Cardiovascular dysfunction in children conceived by assisted reproductive technologies

Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term ‘foetal programming of cardiovascular disease' has been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniousl

Matching Adherence Interventions to Patient Determinants Using the Theoretical Domains Framework

Introduction: Despite much research, interventions to improve medication adherence report disappointing and inconsistent results. Tailored approaches that match interventions and patient determinants of non-adherence were seldom used in clinical trials. The presence of a multitude of theoretical frameworks and models to categorize interventions and patient determinants complicated the development of common categories shared by interventions and determinants. We retrieved potential interventions and patient determinants from published literature on medication adherence, matched them like locks and keys, and categorized them according to the Theoretical Domains Framework (TDF). Methods: We identified the most relevant literature reviews on interventions and determinants in a pragmatic literature search, extracted all interventions and determinants, grouped similar concepts to umbrella terms and assigned them to TDF categories. All steps were finalized in consensus discussion between the authors. Results: Sixteen articles (5 with determinants, 11 with interventions) were included for analysis. We extracted 103 interventions and 42 determinants that we divided in 26 modifiable and 16 unmodifiable determinants. All interventions and modifiable determinants were matched within 11 categories (Knowledge; Skills; Social/professional role and identity; Beliefs about capabilities; Beliefs about consequences; Intentions; Memory, Attention and decision processes; Environmental context and resources; Social influences; Emotion; and Behavioral regulation). Conclusion: In published trials on medication adherence, the congruence between interventions and determinants can be assessed with matching interventions to determinants. To be successful, interventions in medication adherence should target current modifiable determinants and be tailored to the unmodifiable determinants. Modifiable and unmodifiable determinants need to be assessed at inclusion of intervention studies to identify the patients most in need of an adherence intervention. Our matched categories may be useful to develop interventions in trials that investigate the effectiveness of adherence interventions

Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents

OBJECTIVE: To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN: We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS: Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS: Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities

Current perceptions of the term Clinical Pharmacy and its relationship to Pharmaceutical Care:a survey of members of the European Society of Clinical Pharmacy

Background The definitions that are being used for the terms 'clinical pharmacy' and 'pharmaceutical care' seem to have a certain overlap. Responsibility for therapy outcomes seems to be especially linked to the latter term. Both terms need clarification before a proper definition of clinical pharmacy can be drafted. Objective To identify current disagreements regarding the term 'Clinical Pharmacy' and its relationship to 'Pharmaceutical Care' and to assess to which extent pharmacists with an interest in Clinical Pharmacy are willing to accept responsibility for drug therapy outcomes. Setting The membership of the European Society of Clinical Pharmacy. Methods A total of 1,285 individuals affiliated with the European Society of Clinical Pharmacy were invited by email to participate in an online survey asking participants to state whether certain professional activities, providers, settings, aims and general descriptors constituted (a) 'Clinical Pharmacy only', (b) 'Pharmaceutical Care only', (c) 'both' or (d) 'neither'. Further questions examined pharmacists' willingness to accept ethical or legal responsibility for drug therapy outcomes, under current and ideal working conditions. Main outcome measures Level of agreement with a number of statements. Results There was disagreement (&lt;80% agreement among all participants) regarding 'Clinical Pharmacy' activities, whether non-pharmacists could provide 'Clinical Pharmacy' services, and whether such services could be provided in non-hospital settings. There was disagreement (&lt;80% agreement among those linking items to Clinical Pharmacy) as to whether Pharmaceutical care also encompassed certain professional activities, constituted a scientific discipline and targeted cost effectiveness. The proportions of participants willing to accept legal responsibility under current/ideal working conditions were: safety (32.7%/64.3%), effectiveness (17.9%/49.2%), patient-centeredness (17.1%/46.2%), cost-effectiveness (20.3%/44.0%). Conclusions The survey identified key disagreements around the term 'Clinical Pharmacy' and its relationship to 'Pharmaceutical Care', which future discussions around a harmonised definition of 'Clinical Pharmacy' should aim to resolve. Further research is required to understand barriers and facilitators to pharmacists accepting responsibility for drug therapy outcomes.</p

Ambulatory Monitoring of the Cardiovascular System: the Role of Pulse Wave Velocity

Non

Loop Interactions during Catalysis by Dihydrofolate Reductase fromMoritella profunda

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR

Feasibility of joystick guided colonoscopy

The flexible endoscope is increasingly used to perform minimal invasive interventions. A novel add-on platform allows single-person control of both endoscope and instrument at the site of intervention. The setup changes the current routine of handling the endoscope. This study aims to determine if the platform allows effective and efficient manipulation to position the endoscope at potential intervention sites throughout the bowel. Five experts in flexible endoscopy first performed three colonoscopies on a computer simulator using the conventional angulation wheels. Next they trained with the joystick interface to achieve their personal level of intubation time with low pain score. 14 PhD students (novices) without hands-on experience performed the same colonoscopy case using either the conventional angulation wheels or joystick interface. Both novice groups trained to gain the average expert level. The cecal intubation time, pain score and visualization performance (% of bowel wall) were recorded. All experts reached their personal intubation time in 6 ± 6 sessions. Three experts completed their learning curve with low pain score in 8 ± 6 sessions. The novices required 11 ± 6 sessions using conventional angulation wheels, and 12 ± 6 sessions using the joystick interface. There was no difference in the visualization performance between the novice and between the expert groups. This study shows that the add-on platform enables endoscope manipulation required to perform colonoscopy. Experts need only a relatively short training period. Novices are as effective and as efficient in endoscope manipulation when comparing the add-on platform with conventional endoscope contro

Selective Phosphonylation of 5′-Adenosine Monophosphate (5′-AMP) via Pyrophosphite [PPi(III)]

We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O52−; PPi(III)], to the phosphate group of 5′-adenosine mono phosphate (5′-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO−). In this specific case of P-transfer from PPi(III) to 5′-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO−. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5′-AMP, [P(III)P(V)-5′-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus

The Jurassic–Cretaceous depositional and tectonic evolution of the southernwestern margin of the Neotethys Ocean, Northern Oman and United Arab Emirates

The concept that the autochthonous, parautochthonous and allochthonous Permian–Cretaceous sequences in the United Arab Emirates (UAE) and Oman record the transition from platform, slope to basin sedimentation within the southern part of Neotethys has been fundamental to the interpretation of the geological history of the region. The results of a major geological mapping programme of the UAE, carried out by the British Geological Survey for the Federal Government of the UAE, coupled with the detailed examination of key sections within northern Oman has led to a re-evaluation of the geological evolution of this region. This detailed study has led to a greater appreciation of the sedimentology and depositional setting of the sediments laid down along the northeastern Arabian continental margin during the Jurassic to Cretaceous, allowing a more refined model of Neotethys Ocean basin evolution to be established. The model charts the progressive breakup of the Arabian continental margin and closure of Neotethys during the mid to late Cretaceous and is divided into three main stages: Stage 1—Initial rifting and formation of the Neotethys Ocean, followed by a prolonged period of stable, passive margin sedimentation which extended from the Permian to Late Jurassic times; Stage 2—Uplift and erosion of the shelf margin during the Late Jurassic to Early Cretaceous, coincident with increased carbonate-clastic sedimentation in the outer ramp, distal slope and basinal areas; Stage 3—Increased instability during the Late Cretaceous leading to the breakup of the platform margin and foreland basin sedimentation accompanying the obduction of the Oman-UAE ophiolite. Data obtained for the upper part of the platform and platform margin to slope successions has revealed that the topography of the “shelf”-slope-basinal margin was more subdued than previously thought, with this more gentle ramp margin morphology persisting until early to mid-Cretaceous times when the platform margin started to become unstable during ophiolite obduction. The thrust-repeated allochthonous sedimentary rocks of the Hamrat Duru Group were deposited on the outer platform margin/lower slope rise to basinal plain of this basin margin and includes the dismembered remains of two turbidite fan systems which fed carbonate-rich detritus into deeper parts of the ocean. A re-evaluation of the chert-rich sequences, previously equated with deposition on the abyssal plain of Neotethys, has led to the conclusion that they may record sedimentation at a much shallower level within a starved ocean basin, possibly in a mid-ramp (above storm wave base) to outer ramp setting. A marked change in basin dynamics occurred during the mid-Cretaceous leading to the development of a shallow ramp basin margin in Oman with terrestrial to shallow marine sedimentary rocks interdigitating with red siliceous mudstones. By contrast, the contemporaneous succession in the Dibba Zone of the UAE indicates considerable instability on a steep shelf break. This instability is recorded by the presence of several major olistostrome deposits within the Aruma Group of the UAE which are thought to have been generated in advance of the rapidly obducting Oman-UAE ophiolite