The contribution of general practice based research to the development of national policy: case studies from Ireland and Australia

Background

This paper aims to describe the influence of general practice based research on the development of two specific policy initiatives, namely the Heartwatch Programme in Ireland and the Better Outcomes in Mental Health Care (BOiMHC) program in Australia. A case study approach was used to explore the extent to which relevant general practice based research shaped these initiatives.

Results

In both case studies, a range of factors beyond general practice based research shaped the initiative in question, including political will, the involvement of stakeholders (including key opinion leaders), and the historical context. Nonetheless, the research played an important role, and was not merely put to 'symbolic use' to support a position that had already been reached independently. Rather, both case studies provide examples of 'instrumental use': in the case of Heartwatch, the research was considered early in the piece; in the case of the BOiMHC program, it had a specific impact on the detail of the components of the initiative.

Conclusion

General practice based research can influence policy-making and planning processes by strengthening the foundation of evidence upon which they draw. This influence will not occur in a vacuum, however, and general practice researchers can maximise the likelihood of their work being 'picked up' in policy if they consider the principles underpinning knowledge transfer.

     

Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids

Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and depression, which suggests a dysfunction of GABAergic neurotransmission. Socially isolated female mice that have received testosterone propionate (1.45 micromol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2 are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5-hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level downregulation and abolishes aggression. This work underscores the role of neurosteroids in the regulation of aggression elicited by testosterone propionate in socially isolated female mice.     

Differential actions of urocortins on neurons of the myenteric division of the enteric nervous system in guinea pig distal colon

Background and purpose:

Urocortins (Ucns) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related neuropeptides and may be involved in neural regulation of colonic motor functions. Nevertheless, details of the neural mechanism of action for Ucns have been unclear. We have, here, tested the hypothesis that Ucns act in the enteric nervous system (ENS) to influence colonic motor behaviour.

Experimental approach:

We used intracellular recording with ‘sharp’ microelectrodes, followed by intraneuronal injection of biocytin, and immunohistochemical localization of CRF₁ and CRF₂ receptors in guinea pig colonic tissue.

Key results:

Application of Ucn1 depolarized membrane potentials and elevated excitability in 58% of AH-type and 60% of S-type colonic myenteric neurons. In most of the neurons tested, depolarizing responses evoked by Ucn-1 were suppressed by the CRF₁ receptor antagonist NBI 27914, but were unaffected by the CRF₂ receptor antagonist antisauvagine-30. The selective CRF₂ receptor agonists, Ucn2 and Ucn3, evoked depolarizing responses in 12 and 8% of the AH-type myenteric neurons, respectively, and had no effect on S-type neurons. Antisauvagine-30, but not NBI 27914, suppressed these Ucn2- and Ucn3-evoked responses. Immunohistochemical staining identified CRF₁ as the predominant CRF receptor subtype expressed by ganglion cell somas, while CRF₂-immunoreactive neuronal somas were sparse. Ucns did not affect excitatory synaptic transmission in the ENS.

Conclusions and implications:

The results suggest that Ucns act as neuromodulators to influence myenteric neuronal excitability. The excitatory action of Ucn1 in myenteric neurons was primarily at CRF₁ receptors, and the excitatory action of Ucn2 and Ucn3 was at CRF₂ receptors.     

Survival after the diagnosis of de novo malignancy in liver transplant recipients

In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case–control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan–Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all-cancer 10-year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17–6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98–276.74), non-Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15–20.01), head and neck (HR = 4.65; 95% CI: 1.81–11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08–12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post-transplant follow-up to ensure early cancer diagnosis and to improve survival.     

青藏高原地区Arctic-like狂犬病病毒的分子流行病学研究

目的 为了解青海地区狂犬病病毒在人和不同动物中的流行趋势和变异特点。方法 在2012至2016年间,我们从青海不同地区收集194个组织样本,用直接荧光抗体(DFA)进行检测。获得的阳性标本在进行核酸扩增和序列测序分析。结果 从194个标本中获得了38个直接荧光抗体(DFA)阳性标本,从38个阳性标本中获得了8个狂犬病病毒全基因组序列,比较这8个完整核苷酸序列,并与CQH2012D(KM27 2192.1)和来自西藏的2012年的CXZ1201D犬(KC46352)株进行同源性分析,发现他们与2个核苷酸序列之间的相似性在95%和100%之间。对8个G基因和N基因核苷酸序列和从中国和世界的代表株的进化分析,结果表明我们得到的狂犬病病毒核苷酸全序列属于Arctic-like2组,是China Ⅳ基因型,从38个DFA阳性标本的地区分布分析表明,阳性标本的发生率在青海地区有从西向东逐渐减少的趋势。结论 青海流行的狂犬病以Arctic-like2为主,并随动物迁徙有由西向东扩展的趋势, 流行病学数据提示人和家养动物狂犬病的传播途径是感染了狂犬病的犬或狼咬伤而发病。     

Treatment of Sweet's syndrome in pregnancy

Pregnancy‐associated Sweet's syndrome is a rare occurrence (2%), with good prognosis, spontaneous resolution after delivery, and not increased infant morbidity and mortality. However, differential diagnosis is not easy for physician not familiar with skin lesions. Systemic involvement, even though unusual, might occur in nearly every organ of the body, including pericardium, myocardium, and placenta, as well as one report of early fetal miscarriage, questioning the possibility of risks underestimation. We present two further cases, one occurred in a 31‐year‐old woman at 26 weeks of gestation and the other on a 26‐year‐old woman at 24 weeks of gestation, primigravidae. Both presented with tender papules and nodules on their face and upper body parts. Laboratory examinations and skin biopsy histology were pathognomonic. Monitoring of general maternal and fetal conditions showed no signs of sufferance, but the decision to accelerate skin symptoms release, being time to delivery quite distant, challenge the treatment options. There are no recommended treatments for Sweet syndrome and the choice is very limited during pregnancy. A short course of oral steroids was very effective, with lesions healing in few days, no relapses or fetal complications. When pregnant patients exhibit fever, neutrophilia, arthralgia or myalgia, and tender erythematous plaques or nodules, Sweet syndrome should be considered. The trained dermatologist is in the leading position to address the differential diagnosis, reassure the patient, and avoid complications, even if they are rare.     

Synthesis of Pyrryl Aryl Sulfones Targeted at the HIV-1 Reverse Transcriptase

Various aryl 1-pyrryl sulfones were synthesized and tested as inhibitors of HIV-1, 2-Nitrophenyl-2-ethoxycarbonyl-1-pyrryl sulfone, the most active among test derivatives, was selected as lead compound of the aryl pyrryl sulfone series. The in vitro anti-HIV-1 activity and cytotoxicity of 41 compounds is reported. Some structure-activity relationships are discussed also in comparison with the known NPPS (2-nitrophenyl phenyl sulfone).     

Dementia of Alzheimer type (DAT) in a man chronically exposed to pesticides.

A patient chronically exposed to pesticides with dementia of Alzheimer type (DAT) is presented. We evaluate the pathogenic role of these substances in the disease and suggest the usefulness of an epidemiological attention on the environmental factors in certain neurodegenerative diseases.