Psychological resilience is correlated with dynamic changes in functional connectivity within the default mode network during a cognitive task

Resilience is a dynamic process that enables organisms to cope with demanding environments. Resting-state functional MRI (fMRI) studies have demonstrated a negative correlation between resilience and functional connectivities (FCs) within the default mode network (DMN). Considering the on-demand recruitment process of resilience, dynamic changes in FCs during cognitive load increases may reflect essential aspects of resilience. We compared DMN FC changes in resting and task states and their association with resilience. Eighty-nine healthy volunteers completed the Connor–Davidson Resilience Scale (CD-RISC) and an fMRI with an auditory oddball task. The fMRI time series was divided into resting and task periods. We focused on FC changes between the latter half of the resting period and the former half of the task phase (switching), and between the former and latter half of the task phase (sustaining). FCs within the ventral DMN significantly increased during “switching” and decreased during “sustaining”. For FCs between the retrosplenial/posterior cingulate and the parahippocampal cortex, increased FC during switching was negatively correlated with CD-RISC scores. In individuals with higher resilience, ventral DMN connectivities were more stable and homeostatic in the face of cognitive demand. The dynamic profile of DMN FCs may represent a novel biomarker of resilience

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

Martial Arts “Kendo” and the Motivation Network During Attention Processing: An fMRI Study

Japanese martial arts, Budo, have been reported to improve cognitive function, especially attention. However, the underlying neural mechanisms of the effect of Budo on attention processing has not yet been investigated. Kendo, a type of fencing using bamboo swords, is one of the most popular forms of Budo worldwide. We investigated the difference in functional connectivity (FC) between Kendo players (KPs) and non-KPs (NKPs) during an attention-related auditory oddball paradigm and during rest. The analyses focused on the brain network related to “motivation.” Resting-state functional magnetic resonance imaging (rs-fMRI) and task-based fMRI using the oddball paradigm were performed in healthy male volunteers (14 KPs and 11 NKPs). Group differences in FC were tested using CONN-software within the motivation network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. Daily general physical activities were assessed using the International Physical Activity Questionnaire (IPAQ). We also investigated the impact of major confounders, namely, smoking habits, alcohol consumption, IPAQ score, body mass index (BMI), and reaction time (RT) in the oddball paradigm. Resting-state fMRI revealed that KPs had a significantly lower FC than NKPs between the right nucleus accumbens and right frontal eye field (FEF) within the motivation network. Conversely, KPs exhibited a significantly higher FC than NKPs between the left intraparietal sulcus (IPS) and the left precentral gyrus (PCG) within the network during the auditory oddball paradigm [statistical thresholds, False Discovery Rate (FDR) < 0.05]. These results remained significant after controlling for major covariates. Our results suggest that attenuated motivation network integrity at rest together with enhanced motivation network integrity during attentional demands might underlie the instantaneous concentration abilities of KPs

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap‐frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin‐fixed paraffin‐embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

Martial Arts "Kendo" and the Motivation Network During Attention Processing: An fMRI Study

Japanese martial arts, Budo, have been reported to improve cognitive function, especially attention. However, the underlying neural mechanisms of the effect of Budo on attention processing has not yet been investigated. Kendo, a type of fencing using bamboo swords, is one of the most popular forms of Budo worldwide. We investigated the difference in functional connectivity (FC) between Kendo players (KPs) and non-KPs (NKPs) during an attention-related auditory oddball paradigm and during rest. The analyses focused on the brain network related to “motivation.” Resting-state functional magnetic resonance imaging (rs-fMRI) and task-based fMRI using the oddball paradigm were performed in healthy male volunteers (14 KPs and 11 NKPs). Group differences in FC were tested using CONN-software within the motivation network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. Daily general physical activities were assessed using the International Physical Activity Questionnaire (IPAQ). We also investigated the impact of major confounders, namely, smoking habits, alcohol consumption, IPAQ score, body mass index (BMI), and reaction time (RT) in the oddball paradigm. Resting-state fMRI revealed that KPs had a significantly lower FC than NKPs between the right nucleus accumbens and right frontal eye field (FEF) within the motivation network. Conversely, KPs exhibited a significantly higher FC than NKPs between the left intraparietal sulcus (IPS) and the left precentral gyrus (PCG) within the network during the auditory oddball paradigm [statistical thresholds, False Discovery Rate (FDR) < 0.05]. These results remained significant after controlling for major covariates. Our results suggest that attenuated motivation network integrity at rest together with enhanced motivation network integrity during attentional demands might underlie the instantaneous concentration abilities of KPs