Differences in the Volume of Pharmaceutical Advertisements between Print General Medical Journals

Background

Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising.

Methods

Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal''s 2013 advertising price list.

Findings

The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue.

Conclusion

The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue.     

Predator cues alter the timing of developmental events in gastropod embryos

Heterochrony, differences in the timing of developmental events between descendent species and their ancestors, is a pervasive evolutionary pattern. However, the origins of such timing changes are still not resolved. Here we show, using sequence analysis, that exposure to predator cues altered the timing of onset of several developmental events in embryos of two closely related gastropod species: Radix balthica and Radix auricularia. These timing alterations were limited to certain events and were species-specific. Compared with controls, over half (62%) of exposed R. auricularia embryos had a later onset of body flexing and an earlier occurrence of the eyes and the heart; in R. balthica, 67 per cent of exposed embryos showed a later occurrence of mantle muscle flexing and an earlier attachment to, and crawling on, the egg capsule wall. The resultant developmental sequences in treated embryos converged, and were more similar to one another than were the sequences of the controls for both species. We conclude that biotic agents can elicit altered event timing in developing gastropod embryos. These changes were species-specific, but did not occur in all individuals. Such developmental plasticity in the timing of developmental events could be an important step in generating interspecific heterochrony.     

Influence de l'âge des grand-parents sur l'apparition des mâles chez le Rotifère Notommata copeus Ehr.

When parental females (♀♀P = mothers) of the rotifer Notommata copeus are placed in light conditions inducing the appearance of mictic females in their offspring (F₁), the age of the parents of these parental females significantly affects the ratio of mictic females in the F₁ generation.

The preparental females (♀♀PP = grandmothers), the parental females and the F₁ females are isolated in a medium changed at each generation and, in the second experimental series, changed daily: the preparental age effect implicates the transmission of substances on two generations.

This influence of the preparental age is rhythmic: the ratio of mictic females in F₁ related to this age varies in a sinusoidal manner. This influence is endogenous: it persists, always in a sinusoidal form, when the medium in which each grandmother is placed is changed daily.

Furthermore, the net reproduction ratio, Ro, does not vary significantly with the preparental age during these experiments.     

Branching dendrites with resonant membrane: a “sum-over-trips” approach

Dendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the “sum-over-trips” approach (Abbott et al. in Biol Cybernetics 66, 49–60 1991). To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an I _h current contributes to a voltage overshoot at the soma.     

Three αSNAP and 10 ATP Molecules Are Used in SNARE Complex Disassembly by N-ethylmaleimide-sensitive Factor (NSF)

The fusion of intracellular membranes is driven by the formation of a highly stable four-helix bundle of SNARE proteins embedded in the vesicle and target membranes. N-Ethylmaleimide sensitive factor recycles SNAREs after fusion by binding to the SNARE complex through an adaptor protein, αSNAP, and using the energy of ATP hydrolysis to disassemble the complex. Although only a single molecule of αSNAP binds to a soluble form of the SNARE complex, we find that three molecules of αSNAP are used for SNARE complex disassembly. We describe an engineered αSNAP trimer that supports more efficient SNARE complex disassembly than monomeric αSNAP. Using the trimerized αSNAP, we find that N-ethylmaleimide-sensitive factor hydrolyzes 10 ATP molecules on average to disassemble a single SNARE complex.     

The consequences of gustatory deafferentation on body mass and feeding patterns in the rat

The contribution of orosensory signals, especially taste, on body mass, and feeding and drinking patterns in the rat was examined. Gustatory deafferentation was produced by bilateral transection of the chorda tympani, glossopharyngeal, and greater superficial petrosal nerves. Total calories consumed from sweetened-milk diet and oil-chow mash by the nerve-transected rats significantly decreased relative to sham-operated controls, mostly attributable to decreases in bout number, but not size. Nevertheless, caloric intake steadily increased over the postsurgical observation period, but body mass remained below both presurgical baseline and control levels and did not significantly increase over this time. After the sweetened-milk diet/oil-chow mash phase, rats received a series of sucrose preference tests. Interestingly, the nerve-transected rats preferred sucrose, and intake did not differ from controls, likely due to the stimulus sharing some nontaste chemosensory properties with the sweetened-milk diet. The neurotomized rats initiated a greater number of sucrose-licking bouts that were smaller in size and slower in licking rate, compared with control rats, and, unlike in control rats, the latter two bout parameters did not vary across concentration. Thus, in the absence of gustatory neural input, body mass is more stable compared with the progressive trajectory of weight gain seen in intact rats, and caloric intake initially decreases but recovers. The consequences of gustatory neurotomy on processes that determine meal initiation (bout number) and meal termination (bout size) are not fixed and appear to be influenced by presurgical experience with food stimuli coupled with its nongustatory chemosensory properties.     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.     

BECN2 interacts with ATG14 through a metastable coiled‐coil to mediate autophagy

ATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here, we show that the α‐helical, coiled‐coil domain (CCD) of BECN2, a recently identified mammalian BECN1 paralog, forms an antiparallel, curved homodimer with seven pairs of nonideal packing interactions, while the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer stabilized by multiple, conserved polar interactions. Compared to BECN1, the BECN2 CCD forms a weaker homodimer, but binds more tightly to the ATG14 CCD. Mutation of nonideal BECN2 interface residues to more ideal pairs improves homodimer self‐association and thermal stability. Unlike BECN1, all BECN2 CCD mutants bind ATG14, although more weakly than wild type. Thus, polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. These structure‐based mechanistic differences in BECN1 and BECN2 homodimerization and heterodimerization likely dictate competitive ATG14 recruitment.