Recalled pain scores are not reliable after acute trauma

IntroductionPain research in emergency settings can be problematic, as data collection is logistically difficult and pain levels are often poorly documented. Short-term recall of acute pain has been evaluated in postoperative, labour and procedural pain, with variable reported accuracy. The reliability of pain recall in trauma resuscitation patients is unknown. This study aims to determine the accuracy of short-term pain recall 1–2 days after trauma.MethodsProspective, cohort study of trauma resuscitation patients transported by ambulance to a major trauma centre. Patients with haemodynamic instability (SBP < 90, HR > 120) or GCS < 14 on arrival were excluded. Momentary pain scores were measured on an 11-point verbal numerical rating scale by paramedics during prehospital management. Patients were evaluated within 48 h of injury on the recall of their initial pain, pain during transport, and lowest pain score achieved by prehospital analgesia. Spearman's rank correlation and Bland–Altman tests were used to compare ambulance and hospital data.Results88 trauma resuscitation patients (mean age 44 years ± 18 SD, male 74%, mean ISS: 7 ± 5 SD) were enrolled over a 5 month study period. Comparison of immediate and recalled pain scores produced Spearman's correlation coefficients of 0.71 for initial pain, 0.56 for pain during transport, and 0.45 for minimum pain scores.DiscussionIn our study patients did not accurately recall their pain levels 1–2 days after acute trauma. The results suggest that retrospective pain ratings are not reliable in trauma patients.     

Active Wnt/beta-catenin signaling is required for embryonic thymic epithelial development and functionality ex vivo

The Wnt/beta-catenin signaling pathway plays an important role in the commitment and development of thymic epithelial precursors. Here we document similarities of thymic epithelial development during embryogenesis in human and mouse. We stained for thymic epithelial surface markers (EpCAM1, Ly51, K8) and ligand/receptor pair (Wnt4, Fz4). Our results confirm the relevance of using murine test systems to model human embryonic thymic epithelial cell development.     

Bilateral comparison of traditional and alternate electrodermal measurement sites

Advances in mobile and wireless technology have expanded the scope of electrodermal research. Since traditional electrodermal measurement sites are not always suitable for laboratory research and are rarely appropriate for ambulatory measurements, there is a need to explore and contrast alternate measurement locations. We evaluated bilateral electrodermal activity (EDA) from five measurement sites (fingers, feet, wrists, shoulders, and calves). In a counterbalanced, randomized, within-subjects design study, participants (N = 115) engaged in a 4-min-long breathing exercise and were exposed to emotionally laden and neutral stimuli. High within-subject correlations were found between the EDA measured from fingers bilaterally (r = .89), between the left fingers and both feet (r = .72). Moderate correlations were found between EDA measured from the left fingers and wrists (r = .30 and r = .33), low correlations between the left fingers and the shoulders (r = −.03 and r = −.06) or calves (r = .05 and r = .14). Response latency was the shortest on the fingers while it was the longest on the lower body. Short response windows would miss some of the responses from the palmar surfaces and a substantial number from other evaluated locations. The fingers and the feet are the most reliable locations to measure from, followed by the wrists. We suggest setting site-specific response windows for different measurement locations. An investigation of repeatability showed that within-subject correlations, response frequencies, response amplitudes show a similar pattern from the first measurement time to a later one.     

Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals

Purpose

DNA Ligase 4 (LIG4) is a key factor in the non-homologous end-joining (NHEJ) DNA double-strand break repair pathway needed for V(D)J recombination and the generation of the T cell receptor and immunoglobulin molecules. Defects in LIG4 result in a variable syndrome of growth retardation, pancytopenia, combined immunodeficiency, cellular radiosensitivity, and developmental delay.

Methods

We diagnosed a patient with LIG4 syndrome by radiosensitivity testing on peripheral blood cells, and established that two of her four healthy siblings carried the same compound heterozygous LIG4 mutations. An extensive analysis of the immune phenotype, cellular radiosensitivity, telomere length, and T and B cell antigen receptor repertoire was performed in all siblings.

Results

In the three genotypically affected individuals, variable severities of radiosensitivity, alterations of T and B cell counts with an increased percentage of memory cells, and hypogammaglobulinemia, were noticed. Analysis of T and B cell antigen receptor repertoires demonstrated increased usage of alternative microhomology-mediated end-joining (MHMEJ) repair, leading to diminished N nucleotide addition and shorter CDR3 length. However, overall repertoire diversity was preserved.

Conclusions

We demonstrate that LIG4 syndrome presents with high clinical variability even within the same family, and that distinctive immunologic abnormalities may be observed also in yet asymptomatic individuals.

     

Chronic progressive deficits in neuron size, density and number in the trigeminal ganglia of mice latently infected with herpes simplex virus

Numerous epidemiological studies have proposed a link between herpes simplex virus (HSV) infection and several common chronic neuropsychiatric and neurodegenerative diseases. Experimental HSV infection of mice can lead to chronic behavioral and neurological deficits and chronic pain. While neuron injury and loss are well-documented consequences of the acute phase of infection, the pathologic consequences of latent HSV infection are poorly understood. To determine whether latent HSV infection can cause neuronal injury in mice, trigeminal ganglia (TG) derived from adult BALB/c mice 1, 12 and 31 weeks after corneal HSV type 1 (HSV-1) inoculation were analyzed for evidence of productive or latent HSV-1 infection, inflammation and changes in neuron size, density and number. We found that latent HSV-1 infection between 12 and 31 weeks after corneal virus inoculation was associated with inflammation and progressive deficits in mean neuron diameter, neuronal nucleus diameter, neuron density and neuron number in the TG relative to mock-infected controls. The extent of neuronal injury during latent infection correlated with the extent of inflammation. These studies demonstrate that latent HSV infection is associated with progressive neuronal pathology and may lead to a better understanding of the role of HSV infections in chronic neurological diseases.     

Regional differences in the association between land cover and West Nile virus disease incidence in humans in the United States

West Nile virus (WNV) is generally considered to be an urban pathogen in the United States, but studies associating land cover and disease incidence, seroprevalence, or infection rate in humans, birds, domesticated and wild mammals, and mosquitoes report varying and sometimes contradictory results at an array of spatial extents. Human infection can provide insight about basic transmission activity; therefore, we analyzed data on the incidence of WNV disease in humans to obtain a comprehensive picture of how human disease and land cover type are associated across the United States. Human WNV disease incidence in Northeastern regions was positively associated with urban land covers, whereas incidence in the Western United States was positively associated with agricultural land covers. We suggest that these regional associations are explained by the geographic distributions of prominent WNV vectors: Culex pipiens complex (including Cx. pipiens and Cx. quinquefasciatus) in the Northeast and Cx. tarsalis in the Western United States.     

Antioxidant activity of propolis extracts from Serbia: A polarographic approach

Antioxidant activity (AO) of commercial propolis extracts (PEs), available on Serbian market, was determined by direct current (DC) polarography. Polarographic anodic current of 5.0 mmol L⁻¹ alkaline solution of H₂O₂ was recorded at potentials of mercury dissolution. Decrease of the current was plotted against the volume of gradually added PEs. The volume of PE causing 20% current decrease was determined from the linear part of the plot. Antioxidant activity was expressed in H₂O₂ equivalent (HPEq), representing the volume of PE that corresponds to 1.0 mmol L⁻¹ H₂O₂ decrease. Resulting HPEq ranged between 1.71 ± 0.11 and 8.00 ± 0.18 μL. Range of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity was from 0.093 ± 0.004% to 0.346 ± 0.006%. Total phenolic content (TCP) of PE with superior AO activity was 5.31 ± 0.05%g GAE, while the extract with the lowest activity contained 1.45 ± 0.02%g GAE. Antioxidant activity, determined by polarographic method, was correlated with DPPH scavenging activity (R² = 0.991) and TCP (R² = 0.985). Validity of obtained results was further confirmed using ANOVA and post hoc Tukey HSD test.     

Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin

Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected an ESR spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine, N-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNOS(-/-)) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp91(phox-/-)) mice as much as it was in the wild-type mouse. Nitric oxide (*NO) end products were increased in LPS-treated skin. As expected, the *NO end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS.     

Seroma in breast surgery: all the surgeons fault?

Background

Despite a trend for less radical surgical approaches in breast cancer due to better understanding of tumour biology and new treatment options such as neoadjuvant chemotherapy (NAC) and intra-operative radiotherapy (IORT), seroma production remains one of the main surgical side effects that can result in prolonged recovery, delay of radiotherapy and patient discomfort. The aim of this study is to provide an update on risk factors for seroma production after breast cancer surgery considering the latest treatment options.

Methods

A retrospective analysis of seroma production in primary breast cancer patients treated between 01.01.2010 and 31.12.2014 at the Breast Cancer Centre, University Hospital Ulm, was performed. Patients with previous breast/axillary surgery or more than one intervention were excluded. Seroma formation was measured using wound drains placed in breast and axilla.

Results

In total, 581 patients met the inclusion criteria. Median age at diagnosis was 60 years, and median BMI 25.6 kg/m². 60 (10.3%) patients had a mastectomy, 175 (30.1%) patients received IORT, and 72 (12.4%) patients received NAC. Median amount of seroma production was 82.5 ml (range 0–3012.5 ml). Multivariate analysis revealed that most of the observed variation in seroma production was due to type of surgery (mastectomy vs. breast conserving), length of surgery and number of removed lymph nodes. Both NAC and IORT explained a significant but very small amount of the observed variation in seroma production.

Conclusion

The most important factors for seroma production are extent and duration of breast surgery.