ABSTRACT
The antidiabetic drug metformin and antiepileptic drug lamotrigine are contaminants of emerging concern that have been detected in biowaste-derived amendments and in the environment, and their fate must be carefully studied. This work aimed to evaluate their sorption behaviour on soil upon digestate application. Experiments were conducted on soil and digestate-amended soil as a function of time to study kinetic processes, and at equilibrium also regarding the influence of trace metals (Pb, Ni, Cr, Co, Cu, Zn) at ratio pharmaceutical/metal 1/1, 1/10, and 1/100. Pharmaceutical desorption experiments were also conducted to assess their potential mobility to groundwater. Results revealed that digestate amendment increased metformin and lamotrigine adsorbed amounts by 210% and 240%, respectively, increasing organic matter content. Metformin adsorption kinetics were best described by Langmuir model and those of lamotrigine by Elovich and intraparticle diffusion models. Trace metals did not significantly affect the adsorption of metformin in amended soil while significantly decreased that of lamotrigine by 12-39%, with exception for Cu2+ that increased both pharmaceuticals adsorbed amounts by 5 - 8%. This study highlighted the influence of digestate amendment on pharmaceutical adsorption and fate in soil, which must be considered in the circular economy scenario of waste-to-resource.
Subject(s)
Metals, Heavy , Metformin , Soil Pollutants , Trace Elements , Soil , Metals, Heavy/analysis , Lamotrigine , Anticonvulsants , Soil Pollutants/analysis , Adsorption , Pharmaceutical PreparationsABSTRACT
Associative learning and memory mechanisms drive interoceptive signaling along the gut-brain axis, thus shaping affective-emotional reactions and behavior. Specifically, learning to predict potentially harmful, visceral pain is assumed to succeed within very few trials. However, the temporal dynamics of cerebellar and cerebral fMRI signal changes underlying early acquisition and extinction of learned fear signals and the concomitant evolvement of safety learning remain incompletely understood. 3 T fMRI data of healthy individuals from three studies were uniformly processed across the whole brain and the cerebellum. All studies employed differential delay conditioning (N = 94) with one visual cue (CS+) being repeatedly paired with visceral pain as unconditioned stimulus (US) while a second cue remained unpaired (CS-). During subsequent extinction (N = 51), all CS were presented without US. Behavioral results revealed increased CS+-aversiveness and CS--pleasantness after conditioning and diminished valence ratings for both CS following extinction. During early acquisition, the CS- induced linearly increasing neural activation in the insula, midcingulate cortex, hippocampus, precuneus as well as cerebral and cerebellar somatomotor regions. The comparison between acquisition and extinction phases yielded a CS--induced linear increase in the posterior cingulate cortex and precuneus during early acquisition, while there was no evidence for linear fMRI signal changes for the CS+ during acquisition and for both CS during extinction. Based on theoretical accounts of discrimination and temporal difference learning, these results suggest a gradual evolvement of learned safety cues that engage emotional arousal, memory, and cortical modulatory networks. As safety signals are presumably more difficult to learn and to discriminate from learned threat cues, the underlying temporal dynamics may reflect enhanced salience and prediction processing as well as increasing demands for attentional resources and the integration of multisensory information. Maladaptive responses to learned safety signals are a clinically relevant phenotype in multiple conditions, including chronic visceral pain, and can be exceptionally resistant to modification or extinction. Through sustained hypervigilance, safety seeking constitutes one key component in pain and stress-related avoidance behavior, calling for future studies targeting the mechanisms of safety learning and extinction to advance current cognitive-behavioral treatment approaches.
Subject(s)
Magnetic Resonance Imaging , Visceral Pain , Avoidance Learning , Brain Mapping/methods , Extinction, Psychological/physiology , Fear/physiology , Humans , Phobic DisordersABSTRACT
Pupillometry, the measurement of pupil diameter, has become increasingly popular as a tool to investigate human memory. It has long been accepted that the pupil is able to distinguish familiar from completely novel items, a phenomenon known as "pupil old/new effect". Surprisingly, most pupillometric studies on the pupil old/new effect tend to disregard the possibility that the pupillary response to familiarity memory may not be entirely exclusive. Here, we investigated whether the pupillary response to old items correctly judged familiar (hits; accurate familiarity) can be differentiated from the pupillary response to new items wrongly judged familiar (false alarms; inaccurate familiarity). We found no evidence that the two processes could be isolated, as both accurate and inaccurate familiarity showed nearly identical mean and across-time pupillary responses. However, both familiarity hits and false alarms showed pupillary responses unequivocally distinct from those observed during either recollection or novelty detection, which suggests that the pupil measure of familiarity hits and/or false alarms was sufficiently sensitive. The pupillary response to false alarms may have been partially driven by perceptual fluency, since novel objects incorrectly judged to be old (i.e., false alarms) showed a higher degree of similarity to studied images than items correctly judged as novel (i.e., correct rejections). Thus, our results suggest that pupil dilation may not be able to distinguish accurate from inaccurate familiarity using standard recognition memory paradigms, and they also suggest that the pupillary response during familiarity feelings may also partly reflect perceptual fluency.
Subject(s)
Pupil/physiology , Recognition, Psychology/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Reaction Time/physiology , Young AdultABSTRACT
Alzheimer's disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.
Subject(s)
Alzheimer Disease , Apolipoprotein E4 , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoprotein E4/genetics , Entorhinal Cortex , Heterozygote , Humans , Magnetic Resonance Imaging , Young AdultABSTRACT
We investigated stimulus-response (S-R) memory links during object priming using a binary associative size judgement paradigm. At study, participants decided which of two objects was bigger in real life and, at test, made the same or the reverse judgement. We examined the effects of response congruence on item S-R priming in the associative paradigm. In Experiment 1, a task reversal manipulation had minimal impact on RT priming when classifications were congruent for both recombined objects between study and test. Experiment 2 found that RT priming was more disrupted by classification incongruence of the selected than of the nonselected item alone, with incongruence of the nonselected object having no effect on RTs. Experiment 3, however, found that classification incongruence of both items eliminated RT priming, indicating that a significant effect of classification incongruence for the nonselected item is only evident if both items are classification-incongruent. Finally, across all experiments, we found that accuracy was more sensitive than RTs to decision/action incongruence. We interpret these findings in light of a two-stream account of S-R priming, and suggest a few extensions to account for interactions between S-R links of recombined items.
Subject(s)
Judgment , Adult , Humans , Photic Stimulation , Reaction Time , Repetition Priming , Young AdultABSTRACT
In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
Subject(s)
Clostridioides difficile/pathogenicity , Clostridium Infections/therapy , Postoperative Complications/therapy , Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship , Clostridium Infections/diagnosis , Enterocolitis, Pseudomembranous/etiology , Enterocolitis, Pseudomembranous/prevention & control , Fecal Microbiota Transplantation/methods , Fecal Microbiota Transplantation/trends , Guidelines as Topic , Humans , Incidence , Infection Control/methods , Infection Control/trends , Risk FactorsABSTRACT
Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.
Subject(s)
Health Knowledge, Attitudes, Practice , Infection Control/methods , Surgeons/psychology , Adult , Female , Humans , Infection Control/standards , Male , Middle Aged , Surgeons/standards , Surgical Wound Infection/prevention & control , United StatesABSTRACT
Background: Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. Methods: This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. Results: A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. Conclusions: The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.
Subject(s)
Appendectomy/standards , Appendicitis/surgery , Acute Disease/therapy , Adult , Appendectomy/adverse effects , Appendectomy/methods , Chi-Square Distribution , Female , Hospitalization/statistics & numerical data , Humans , Laparoscopy/methods , Laparoscopy/statistics & numerical data , Length of Stay/statistics & numerical data , Logistic Models , Male , Prospective Studies , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
The Global Alliance for Infections in Surgery appreciates the great effort of the task force who derived and validated the Sepsis-3 definitions and considers the new definitions an important step forward in the evolution of our understanding of sepsis. Nevertheless, more than a year after their publication, we have a few concerns regarding the use of the Sepsis-3 definitions.
Subject(s)
Data Accuracy , Sepsis/classification , Severity of Illness Index , Arterial Pressure , Consensus , Glasgow Coma Scale , Humans , Organ Dysfunction Scores , Sensitivity and Specificity , Sepsis/mortalityABSTRACT
Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.
Subject(s)
Guidelines as Topic , Intraabdominal Infections/drug therapy , Intraabdominal Infections/surgery , Societies, Medical/trends , Abdominal Injuries/drug therapy , Abdominal Injuries/surgery , Anti-Bacterial Agents/therapeutic use , Disease Management , Humans , Organ Dysfunction Scores , Peritonitis/drug therapy , Sepsis/drug therapy , Sepsis/surgery , Societies, Medical/organization & administration , Surgeons/organization & administration , Surgeons/trendsABSTRACT
It is currently unclear whether objects have to be explicitly identified at encoding for reliable behavioral long-term object priming to occur. We conducted two experiments that investigated long-term object and non-object priming using a selective-attention encoding manipulation that reduces explicit object identification. In Experiment 1, participants either counted dots flashed within an object picture (shallow encoding) or engaged in an animacy task (deep encoding) at study, whereas, at test, they performed an object-decision task. Priming, as measured by reaction times (RTs), was observed for both types of encoding, and was of equivalent magnitude. In Experiment 2, non-object priming (faster RTs for studied relative to unstudied non-objects) was also obtained under the same selective-attention encoding manipulation as in Experiment 1, and the magnitude of the priming effect was equivalent between experiments. In contrast, we observed a linear decrement in recognition memory accuracy across conditions (deep encoding of Experiment 1 > shallow encoding Experiment 1 > shallow encoding of Experiment 2), suggesting that priming was not contaminated by explicit memory strategies. We argue that our results are more consistent with the identification/production framework than the perceptual/conceptual distinction, and we conclude that priming of pictures largely ignored at encoding can be subserved by the automatic retrieval of two types of instances: one at the motor level and another at an object-decision level.
ABSTRACT
The copper(II) complex formation equilibria of N-(2-carboxyethyl)chitosans with three different degrees of substitution (DS = 0.42, 0.92, and 1.61) were studied in aqueous solution by pH-potentiometric and UV-spectrophotometric techniques. It was demonstrated that the complexation model of CE-chitosans depends on DS: the [Cu(Glc-NR(2))(2)] complexes are predominant for two lower substituted samples ("bridge model", log beta(12) = 10.06 and 11.6, respectively), whereas the increase of DS leads to formation mainly of the [Cu(Glc-NR(2))] complexes ("pendant model", log beta(11) = 6.41). As a model for copper complexation with a disubstituted residue of CE-chitosan, the complex of N-methyliminodipropionate [CuMidp(H(2)O)].(H(2)O) was synthesized and structurally characterized by XRD. The unit cell consists of two crystallographically nonequivalent Cu atoms having slightly distorted square pyramidal coordination; Midp constitutes the basal plane of the pyramid and acts as a tetradentate NO(3) chelate-bridging ligand by the formation of two six-membered chelate rings (average Cu-O 1.99 A, Cu-N 2.04 A) and a bridge via carbonyl O atom (average Cu-O 1.99 A), an apical position is occupied by a water molecule (average Cu-Ow 2.30 A).
Subject(s)
Chitosan/analogs & derivatives , Chitosan/chemistry , Copper/chemistry , Models, Molecular , Organometallic Compounds/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Crystallography, X-Ray , Hydrogen-Ion Concentration , Molecular Sequence Data , Potentiometry/methods , Spectrophotometry, Ultraviolet/methodsABSTRACT
The antioxidant and antimutagenic activities of the novel carboxyethyl derivatives of chitosan with three different degrees of substitution have been assayed in vitro in the unicellular flagellate Euglena gracilis subjected to the action of genotoxic agents acridine orange and ofloxacin. It has been demonstrated that chitosan derivatives exhibit concentration-dependent protective antigenotoxic activity against both mutagens. It is suggested that different mechanisms may be involved in its protective action--antioxidant activity in case of ofloxacin-induced DNA damage, as well as possible interaction with the cell membrane that prevents acridine orange from reaching the genetic compartments and subsequent damaging DNA through intercalative binding. Direct adsorption of acridine orange on chitosan derivatives was ruled out as a possible mechanism of protection on the basis of spectrophotometric measurements. Dependence of the antimutagenic properties of the studied chitosan derivatives on the degree of substitution was reversed in experiments involving acridine orange and ofloxacin, which also indicated different mechanisms of protection involved in these two cases.
Subject(s)
Antimutagenic Agents/pharmacology , Antioxidants/pharmacology , Chitosan/analogs & derivatives , Chitosan/pharmacology , Acridine Orange/toxicity , Algorithms , Animals , Benzothiazoles , Carbohydrate Sequence , Chloroplasts/genetics , Chloroplasts/metabolism , Chromans/pharmacology , DNA Damage , Esters , Euglena gracilis/genetics , Euglena gracilis/metabolism , Molecular Sequence Data , Mutagenicity Tests , Mutagens/toxicity , Ofloxacin/antagonists & inhibitors , Ofloxacin/toxicity , Oxidants/pharmacology , Spectrophotometry, Ultraviolet , Sulfonic AcidsABSTRACT
N-(2-Carboxyethyl)chitosans were obtained by reaction of low molecular weight chitosan with a low degree of acetylation and 3-halopropionic acids under mild alkaline media (pH 8-9, NaHCO3) at 60 degrees C. The chemical structure of the derivatives obtained was determined by 1H and 13C NMR spectroscopies. It was found that alkylation of chitosan by 3-halopropionic acids proceeds exclusively at the amino groups. The products obtained are described in terms of their degrees of carboxyethylation and ratio of mono-, di-substitution and free amine content. The protonation constants of amino and carboxylate groups of a series of N-(2-carboxyethyl)chitosans were determined by pH-titration at ionic strength 0.1 M KNO3 and 25 degrees C.
Subject(s)
Chitin/analogs & derivatives , Chitin/chemical synthesis , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Chitin/chemistry , Chitosan , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular Structure , Static ElectricityABSTRACT
Procedimentos, como o transplante de medula óssea, a quimioterapia, a nutriçäo parenteral total e a hemodiálise, exigem a necessidade cada vez maior do acesso venoso central de longa duraçäo (AVCLD). Utilizam-se, de acordo com a indicaçäo, cateteres totalmente implantáveis (com reservatório) e parcialmente implantáveis (Broviac-Hickman). Foram avaliados setenta e nove (79) cateteres implantados, consecutivamente, em sessenta e seis (66) pacientes, tratados no Hospital das Clínicas da Faculdade de Medicina de Ribeiräo Preto da USP, no período de janeiro de 1993 a junho de 1997. Avaliaram-se os seguintes parâmetros: indicaçäo do acesso venoso, tipo de cateter implantado, técnica utilizada, complicaçöes precoces e tardias e duraçäo do implante. Dos sessenta e seis (66) pacientes, trinta e quatro (34) (51,5 por cento) eram homens. A idade média foi de 28,2 anos. Houve predomínio de indicaçäo de implante de cateter para realizar-se a quimioterapia em cinquenta e cinco (55) (69,5 por cento) pacientes e transplante de medula óssea em doze (12) (15,2 por cento). Foram implantados vinte e oito (28) (35,5 por cento) cateteres com reservatório e cinquenta e um (51) (64,5 por cento) parcialmente implantáveis. Quanto à técnica utilizada, 71,4 por cento foram implantados por punçäo percutânea e os demais por dissecçäo e cateterizaçäo venosa, a céu aberto. Ocorreram duas complicaçöes relacionadas à tecnica, nove (9) infecçöes e oito (8) oclusöes tardias. A duraçäo média da implantaçäo dos cateteres foi trezentos e setenta e um (371) dias para os cateteres Broviac-Hickman e trezentos e noventa e cinco (395) para o totalmente implantável. Näo houve óbito associado aos implantes. Os índices de complicaçöes precoces e tardias, observadas nesta casuística, assemelham-se aos dados encontrados na literatura.