Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

Factors associated with the designation of a health care proxy and writing advance directives for patients suffering from haematological malignancies

Background

During the last few decades, patients’ rights have been reinforced in many countries by acts of law. Measures now include health care proxies to uphold the doctor-patient relationship and advance directives for end-of-life patients. These could be relevant tools as early as the initial diagnosis of haematological malignancies because of the uncertain disease course. The aim of this research was to assess the factors associated with the designation of a proxy and writing advance directives by patients in a haematology department in France.

Methods

After a specific programme to encourage discussions about end-of-life preferences, we conducted a mixed-methods study comprising retrospective analysis of a random sample of 200 patients’ medical records, crossed with a qualitative analysis of the content of advance directives. Statistical analysis was performed by the RKward V 0.6.1 software with 0.05 denoting significance. The study was performed and presented in accordance with the STROBE guidelines. A thematic analysis of the advance directives was performed by two researchers.

Results

A total of 197 medical records were evaluable. The mean age of the patients was 66 years (range: 18–91). Nearly 2/3 of them (64.5%) designated a proxy, 6.1% wrote advance directives, and 8.1% and 4.6% expressed a wish to meet a religious representative or a volunteer, respectively. The 2-year survival rate was 78.4% [95%CI: 68.2-90.2]. Patients who wrote advance directives were statistically older (p <0.00025). Patients who wrote an advance directive were more likely to have expressed a wish to meet a religious representative (p <0.001) or a volunteer (p = 0.003). Marital status was a significant factor in appointing a proxy (p = 0.04).

Conclusions

To the best of our knowledge, this is the first paper to identify influencing factors for proxies and advance directives in a homogenous population of patients with haematological malignancies. Most patients chose a proxy. However, despite several training programmes for the carers and a care planning programme, few patients wrote advance directives. Our findings suggest that influencing factors are advanced age and a wish to see a religious representative. This study highlights the importance of oral communication about end-of-life issues between carers, patients and their relatives.

     

Hepatic,Renal and Inflammatory Biomarkers are Positively Associated with Blood Pressure Changes in Healthy Pregnant Women: A Prospective Cohort

This article evaluates the association of hepatic, renal, and inflammatory biomarkers with changes in systolic (SBP) and diastolic (DBP) blood pressure (BP) during healthy pregnancies.A prospective cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro, Brazil. SBP and DBP were evaluated throughout pregnancy (5th–13th, 20th–26th, and 30th–36th gestational weeks) and were the outcomes. The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), creatinine (Cr), and C-reactive protein (CRP) concentrations. The statistical analysis included 3 stages of modeling with the longitudinal linear mixed-effects procedures: Model 1 was adjusted for gestational age and quadratic gestational age; Model 2 included interactions between the biomarkers and gestational age; and Model 3 was adjusted for self-reported skin color, education, parity, early-pregnancy body mass index (BMI) (under/normal <25; overweight/obese ≥25 kg/m²), smoking habit, and leisure-time physical activity. Additional models were performed for CRP and UA with the inclusion of interaction terms between the biomarkers and BMI.Women classified in the third tertile of the ALP (≥61.1 U/L; β_SBP = 3.474; 95% confidence interval [CI]: 0.955–5.992; β_DBP = 3.291; 95% CI: 1.098–5.485), ALT (≥14.3 U/L; β_SBP = 2.232; 95% CI: 0.221–4.242; β_DBP = 2.355; 95% CI: 0.721–3.989), and Cr values (≥48.6 μmol/L; β_DBP = 1.927; 95% CI: 0.347–3.508) presented higher BP levels during pregnancy compared to those in the first and second tertiles. Women in the highest tertile of the ALP concentration distribution presented a lower rate of change in SBP and DBP during pregnancy (interaction term with gestational age β_SBP = −0.004; 95% CI: −0.007 to −0.001; P = 0.02; β_DBP = −0.003; 95% CI: −0.006 to −0.001; P = 0.01). Higher UA concentrations were associated with higher SBP levels only in overweight/obese women (β = 3.878; 95% CI: 0.687–7.068), whereas higher CRP concentrations (≥2.6 mg/L) were associated with higher DBP in under/normal weight women (β =2.252; 95% CI: 0.267–4.236).ALP, ALT, and Cr concentrations were positively associated with BP levels, whereas ALP was associated with a lower rate of change in BP. The associations of UA and CRP with BP differ according to the early-pregnancy BMI.