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The authors hope that the combination of ScopeGuide imager (to make sense of colon looping) and the new-generation Colonoscopy Simulator (allowing structured teaching and repetitive practice) will make it possible to accelerate colonoscopy training and perhaps also will provide an acceptable way of re-honing the skills of existing endoscopists.
Life-history theory predicts that as organisms approach the end of their life, they should increase their reproductive effort (RE). However, studies on mammals often find that measures of RE do not vary with maternal age. This might be because offspring have some control over energy transfer which may constrain adaptive variation in RE by mothers, particularly in eutherian mammals where placental function is primarily controlled by offspring. However, in marsupials, energy transfer is primarily by lactation and under maternal control, leaving marsupial mothers free to vary RE. Here, we provide the first analysis, to our knowledge, of age-specific RE in a marsupial, the common brushtail possum. RE, measured as the proportion of maternal mass lost during lactation, was strongly correlated with offspring mass as a yearling. Older females had higher RE, gave birth earlier in the season and were more likely to produce two offspring in a year. Females with high RE in one year were lighter at the beginning of the next breeding season. These results provide the clearest support yet for terminal RE in a mammal.
The West Indian manatee (Trichechus manatus latirostris) has become endangered partly because of a growing number of collisions with boats. A system to warn boaters of the presence of manatees, based upon the vocalizations of manatees, could potentially reduce these boat collisions. The feasibility of this warning system would depend mainly upon two factors: the rate at which manatees vocalize and the distance in which the manatees can be detected. The research presented in this paper verifies that the average vocalization rate of the West Indian manatee is approximately one to two times per 5-min period. Several different manatee vocalization recordings were broadcast to the manatees and their response was observed. It was found that during the broadcast periods, the vocalization rates for the manatees increased substantially when compared with the average vocalization rates during nonbroadcast periods. An array of four hydrophones was used while recording the manatees. This allowed for position estimation techniques to be used to determine the location of the vocalizing manatee. Knowing the position of the manatee, the source level was determined and it was found that the mean source level of the manatee vocalizations is approximately 112 dB (re 1 microPa) @ 1 m.
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A systematic study of the novel charge-transfer [(f)14-(pi)0-(f)14 --> (f)13-(pi)2-(f)13] electronic state found in 2:1 metal-to-ligand adducts of the type [(Cp)2Yb](BL)[Yb(Cp)2] [BL = tetra(2-pyridyl)pyrazine (tppz) (1), 6',6' '-bis(2-pyridyl)-2,2':4',4'':2'',2'''-quaterpyridine (qtp) (2), 1,4-di(terpyridyl)-benzene (dtb) (3), Cp = (C5Me5)] has been conducted with the aim of determining the effects of increased Yb-Yb separation on the magnetic and electronic properties of these materials. The neutral [(f)13-(pi)2-(f)13], cationic [(f)13-(pi)1-(f)13] and dicationic [(f)13-(pi)0-(f)13] states of these complexes were studied by cyclic voltammetry, UV-vis-NIR electronic absorption spectroscopy, NMR, X-ray crystallography, and magnetic susceptibility measurements. The spectroscopic and magnetic data for the neutral bimetallic complexes is consistent with an [(f)13(pi)2(f)13] ground-state electronic configuration in which each ytterbocene fragment donates one electron to give a singlet dianionic bridging ligand with two paramagnetic Yb(III) centers. The voltammetric data demonstrate that the electronic interaction in the neutral molecular wires 1-3, as manifested in the separation between successive metal reduction waves, is large compared to analogous transition metal systems. Electronic spectra for the neutral and monocationic bimetallic species are dominated by pi-pi and pi-pi transitions, masking the f-f bands that are expected to best reflect the electronic metal-metal interactions. However, these metal-localized transitions are observed when the electrons are removed from the bridging ligand via chemical oxidation to yield the dicationic species, and they suggest very little electronic interaction between metal centers in the absence of pi electrons on the bridging ligands. Analysis of the magnetic data reveals that the qtp complex displays antiferromagnetic coupling of the type Yb(alpha)(alphabeta)Yb(beta) at approximately 13 K.
(C5Me5)2Yb x OEt2 reacts with terpyridine and tetrapyridinylpyrazine to afford new mixed-valent systems.
The prion protein (PrP) is a Cu(2+) binding cell surface glycoprotein that can misfold into a beta-sheet-rich conformation to cause prion diseases. The majority of copper binding studies have concentrated on the octarepeat region of PrP. However, using a range of spectroscopic techniques, we show that copper binds preferentially to an unstructured region of PrP between residues 90 and 115, outside of the octarepeat domain. Comparison of recombinant PrP with PrP-(91-115) indicates that this prion fragment is a good model for Cu(2+) binding to the full-length protein. In contrast to previous reports we show that Cu(2+) binds to this region of PrP with a nanomolar dissociation constant. NMR and EPR spectroscopy indicate a square-planar or square-pyramidal Cu(2+) coordination utilizing histidine residues. Studies with PrP analogues show that the high affinity site requires both His(96) and His(111) as Cu(2+) ligands, rather than a complex centered on His(96) as has been previously suggested. Our circular dichroism studies indicate a loss of irregular structure on copper coordination with an increase in beta-sheet conformation. It has been shown that this unstructured region, between residues 90 and 120, is vital for prion propagation and different strains of prion disease have been linked with copper binding. The role of Cu(2+) in prion misfolding and disease must now be re-evaluated in the light of these findings.
We have systematically studied the subjective postural vertical (SPV) and the location of the centre of gravity (COG) in right brain damaged patients, classified according to the severity of their hemispatial neglect. The results indicate that the patients lean towards the side of space where they feel aligned with their ipsilesionally displaced SPV, resulting in a ipsilesional deviation of the COG. This displacement can be reduced by the effect of contralesionally applied transcutaneous electrical nerve stimulation (TENS). However, in the severe neglect patients, an increasing mismatch arose between the perceived body orientation and the direction of the gravitational force. The results indicate that this conflict is compensated by a contraversive shift of the COG towards the contraversive side in order to re-align the SPV with the gravitational vertical.
Wound repair is a physiological event in which tissue injury initiates a repair process leading to restoration of structure and function of the tissue. Cutaneous wound repair can be divided into a series of overlapping phases including formation of fibrin clot, inflammatory response, granulation tissue formation incorporating re-epithelialisation and angiogenesis and finally, matrix formation and remodelling. Matrix metalloproteases (MMPs) are a family of neutral proteases that play a vital role throughout the entire wound healing process. They regulate inflammation, degrade the extracellular matrix (ECM) to facilitate the migration of cells and remodel the new ECM. However, excessive MMP activity contributes to the development of chronic wounds. Selective control of MMP activity may prove to be a valuable therapeutic approach to promote healing of chronic ulcers. Recent evidence indicates that the anticoagulant, activated protein C may be useful in the treatment of non-healing wounds by preventing excessive protease activity through inhibition of inflammation and selectively increasing MMP-2 activity to enhance angiogenesis and re-epithelialisation.
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Two cases of aneurysmal re-rupture during intracranial angiography are presented. This event is accompanied by disastrous consequences with regard to the clinical condition of the patient, as is evident from the cases presented as well as from the literature. Acute alterations of intraluminal pressure as well as a time interval of less than 6 h seems to increase the risk of re-bleeding during angiography. The introduction of and the growing experience with CT and MR angiography may in the near future provide sufficient diagnostic information for surgical planning and thus help to overcome the risk of aneurysmal re-rupture during intra-arterial angiography.
A new ion source has been developed for Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) that enables quick changes between matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) modes. When operating as an ESI source, the sample solution is sprayed through an angled nebulizer. The generated ions pass through a glass capillary followed by a skimmer and three sequential hexapole ion guides. Ions can be accumulated in the third hexapole (storage hexapole) before they are injected into the ICR trap. The second hexapole is mounted on a movable platform which also carries the MALDI sample plate. During the switch from ESI to MALDI, this platform moves the second hexapole out of the hexapole series and locates a MALDI sample plate with 384 sample positions into the area directly in front of the storage hexapole. The storage hexapole is in a medium pressure chamber (MPC) which has windows both for the incoming laser beam and for the observation optics, as well as a gas tube for pulsing collision gas into the chamber. During the MALDI operation the focused laser beam enters the MPC, passes between the hexapole rods and irradiates a MALDI sample on the target plate. The sample molecules are desorbed/ionized into the storage hexapole and simultaneously cooled by collisions with the pulsed gas. Ions desorbed from multiple laser shots can be accumulated in this hexapole before they are transferred to the ICR trap. With the combined ion source a computer-controlled switch between MALDI and ESI modes is possible in less than a minute, depending on the position of the MALDI target on the 384-spot plate. Immediate acquisition of mass spectra is possible after mode switching without the need for tuning or re-calibration.
Eph receptors and ligands are two families of proteins that control axonal guidance during development. Their expression was originally thought to be developmentally regulated but recent work has shown that several EphA receptors are expressed postnatally. The EphB3 receptors are expressed during embryonic development in multiple regions of the central nervous system but their potential expression and functional role in the adult brain is unknown. We used in situ hybridization, immunohistochemistry, and receptor affinity probe in situ staining to investigate EphB3 receptors mRNA, protein, and ligand (ephrin-B) expression, respectively, in the adult rat brain. Our results indicate that EphB3 receptor mRNA and protein are constitutively expressed in discrete regions of the adult rat brain including the cerebellum, raphe pallidus, hippocampus, entorhinal cortex, and both motor and sensory cortices. The spatial profile of EphB3 receptors was co-localized to regions of the brain that had a high level of EphB3 receptor binding ligands. Its expression pattern suggests that EphB3 may play a role in the maintenance of mature neuronal connections or re-arrangement of synaptic connections during late stages of development.
BACKGROUND: Despite increases in genetic testing, longitudinal data regarding changes in diagnostic yield and variant reclassification for inherited arrhythmia syndromes are limited. OBJECTIVE: Determine longitudinal changes in diagnostic yield and variant classification. METHODS: Single-center retrospective study of probands <18 years undergoing genetic testing for suspected inherited cardiac conditions associated with arrhythmias, 2007 to 2018. Variants were classified as diagnostic (pathogenic/likely pathogenic), non-diagnostic (benign/likely benign [B/LB]), or variants of uncertain significance (VUS). Variant reclassification was performed in October 2023 using VarSome and American College of Medical Genetics criteria. We evaluated results by era (early 2007-2013 vs. later 2014-2018, coinciding with Sanger and next-generation sequencing, respectively) and by likelihood of disease based on clinical evaluation. RESULTS: Of 306 probands, initial testing was 23.2% diagnostic, 55.6% non-diagnostic (33.7% no variant, 21.9% B/LB), and 21.2% VUS. When comparing eras, diagnostic yield decreased (34.1%-15.3%), VUS increased (9.3%-29.9%), and non-diagnostic remained similar (55% to 57%). Variants for 22.7% (46/203) of probands with ≥1 variant changed: 9.9% of diagnostic variants (7/71) downgraded to VUS or non-diagnostic, and 60.0% of VUS changed (23.1% upgraded, 36.9% downgraded). B/LB variants did not change. Probands with higher disease likelihood had 6-times the odds of diagnostic results compared to lower disease likelihood, regardless of era (odds ratio 6.3, 95% confidence interval 3.2-12.4, P < .0001). CONCLUSION: Variant reclassification led to changes in 23% of probands, both downgrading and upgrading status, even among probands initially thought to be pathogenic. When comparing later to earlier eras, VUS variants increased while diagnostic yield decreased. Findings support the need for variant re-interpretation and periodic reclassification over time.
BACKGROUND: There are no randomized trials comparing outcomes after mitral valve (MV) repair and replacement. Propensity scoring is a powerful tool that has the potential to reduce selection bias in nonrandomized studies. METHODS: From the BC Cardiac Registries, 2,060 patients presented for MV surgery, with or without CABG between 1991 and 2000. We then identified 322 MV repairs who were then matched by propensity score to an equal number of MV replacement patients. We compared survival and freedom from re-operation outcomes using Cox proportional hazards model analysis. Multivariable analysis was then used to compare outcomes in 358 MV repair patients with 352 MV replacement patients who had undergone chordal sparing surgery. RESULTS: The comparison groups generated using propensity scores were well balanced with respect to all collected baseline risk factors. Median follow-up time was 3.4 years. Patients undergoing MV repair had significantly improved survival (RR 0.46; 95% CI, 0.28 to 0.75) but a trend toward more re-operations (RR 2.11; 95% CI, 1.00 to 4.47) compared with patients undergoing replacement. Mitral valve repair patients still had better survival (RR 0.52; 95% CI, 0.32 to 0.85) compared with MV replacement patients who had undergone chordal sparing surgery. CONCLUSIONS: We used propensity score methods to reduce selection bias in a population-based cohort of patients undergoing MV repair/replacement. Repair was associated with better survival, but a trend to increased re-operation.
GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process requiring access of its associated peptides into the MHC class I cross-presentation pathway of APCs. Entry into this pathway requires receptor-mediated endocytosis, and CD91 (low-density lipoprotein receptor-related protein) has been reported to be the receptor mediating GRP94 uptake into APC. However, a direct role for CD91 in chaperone-based peptide Ag re-presentation has not been demonstrated. We investigated the contribution of CD91 to GRP94 cell surface binding, internalization, and trafficking in APCs. Whereas a clear role for CD91 in alpha(2)-macroglobulin binding and uptake was readily obtained, the addition of excess CD91 ligand, activated alpha(2)-macroglobulin, or receptor-associated protein, an antagonist of all known CD91 ligands, did not affect GRP94 cell surface binding, receptor-mediated endocytosis, or peptide re-presentation. These data identify a CD91-independent, GRP94 internalization pathway that functions in peptide Ag re-presentation.
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Impaired self- and own body processing in patients with schizophrenia and individuals along the schizophrenia spectrum have been associated with dysfunctional cortical activation at the temporo-parietal junction. Here we investigated whether strength or duration of temporo-parietal junction activation during an own body processing task correlates with level of abnormal self-processing in healthy subjects as measured by the frequency of spontaneously experienced schizotypal body schema alterations (perceptual aberrations) and dissociative experiences. Participants carried out a mental imagery task with respect to their own body. Behavioral data and high density EEG were measured. EEG data were analyzed using evoked potential mapping and electrical neuroimaging. Participants completed two validated self-report questionnaires, one asking about perceptual aberration and one about dissociative experiences. The own body transformation task activated the right temporo-parietal junction at 310-390 ms. Participants' reaction times and duration of activation at the right temporo-parietal junction, but not its strength, were found to correlate positively with perceptual aberration scores. No relationship was found with dissociative experiences scores. Brain activations proceeding and following activation of the right temporo-parietal junction did not correlate with scores on either scale. The positive correlation between performance and right temporo-parietal activation in an own body transformation task with perceptual aberrations scores in our healthy population suggests that disturbances in self- and body processing in individuals along the schizophrenia spectrum might be due to prolonged, rather than stronger activation of the right temporo-parietal junction. We argue that this might reflect local pathology, pathologies in cortico-cortical connections and/or re-entry of top-down processing.