Life during COVID-19 lockdown in Italy: the influence of cognitive state on psychosocial, behavioral and lifestyle profiles of older adults.

Few studies have examined lockdown effects on the way of living and well-being of older adults stratified by cognitive state. Since cognitive deficits are common in this population, we investigated how cognition influenced their understanding of the pandemic, socio-behavioral responses and lifestyle adaptations during lockdown, and how these factors affected their mood or memory.Telephone-based survey involving 204 older adults ≥65 y/o (median: 82) with previous assessments of cognitive state: 164 normal-old (NOLD), 24 mild-neurocognitive disorder (mild-NCD), 18 mild-moderate dementia. A structured questionnaire was developed to assess psychological and socio-behavioral variables. Logistic regression was used to ascertain their effects on mood and memory.With increasing cognitive deficits, understanding of the pandemic and the ability to follow lockdown policies, adapt to lifestyle changes, and maintain remote interactions decreased. Participants with dementia were more depressed; NOLDs remained physically and mentally active but were more bored and anxious. Sleeping and health problems independently increased the likelihood of depression (OR: 2.29; CI: 1.06-4.93;NOLD and mild-NCD groups showed similar mood-behavioral profiles suggesting better tolerance of lockdown. Those with dementia were unable to adapt and suffered from depression and cognitive complaints. To counteract lockdown effects, physical and mental activities and digital literacy should be encouraged

Expression pattern of perilipins in human brain during aging and in Alzheimer's disease

Aims: Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1-Plin5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. Methods: We performed real-time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. Results: Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, whereas Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with early tauopathy or Alzheimer's disease and is associated with IL-6 expression. Conclusions: Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration

CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless of the mutational background, microsatellite stability, and consensus molecular subtype. Synergistic combination of NORA234 and CHK1 (rabusertib) targeting is synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. These data could provide a rational basis to develop an effective strategy for the treatment of patients with CRC

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older

COVID-19-related neuropathology and microglial activation in elderly with and without dementia

The actual role of SARS-CoV-2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS-CoV-2 or by pre-existing conditions. Findings of 9 Coronavirus disease 2019 (COVID-19) cases and 6 matched non-COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS-CoV-2, lymphocytes, astrocytes, endothelium, and microglia. A semi-quantitative scoring was applied to grade microglial activation. Thal-Braak stages and the presence of small vessel disease were determined in all cases. COVID-19 cases had a relatively short clinical course (0-32 days; mean: 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID-19 cases showed non-SARS-CoV-2-specific changes including hypoxic-agonal alterations, and a variable degree of neurodegeneration and/or pre-existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS-CoV-2 were detected. Microglial activation in the brainstem was significantly greater in COVID-19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS-CoV-2 infection. In COVID-19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID-19, cortical neuroinflammation is not related to COVID-19 per se but mostly to pre-existing neurodegeneration. COVID-19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS-CoV-2-specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID-19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the "COVID-19 encephalopathic syndrome" in the elderly

Prevalence and prognostic value of Delirium as the initial presentation of COVID-19 in the elderly with dementia: An Italian retrospective study

Background: Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis and care of elderly patients with dementia. We aim to identify the prevalence and prognostic significance of delirium as the sole onset manifestation of COVID-19.Methods: This is a retrospective single-centre study based on review of medical charts, conducted during the outbreak peak (March 27-April 18, 2020) in a Lombard dementia facility, including 59 elderly subjects with dementia and laboratory-confirmed COVID-19.Findings: Of the 59 residents, 57 (96.6%) tested positive (mean age: 82.8; women: 66.7%). Comorbidities were present in all participants, with 18/57 (31.6%) having three or more concomitant diseases. Delirium-Onset COVID-19 (DOC) was observed in 21/57 (36.8%) subjects who were chiefly older (mean age: 85.4 y/o) and with multiple comorbidities. Eleven/21 DOC patients (52.4%) had hypoactive delirium, while hyperactive delirium occurred in ten/21 (47.6%). Lymphopenia was present in almost all subjects (median: 1.3 x 10(9)/L). Overall mortality rate was 24.6% (14/57) and dementia severity per se had no impact on short-term mortality due to COVID-19. DOC was strongly associated with higher mortality (p<0.001). Also, DOC and male gender were independently associated with increased risk of mortality (OR: 17.0, 95% CI: 2.8-102.7, p = 0.002 and 13.6, 95% CI: 2.3-79.2, p = 0.001 respectively).Interpretation: Delirium occurrence in the elderly with dementia may represent a prodromal phase of COVID-19, and thus deserves special attention, especially in the presence of lymphopenia. Hypoxia and a severe inflammatory state may develop subsequently. DOC cases have higher short-term mortality rate. (C) 2020 The Author(s). Published by Elsevier Ltd

Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults.

Background: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available. Aims: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy. Methods: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE). Results: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings. Conclusion: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality

The enhanced x-ray timing and polarimetry mission – eXTP: an update on its scientific cases, mission profile and development status

The enhanced x-ray timing and polarimetry mission (eXTP) is a flagship observatory for x-ray timing, spectroscopy and polarimetry developed by an international consortium. Thanks to its very large collecting area, good spectral resolution and unprecedented polarimetry capabilities, eXTP will explore the properties of matter and the propagation of light in the most extreme conditions found in the universe. eXTP will, in addition, be a powerful x-ray observatory. The mission will continuously monitor the x-ray sky, and will enable multi-wavelength and multi-messenger studies. The mission is currently in phase B, which will be completed in the middle of 2022