Three-Component Domino Process for the Pyrrolizine Skeleton via [3 + 2]-Cycloaddition–Enamine Cyclization Triggered by a Gold Catalyst

Pyrrolizines are bicyclic fused azaheterocycles with a bridgehead nitrogen contained in a core skeleton and are often found in biologically active compounds. Despite their importance, there have been few reports on concise and flexible syntheses of pyrrolizines. A novel one-pot, convergent method is described for pyrrolizines by simple mixing of iminoesters, acetylenes, and dipolarophiles in the presence of a cationic gold catalyst and an acid additive. This domino process affords multisubstituted pyrrolizines without handling unstable intermediates

Comparison of two screening tests for HIV-Associated Neurocognitive Disorder suspected Japanese patients with respect to cART usage

<div><p>In this study, we demonstrated the pervasiveness of HIV-associated neurocognitive disorders (HAND) among a selection of Japanese patients as well as evaluated and compared the Mini Mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) for use as a screening tool among combination anti-retroviral therapy (cART)-naïve and cART experienced patients. The MMSE and the IHDS have both been used as HAND screening tests around the world with variable success. It has been reported the increased usage of cART the utility of these screening tests may have been diminished due to the decreased severity of impairment and the altered pattern of neurocognitive impairments in cART era HAND patients. It is therefore possible the MMSE and the IHDS may still be useful among cART-naïve patients even in the cART era. However, only one study has investigated and compared the screening results of the IHDS among cART-naïve and cART experienced patients. All HIV positive patients who visited, or were admitted, to the Ryukyu University Hospital between January 2009 and March 2014 were evaluated for inclusion. Selected patients (n = 49) had data without omission for all tests. The overall prevalence of HAND in our cohort was 44%. The area under the curve (AUC), for all subjects using the MMSE and the IHDS, were 0.60 and 0.69, respectively. However, the AUC among cART-naïve patients were 0.58 and 0.76 for the MMSE and the IHDS, respectively. Whereas, cART experienced patients had an AUC of 0.60 and 0.61, respectively. Overall, the MMSE demonstrated a poor screening ability for HAND, regardless of cART usage (the cut-off value of 27 had a Youden's J-Index of 0.1, in all groups). Alternatively, the IHDS was moderately useful for HAND screening among cART-naïve patients (the cut-off value of 11 had a Youden's J-Index of 0.4), but performed poorly as a screening test among cART experienced patients (the cut-off value of 11 had a Youden's J-Index of 0.1).</p></div

Patient scores for each neurophychological test for HAND diagnosis (n = 49).

<p>Impairment (Imp) was considered as mental deterioration of at least 1 standard deviation. Non-impairment (non-Imp) patients were considered as having minimal mental deterioration ranging from less than 1 standard deviation to normal cognitive abilities. Abbreviations: DST: Digit Symbol Test, TMT-A; Trail Making Test Part A, TMT-B; Trail Making Test Part B, ST; Stroop Test, DS; Digit Span.</p

ROC curve of MMSE and IHDS among cART-naïve (n = 27) and cART experienced patients (n = 22).

<p>Receiver Operator Characteristic (ROC) curve for cART-naïve and cART experienced patients generated by using the results from the neuropsychological test battery as a gold standard for HAND diagnosis.</p

Patient score distribution for MMSE and IHDS (n = 49).

<p>Black and white bar indicate cART-naive and cART experienced patients, respectively.</p

ROC curve of MMSE and IHDS among all subjects (n = 49).

<p>Receiver Operator Characteristic (ROC) curve generated by using the results from the neuropsychological test battery as a gold standard for HAND diagnosis.</p

Patient background and laboratory findings.

<p>Patient background and laboratory findings.</p