Estimation of postmortem interval using vitreous potassium levels in cases of fatal road traffic collision

AIM OF THE STUDY: To produce a formula that can accurately predict postmortem interval (PMI) based on vitreous potassium levels using road traffic collision fatalities. MATERIAL AND METHODS: Vitreous humour samples were taken from 78 individuals who had died following road traffic collisions between 2010 and 2015. Samples were obtained from both eyes and were sent for on-site analysis. Measurement of potassium was by an indirect ion-specific electrode Siemens diagnostics ADVIA 2400 chemistry system. Exact time of death was known from police reports, the time of postmortem was recorded and the postmortem interval was calculated. Linear regression was then used to analyse the relationship between the two. The impact of age was also assessed. RESULTS: PMI was between 6 and 162 hours. As vitreous potassium increases, the PMI also increases; exhibiting a linear relationship. This is illustrated by a regression equation of PMI = 6.42[K+] - 40.94, R = 0.67 (p < 0.001). This produced a formula closely comparable with three other studies proposed in previous literature and produces estimates that may exceed one calendar day. When both age and medical intervention are accounted for there is an insignificant improvement in prediction. CONCLUSIONS: Validated methods have been used to produce a formula for prediction of PMI using vitreous potassium. Although this is specific to road traffic collisions, the methods are transferable and can be seen to be comparable with other recently published methods. Nonetheless, if greater levels of accuracy are required it is suggested that biomarkers delivering a higher level of precision should still be sought.

Intracellular delivery of a protein antigen with an endosomal-releasing polymer enhances CD8 T-cell production and prophylactic vaccine efficacy.

Protein-based vaccines have significant potential as infectious disease and anticancer therapeutics, but clinical impact has been limited in some applications by their inability to generate a coordinated cellular immune response. Here, a pH-responsive carrier incorporating poly(propylacrylic acid) (PPAA) was evaluated to test whether improved cytosolic delivery of a protein antigen could enhance CD8+ cytotoxic lymphocyte generation and prophylactic tumor vaccine responses. PPAA was directly conjugated to the model ovalbumin antigen via reducible disulfide linkages and was also tested in a particulate formulation after condensation with cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA). Intracellular trafficking studies revealed that both PPAA-containing formulations were stably internalized and evaded exocytotic pathways, leading to increased intracellular accumulation and potential access to the cytosolic MHC-1 antigen presentation pathway. In an EG.7-OVA mouse tumor protection model, both PPAA-containing carriers robustly inhibited tumor growth and led to an approximately 3.5-fold increase in the longevity of tumor-free survival relative to controls. Mechanistically, this response was attributed to the 8-fold increase in production of ovalbumin-specific CD8+ T-lymphocytes and an 11-fold increase in production of antiovalbumin IgG. Significantly, this is one of the first demonstrated examples of in vivo immunotherapeutic efficacy using soluble protein-polymer conjugates. These results suggest that carriers enhancing cytosolic delivery of protein antigens could lead to more robust CD8+ T-cell response and demonstrate the potential of pH-responsive PPAA-based carriers for therapeutic vaccine applications.

Common blood laboratory values are associated with cognition among older inpatients referred for neuropsychological testing.

The purpose of this study was to examine the relationship between common laboratory values and cognitive functioning among 129 inpatients referred for neuropsychological evaluation. Laboratory values were recorded at admission, at the time point closest to neuropsychological evaluation, and at the time of peak metabolic derangement. Cognitive status was evaluated with the modified Mini-Mental State Exam. Patients with hyperglycemia, hypochloremia, and/or elevated creatinine at admission exhibited cognitive deficits. Patients with hyperglycemia, hyperchloremia, hypernatremia, hyperkalemia, leukocytosis, low hemoglobin, elevated blood urea nitrogen, and/or elevated creatinine at the time of peak metabolic derangement exhibited cognitive deficits. Different lab abnormalities at the time of peak metabolic derangement accounted for unique patterns of neuropsychological impairment. Lab values drawn at the time point closest to neuropsychological evaluation were not significantly associated with cognitive functioning. Results support and quantify common clinical beliefs that metabolic abnormalities are associated with global cognitive changes among elderly inpatients.

High risk of reading disability and speech sound disorder in rolandic epilepsy families: case-control study.

PURPOSE: Associations between rolandic epilepsy (RE) with reading disability (RD) and speech sound disorder (SSD) have not been tested in a controlled study. We conducted a case-control study to determine whether (1) RD and SSD odds are higher in RE probands than controls and (2) an RE proband predicts a family member with RD or SSD, hence suggesting a shared genetic etiology for RE, RD, and SSD. METHODS: Unmatched case-control study with 55 stringently defined RE cases, 150 controls in the same age range lacking a primary brain disorder diagnosis, and their siblings and parents. Odds ratios (OR) were calculated by multiple logistic regression, adjusted for sex and age, and for relatives, also adjusted for comorbidity of RD and SSD in the proband. RESULTS: RD was strongly associated with RE after adjustment for sex and age: OR 5.78 (95% CI: 2.86-11.69). An RE proband predicts RD in family members: OR 2.84 (95% CI: 1.38-5.84), but not independently of the RE proband's RD status: OR 1.30 (95% CI: 0.55-12.79). SSD was also comorbid with RE: adjusted OR 2.47 (95%CI: 1.22-4.97). An RE proband predicts SSD in relatives, even after controlling for sex, age and proband SSD comorbidity: OR 4.44 (95% CI: 1.93-10.22). CONCLUSIONS: RE is strongly comorbid with RD and SSD. Both RD and SSD are likely to be genetically influenced and may contribute to the complex genetic etiology of the RE syndrome. Siblings of RE patients are at high risk of RD and SSD and both RE patients and their younger siblings should be screened early.

Psychosocial predictors of dementia caregiver desire to institutionalize: caregiver, care recipient, and family relationship factors.

Several factors influence dementia caregiver desire to institutionalize; however, little is known about differences in caregivers who desire institutionalization versus those who do not. The current study compares predictors of desire to institutionalize in dementia caregivers. Seventy-two caregivers completed the Desire to Institutionalize Scale (DIS) and several psychosocial measures, including burden, dementia knowledge, self-efficacy, depression, health, care recipient daily functioning and memory/behavior problems, family functioning, and social support. Based on DIS responses, caregivers were divided into No DI versus DI groups. DI caregivers had significantly higher burden, greater dementia knowledge, more family dysfunction, and decreased social support compared with No DI caregivers. Findings emphasize the importance of caregiver and family relationship variables in DIS, suggesting potentially modifiable targets for caregiver interventions. Dementia knowledge was associated with higher DIS, suggesting that educational programs alone may not be helpful to delay institutionalization.

Recruitment and retention of minority students: diversity in nursing education.

A culturally diverse nursing workforce is essential to meet the health needs of an increasingly diverse Canadian population. The recruitment and retention of nursing students representing diverse backgrounds are vital to the building of this diversified work force. Studies have shown that diversity within the student body benefits everyone. For example, students who study and work within a diverse environment are better able to understand and consider multiple perspectives and to appreciate the benefits inherent in diversity. This paper describes one school of nursing's project on the Recruitment and Retention of Black students into their Bachelor of Science Nursing (BScN) Program. The project goals are to increase diversity, foster student learning, and ultimately improve health care for the Black community. Presented in this paper are the project background, implementation process, challenges and outcomes. This may provide learned lessons and future directions for similar initiatives in other institutions.

Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal epithelium taken from patients undergoing nasal allergen challenge.

Nasal allergen challenge of patients with allergic rhinitis results in increased numbers of inflammatory cells and increased production of pro-inflammatory cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and have used this method to detect alterations of IL-5 mRNA from patients undergoing a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged out of season with appropriate pollen extracts at sufficient dose to give a rhinitis total symptom score of 5 on a scale of 12. After allergen exposure, symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted proteins were collected on filter paper strips and two superficial scrapings of nasal epithelium were obtained. The scrapings of epithelium were immediately immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR was performed. cDNA for IL-5 was then measured by real-time fluorescence quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA. Data were normalized for content of ribosomal RNA. The relative amount of cDNA for IL-5 was calculated by comparison with internal standards prepared from phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h (p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8 ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5 protein did not correlate significantly with the symptoms score or with changes in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in IL-5 mRNA in patients with allergic rhinitis undergoing an allergen challenge correlate with total symptom scores better than changes in IL-5 protein eluted from filter paper. Furthermore, these changes can be measured quantitatively in very small amounts of tissue.