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1.
Am J Transplant ; 24(6): 1057-1069, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38307417

ABSTRACT

Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients. Risks for death/retransplantation, CLAD, or RAS/mixed, were assessed by adjusted cause-specific Cox proportional-hazards models. CMV viral load (VL) was primarily modeled as a categorical variable: undetectable, detectable to 999, 1000 to 9999, and ≥10 000 IU/mL. In multivariable models, CMV VL was significantly associated with death/retransplantation (≥10 000 IU/mL: HR = 2.65 [1.78-3.94]; P < .01), but was not associated with CLAD, whereas CMV serostatus mismatch was (D+R-: HR = 2.04 [1.30-3.21]; P < .01). CMV VL was not associated with RAS/mixed in univariable analysis. Secondary analyses with a 7-level categorical or 4-level ordinal CMV VL confirmed similar results. In conclusion, CMV DNAemia is a significant risk factor for death/retransplantation, but not for CLAD or RAS/mixed. CMV serostatus mismatch may have an impact on CLAD through a pathway independent of DNAemia.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Graft Rejection , Graft Survival , Lung Transplantation , Postoperative Complications , Viremia , Humans , Lung Transplantation/adverse effects , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/epidemiology , Male , Female , Retrospective Studies , Middle Aged , Viremia/virology , Viremia/epidemiology , Cytomegalovirus/isolation & purification , Risk Factors , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/virology , Prognosis , Postoperative Complications/virology , Postoperative Complications/epidemiology , Adult , Viral Load , Survival Rate , Transplant Recipients/statistics & numerical data
2.
Mol Psychiatry ; 28(8): 3194-3206, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37612363

ABSTRACT

Social behaviors, how individuals act cooperatively and competitively with conspecifics, are widely seen across species. Rodents display various social behaviors, and many different behavioral paradigms have been used for investigating their neural circuit bases. Social behavior is highly vulnerable to brain network dysfunction caused by neurological and neuropsychiatric conditions such as autism spectrum disorders (ASDs). Studying mouse models of ASD provides a promising avenue toward elucidating mechanisms of abnormal social behavior and potential therapeutic targets for treatment. In this review, we outline recent progress and key findings on neural circuit mechanisms underlying social behavior, with particular emphasis on rodent studies that monitor and manipulate the activity of specific circuits using modern systems neuroscience approaches. Social behavior is mediated by a distributed brain-wide network among major cortical (e.g., medial prefrontal cortex (mPFC), anterior cingulate cortex, and insular cortex (IC)) and subcortical (e.g., nucleus accumbens, basolateral amygdala (BLA), and ventral tegmental area) structures, influenced by multiple neuromodulatory systems (e.g., oxytocin, dopamine, and serotonin). We particularly draw special attention to IC as a unique cortical area that mediates multisensory integration, encoding of ongoing social interaction, social decision-making, emotion, and empathy. Additionally, a synthesis of studies investigating ASD mouse models demonstrates that dysfunctions in mPFC-BLA circuitry and neuromodulation are prominent. Pharmacological rescues by local or systemic (e.g., oral) administration of various drugs have provided valuable clues for developing new therapeutic agents for ASD. Future efforts and technological advances will push forward the next frontiers in this field, such as the elucidation of brain-wide network activity and inter-brain neural dynamics during real and virtual social interactions, and the establishment of circuit-based therapy for disorders affecting social functions.


Subject(s)
Autism Spectrum Disorder , Mice , Animals , Prefrontal Cortex , Brain , Nucleus Accumbens , Social Behavior
3.
Circ J ; 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38403681

ABSTRACT

BACKGROUND: Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is unknown.Methods and Results: We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment [MRA]). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583-63.221; P=0.002). CONCLUSIONS: Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.

4.
Transpl Int ; 37: 12556, 2024.
Article in English | MEDLINE | ID: mdl-38650846

ABSTRACT

Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an anti-alcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280-300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-ß-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No post-transplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression.


Subject(s)
Disulfiram , Graft Rejection , Lung Transplantation , Macrophages , Rats, Inbred F344 , Rats, Inbred Lew , Animals , Lung Transplantation/adverse effects , Graft Rejection/prevention & control , Graft Rejection/immunology , Male , Disulfiram/pharmacology , Disulfiram/therapeutic use , Rats , Macrophages/drug effects , Macrophages/metabolism , Allografts , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Chemokine CCL2/metabolism , Lung/pathology , Lung/drug effects
5.
Surg Today ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619591

ABSTRACT

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

6.
PLoS Biol ; 18(9): e3000584, 2020 09.
Article in English | MEDLINE | ID: mdl-32956387

ABSTRACT

The insular cortex (IC) participates in diverse complex brain functions, including social function, yet their cellular bases remain to be fully understood. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely moving and restrained social targets, we identified 2 subsets of AI neurons-a larger fraction of "Social-ON" cells and a smaller fraction of "Social-OFF" cells-that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during exploration under a particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.


Subject(s)
Behavior, Animal/physiology , Cerebral Cortex/physiology , Social Behavior , Animals , Cerebral Cortex/cytology , Male , Mice
7.
Heart Vessels ; 38(3): 438-447, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36205773

ABSTRACT

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery.


Subject(s)
Emergence Delirium , Aged , Humans , Heart Rate/physiology , Patient Readmission , Retrospective Studies , Intensive Care Units
8.
J Artif Organs ; 26(1): 84-88, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35731429

ABSTRACT

In Japan, successful cases of a bridge to lung transplantation (BTT) by extracorporeal membrane oxygenation (ECMO) are rare. We present the case of a man in his thirties, diagnosed with interstitial pneumonia 6 years prior and registered for lung transplant 1 year prior due to disease progression despite treatment. Due to the patient's worsening respiratory failure, he was transferred to our hospital for BTT by ECMO. Since long-term management was expected and pulmonary hypertension was present, veno-arterial (V-A) ECMO was conducted using the right atrial blood outflow via the right internal jugular vein and right axillary artery inflow via a vascular graft. After tracheostomy, he was managed as "Awake ECMO". In addition, interprofessional collaboration such as physiotherapist rehabilitation, nurses, and liaison teams prevented muscle weakness and supported the mental aspect. We were able to minimize complications such as severe infections and bleeding. A compatible brain-dead donor was found on day 108 after introducing ECMO, and the patient was transferred to a transplant facility on day 109. The peripheral upper V-A ECMO is one of the configurations suitable for long-term BTT management.


Subject(s)
Extracorporeal Membrane Oxygenation , Lung Diseases, Interstitial , Lung Transplantation , Respiratory Insufficiency , Male , Humans , Extracorporeal Membrane Oxygenation/methods , Respiratory Insufficiency/therapy , Brain
9.
Surg Today ; 53(10): 1188-1198, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37074401

ABSTRACT

PURPOSE: To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. METHODS: Patients' data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. RESULTS: Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient's age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. CONCLUSION: The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.


Subject(s)
Lung Transplantation , Transplant Recipients , Female , Humans , Male , Middle Aged , Age Factors , East Asian People , Graft Survival , Lung , Prognosis , Retrospective Studies , Tissue Donors , Sex Factors
10.
Kyobu Geka ; 76(1): 40-47, 2023 Jan.
Article in Japanese | MEDLINE | ID: mdl-36731832

ABSTRACT

The Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L trial has recently reported that in small lung cancer, segmentectomy has a higher overall survival rate than lobectomy, increasing the significance of sublobar resection. However, local recurrence is a major concern after sublobar resection, and an insufficient surgical margin is a significant risk factor for locoregional recurrence. Therefore, since 2014, we have performed virtual-assisted lung mapping (VALMAP), a preoperative bronchoscopic multiple-spot dye-marking technique, using indigo carmine as a preoperative localization technique to identify hardly detectable pulmonary nodules and confirm the adequacy of the surgical margin. However, conventional VAL-MAP (VAL-MAP 1.0) faced some chal-lenges. One issue is that approximately 10% marks were invisible and unidentifiable due to patient factors or technical issues. Another problem was that, in some cases requiring large resection depth, VAL-MAP did not lead to successful resection with adequate surgical margin. Thus, we have invented several novel techniques to solve these issues. VAL-MAP dual staining is a technique using indocyanine green (ICG) as well as indigo carmine that has improved the success rate of marking detection during surgery without causing additional complications. VAL-MAP 2.0 is a proximal mapping technique that involves the use of a coil, enabling three-dimensional mapping and making sublobar resection more accurate, particularly for a deeply located tumor.


Subject(s)
Indigo Carmine , Lung Neoplasms , Humans , Margins of Excision , Pneumonectomy/methods , Bronchoscopy/methods , Lung/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Lung Neoplasms/pathology
11.
J Neurosci ; 41(24): 5315-5329, 2021 06 16.
Article in English | MEDLINE | ID: mdl-33980545

ABSTRACT

Impairment of episodic memory, a class of memory for spatiotemporal context of an event, is an early symptom of Alzheimer's disease. Both spatial and temporal information are encoded and represented in the hippocampal neurons, but how these representations are impaired under amyloid ß (Aß) pathology remains elusive. We performed chronic imaging of the hippocampus in awake male amyloid precursor protein (App) knock-in mice behaving in a virtual reality environment to simultaneously monitor spatiotemporal representations and the progression of Aß depositions. We found that temporal representation is preserved, whereas spatial representation is significantly impaired in the App knock-in mice. This is because of the overall reduction of active place cells, but not time cells, and compensatory hyperactivation of remaining place cells near Aß aggregates. These results indicate the differential impact of Aß aggregates on two major modalities of episodic memory, suggesting different mechanisms for forming and maintaining these two representations in the hippocampus.


Subject(s)
Alzheimer Disease/pathology , CA1 Region, Hippocampal/pathology , Memory Disorders/pathology , Neurons/pathology , Amyloid beta-Protein Precursor/metabolism , Amyloid beta-Protein Precursor/toxicity , Animals , Disease Models, Animal , Male , Memory, Episodic , Mice
12.
Ann Surg Oncol ; 29(3): 1816-1824, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34997412

ABSTRACT

BACKGROUND: Few studies have assessed the comprehensive skeletal muscle depletion associated with loss of muscle quantity (sarcopenia) and reduced muscle quality in cancer patients. This study aimed to clarify the impact of skeletal muscle depletion on outcomes after non-small cell lung cancer surgery. METHODS: Data for 341 patients with pathologic stages 1 to 3A non-small cell lung cancer who underwent lobectomy and mediastinal lymph node dissection from 2009 to 2013 were retrospectively reviewed. The integrative pectoralis muscle index (IPMI) was assessed by multiplying the normalized pectoralis muscle area (area/body mass index) and mean radiodensity on chest images. Postoperative outcomes were compared among sex-specific quartiles of IPMI. The trend of continuous and categorical variables was analyzed using the Jonckheere-Terpstra test and the Cochrane-Armitage test, respectively. RESULTS: Respiratory strength declined with decreasing quartiles of IPMI (P < 0.001). The risk of major complications escalated with the decrease of IPMI among four quartiles (7.1 %, 16.7 %, 18.4 %, and 22.4 %; P = 0.008). The hospital stay was prolonged for patients with reduced IPMI (P = 0.001). Patients in the lowest and highest quartiles had the worst and best 5-year overall survival, respectively, compared with those in the two intermediate quartiles of IPMI (67.0 %, 87.9 %, and 81.2 %, respectively; P=0.001). Multivariate analysis identified the lowest quartile of IPMI as an independent poor prognostic factor (hazard ratio, 1.88; 95 % confidence interval, 1.11-3.19; P = 0.020). CONCLUSION: Comprehensive skeletal muscle profiling, including morphometric mass and componential density on chest imaging, has the potential to refine risk stratification and prognostication in non-small cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Sarcopenia , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Postoperative Complications/pathology , Prognosis , Retrospective Studies , Sarcopenia/diagnostic imaging , Sarcopenia/etiology , Sarcopenia/pathology , Tomography, X-Ray Computed
13.
Surg Today ; 52(10): 1497-1503, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35237884

ABSTRACT

PURPOSE: It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 953 patients with pathological stage I-III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups. RESULTS: After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05). CONCLUSIONS: The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Biopsy, Needle , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Neoplasm Staging , Pneumonectomy , Propensity Score , Retrospective Studies
14.
Kyobu Geka ; 75(4): 254-258, 2022 Apr.
Article in Japanese | MEDLINE | ID: mdl-35342154

ABSTRACT

Multiple situations necessitate extracorporeal membrane oxygenation( ECMO) during lung transplantation. ECMO can also be used as a bridge to lung transplantation. We describe five cases in which bridging ECMO was successfully utilized, including three cases of living donor lung transplantation. ECMO can also be used as an alternative to cardiopulmonary bypass for intraoperative support during lung transplantation, and postoperatively, primary graft dysfunction, rejection, and infection can cause reversible respiratory failure which warrants ECMO. It can also be used for patients with pulmonary arterial hypertension in the early postoperative period to help their hearts adjust to new circulation. Eight patients with pulmonary arterial hypertension who underwent lung transplantation at our institu-tion received intraoperative and early postoperative ECMO support and their postoperative courses were uneventful. In this report, we review the indications for ECMO and the type of ECMO required for each of the various issues that can arise during lung transplantation, based on the literature and our experiences.


Subject(s)
Extracorporeal Membrane Oxygenation , Lung Transplantation , Respiratory Insufficiency , Cardiopulmonary Bypass , Humans , Respiratory Insufficiency/etiology , Respiratory Insufficiency/surgery , Treatment Outcome
15.
Kyobu Geka ; 75(6): 476-479, 2022 Jun.
Article in Japanese | MEDLINE | ID: mdl-35618696

ABSTRACT

A 23-year-old man was referred to our department for chest abnormal shadow. Computed tomography (CT) of the chest revealed a well-defined 1.2 cm nodule in the S4 segment of the right middle lobe and a well-defined 1.8 cm nodule in the S10 segment of the right lower lobe. The patient was found to have a fracture in the left fifth rib due to the falling accident at playing snowboard, two months before. He was diagnosed with a benign tumor in the right middle lobe and the right lower lobe and was performed surgery. Thoracoscopy revealed a yellowish-brown tumor in the right middle lobe( S4) and a yellow-brown tumor in the right lower lobe( S10). Both lesions were diagnosed as clots by rapid intraoperative pathologic diagnosis. Histopathological diagnosis was an intrapulmonary hematoma.


Subject(s)
Lung Diseases , Lung Neoplasms , Thoracic Injuries , Adult , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/surgery , Humans , Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Thoracic Injuries/complications , Thoracic Injuries/diagnostic imaging , Thoracic Injuries/surgery , Young Adult
16.
Aust Occup Ther J ; 69(1): 15-24, 2022 02.
Article in English | MEDLINE | ID: mdl-34580881

ABSTRACT

INTRODUCTION: Occupational therapy often involves handwriting acquisition practices that include the non-dominant hand when improvements in the dominant hand function are not possible because of trauma or stroke. This study explored whether character tracing and using a pegboard can effectively improve the handwriting of the non-dominant hand. METHODS: A randomised controlled trial involving 60 healthy university students aged ≥18 years was conducted. Participants were randomly assigned to the writing group, peg group or control group. The character recognition rate was evaluated by computer software. Furthermore, character quality and writing speed were evaluated by humans using global legibility scales. Evaluations were performed before the intervention (baseline) and on days 5 and 10 of the intervention. Using the non-dominant hand, the writing group traced characters on paper with a ballpoint pen, and the peg group used a pegboard for 15 min/day for 10 days. RESULTS: Compared with the peg and control groups, the writing group showed significant improvements in the character recognition rate and global legibility scale score. However, the global legibility scale score did not improve to the same level as that achieved with the dominant hand. None of the evaluation scores of the peg group showed significant improvements compared with those of the control group. There were no significant differences in improvements in the writing speed of the writing and peg groups compared with the control group. CONCLUSION: Tracing characters can improve the handwriting ability of the non-dominant hand, but using a pegboard may be less effective. Future research is needed to examine how much practice is necessary to improve the handwriting ability of the non-dominant hand sufficiently.


Subject(s)
Occupational Therapy , Stroke , Adolescent , Adult , Handwriting , Humans
17.
J Neurosci ; 40(25): 4936-4944, 2020 06 17.
Article in English | MEDLINE | ID: mdl-32414785

ABSTRACT

Hippocampus receives dense serotonergic input specifically from raphe nuclei. However, what information is carried by this input and its impact on behavior has not been fully elucidated. Here we used in vivo two-photon imaging of activity of hippocampal median raphe projection fibers in behaving male and female mice and identified two distinct populations: one linked to reward delivery and the other to locomotion. Local optogenetic manipulation of these fibers confirmed a functional role for these projections in the modulation of reward-induced behavior. The diverse function of serotonergic inputs suggests a key role in integrating locomotion and reward information into the hippocampal CA1.SIGNIFICANCE STATEMENT Information constantly flows in the hippocampus, but only some of it is captured as a memory. One potential process that discriminates which information should be remembered is concomitance with reward. In this work, we report a neuromodulatory pathway, which delivers reward signal as well as locomotion signal to the hippocampal CA1. We found that the serotonergic system delivers heterogeneous input that may be integrated by the hippocampus to support its mnemonic functions. It is dynamically involved in regulating behavior through interaction with the hippocampus. Our results suggest that the serotonergic system interacts with the hippocampus in a dynamic and behaviorally specific manner to regulate reward-related information processing.


Subject(s)
Behavior, Animal/physiology , Hippocampus/physiology , Locomotion/physiology , Neural Pathways/physiology , Reward , Animals , Female , Male , Mice , Mice, Inbred C57BL , Serotonergic Neurons/physiology
18.
Am J Physiol Cell Physiol ; 320(6): C1153-C1163, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33881935

ABSTRACT

Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here, we suggest that the mechanosensitive behavior of myosin II, a major cross-linker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light-chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.


Subject(s)
Actin Cytoskeleton/metabolism , Actin Depolymerizing Factors/metabolism , Actins/metabolism , Myosin Type II/metabolism , Stress Fibers/metabolism , Actomyosin/metabolism , Animals , Cattle , Cell Line, Tumor , Cells, Cultured , Cytoskeletal Proteins/metabolism , Humans , Muscle Contraction/physiology , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Osteosarcoma/metabolism , Stress, Mechanical
19.
Hippocampus ; 31(3): 235-243, 2021 03.
Article in English | MEDLINE | ID: mdl-33452849

ABSTRACT

In the hippocampus, spatial and nonspatial information are jointly represented as a neural map in which locations associated with salient features are over-represented by increased densities of relevant place cells. Although we recently demonstrated that experience-dependent establishment of these disproportionate maps is governed by selective stabilization of salient place cells following their conversion from non-place cells, the underlying mechanism for pre-established map reorganization remained to be understood. To this end, we investigated the changes in CA1 functional cellular maps imaged using two-photon calcium imaging in mice performing a reward-rearrangement task in virtual reality. Mice were pre-trained on a virtual linear track with a visual landmark and a reward in two distinct locations. Then, they were re-trained on the same track with the exception that the location of reward was shifted to match the landmark location. We found that, in contrast to de novo map formation, robust map reorganization occurred through parallel coordination of new place field formation, lateral shifting of existing place fields, and selective stabilization of place fields encoding salient locations. Our findings demonstrate that intricate interplay between multiple forms of cellular dynamics enables rapid updating of information stored in hippocampal maps.


Subject(s)
CA1 Region, Hippocampal , Place Cells , Animals , Hippocampus , Mice , Reward
20.
Am J Transplant ; 21(10): 3461-3464, 2021 10.
Article in English | MEDLINE | ID: mdl-33934506

ABSTRACT

When performing living-donor lobar lung transplantation on small children of height 100 cm or under, accommodation of an oversized adult lobar graft is problematic, sometimes necessitating single lobar transplantation in combination with contralateral pneumonectomy. We here report a unique case of living-donor lobar lung transplantation in a 9-year-old boy with congenital pulmonary hypoplasia. Although he was 104 cm tall, and the available adult lower lobe graft appeared to be oversized, his right lung was hypoplastic, resulting in his mediastinum being shifted to the right and thus already showing "postpneumonectomy-like" anatomy. His father's left lower lobe was successfully transplanted into the left thorax without performing a contralateral pneumonectomy. Three-dimensional reconstruction of computed tomography images and computed tomography volumetry were extremely helpful in matching the size of the graft and planning this unique surgery.


Subject(s)
Hernias, Diaphragmatic, Congenital , Lung Transplantation , Adult , Child , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Hernias, Diaphragmatic, Congenital/surgery , Humans , Living Donors , Lung/diagnostic imaging , Lung/surgery , Lung Transplantation/adverse effects , Male , Pneumonectomy
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