Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?

INTRODUCTION: The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term. // OBJECTIVES: To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of neuropathic pain. // METHODS: Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.), buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®), lidocaine/bupivacaine mixture (local irrigation) or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days. // RESULTS: None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery, but depressive effects on food intake and body weight later during the first week. // CONCLUSION: Post-operative analgesia does not appear to affect established neuropathic hypersensitivity outcome in the SNI model

Diabetes is a Risk Factor for Pulmonary Tuberculosis: A Case-Control Study from Mwanza, Tanzania.

Diabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent. A case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants. Among 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants. Diabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control

Analysis of the Promoter of Emb5 from Zea mays Identifies a Region of 523 bp Responsible for Its Embryo-Specific Activity

The maize Emb5 is an abscisic acid–responsive gene which is specifically expressed in the late embryo during seed maturity. To further dissect and identify the elements specific for its embryo expression pattern, we investigated the activity of the − 1653 bp upstream of the “full-length” promoter region of this gene in transgenic Arabidopsis plants. We first confirmed that the “full-length” promoter could indeed drive the expression of β-glucuronidase reporter gene (GUS) in the transgenic Arabidopsis seed embryo. Subsequently, DNA fragments of ~ 500 bp in length were generated after a series of progressive deletions from positions − 1653 bp to − 1 bp relative to the transcriptional initiation site. These fragments were fused with GUS and introduced into Arabidopsis. Measurement of the GUS activity in the immature seeds isolated from the transgenic plants revealed that the region between positions − 523 bp and − 1 bp, namely ProEm-D, is absolutely required and sufficient for the temporal and embryo-specific expression of GUS with an activity comparable with the full-length Emb5 promoter in Arabidopsis. Therefore, our results clearly demonstrated that the 523 bp ProEm-D can replace the − 1653 bp Emb5 promoter to drive embryo-specific expression in Arabidopsis seed. Because of its small size and strong embryo-specific activity, it could become the promoter of choice in metabolic pathway engineering to transfer multiple genes for the production of valuable pharmaceutical products in seeds, such as polyunsaturated fatty acids found in fish oils, or pro-vitamin A where at least three transgenes are required to assemble the entire metabolic pathways

TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic lupus erythematosus in Japanese women: a case-control association study

IntroductionThe Toll-like receptor 7 (TLR7) gene, encoded on human chromosome Xp22.3, is crucial for type I interferon production. A recent multicenter study in East Asian populations, comprising Chinese, Korean and Japanese participants, identified an association of a TLR7 single-nucleotide polymorphism (SNP) located in the 3\u27 untranslated region (3\u27 UTR), rs3853839, with systemic lupus erythematosus (SLE), especially in males, although some difference was observed among the tested populations. To test whether additional polymorphisms contribute to SLE in Japanese, we systematically analyzed the association of TLR7 with SLE in a Japanese female population.MethodsA case-control association study was conducted on eight tag SNPs in the TLR7 region, including rs3853839, in 344 Japanese females with SLE and 274 healthy female controls.ResultsIn addition to rs3853839, two SNPs in intron 2, rs179019 and rs179010, which were in moderate linkage disequilibrium with each other (r2 = 0.53), showed an association with SLE (rs179019: P = 0.016, odds ratio (OR) 2.02, 95% confidence interval (95% CI) 1.15 to 3.54; rs179010: P = 0.018, OR 1.75, 95% CI 1.10 to 2.80 (both under the recessive model)). Conditional logistic regression analysis revealed that the association of the intronic SNPs and the 3\u27 UTR SNP remained significant after we adjusted them for each other. When only the patients and controls carrying the risk genotypes at the 3\u27 UTR SNPpositionwere analyzed, the risk of SLE was significantly increased when the individuals also carried the risk genotypes at both of the intronic SNPs (P = 0.0043, OR 2.45, 95% CI 1.31 to 4.60). Furthermore, the haplotype containing the intronic risk alleles in addition to the 3\u27 UTR risk allele was associated with SLE under the recessive model (P = 0.016, OR 2.37, 95% CI 1.17 to 4.80), but other haplotypes were not associated with SLE.ConclusionsThe TLR7 intronic SNPs rs179019 and rs179010 are associated with SLE independently of the 3\u27 UTR SNP rs3853839 in Japanese women. Our findings support a role of TLR7 in predisposition for SLE in Asian populations

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir-2(dimen)(4)](2+), where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.1

Happy Aged People Are All Alike, While Every Unhappy Aged Person Is Unhappy in Its Own Way

Aging of the world's population represents one of the most remarkable success stories of medicine and of humankind, but it is also a source of various challenges. The aim of the collaborative cross-cultural European study of adult well being (ESAW) is to frame the concept of aging successfully within a causal model that embraces physical health and functional status, cognitive efficacy, material security, social support resources, and life activity. Within the framework of this project, we show here that the degree of heterogeneity among people who view aging in a positive light is significantly lower than the degree of heterogeneity of those who hold a negative perception of aging. We base this conclusion on our analysis of a survey involving 12,478 people aged 50 to 90 from six West European countries. We treat the survey database as a bipartite network in which individual respondents are linked to the actual answers they provide. Taking this perspective allows us to construct a projected network of respondents in which each link indicates a statistically validated similarity of answers profile between the connected respondents, and to identify clusters of individuals independently of demographics. We show that mental and physical well-being are key factors determining a positive perception of aging. We further observe that psychological aspects, like self-esteem and resilience, and the nationality of respondents are relevant aspects to discriminate among participants who indicate positive perception of aging

Case-control study on uveal melanoma (RIFA): rational and design

BACKGROUND: Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. METHODS/DESIGN: We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding