Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model

SummaryBipolar disorder, also known as manic-depressive illness, causes swings in mood and activity levels at irregular intervals. Such changes are difficult to predict, and their molecular basis remains unknown. Here, we use infradian (longer than a day) cyclic activity levels in αCaMKII (Camk2a) mutant mice as a proxy for such mood-associated changes. We report that gene-expression patterns in the hippocampal dentate gyrus could retrospectively predict whether the mice were in a state of high or low locomotor activity (LA). Expression of a subset of circadian genes, as well as levels of cAMP and pCREB, possible upstream regulators of circadian genes, were correlated with LA states, suggesting that the intrinsic molecular circuitry changes concomitant with infradian oscillatory LA. Taken together, these findings shed light onto the molecular basis of how irregular biological rhythms and behavior are controlled by the brain

Categorical discrimination of human body parts by magnetoencephalography

Humans recognize body parts in categories. Previous studies have shown that responses in the fusiform body area (FBA) and extrastriate body area (EBA) are evoked by the perception of the human body, when presented either as whole or as isolated parts. These responses occur approximately 190 ms after body images are visualized. The extent to which body-sensitive responses show specificity for different body part categories remains to be largely clarified. We used a decoding method to quantify neural responses associated with the perception of different categories of body parts. Nine subjects underwent measurements of their brain activities by magnetoencephalography (MEG) while viewing 14 images of feet, hands, mouths, and objects. We decoded categories of the presented images from the MEG signals using a support vector machine (SVM) and calculated their accuracy by 10-fold cross-validation. For each subject, a response that appeared to be a body-sensitive response was observed and the MEG signals corresponding to the three types of body categories were classified based on the signals in the occipitotemporal cortex. The accuracy in decoding body- part categories (with a peak at approximately 48%) was above chance (33.3%) and significantly higher than that for random categories. According to the time course and location, the responses are suggested to be body-sensitive and to include information regarding the body-part category. Finally, this non-invasive method can decode category information of a visual object with high temporal and spatial resolution and this result may have a significant impact in the field of brain-machine interface research

Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan

<p>Abstract</p> <p>Background</p> <p>We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases.</p> <p>Methods</p> <p>Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records.</p> <p>Results</p> <p>Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, <it>p </it>= 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, <it>p </it>= 0.02), women (HR = 1.81, CI: 1.11-2.94, <it>p </it>= 0.02), and age (HR = 0.98, CI: 0.97-1.00, <it>p </it>= 0.02).</p> <p>Conclusions</p> <p>Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing.</p

Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy‐refractory or relapsed disease prior to allogeneic stem cell transplantation

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is one of the curative treatment options for acute lymphoblastic leukaemia (ALL). However, the outcomes in patients transplanted without complete remission (non-CR) have not yet been fully reported, and detailed analyses are required to identify subgroups in which optimal prognosis is expected and to optimize pre-transplant therapeutic strategies. Hence, we performed a multicentred retrospective cohort study including a total of 663 adult ALL patients transplanted at non-CR status; the median bone marrow (BM) blast counts at HSCT was 13·2%, and 203 patients (30·6%) were treated at primary induction failure status. The overall survival (OS) was 31·1% at two years, and the multivariate analyses identified five prognostic risk factors, including older age (≥50 years), increased BM blasts (≥10%), poor performance status, high haematopoietic cell transplantation (HCT)-comorbidity index, and relapsed disease status, among which BM blast was the most significantly related. A predictive scoring system composed of these risk factors clearly stratified OS (15·6-59·5% at two years). In conclusion, this is the first large-scale study to analyze the correlation of patient characteristics with post-transplant prognosis in ALL transplanted at non-CR status. The importance of blast control before HSCT should be focused on for better patient prognosis

Humoral and cellular immune response to second and third severe acute respiratory syndrome coronavirus 2 mRNA vaccine in patients with plasma cell dyscrasia

Abstract Background The recently developed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). Methods We retrospectively measured serum SARS‐CoV‐2 antibodies against the spike protein (S‐IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S‐IgG titers ≥300 antibody units/mL). Results Although active anti‐myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B‐cell maturation antigen‐targeted therapy. Dose 3 (booster vaccination) led to significantly higher S‐IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine‐induced cellular immune response in patients using T‐spot Discovery SARS‐CoV‐2 kit, revealed an enhanced cellular immune response after Dose 3. Conclusions This study highlighted the significance of booster SARS‐CoV‐2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine‐induced humoral immune response