All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts.

To examine the suitability of age specific limits for alcohol consumption and to explore the association between alcohol consumption and mortality in different age groups

A comparison of standard and high dose adenosine protocols in routine vasodilator stress cardiovascular magnetic resonance: dosage affects hyperaemic myocardial blood flow in patients with severe left ventricular systolic impairment

Background: Adenosine stress perfusion cardiovascular magnetic resonance (CMR) is commonly used in the assessment of patients with suspected ischaemia. Accepted protocols recommend administration of adenosine at a dose of 140 µg/kg/min increased up to 210 µg/kg/min if required. Conventionally, adequate stress has been assessed using change in heart rate, however, recent studies have suggested that these peripheral measurements may not reflect hyperaemia and can be blunted, in particular, in patients with heart failure. This study looked to compare stress myocardial blood flow (MBF) and haemodynamic response with different dosing regimens of adenosine during stress perfusion CMR in patients and healthy controls. Methods: 20 healthy adult subjects were recruited as controls to compare 3 adenosine perfusion protocols: standard dose (140 µg/kg/min for 4 min), high dose (210 µg/kg/min for 4 min) and long dose (140 µg/kg/min for 8 min). 60 patients with either known or suspected coronary artery disease (CAD) or with heart failure and different degrees of left ventricular (LV) dysfunction underwent adenosine stress with standard and high dose adenosine within the same scan. All studies were carried out on a 3 T CMR scanner. Quantitative global myocardial perfusion and haemodynamic response were compared between doses. Results: In healthy controls, no significant difference was seen in stress MBF between the 3 protocols. In patients with known or suspected CAD, and those with heart failure and mild systolic impairment (LV ejection fraction (LVEF) ≥ 40%) no significant difference was seen in stress MBF between standard and high dose adenosine. In those with LVEF < 40%, there was a significantly higher stress MBF following high dose adenosine compared to standard dose (1.33 ± 0.46 vs 1.10 ± 0.47 ml/g/min, p = 0.004). Non-responders to standard dose adenosine (defined by an increase in heart rate (HR) < 10 bpm) had a significantly higher stress HR following high dose (75 ± 12 vs 70 ± 14 bpm, p = 0.034), but showed no significant difference in stress MBF. Conclusions: Increasing adenosine dose from 140 to 210 µg/kg/min leads to increased stress MBF in patients with significantly impaired LV systolic function. Adenosine dose in clinical perfusion assessment may need to be increased in these patients

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

A Geological Itinerary Through the Southern Apennine Thrust-Belt (Basilicata—Southern Italy)

Open access via Springer Compact AgreementPeer reviewedPublisher PD

A comparison of standard and high dose adenosine protocols in routine vasodilator stress cardiovascular magnetic resonance: dosage affects hyperaemic myocardial blood flow in patients with severe left ventricular systolic impairment

Background Adenosine stress perfusion cardiovascular magnetic resonance (CMR) is commonly used in the assessment of patients with suspected ischaemia. Accepted protocols recommend administration of adenosine at a dose of 140 µg/kg/min increased up to 210 µg/kg/min if required. Conventionally, adequate stress has been assessed using change in heart rate, however, recent studies have suggested that these peripheral measurements may not reflect hyperaemia and can be blunted, in particular, in patients with heart failure. This study looked to compare stress myocardial blood flow (MBF) and haemodynamic response with different dosing regimens of adenosine during stress perfusion CMR in patients and healthy controls. Methods 20 healthy adult subjects were recruited as controls to compare 3 adenosine perfusion protocols: standard dose (140 µg/kg/min for 4 min), high dose (210 µg/kg/min for 4 min) and long dose (140 µg/kg/min for 8 min). 60 patients with either known or suspected coronary artery disease (CAD) or with heart failure and different degrees of left ventricular (LV) dysfunction underwent adenosine stress with standard and high dose adenosine within the same scan. All studies were carried out on a 3 T CMR scanner. Quantitative global myocardial perfusion and haemodynamic response were compared between doses. Results In healthy controls, no significant difference was seen in stress MBF between the 3 protocols. In patients with known or suspected CAD, and those with heart failure and mild systolic impairment (LV ejection fraction (LVEF) ≥ 40%) no significant difference was seen in stress MBF between standard and high dose adenosine. In those with LVEF < 40%, there was a significantly higher stress MBF following high dose adenosine compared to standard dose (1.33 ± 0.46 vs 1.10 ± 0.47 ml/g/min, p = 0.004). Non-responders to standard dose adenosine (defined by an increase in heart rate (HR) < 10 bpm) had a significantly higher stress HR following high dose (75 ± 12 vs 70 ± 14 bpm, p = 0.034), but showed no significant difference in stress MBF. Conclusions Increasing adenosine dose from 140 to 210 µg/kg/min leads to increased stress MBF in patients with significantly impaired LV systolic function. Adenosine dose in clinical perfusion assessment may need to be increased in these patients

Urinary C-Peptide of Insulin as a Non-Invasive Marker of Nutritional Status: Some Practicalities

Nutritional status is a critical element of many aspects of animal ecology, but has proven difficult to measure non-invasively in studies of free-ranging animals. Urinary C-peptide of insulin (UCP), a small polypeptide cleaved in an equimolar ratio from proinsulin when the body converts it to insulin, offers great promise in this regard, and recent studies of several non-human primate species have utilized it with encouraging results. Despite this, there are a number of unresolved issues related to the collection, processing, storage and transport of samples. These include: contamination of samples on collection (most commonly by dirt or faeces), short-term storage before returning to a field station, differences in processing and long-term storage methods (blotting onto filter paper, freezing, lyophilizing), and for frozen samples, transportation while keeping samples frozen. Such issues have been investigated for urine samples in particular with respect to their effects on steroid hormone metabolites, but there has been little investigation of their effects on UCP measurement. We collected samples from captive macaques, and undertook a series of experiments where we systematically manipulated samples and tested the effects on subsequent UCP measurements. We show that contamination of urine samples by faeces led to a decrease in UCP levels by >90%, but that contamination with dirt did not have substantial effects. Short-term storage (up to 12 hours) of samples on ice did not affect UCP levels significantly, but medium-term storage (up to 78 hours) did. Freezing and lyophilization for long-term storage did not affect UCP levels, but blotting onto filter paper did. A transportation simulation showed that transporting frozen samples packed in ice and insulated should be acceptable, but only if it can be completed within a period of a few days and if freeze-thaw can be avoided. We use our data to make practical recommendations for fieldworkers

Looking for interaction: quantitative measurement of research utilization by Dutch local health officials

Background: In the Netherlands, local authorities are required by law to develop local health memoranda, based on epidemiological analyses. The purpose of this study was to assess the actual use of these epidemiological reports by municipal health officials and associated factors that affect this use.Method: Based on a conceptual framework, we designed a questionnaire in which we operationalized instrumental, conceptual, and symbolic use, the interaction between researchers and local health officials, and four clusters of barriers in this interaction process. We conducted an internet survey among 155 Dutch local health officials representing 35% of all Dutch municipalities. By means of multiple regression analyses, we gained insight into the related factors for each of the three types of research utilization.Results: The results show that local health officials use epidemiological research more often in a conceptual than an instrumental or symbolic way. This can be explained by the complexity of the local policy process which is often linked to policies in other areas, and the various policy actors involved. Conceptual use was statistically associated with a presentation given by the epidemiologist during the policy process, the presence of obstructions regarding the report's accessibility, and the local official's personal belief systems and interests originating from different professional values and responsibilities. Instrumental and symbolic use increased with the involvement of local officials in the research process.Conclusions: The results of this study provide a partial solution to understanding and influencing research utilization. The quantitative approach underpins earlier qualitative findings on this topic. The outcomes suggest that RPHS epidemiologists can use different strategies to improve research utilization. 'Blurring the boundaries', and the enhancement of interfaces between epidemiologists and local health officials, like direct interactions into each other's work processes, is expected to create better possibilities for optimizing research use

Short and Intense Tailor-Made Notched Music Training against Tinnitus: The Tinnitus Frequency Matters

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice

Human parvovirus B19 infection and hydrops fetalis in Rio de Janeiro, Brazil

Formalin-fixed paraffin embedded lung and liver tissue from 23 cases of non immune hydrops fetalis and five control cases, in which hydrops were due to syphilis (3) and genetic causes (2), were examined for the presence of human parvovirus B19 by DNA hybridisation. Using in situ hybridisation with a biotynilated probe one positive case was detected. Using 32P-labelled probes in a dot blot assay format, five further positives were obtained. These were all confirmed as positive by a nested polymerase chain reaction assay. Electron microscopy revealed virus in all these five positive cases. The six B19 DNA positive cases of hydrops fetalis were from 1974, 1980, 1982, 1987 and 1988, four of which occurred during the second half of the year, confirming the seasonality of the disease