Use of a tool-set by Pan troglodytes troglodytes to obtain termites (Macrotermes) in the periphery of the Dja Biosphere Reserve, southeast Cameroon

At the northern periphery of the Dja Biosphere Reserve (southeastern Cameroon) we recorded a new use of a tool-set by Pan troglodytes troglodytes to prey on Macrotermes muelleri, M. renouxi, M. lilljeborgi, and M. nobilis. We recovered 79 puncturing sticks and 47 fishing probes at 17 termite nests between 2002 and 2005. The mean length of the puncturing sticks (n = 77) and fishing probes (n = 45) was 52 cm and 56 cm, respectively, and the mean diameter was 9 mm and 4.5 mm, respectively. Sixty-eight percent of 138 chimpanzee fecal samples contained major soldiers of four Macrotermes species. The chimpanzees in southeastern Cameroon appeared to be selective in their choice of plant material to make their tools. The tools found at our study site resemble those from other sites in this region. However, in southeastern Cameroon only one tool-set type was found, whereas two tool-set types have been reported in Congo. Our study suggests that, along with the different vegetation types and the availability of plant material around termite nests, the nest and gallery structure and foraging behavior of the different Macrotermes spp. at all Central African sites must be investigated before we can attribute differences in tool-use behavior to culture.     

Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity

MuO-conotoxin MrVIB is a blocker of voltage-gated sodium channels, including TTX-sensitive and -resistant subtypes. A comprehensive characterization of this peptide has been hampered by the lack of sufficient synthetic material. Here, we describe the successful chemical synthesis and oxidative folding of MrVIB that has made an investigation of the pharmacological properties and therapeutic potential of the peptide feasible. We show for the first time that synthetic MrVIB blocks rat NaV1.8 sodium channels and has potent and long-lasting local anesthetic effects when tested in two pain assays in rats. Furthermore, MrVIB can block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations from rat. Our work provides the first example of analgesia produced by a conotoxin that blocks sodium channels. The emerging diversity of antinociceptive mechanisms targeted by different classes of conotoxins is discussed.     

Cost-Effectiveness of Collaborative Care for Depression in UK Primary Care: Economic Evaluation of a Randomised Controlled Trial (CADET)

Background

Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking.

Aims

To assess the cost-effectiveness of collaborative care in a UK primary care setting.

Methods

An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane.

Results

The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: –0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: –202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual.

Conclusion

Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting.     

Cross-talk between fibroblast growth factor and bone morphogenetic proteins regulates gap junction-mediated intercellular communication in lens cells

Homeostasis in the lens is dependent on an extensive network of cell-to-cell gap junctional channels. Gap junction-mediated intercellular coupling (GJIC) is higher in the equatorial region of the lens than at either pole, an asymmetry believed essential for lens transparency. Primary cultures of embryonic chick lens epithelial cells up-regulate GJIC in response to purified fibroblast growth factor (FGF)1/2 or to medium conditioned by vitreous bodies, the major reservoir of factors (including FGF) for the lens equator. We show that purified bone morphogenetic protein (BMP)2, -4, and -7 also up-regulate GJIC in these cultures. BMP2, -4, or both are present in vitreous body conditioned medium, and BMP4 and -7 are endogenously expressed by lens cells. Remarkably, lens-derived BMP signaling is required for up-regulation of GJIC by purified FGF, and sufficient for up-regulation by vitreous humor. This is the first demonstration of an obligatory interaction between FGF and BMPs in postplacode lens cells, and of a role for FGF/BMP cross-talk in regulating GJIC in any cell type. Our results support a model in which the angular gradient in GJIC in the lens, and thus proper lens function, is dependent on signaling between the FGF and BMP pathways.     

Unintended Consequences of Incentive Provision for Behaviour Change and Maintenance around Childbirth

Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation.     

Plasma neurofilament heavy chain levels correlate to markers of late stage disease progression and treatment response in SOD1(G93A) mice that model ALS

Background

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterised by progressive degeneration of motor neurons leading to death, typically within 3–5 years of symptom onset. The diagnosis of ALS is largely reliant on clinical assessment and electrophysiological findings. Neither specific investigative tools nor reliable biomarkers are currently available to enable an early diagnosis or monitoring of disease progression, hindering the design of treatment trials.

Methodology/Principal Findings

In this study, using the well-established SOD1^G93A mouse model of ALS and a new in-house ELISA method, we have validated that plasma neurofilament heavy chain protein (NfH) levels correlate with both functional markers of late stage disease progression and treatment response. We detected a significant increase in plasma levels of phosphorylated NfH during disease progression in SOD1^G93A mice from 105 days onwards. Moreover, increased plasma NfH levels correlated with the decline in muscle force, motor unit survival and, more significantly, with the loss of spinal motor neurons in SOD1 mice during this critical period of decline. Importantly, mice treated with the disease modifying compound arimoclomol had lower plasma NfH levels, suggesting plasma NfH levels could be validated as an outcome measure for treatment trials.

Conclusions/Significance

These results show that plasma NfH levels closely reflect later stages of disease progression and therapeutic response in the SOD1^G93A mouse model of ALS and may potentially be a valuable biomarker of later disease progression in ALS.     

The Effects of a Therapy Dog on the Blood Pressure and Heart Rate of Older Residents in a Nursing Home

The aim of the present project was to investigate whether repeated visits by a therapy dog to nursing homes might affect the older residents’ systolic blood pressure and heart rate. A secondary aim was to investigate and compare effects (differences in responses) in older people with high and normal systolic blood pressure. The project consisted of two consecutive studies; the dog study (two researchers and a therapy dog with a handler visited the residents at three nursing homes, n = 13), and the control study (the two researchers alone visited the residents at three different nursing homes, n = 13). The studies were divided into three periods; period 1 (weeks 1–2), period 2 (weeks 3–4), and period 3 (weeks 5–6) and included two visits per week. The dog and her handler visited during periods 2 and 3 in the dog study. Participants’ heart rate and blood pressure were measured at 0 and 20 minutes at each visit. The data were analyzed using Friedman's two- way analysis of Variance by Rank with post-hoc analysis using Wilcoxon signed-rank tests with a Bonferroni correction, and also with the Mann-Whitney U test for independent samples. In the dog study, participants’ heart rate decreased significantly (p = 0.006) from period 1 to period 3. Participants with an initial systolic blood pressure ≥ 130 mmHg had a significant decrease in both systolic blood pressure (p = 0.009) and heart rate (p = 0.009). In the control study, participants’ heart rate and systolic blood pressure did not change significantly. The participants in the dog study had a significantly lower systolic blood pressure during period 3 (p = 0.016) compared with those in the control study. In conclusion, repeated visits by a therapy dog–handler team decreased the older adults’ heart rate, and for those with high initial systolic blood pressure, blood pressure also decreased. In addition, systolic blood pressure decreased significantly in the dog group when compared with the control group.     

Functional activity of the complement regulator encoded by Kaposi's sarcoma-associated herpesvirus

Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with Kaposi's sarcoma and certain B-cell lymphomas. The fourth open reading frame of the KSHV genome encodes a protein (KSHV complement control protein (KCP, previously termed ORF4)) predicted to have complement-regulating activity. Here, we show that soluble KCP strongly enhanced the decay of classical C3-convertase but not the alternative pathway C3-convertase, when compared with the host complement regulators: factor H, C4b-binding protein, and decay-accelerating factor. The equilibrium affinity constant (KD) of KCP for C3b and C4b was determined by surface plasmon resonance analysis to range between 0.47-10 microM and 0.025-6.1 microM, respectively, depending on NaCl concentration and cation presence. Soluble and cell-associated KCP acted as a cofactor for factor I (FI)-mediated cleavage of both C4b and C3b and induced the cleavage products C4d and iC3b, respectively. In the presence of KCP, FI further cleaved iC3b to C3d, which has never been described before as complement receptor 1 only mediates the production of C3dg by FI. KCP would enhance virus pathogenesis through evading complement attack, opsonization, and anaphylaxis but may also aid in targeting KSHV to one of its host reservoirs since C3d is a ligand for complement receptor 2 on B-cells.