Scalable diagnostic screening of mild cognitive impairment using AI dialogue agent.

The search for early biomarkers of mild cognitive impairment (MCI) has been central to the Alzheimer's Disease (AD) and dementia research community in recent years. To identify MCI status at the earliest possible point, recent studies have shown that linguistic markers such as word choice, utterance and sentence structures can potentially serve as preclinical behavioral markers. Here we present an adaptive dialogue algorithm (an AI-enabled dialogue agent) to identify sequences of questions (a dialogue policy) that distinguish MCI from normal (NL) cognitive status. Our AI agent adapts its questioning strategy based on the user's previous responses to reach an individualized conversational strategy per user. Because the AI agent is adaptive and scales favorably with additional data, our method provides a potential avenue for large-scale preclinical screening of neurocognitive decline as a new digital biomarker, as well as longitudinal tracking of aging patterns in the outpatient setting.

Resveratrol induces cell death and inhibits human herpesvirus 8 replication in primary effusion lymphoma cells.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been reported to inhibit proliferation of various cancer cells. However, the effects of resveratrol on the human herpesvirus 8 (HHV8) harboring primary effusion lymphoma (PEL) cells remains unclear. The anti-proliferation effects and possible mechanisms of resveratrol in the HHV8 harboring PEL cells were examined in this study. Results showed that resveratrol induced caspase-3 activation and the formation of acidic vacuoles in the HHV8 harboring PEL cells, indicating resveratrol treatment could cause apoptosis and autophagy in PEL cells. In addition, resveratrol treatment increased ROS generation but did not lead to HHV8 reactivation. ROS scavenger (N-acetyl cysteine, NAC) could attenuate both the resveratrol induced caspase-3 activity and the formation of acidic vacuoles, but failed to attenuate resveratrol induced PEL cell death. Caspase inhibitor, autophagy inhibitors and necroptosis inhibitor could not block resveratrol induced PEL cell death. Moreover, resveratrol disrupted HHV8 latent infection, inhibited HHV8 lytic gene expression and decreased virus progeny production. Overexpression of HHV8-encoded viral FLICE inhibitory protein (vFLIP) could partially block resveratrol induced cell death in PEL cells. These data suggest that resveratrol-induced cell death in PEL cells may be mediated by disruption of HHV8 replication. Resveratrol may be a potential anti-HHV8 drug and an effective treatment for HHV8-related tumors.

Chronology of illness in dual diagnosis heroin addicts: The role of mood disorders.

BACKGROUND: Recent celebrity deaths have been widely reported in the media and turned the public attention to the coexistence of mood, psychiatric and substance-abuse disorders. These tragic and untimely deaths motivated us to examine the scientific and clinical data, including our own work in this area. The self-medication hypothesis states that individuals with psychiatric illness tend to use heroin to alleviate their symptoms. This study examined the correlations between heroin use, mood and psychiatric disorders, and their chronology in the context of dual diagnosis. METHODS: Out of 506 dual diagnosed heroin addicts, 362 patients were implicated in heroin abuse with an onset of at least one year prior to the associated mental disorder (HER-PR), and 144 patients were diagnosed of mental illness at least one year prior to the associated onset of heroin use disorder (MI-PR). The retrospective cross-sectional analysis of the two groups compared their demographic, clinical and diagnostic characteristics at univariate and multivariate levels. RESULTS: Dual diagnosis heroin addicts whose heroin dependences existed one year prior to their diagnoses (HER-PR) reported more frequent somatic comorbidity (p≤0.001), less major problems at work (p=0.003), more legal problems (p=0.004) and more failed treatment for their heroin dependence (p<0.001) in the past. More than 2/3 reached the third stage of heroin addiction (p=<0.001). Their length of dependence was longer (p=0.004). HER-PR patients were diagnosed more frequently as affected by mood disorders and less frequently as affected by psychosis (p=0.004). At the multivariate level, HER-PR patients were characterized by having reached stage 3 of heroin dependence (OR=2.45), diagnosis of mood disorder (OR=2.25), unsuccessful treatment (OR=2.07) and low education (OR=1.79). LIMITATIONS: The main limitation is its retrospective nature. Nonetheless, it does shed light on what needs to be done from a clinical and public health perspective and especially prevention. CONCLUSIONS: The data emerging from this study, does not allow us to determine a causal relation between heroin use and mental illness onset. However, this data, even if requiring longitudinal studies, suggest that self-medication theory, in these patients, can be applied only for chronic psychoses, but should not be applied to patients with mood disorders using heroin.