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Then, we will present the mechanisms leading to lipid malabsorption in small intestinal bacterial overgrowth (SIBO), a disease in which the jejunal microbiota is altered and which highlights the strong interactions among this triad. We will finally review the recent literature about the interactions among members of the triad, which should encourage research teams to further explore the mechanisms by which specific microbial strains or metabolites, alone or in concert, can mediate, control or modulate lipid absorption in the jejunum.G-quadruplexes are promising targets for innovative anticancer therapy. Hence, many efforts are being made to find selective ligands. Drug design is often based on the available high-resolution structures, obtained for the thermodynamically stable forms. However, the complexity of the G-quadruplex folding landscape has clearly emerged in recent years, with the discovery of intermediate conformations that persist on the second to the minute time scale. In the case of the KIT2 G-quadruplex forming sequence, found within human c-KIT promoter, we recently identified a long-lived folding intermediate, characterized by guanine stacking in alternating orientation (as determined by circular dichroism). Given the rate of transcriptional processes, a physiological role of this arrangement should not be excluded. In the present study, we applied circular dichroism (CD) spectroscopy, native electrospray ionization mass spectrometry (ESI-MS) and electrophoretic mobility shift assays (EMSA) to show that a perylene derivative (K20) selects this topology. Interestingly, ESI-MS spectra revealed the presence of a single specifically coordinated K+ ion in the structure, which is thus presumably composed of only two consecutive G-quartets. The parent ligand PIPER failed to promote the same conformational selection, which is therefore a process strictly dependent on the perylene side chains composition. The greater affinity of K20 for the two-quartet antiparallel topology, compared to PIPER, was finally corroborated by evaluating their binding to the KIT∗ G-quadruplex, which is also found within the human promoter of c-KIT.
The defibrillator prompt, which directs callers to retrieve a defibrillator during out-of-hospital cardiac arrest, is crucial to the emergency call because it can save lives. We evaluated communicative effectiveness of the prompt instated by the Medical Priority Dispatch System™ Version 13, namely if there is a defibrillator (AED) available, send someone to get it now, and tell me when you have it.
Using Conversation Analysis and descriptive statistics, we examined linguistic features of the defibrillator sequences (call-taker prompt and caller response) in 208 emergency calls where non-traumatic out-of-hospital cardiac arrest was confirmed by the emergency medical services, and they attempted resuscitation, in the first six months of 2019. Defibrillator sequence durations were measured to determine impact on time to CPR prompt. The proportion of cases where bystanders retrieved defibrillators was also assessed.
There was low call-taker adoption of the Medical Priority Dispatch System™ Version 13 prompt (99/208) compared to alternative prompts (86/208) or no prompt (23/208). Caller responses to the Version 13 prompt tended to be longer, more ambiguous or unrelated, and have more instances of repair (utterances to address comprehension trouble). Defibrillators were rarely brought to the scene irrespective of defibrillator prompt utilised.
While the Version 13 prompt aims to ensure the use of an available automatic external defibrillator, its effectiveness is undermined by the three-clause composition of the prompt and exclusion of a question structure. We recommend testing of a re-phrased defibrillator prompt in order to maximise comprehension and caller action.
While the Version 13 prompt aims to ensure the use of an available automatic external defibrillator, its effectiveness is undermined by the three-clause composition of the prompt and exclusion of a question structure. We recommend testing of a re-phrased defibrillator prompt in order to maximise comprehension and caller action.
To summarise in a systematic review the effectiveness of interventions to treat foreign body airway obstructions (FBAO).
We searched MEDLINE, EMBASE, and the Cochrane library from inception on 30th September 2019 for studies that described the effectiveness of interventions to treat FBAO in adults and children. We included randomised controlled trials, observational studies and case series (≥5 cases) that described evidence of benefit. For evidence of harm/complications, we included case reports. Two reviewers independently assessed study eligibility, extracted study data, and assessed risk of bias. Data are summarised in a narrative synthesis. The GRADE system is used to assess evidence certainty.
We included 69 publications, comprising three cross-sectional studies (557 patients); eight case series (755 patients), and 59 were case reports (64 patients). One paper was included as a case series and cross-sectional study. For all interventions and associated outcomes, evidence certainty was very low. Early removal of FBAO by bystanders was associated with improved neurological survival (odds ratio 6.0, 95% confidence interval 1.5 to 23.4). Identified evidence showed that key interventions (back blows, abdominal thrusts, chest thrusts/compressions, Magill forceps, manual removal of obstructions from the mouth, suction-based airway clearance devices) are effective in relieving FBAO. We identified reports of harm in relation to back blows, abdominal thrusts, chest thrusts/compressions, and blind finger sweeps.
Key interventions successfully relieve FBAO, but may be associated with important harms. Guidelines for FBAO management should balance the benefits and harms of interventions.
Key interventions successfully relieve FBAO, but may be associated with important harms. Guidelines for FBAO management should balance the benefits and harms of interventions.Social rewards represent a strong driving force behind decisions and behaviors. Previous research suggests that the processing of a reward depends on the initial state of the individual. However, empirical research in humans on the influence of motivational states on reward processing is scant, especially for rewards of social nature. In the present study, we aimed at investigating how aversive and appetitive motivation affects the processing of social rewards, such as interpersonal touch. Participants (n = 102) were assigned to an appetitive (positive) or aversive (negative) motivational state condition (via modified versions of the Trier Social Stress Test) or to a control condition. Tuvusertib chemical structure After the state induction, their (a) self-reports of wanting and liking, (b) effort, and (c) hedonic facial reactions during anticipation and consumption of interpersonal touch, were measured. Participants in the aversive group showed higher subjective wanting of interpersonal touch, but no changes in subjective liking, compared to the control group. The aversive group also showed stronger positive hedonic facial reactions during reward anticipation, reflecting stronger anticipatory pleasure. No significant effects were found for the appetitive group. The results indicate that, after being exposed to an aversive experience, the motivation to obtain interpersonal touch, as well as the associated anticipatory pleasure, increase, without a corresponding change in liking during or after its consumption. The findings point to differential state-dependent effects on the processing of social rewards, possibly due to the action of different neurobiological systems regulating reward anticipation and consumption.The geometry of the glutamatergic mossy-parallel fibre and climbing fibre inputs to cerebellar cortical Purkinje cells has powerfully influenced thinking about cerebellar functions. The compartmentation of the cerebellum into parasagittal zones, identifiable in olivo-cortico-nuclear projections, and the trajectories of the parallel fibres, transverse to these zones and following the long axes of the cortical folia, are particularly important. Two monoaminergic afferent systems, the serotonergic and noradrenergic, are major inputs to the cerebellar cortex but their architecture and relationship with the cortical geometry are poorly understood. Immunohistochemistry for the serotonin transporter (SERT) and for the noradrenaline transporter (NET) revealed strong anisotropy of these afferent fibres in the molecular layer of rat cerebellar cortex. Individual serotonergic fibres travel predominantly medial-lateral, along the long axes of the cortical folia, similar to parallel fibres and Zebrin II immunohistochemistry revealed that they can influence multiple zones. In contrast, individual noradrenergic fibres run predominantly parasagittally with rostral-caudal extents significantly longer than their medial-lateral deviations. Their local area of influence has similarities in form and size to those of identified microzones. Within the molecular layer, the orthogonal trajectories of these two afferent systems suggest different information processing. An individual serotonergic fibre must influence all zones and microzones within its medial-lateral trajectory. In contrast, noradrenergic fibres can influence smaller cortical territories, potentially as limited as a microzone. Evidence is emerging that these monoaminergic systems may not supply a global signal to all of their targets and their potential for cerebellar cortical functions is discussed.The nervous system relies upon correct interconnections to exert its normal function. During vertebrate embryonic development, highly stereotyped scaffolds of axon tracts are formed early in the brain to set the foundation for the neuronal interconnections. During zebrafish early development, anterior dorsal telencephalic (ADt) neurons extend axons along the ipsilateral supraoptic tract (SOT) and the contralateral anterior commissure (AC). Our previous study shows axonal outgrowths along the AC/SOT tracts are coordinated by the guidance molecules Dcc-Netrin and Robo2-Slit, but it is not known how the expressions of these guidance molecules are regulated in the forebrain tissues. Here we show ectopic activation of Wnt signaling abolishes the ipsilateral SOT originating from the ADt neurons. Further mechanistic studies show ectopic activation of Wnt signaling significantly reduces Slits' expression, whilst mis-expression of Slit3 rescues SOT outgrowth. Together, our findings indicate Wnt signaling controls the ipsilateral axonal outgrowth through the regulation of slits' expression in the zebrafish forebrain.Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The aim of this study was to further characterise the K3 mouse model by examining functional alterations to the striatum. Whole-cell patch-clamp electrophysiology was used to investigate the properties of striatal neurons in K3 mice and wildtype controls. Additionally, striatal-based instrumental learning tasks were conducted to assess goal-directed versus habitual behaviours (i.e., by examining sensitivity to outcome devaluation and progressive ratios). The K3 model demonstrated significant alterations in the discharge properties of striatal neurons relative to wildtype mice, which manifested as a shift in neuronal output towards a burst firing state.