The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

Regional Brain Responses in Nulliparous Women to Emotional Infant Stimuli

Infant cries and facial expressions influence social interactions and elicit caretaking behaviors from adults. Recent neuroimaging studies suggest that neural responses to infant stimuli involve brain regions that process rewards. However, these studies have yet to investigate individual differences in tendencies to engage or withdraw from motivationally relevant stimuli. To investigate this, we used event-related fMRI to scan 17 nulliparous women. Participants were presented with novel infant cries of two distress levels (low and high) and unknown infant faces of varying affect (happy, sad, and neutral) in a randomized, counter-balanced order. Brain activation was subsequently correlated with scores on the Behavioral Inhibition System/Behavioral Activation System scale. Infant cries activated bilateral superior and middle temporal gyri (STG and MTG) and precentral and postcentral gyri. Activation was greater in bilateral temporal cortices for low- relative to high-distress cries. Happy relative to neutral faces activated the ventral striatum, caudate, ventromedial prefrontal, and orbitofrontal cortices. Sad versus neutral faces activated the precuneus, cuneus, and posterior cingulate cortex, and behavioral activation drive correlated with occipital cortical activations in this contrast. Behavioral inhibition correlated with activation in the right STG for high- and low-distress cries relative to pink noise. Behavioral drive correlated inversely with putamen, caudate, and thalamic activations for the comparison of high-distress cries to pink noise. Reward-responsiveness correlated with activation in the left precentral gyrus during the perception of low-distress cries relative to pink noise. Our findings indicate that infant cry stimuli elicit activations in areas implicated in auditory processing and social cognition. Happy infant faces may be encoded as rewarding, whereas sad faces activate regions associated with empathic processing. Differences in motivational tendencies may modulate neural responses to infant cues

Complications in routine endoscopic examination of the upper digestive tract

L'endoscopie diagnostique du tractus digestif supérieur, dont la diffusion est considérable, jouit d'une réputation d'inocuité. Les complications mécaniques ― perforations œsophagiennes et gastriques ― sont devenues exceptionnelles depuis l'usage d'instruments de fin calibre. En revanche, les complications rares ― publiées isolément ― doivent retenir l'attention: perforations dues à la biopsie intestinale, hématome duodénal, traumatisme splénique, syndrome de Mallory-Weiss post endoscopique. Les complications infectieuses, moins fréquentes qu'après CPRE ou coloscopie, sont graves et justifient le strict respect des règles de nettoyage et de désinfection des instruments et des accessoires. Les complications à haut risque de la sédation sont fréquentes et souvent méconnues chez les sujets âgés, anémiques ou obèse

Complication of pharyngeal anaesthesia with tetracaïne: report of reversible complication

L'anesthésie topique du pharynx avant les endoscopies digestives supérieures est couramment pratiquée par une majorité d'endoscopistes en vue d'améliorer le confort et la qualité de l'examen. Cette pratique est généralement considerée comme dénuée de tout danger. Nous rapportons le cas d'une complication réversible après administration de tétracaïne et envisageons les tableaux symptomatiques principaux, les facteurs de risque ainsi que les mesures préventives et thérapeutiques à mettre en œuvr

Complications of topical anesthesia of the pharynx before upper digestive endoscopy

L'anesthésie topique du pharynx avant les endoscopies digestives supérieures est couramment pratiquée par une majorité d'endoscopistes en vue d'améliorer le confort et la qualité de l'examen. Aucune étude, à ce jour, ne permet cependant d'affirmer l'utilité de cette pratique. Bien plus, elle peut entraîner des effets indésirables potentiellement graves, que nous revoyons en détail, à la lumière des données pharmacologiques. Nous comparons les anesthésiques topiques couramment employés et terminons par les recommandations afin de prévenir et de traiter les éventuelles complication

[Atypical Pneumonitis and Chronic Ulcerative-colitis - Role of Methotrexate]

The authors report the case of a 46-year-old man with refractory ulcerative colitis treated with methotrexate who was admitted in the hospital for asthenia, fever, cough and dyspnea. Owing to the development of adult respiratory distress syndrome despite broad spectrum antibiotherapy, the patient was transfered to the intensive care unit. A diagnosis of pneumonitis due to methotrexate was made. Patient's condition improved after discontinuation of the drug, mechanical ventilation, and corticosteroids. The increasing use of methotrexate in several gastroenterological diseases warrants further consideration of the potential devasting side effects of this drug, particularly on the lungs. A review of the literature on this topic is provided in the ''discussion'' section