No abstract

PRRXL1 [paired related homeobox-like 1; also known as DRG11 (dorsal root ganglia 11)] is a paired-like homeodomain transcription factor expressed in DRG and dSC (dorsal spinal cord) nociceptive neurons. PRRXL1 is crucial for the establishment and maintenance of nociceptive circuitry, as Prrxl1(-/-) mice present neuronal loss, reduced pain sensitivity and failure to thrive. In the present study, we show that PRRXL1 is highly phosphorylated in vivo, and that its multiple band pattern on electrophoretic analysis is the result of different phosphorylation states. PRRXL1 phosphorylation appears to be differentially regulated along the dSC and DRG development and it is mapped to two functional domains. One region comprises amino acids 107-143, whereas the other one encompasses amino acids 227-263 and displays repressor activity. Using an immunoprecipitation-MS approach, two phosphorylation sites were identified, Ser¹¹⁹ and Ser²³⁸. Phosphorylation at Ser¹¹⁹ is shown to be determinant for PRRXL1 conformation and transcriptional activity. Ser¹¹⁹ phosphorylation is thus proposed as a mechanism for regulating PRRXL1 function and conformation during nociceptive system development.

<b><i>Background/Aims:</i></b> Cognitive impairment is prevalent in older inpatients but may be unrecognized. Screening to identify cognitive deficits is therefore important to optimize care. The 10-point Abbreviated Mental Test Score (AMTS) is widely used in acute hospital settings but its reliability for mild versus more severe cognitive impairment is unknown. We therefore studied the AMTS versus the 30-point Montreal Cognitive Assessment (MoCA) in older (≥75 years) inpatients. <b><i>Methods:</i></b> The AMTS and MoCA were administered to consecutive hospitalized patients at ≥72 h after admission in a prospective observational study. MoCA testing time was recorded. Reliability of the AMTS for the reference standard defined as mild (MoCA &#x3c;26) or moderate/severe (MoCA &#x3c;18) cognitive impairment was assessed using the area under the receiver-operating curve (AUC). Sensitivity, specificity, positive and negative predictive values of low AMTS (&#x3c;8) for cognitive impairment were determined. <b><i>Results:</i></b> Among 205 patients (mean/SD age = 84.9/6.3 years, 96 (46.8%) male, 74 (36.1%) dementia/delirium), mean/SD AMTS was 7.2/2.3, and mean/SD MoCA was 16.1/6.2 with mean/SD testing time = 17.9/7.2 min. 96/205 (46.8%) had low AMTS whereas 174/185 (94%) had low MoCA: 74/185 (40.0%) had mild and 100 ( 54.0%) had moderate/severe impairment. Moderate/severe cognitive impairment was more prevalent in the low versus the normal AMTS group: 74/83 (90%) versus 25/102 (25%, <i>p</i> &#x3c; 0.0001). AUC of the AMTS for mild and moderate/severe impairment were 0.86 (95% CI = 0.80–0.93) and 0.88 (0.82–0.93), respectively. Specificity of AMTS &#x3c;8 for both mild and moderate/severe cognitive impairment was high (100%, 71.5–100, and 92.7%, 84.8–97.3) but sensitivity was lower (44.8%, 37.0–52.8, and 72.8%, 62.6–81.6, respectively). The negative predictive value of AMTS &#x3c;8 was therefore low for mild impairment (10.9%, 5.6–18.7) but much higher for moderate/severe impairment (75.2%, 65.7–83.3). All MoCA subtests discriminated between low and normal AMTS groups (all <i>p</i> &#x3c; 0.0001, except <i>p</i> = 0.002 for repetition) but deficits in delayed recall, verbal fluency and visuo-executive function were prevalent even in the normal AMTS group. <b><i>Conclusion:</i></b> The AMTS is highly specific but relatively insensitive for cognitive impairment: a quarter of those with normal AMTS had moderate/severe impairment on the MoCA with widespread deficits. The AMTS cannot therefore be used as a “rule-out” test, and more detailed cognitive assessment will be required in selected patients.

No abstract

No abstract