLINE | ID: mdl-27515494

ABSTRACT

We report a new photocatalytic protocol for the redox-neutral isomerization of cyclic alcohols to linear ketones via C-C bond scission. Mechanistic studies demonstrate that key alkoxy radical intermediates in this reaction are generated via the direct homolytic activation of alcohol O-H bonds in an unusual intramolecular PCET process, wherein the electron travels to a proximal radical cation in concert with proton transfer to a weak Brønsted base. Effective bond strength considerations are shown to accurately forecast the feasibility of alkoxy radical generation with a given oxidant/base pair.


Subject(s)
Alcohols/chemistry , Hydrogen/chemistry , Oxygen/chemistry , Catalysis , Electron Transport
12.
Springerplus ; 5: 617, 2016.
Article in English | MEDLINE | ID: mdl-27330883

ABSTRACT

INTRODUCTION: The 2014 FIFA World Cup was held in Brazil, where the climatic conditions presented a significant thermoregulatory and perceptual challenge to those unfamiliar with the heat and humidity. CASE PRESENTATION: This case report documents the adaptation induced by a novel mixed methods (isothermic and passive) heat acclimation (HA) regime for a northern European professional soccer match official prior to the tournament. The intervention involved 13 HA sessions over an 18 day period comprising five isothermic HA sessions whereby intermittent running was used to target and maintain tympanic temperature (Tytemp) at 38 °C for 90 min, and seven passive HA sessions of 48 °C water bathing for 30 min. The athlete performed a heat stress test (HST) (35 min running at four incremental intensities in 30 °C) and a repeated high-intensity running test (as many 30 s self-paced efforts as possible, to a maximum of 20, with 30 s passive recovery) before and after the intervention. The mixed methods HA regime increased plasma volume (+7.1 %), and sweat loss (+0.9 L h(-1)), reduced exercising Tytemp (-0.6 °C), and mean body temperature (-0.5 °C). High-intensity running performance improved after HA (+29 %), as did the perception of thermal comfort during exercise (-0.3 units). CONCLUSION: This data evidences the effectiveness of a practical, mixed methods HA strategy, remotely implemented around training and competition, at inducing the heat acclimation phenotype in a high-level soccer match official.

13.
J Psychopharmacol ; 30(6): 495-553, 2016 06.
Article in English | MEDLINE | ID: mdl-26979387

ABSTRACT

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.


Subject(s)
Bipolar Disorder/therapy , Evidence-Based Medicine , Practice Guidelines as Topic , Antidepressive Agents/therapeutic use , Bipolar Disorder/diagnosis , Combined Modality Therapy , Consensus , Diagnosis, Differential , Humans , Medication Adherence , Patient Education as Topic , Psychopharmacology , Secondary Prevention
14.
J Am Chem Soc ; 137(42): 13492-5, 2015 Oct 28.
Article in English | MEDLINE | ID: mdl-26439818

ABSTRACT

Here we report a ternary catalyst system for the intramolecular hydroamidation of unactivated olefins using simple N-aryl amide derivatives. Amide activation in these reactions occurs via concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex and weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom, electron, and proton transfer events with a thiophenol cocatalyst furnish the product and regenerate the active forms of the photocatalyst and base. Mechanistic studies indicate that the amide substrate can be selectively homolyzed via PCET in the presence of the thiophenol, despite a large difference in bond dissociation free energies between these functional groups.


Subject(s)
Alkenes/chemistry , Amides/chemistry , Protons , Catalysis , Electron Transport , Molecular Structure
15.
QJM ; 108(12): 929-33, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25770158

ABSTRACT

BACKGROUND: Analysis of anonymous pooled urine samples from street urinals has been used to demonstrate time-trends in the detection of classical recreational drugs and novel psychoactive substances (NPS). AIM: This study aimed to expand this to undertake a geographical trend analysis of classical recreational drugs/NPS across UK. METHODS: Samples of anonymous pooled urine were collected from street urinals that had been in place for one night in April 2014 in nine cities across the UK. Collected samples were then analysed for the presence of recreational drugs, NPS anabolic steroids using high-performance liquid chromatography coupled to high-resolution accurate mass full-scan mass spectrometry and gas chromatography coupled to electron impact ionization mass spectrometry operating in selected ion monitoring and full-scan modes. RESULTS: Ten classical recreational drugs, nine NPS and four anabolic steroids were detected across the nine cities; the range of detection was from 1 in Leeds to 14 in London. The most common classical drugs were cocaine (9 cities) and 3,4-methylenedioxy-methamphetamine (8 cities); the most common NPS was 4-methylmethcathinone (5 cities). In addition there was variation in the detection of NPS, with methylhexaneamine detected only in Bristol and London, piperazines (3-trifluoromethylphenylpiperazine and 1-benzylpiperazine) and pentedrone only detected in Birmingham and the cathinone methylone only detected in London. CONCLUSIONS: There is variability in the detection of classical recreational drugs, NPS and anabolic steroids across UK, likely reflecting variation in their use. This technique can be used to supplement drug use surveys to determine geographical and time trends in the use of these substances. This is important to ensure appropriate targeting of drug-related interventions.


Subject(s)
Substance Abuse Detection/methods , Substance-Related Disorders/epidemiology , Anabolic Agents/urine , Anonymous Testing/methods , Chromatography, High Pressure Liquid/methods , Cross-Sectional Studies , Humans , Illicit Drugs/urine , Male , Psychotropic Drugs/urine , Substance-Related Disorders/diagnosis , Toilet Facilities/statistics & numerical data , United Kingdom/epidemiology
16.
Hum Exp Toxicol ; 34(5): 557-60, 2015 May.
Article in English | MEDLINE | ID: mdl-25233895

ABSTRACT

Synthetic cannabinoid use has become widespread, leading to increased burdens on health care providers. Symptoms range from agitation and psychosis to seizures and acute kidney injury. We report a case where a patient was assessed and treated twice within 12 h for seizures following synthetic cannabinoid intoxication. Blood sample determinations showed low concentrations of analogues not previously reported, some of which are legal. Clinicians should be aware that synthetic cannabinoids may cause an array of severe health consequences. Given the ever evolving structure of available analogues, clinicians must also be prepared for other unexpected adverse effects.


Subject(s)
Cannabinoids/toxicity , Illicit Drugs/toxicity , Seizures/chemically induced , Substance-Related Disorders/diagnosis , Cannabinoids/blood , Humans , Illicit Drugs/blood , Male , Seizures/diagnosis , Seizures/therapy , Substance Abuse Detection , Substance-Related Disorders/blood , Treatment Outcome , Young Adult
17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 1413-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26736534

ABSTRACT

Due to rapid evolution of new technologies the concept of personalized medicine has evolved. Components include molecular biology, proteomics, metabolomic analysis, genetic testing, and molecular medicine for diagnostics. In addition to diagnostics these methods can be used to determine individual susceptibility to diseases and conditions. In conjunction with new diagnostic methods, new therapies can be tailored to the individual. These new technologies present a challenge in terms of the expansion of the medical record as well as the development of new methods for creating disease profiles. This article focuses on a computer-aided support for personalized medicine. Specific approaches are explored that permit automated data analysis for prognosis and treatment based on analysis methods for numeric and pictorial data. Although personalized medicine based on the genome of the patient are occasionally performed, because of the large amount of data new methods are needed to form general disease models as well as specific profiles of the individual patient.


Subject(s)
Precision Medicine , Humans , Prognosis , Proteomics
18.
Child Care Health Dev ; 41(2): 329-33, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25039946

ABSTRACT

BACKGROUND: Maternal responsiveness is important in early language development, but its measurement by direct observation has to date been unrealistic in community settings because of training and time constraints. We report on the development and cross-sectional comparison of a global rating of maternal responsiveness against a detailed measure of responsiveness at age 24 months. METHODS: The community-based sample comprised 246 toddlers and their mothers, identified as being slow-to-talk at age 18 months within the Let's Learn Language population-based randomized controlled trial. At age 24 months, mother-child dyads were videotaped during 15 minutes of free-play and children undertook a standardized language assessment. Videos were blindly rated on both the new global measure, comprising a single rating of responsiveness on a five-point Likert scale, and a detailed rating of responsiveness known to predict language outcomes, comprising a sum of specific maternal responsive behaviours. RESULTS: The global rating scale required relatively little training and ratings could be conducted in real time. The global and detailed ratings of maternal responsiveness showed moderate correlation (r = 0.44; P < 0.001). Small positive correlations were found between the global rating and expressive (r = 0.23; P < 0.001), receptive (r = 0.28, P < 0.001) and total language (r = 0.28; P < 0.001) at age 24 months. CONCLUSION: The global rating scale was efficient and moderately effective as a measure of maternal responsiveness. It is possible that, combined with other risk measures including concurrent language skills, it could strengthen prediction of which children will and will not go on to experience lasting language difficulties.


Subject(s)
Language Development Disorders/psychology , Mother-Child Relations/psychology , Mothers/psychology , Cross-Sectional Studies , Female , Humans , Infant , Language Development , Male , Maternal Behavior , Psychometrics , Videotape Recording
19.
Neuroscience ; 277: 239-49, 2014 Sep 26.
Article in English | MEDLINE | ID: mdl-25034513

ABSTRACT

Stressful events promote a wide range of neurotransmitter and neuroendocrine changes, which likely serve in an adaptive capacity. However, with repeated stressor exposure, behavioral disturbances, such as anxiety and depression, may develop. Moreover, re-exposure to a stressor for some time following an initial aversive experience may instigate especially pronounced neurochemical variations that favor the emergence of depression and anxiety. These outcomes may stem from any number of neurobiological changes, but increasing attention has focused on the potential contribution of inflammatory factors, such as cytokines. Given the distinct differences in stressor responsiveness that have been reported between males and females, alongside a much higher rate of mood disorders in females, we sought to examine whether repeated exposure to stressors would differentially influence elevated plus-maze behavior in male and female CD-1 mice, and whether such changes would be paralleled by variations of pro-inflammatory mRNA cytokine expression within the prefrontal cortex (PFC) and the hippocampus. In males, the sensitization of interleukin (IL)-1ß was evident in both brain regions in those mice that had initially been stressed and then 6 weeks later re-exposed to a stressor exhibiting higher IL-1ß expression than did mice stressed on only a single occasion. Females demonstrated higher baseline expression of cytokine expression within the hippocampus, but neither a single exposure nor re-exposure stressor treatment produced significant cytokine elevations. In the PFC an acute stressor treatment increased IL-1R expression, but otherwise had little effect. In a plus-maze test, stressed male mice displayed markedly reduced latencies to the open arms that was evident in a test 6 weeks later irrespective of whether mice were re-exposed to a stressor, whereas in females this outcome was less evident. These studies are consistent with the perspective that female mice are relatively resilient toward stressor-induced cytokine elevations even though in humans females are generally more prone to developing mood disturbances.


Subject(s)
Hippocampus/physiopathology , Prefrontal Cortex/physiopathology , Sex Characteristics , Stress, Psychological/physiopathology , Animals , Exploratory Behavior/physiology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Maze Learning , Mice , Neuropsychological Tests , RNA, Messenger/metabolism , Random Allocation , Receptors, Interleukin-1/metabolism , Receptors, Interleukin-6/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/metabolism
20.
J Neuroinflammation ; 11: 85, 2014 May 06.
Article in English | MEDLINE | ID: mdl-24886300

ABSTRACT

BACKGROUND: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. METHODS: Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. RESULTS: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1ß and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1ß, IFN-γ, RANTES, TNF-α and IL-6 levels. CONCLUSIONS: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.


Subject(s)
Fasting , Inflammation/chemically induced , Inflammation/therapy , Lipopolysaccharides/toxicity , Memory Disorders/chemically induced , Memory Disorders/therapy , Animals , Avoidance Learning/drug effects , Avoidance Learning/physiology , Brain/drug effects , Brain/metabolism , Brain/pathology , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Electrophoretic Mobility Shift Assay , Gene Expression Regulation/drug effects , Male , Maze Learning/drug effects , Memory Disorders/pathology , Motor Activity/drug effects , Motor Activity/physiology , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Rats , Rats, Wistar , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
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