Escaping from Flatland: Antimalarial Activity of sp3-Rich Bridged Pyrrolidine Derivatives

We utilized synthetic photochemistry to generate novel sp³-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold. Preliminary antimalarial screening of the library provided promising compounds with activity in the 1–5 μM range with an enhanced hit rate. Further evaluation (solubility, drug metabolism and pharmacokinetics (DMPK), and toxicity) of a selected compound (9) suggested that this series represents an excellent opportunity for further optimization with the framework offering multiple opportunities for the addition of uniquely vectorally positioned extra functionality.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

Factors associated with increasing functional decline in multimorbid independently living older people

Objectives

With increasing age the levels of activities of daily living (ADL) deteriorate. In this study we aimed to investigate which demographic characteristics and disorders are associated with ADL disabilities in multi-morbid older people.

Study design

We performed a cross-sectional study with baseline patient data from a large Dutch trial in independently living multi-morbid older people combined with the reimbursed healthcare data for the same subjects.

Main outcome measures

The primary outcome of our study was the level of independence of activities of daily living (ADL) as assessed with the Modified Katz Activities of Daily Living (KATZ-15) scale.

Results

In our study we were able to include 1187 persons (63.0% female) for whom both questionnaire data and reimbursed healthcare data was available. In total, 59% had a Katz-15 score of 1 or higher. The strongest associations with ADL disabilities in women were psychiatric disorders, with prevalence rate (PR) estimates of 1.37 (95% confidence interval (CI): 1.17–1.60) and transient ischaemic attacks and cerebrovasculair accidents in men, with PR estimates of 1.94 (95% CI: 1.41–2.66). Although univariate analysis seemed to also reveal associations with socio-demographic factors such as living together with a partner or the socio-economic status, these factors were not independently associated with ADL disabilities.

Conclusions

In this cross-sectional study we found that 71% of the multi-morbid female elderly had a sub-optimal level of activities of daily living, as assessed with the Katz-15 scale. The results of our study show that multiple disorders are associated with ADL disabilities in multi-morbid older men and women. We found socio-demographic characteristics not to be independently associated ADL disabilities.     

Human Cytomegalovirus and Epstein-Barr virus specific immunity in patients with ulcerative colitis

Clinical and Experimental Medicine - Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in...