Bioethical implications of end-of-life decision-making in patients with dementia:a tale of two societies

End-of-life decision-making in patients with dementia is a complex topic. Belgium and the Netherlands have been at the forefront of legislative advancement and progressive societal changes concerning the perspectives toward physician-assisted death (PAD). Careful consideration of clinical and social aspects is essential during the end-of-life decision-making process in patients with dementia. Geriatric assent provides the physician, the patient and his family the opportunity to end life with dignity. Unbearable suffering, decisional competence, and awareness of memory deficits are among the clinical considerations that physicians should incorporate during the end-of-life decision-making process. However, as other societies introduce legislature granting the right of PAD, new social determinants should be considered; Mexico City is an example. Current perspectives regarding advance euthanasia directives (AED) and PAD in patients with dementia are evolving. A new perspective that hinges on the role of the family and geriatric assent should help culturally heterogeneous societies in the transition of their public health care policies regarding end-of-life choices.</p

Postural instability during attacks of migraine without aura

Background and purpose: Migraine has long been associated with unsteadiness and dizziness but postural control has not been studied in the ictal state. Here, the stability of upright stance during migraine attacks was measured. Methods: Static balance was assessed prospectively in migraine patients (n = 30) during quiet stance for 40 s on a posturographic force platform. Recordings were performed both ictally and in the pain-free interval. Subjects were assessed under four different conditions yielding different visual and proprioceptive feedback environments. Both ictal and interictal data were compared with age-matched healthy controls (n = 30). Results: Postural instability increased significantly under all experimental conditions during migraine attacks. Whilst standing on a foam pad with eyes closed, median sway area was 353 mm2 in control subjects, 318 mm2 in migraineurs in the pain-free period and 618 mm2 in the ictal state. However, Romberg and vestibular Romberg quotients were not altered during migraine attacks. Spectral analyses of postural sway also showed similar profiles in migraineurs and controls. The severity of headache was inversely correlated to Romberg quotients. Conclusions: The demonstrated pattern of balance disorder during migraine attacks suggests a transient cerebellar dysfunction. Our findings also indicate that intense headache induces a re-weighting of sensory processing toward less dependence on visual and proprioceptive information. © 2018 EA

Development of a predictive pharmacophore model and a 3D-QSAR study for an in Silico screening of new potent BCR-ABL kinase inhibit

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder, characterized, in most cases, by the presence of the Bcr-Abl fusion oncogene. Bcr-Abl is a constitutively active tyrosine kinase that is responsible for the malignant transformation. Targeting the Bcr-Abl kinase is an attractive treatment strategy for CML. First and second generation Bcr-Abl inhibitors have focused on targeting the ATP-binding domain of the kinase. Mutations in that region are relatively resistant to drug manipulation. Therefore, non-ATP-competitive agents have been recently developed and tested. In the present study, in an attempt to aid the design of new chemotypes with enhanced cytotoxicity against K562 cells, 3D pharmacophore models were generated and 3D-QSAR CoMFA and CoMSIA studies were carried out on the 33 novel Abl kinase inhibitors (E)-&amp;#945;-benzylthio chalcones synthesized by Reddy et al. A five-point pharmacophore with a hydrogen bond acceptor, two hydrophobic groups and two aromatic rings as pharmacophore features, and a statistically significant 3D-QSAR model with excellent predictive power were developed. The pharmacophore model was also used for alignment of the 33 compounds in a CoMFA/CoMSIA analysis. The contour maps of the fields of CoMFA and CoMSIA models were utilized to provide structural insight into how these molecules promote their toxicity. The possibility of using this model for the design of drugs for the treatment of &amp;#946;-thalassemia and sickle cell disease (SCD), since several Bcr-Abl inhibitors are able to promote erythroid differentiation and &amp;#947;-globin expression in CML cell lines and primary erythroid cells is discussed

Preliminary evidence for gender effects of levetiracetam monotherapy duration on bone health of patients with epilepsy

Enzyme-inducing antiepileptic drugs AEDs have adverse effects on bone mineral density (BMD), whereas studies on levetiracetam (LEV), a nonenzyme-inducing agent, have showed conflicting results. The aim of this study was to further elucidate the role of LEV in bone health. A sample of forty-six patients with epilepsy (mean age: 35.7 years, range: 20.2-64.2 years, 39.1% males) on LEV monotherapy for at least one year (range: 1.5-14.5 years, median 5.5 years) underwent femoral neck (FN) and lumbar spine (LS) BMD measurements. The T- and Z-scores were calculated. Results showed that 15.2% of the patients were identified with osteopenia and none with osteoporosis. Pearson&apos;s correlations revealed a negative but not significant association of LEV duration with bone-related measurements (range of rhos: from - 0.004 to - 0.23), except for LS T-scores. In terms of FN BMD measurements, Z-scores, and T-scores, longer LEV therapy duration had adverse but not significant effects on bone health after adjusting for age and gender. With regard to LS BMD measurements, Z-scores, and T-scores, men taking LEV for at least 5.5 years had better, although not significant, bone health compared with men with shorter LEV exposure, after adjusting for age. The opposite was found in women, although differences did not reach significance. These preliminary results are indicative of a differential effect of LEV therapy duration in men and women, which could presumably account for the incongruity of the already published studies. Also, LS assessments were more sensitive to these gender differences. Future larger studies should validate these results. © 2015 Elsevier Inc