Abstract Objective Delirium superimposed on dementia is common and potentially distressing for patients, caregivers, and health care staff. We quantitatively and qualitatively assessed the experience ...of informal caregiver and staff (staff nurses, nurse aides, physical therapists) caring for patients with delirium superimposed on dementia. Methods Caregivers' and staff experience was evaluated three days after delirium superimposed on dementia resolution (T0) with a standardized questionnaire (quantitative interview) and open-ended questions (qualitative interview); caregivers were also evaluated at 1-month follow-up (T1). Results A total of 74 subjects were included; 33 caregivers and 41 health care staff (8 staff nurses, 20 physical therapists, 13 staff nurse aides/health care assistants). Overall, at both T0 and T1, the distress level was moderate among caregivers and mild among health care staff. Caregivers reported, at both T0 and T1, higher distress related to deficits of sustained attention and orientation, hypokinesia/psychomotor retardation, incoherence and delusions. The distress of health care staff related to each specific item of the Delirium-O-Meter was relatively low except for the physical therapists who reported higher level of distress on deficits of sustained/shifting attention and orientation, apathy, hypokinesia/psychomotor retardation, incoherence, delusion, hallucinations, and anxiety/fear. The qualitative evaluation identified important categories of caregivers' and staff feelings related to the delirium experience. Conclusions This study provides information on the implication of the experience of delirium on caregivers and staff. The distress related to delirium superimposed on dementia underlines the importance of providing continuous training, support and experience for both the caregivers and health care staff to improve the care of patients with delirium superimposed on dementia.
Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric disorder whose etiology is a thiamine deficiency (TD), with alcoholism being the main underlying cause. Previous evidence suggests the presence ...of initial neuroinflammation and oxidative/nitrosative stress in the physiopathology, although the specific molecular mechanisms underlying TD-induced brain damage and behavioral disabilities are unknown.
We explored the specific role of the innate immune receptor TLR4 in three murine models of WKS, based on the combination of a thiamine-deficient diet and pyrithiamine injections (0.25 mg/kg, i.p.) over time. The Symptomatic Model (SM) allowed us to describe the complete neurological/neurobehavioral symptomatology over 16 days of TD. Animals showed an upregulation of the TLR4 signaling pathway both in the frontal cortex (FC) and cerebellum and clear motor impairments related with cerebellar dysfunction. However, in the Pre-Symptomatic Model (PSM), 12 days of TD induced the TLR4 pathway upregulation in the FC, which correlated with disinhibited-like behavior, but not in the cerebellum, and no motor impairments. In addition, we tested the effects of the biolipid oleoylethanolamide (OEA, 10 mg/kg, i.p., once daily, starting before any symptom of the pathology is manifested) through the Glucose-Precipitated Model (GPM), which was generated by glucose loading (5 g/kg, i.v., last day) in thiamine-deficient animals to accelerate damage. Pretreatment with OEA prevented the TLR4-induced signature in the FC, as well as an underlying incipient memory disability and disinhibited-like behavior.
This study suggests a key role for TLR4 in TD-induced neuroinflammation in the FC and cerebellum, and it reveals different vulnerability of these brain regions in WKS over time. Pre-treatment with OEA counteracts TD-induced TLR4-associated neuroinflammation and may serve as co-adjuvant therapy to prevent WKS-induced neurobehavioral alterations.
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•Pivotal role of TLR4 in thiamine deficiency-induced neuroinflammation in three animal models of Wernicke-Korsakoff Syndrome.•Different vulnerability of frontal cortex and cerebellum to thiamine deficiency-induced TLR4 cascade upregulation over time.•Changes in the frontal cortex and cerebellum correlate with disinhibited-like behavior and motor dysfunction, respectively.•OEA pretreatment prevents the TLR4 cascade in frontal cortex, a light memory impairment and the disinhibition-like behavior.
Extraction of Airways From CT (EXACT'09) Lo, Pechin; van Ginneken, Bram; Reinhardt, Joseph M. ...
IEEE transactions on medical imaging,
11/2012, Letnik:
31, Številka:
11
Journal Article
Odprti dostop
This paper describes a framework for establishing a reference airway tree segmentation, which was used to quantitatively evaluate 15 different airway tree extraction algorithms in a standardized ...manner. Because of the sheer difficulty involved in manually constructing a complete reference standard from scratch, we propose to construct the reference using results from all algorithms that are to be evaluated. We start by subdividing each segmented airway tree into its individual branch segments. Each branch segment is then visually scored by trained observers to determine whether or not it is a correctly segmented part of the airway tree. Finally, the reference airway trees are constructed by taking the union of all correctly extracted branch segments. Fifteen airway tree extraction algorithms from different research groups are evaluated on a diverse set of 20 chest computed tomography (CT) scans of subjects ranging from healthy volunteers to patients with severe pathologies, scanned at different sites, with different CT scanner brands, models, and scanning protocols. Three performance measures covering different aspects of segmentation quality were computed for all participating algorithms. Results from the evaluation showed that no single algorithm could extract more than an average of 74% of the total length of all branches in the reference standard, indicating substantial differences between the algorithms. A fusion scheme that obtained superior results is presented, demonstrating that there is complementary information provided by the different algorithms and there is still room for further improvements in airway segmentation algorithms.
Abstract Objective Delirium superimposed on dementia is common and is associated with adverse outcomes. Yet little is known about the patients' personal delirium experiences. We used quantitative and ...qualitative methods to assess the delirium superimposed on dementia experience among older patients. Methods We conducted a prospective cohort study among patients with delirium superimposed on dementia who were admitted to a rehabilitation ward. Delirium was diagnosed using DSM-IV-TR criteria. Delirium severity and symptoms were evaluated with the Delirium-O-Meter (D-O-M). The experience of delirium was assessed after delirium resolution (T0) and one month later (T1) with a standardized questionnaire and a qualitative interview. Level of distress was measured with the Delirium Experience Questionnaire. Results Of the 30 patients included in the study, 50% had mild dementia; 33% and 17% had moderate and severe dementia. Half of the patients had evidence of the full range of D-O-M delirium symptoms. We evaluated 30 patients at T0 and 20 at T1. At T0, half of the patients remembered being confused as part of the delirium episode, and reported an overall moderate level of related distress. Patients reported high distress related to memories of anxiety/fear, delusions, restlessness, hypokinesia, and impaired orientation. Qualitative interviews revealed six main aspects of patient delirium experiences: Emotions; Cognitive Impairment; Psychosis; Memories; Awareness of Change; and Physical Symptoms. Conclusions The study provides novel information on the delirium experience in patients with dementia. These findings are the key for health care providers to improve the everyday care of this important group of frail older patients.
JCO
The Suppression of Ovarian Function Trial (SOFT; ClinicalTrials.gov identifier: NCT00066690) randomly assigned premenopausal women with hormone receptor-positive breast cancer to 5 years of ...adjuvant tamoxifen, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. The primary analysis compared disease-free survival (DFS) between tamoxifen plus OFS versus tamoxifen alone; exemestane plus OFS versus tamoxifen was a secondary objective. After 8 years, SOFT reported a significant reduction in recurrence and improved overall survival (OS) with adjuvant tamoxifen plus OFS versus tamoxifen alone. Here, we report outcomes after median follow-up of 12 years. DFS remained significantly improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.82; 95% CI, 0.69 to 0.98) with a 12-year DFS of 71.9% with tamoxifen, 76.1% with tamoxifen plus OFS, and 79.0% with exemestane plus OFS. OS was improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.78; 95% CI, 0.60 to 1.01) and was 86.8% with tamoxifen, 89.0% with tamoxifen plus OFS, and 89.4% with exemestane plus OFS at 12 years. Among those who received prior chemotherapy for human epidermal growth factor receptor-2-negative tumors, OS was 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS, and 84.4% with exemestane plus OFS. In conclusion, after 12 years, there remains a benefit from including OFS in adjuvant endocrine therapy, with an absolute improvement in OS more apparent with higher baseline risk of recurrence.Media: see text.
Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and ...immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.
Early-life stress is associated with an increased risk of developing affective disorders and chronic pain conditions. This study examined the effect of maternal deprivation (MD) on nociceptive ...responding prior to and following peripheral nerve injury (L5-L6 spinal nerve ligation SNL). Because neuroimmune signaling plays an important role in pain and affective disorders, associated alterations in glial and cytokine expression were assessed in key brain regions associated with emotional and nociceptive responding, the hippocampus and prefrontal cortex. MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia compared with control (non-MD) counterparts. SNL resulted in mechanical and cold allodynia in MD and control rats of both sexes. However, MD females exhibited enhanced SNL-induced allodynic responding compared with non-MD counterparts. Interleukin 6 (IL-6) expression was reduced in the prefrontal cortex of MD-SNL males when compared with non-SNL counterparts. Glial fibrillary acidic protein and IL-1β expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced tumor necrosis factor alpha in the prefrontal cortex with a concomitant increase in IL-6 and tumor necrosis factor alpha expression in the hippocampus, compared with either MD or SNL alone. In conclusion, MD female, but not male, rats exhibit enhanced nociceptive responding following peripheral nerve injury, effects that may relate to the distinct neuroinflammatory profile observed in female versus male rats.
This study demonstrates that females rats exposed to early-life stress exhibit enhanced neuropathic pain responding, effects that are associated with alterations in neuroinflammatory mediators. Increased understanding of the interactions among early-life stress, gender, and pain may lead to the identification of novel therapeutic targets for the treatment of chronic pain disorders.
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