Asymmetry in the emotional content of lateralised multimodal hallucinations following right thalamic stroke

The thalamus has been described as a "relay station" for sensory information from most sensory modalities projecting to cortical areas. Therefore injury to the thalamus may result in multimodal sensory and motor deficits. In the present study, a 61-year-old woman suffered a right thalamic cerebral vascular accident (CVA; as evidenced by a computerised tomography [CT] scan). Secondary to this incident, she complained of altered sensations across multiple sensory modalities, including olfactory, visual, auditory, tactile, temperature, and pain sensation. Interestingly, during recovery from the thalamic CVA, the patient reported hallucinations in all the modalities cited above. Multimodal dysaethesias (odd sensations) and hallucinations showed reliable laterality in the affective valence across modalities with positive associations within right hemispace and negative associations within left hemispace. Overall, the results support multimodal role of the thalamus and provide evidence for lateralisation of positive and negative affect within the right and left hemispheres respectively.     

MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2

Matrix metalloproteinase 2 (MMP2) is important in breast cancer (BC) invasion and metastasis. We previously reported that BC brain metastases, in a rat syngeneic model developed in our laboratory, have high expression and activity of MMP2. The MMP2 mechanism of action in the brain is still under intense scrutiny. To study the role of MMP2 in the development of BC brain metastasis we transfected ENU1564 rat mammary adenocarcinoma cells with tissue inhibitor of MMP2 (TIMP2). Animals inoculated with ENU1564-TIMP2 cells had decreased orthotopic tumor growth, decreased orthotopic metastastic behavior and did not develop brain metastases. These results were associated with decreased MMP2 activity, demonstrated by gel zymography. Mitogen activated protein kinase (MAPK) pathway components, such as ERK1/2, have been correlated to MMP expression and/or astrocyte activity. We found that BC brain metastases have peripheral astrocyte reactivity and higher expression of glial fibrillary acidic protein (GFAP) and phosphorylated-ERK1/2 (p-ERK1/2). Additionally, rat astrocyte-conditioned media increased in vitro invasion of ENU1564 cancer cells and increased expression of MMP2 and p-ERK1/2. Blockage of ERK1/2 phosphorylation by treatment with MEK inhibitor (PD98059) decreased the expression of MMP2 in cancer cells grown in rat astrocyte-conditioned media. Our results are highly suggestive that MMP2 plays a role in the development of BC metastases, in particular to the brain. Furthermore, our results suggest that astrocyte factors and the ERK1/2 signaling pathway may be associated with BC brain metastasis development; and that ERK1/2 may regulate MMP2 in a way that is modifiable by astrocyte factors.     

Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low‐density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome‐wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea‐blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha‐helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.     

Accuracy and precision of manufacturer-supplied liquid medication administration devices before and after patient education

ObjectiveTo compare the accuracy and precision of a manufacturer-supplied dropper versus a pharmacy-supplied syringe when measured by a trained student pharmacist and to evaluate patients' ability to accurately measure a prescribed amount of medication with these devices before and after counseling on their use.MethodsThis was a two-phased study with a pretest/posttest design of 125 community pharmacy patrons of Virginia community pharmacies. Deliverable volume was measured by a student pharmacist for nystatin suspension and digoxin elixir using the manufactured-supplied device. Patients at pharmacies were asked to complete a short survey, then asked to measure a specified dose of nystatin suspension and digoxin elixir (using the manufacturer-supplied administration device). The patients repeated this a second time after a student provided education on how to properly use each administration device. The main outcomes measure was whether education on an administration device would provide more measurement accuracy using medications with different physical properties.ResultsFor nystatin, 88% and 85.6% of patients measured with an error of greater than or equal to 20% before and after counseling, respectively. For digoxin, the totals were 24.8% before counseling and 4% after. A statistically significant (P < 0.05) difference was observed in the percent measurement error before and after counseling for nystatin and digoxin both for patients who had been educated before the study and for those who had not been counseled.ConclusionIn general, the accuracy of medication dosage devices seems to be most affected by viscosity of the liquid being measured. With education on proper use, the oral syringe provides a statistically and clinically significant improvement in dosing accuracy for viscous medications compared with the manufacturer-supplied dropper. Pharmacists must review with patients the proper way to use a manufacturer- or pharmacy-supplied oral delivery device for appropriate dosing measurements.     

Postpartum psychological distress after emergency team response during childbirth

Purpose: To evaluate the feasibility and acceptability of a protocol determining the relationship between emergency team response (ETR) during childbirth and acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) symptoms.

Methods: In a prospective, observational, cohort design, women experiencing ETR during childbirth were approached and recruited on postpartum day-1 and followed for six weeks. Demographics, obstetric and birth characteristics, ASD scores and PTSD scores (by Impact of Events Scale, IES and PCL-civilian) were recorded. Recruitment and retention rates were recorded, and scores were compared to women who did not experience ETR.

Results: Three hundred sixty-nine were approached and 249 were enrolled (67.5% recruitment rate). One hundred twenty-five completed all procedures (50.2% retention). Twenty experienced ETR (3.5% event rate), 12 enrolled (60.0% recruitment rate) and 8 completed the study (66.7% retention). The ETR group had higher PCL and IES scores (PCL: ETR median 12, non-ETR median 2, p?=?.08; IES: ETR median 22.5, non-ETR median 20, p?=?.08). ASD scores were similar between groups.

Conclusions: Methodology investigating the link between ETR and postpartum psychological distress is feasible and acceptable. A relationship between ETR and PTSD symptoms appears to exist, with ETR being associated with higher PTSD scores compared to non-ETR childbirths. Methods that incorporate awareness of the unique concerns of vulnerable populations are needed.