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Abstract Spinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.

In cases where vision is not sufficiently reliable for robots to recognize an object, tactile sensing can be a promising alternative for estimating the object’s pose. In this paper, we consider the task of a robot estimating the pose of a container aperture in order to select an object. In such a task, if the robot can determine whether its hand with equipped contact sensor is inside or outside the container, estimation of the object’s pose can be improved by reflecting the discrimination to the robotic hand’s exploration strategy. We propose an exploration strategy and an estimation method using discrete state recognition on the basis of a particle filter. The proposed method achieves superior estimation in terms of the number of contact actions, operation time, and stability of estimation efficiency. The pose is estimated with sufficient accuracy that the hand can be inserted into the container.

Abstract Background Microscopic examination of stool samples can contribute to the early diagnosis of Campylobacter gastroenteritis. However, it is unclear whether the diagnostic performance is reliable when performed by physicians. Methods This prospective study included fresh stool samples collected from patients with gastroenteritis between August 2018 and March 2020. The samples were used for microscopic examination through Gram staining. Two physicians, a clinical laboratory technician, and microbiologists performed the examinations. In addition, antigen tests (QuickNavi‐Campylobacter; Denka Co., Ltd.) were evaluated for the samples collected between May 2019 and March 2020. Infection with Campylobacter spp. was confirmed when stool cultures or polymerase chain reaction tests provided positive results. Results Microscopic examination was performed on 205 samples, of which 46 (22.4%) were positive for Campylobacter spp. For the microscopic examination, the sensitivity and specificity were 53.5% and 98.1% for physician A, 46.7% and 96.2% for physician B, 63.0% and 100% for the clinical laboratory technician, and 67.4% and 100% for microbiologists, respectively. The antigen testing was evaluated in 131 of the 205 samples and showed a sensitivity of 93.3% and specificity of 99.0%. Conclusions Microscopic examination of the stool samples showed high specificity. The sensitivity when the examinations were performed by the physicians was insufficient. The rapid antigen tests can reliably detect Campylobacter spp. in stool samples.

Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and their pathological changes is not fully elucidated. In this research, we aimed to understand the activity-dependent OC responses and their different properties by observing OCs using in vivo two-photon microscopy. We clarified that the Ca2+ activity in OCs is neuronal activity dependent and differentially regulated by neurotransmitters such as glutamate or adenosine triphosphate (ATP). Furthermore, in 5-month-old mice models of Alzheimer’s disease, a period before the appearance of behavioral abnormalities, the elevated Ca2+ responses in OCs are ATP dependent, suggesting that OCs receive ATP from damaged tissue. We anticipate that our research will help in determining the correct therapeutic strategy for neurodegenerative diseases beyond the synapse.

Abstract Background Renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are representative malignancies that respond well to immune checkpoint inhibitors (ICIs). Research has been conducted to identify biomarkers, such as programmed death ligand-1 (PD-L1), that would allow the response to ICI therapy to be predicted; however, the complex tumor immune system consisting of both host and tumor factors may also exert an influence. Case presentation Computed tomographic imaging (CT) incidentally revealed a left renal mass, and a left pulmonary nodule with multiple lymph node metastases (LNMs). Firstly, video-assisted thoracic surgery revealed a lung tumor invading the chest wall. Histologically, the findings of the tumor were consistent with squamous cell carcinoma (SCC), and immunohistochemistry (IHC) showed positive PD-L1 expression. The renal tumor was excised by robotic-assisted partial nephrectomy (RAPN). Histologically, the renal tumor showed the features of clear cell carcinoma (CCC). Four months after the RAPN, CT revealed left hydronephrosis caused by an enhancing ureteral tumor. Then, multiple right lung metastases appeared, and the left lung tumor increased. Following treatment including atezolizumab, the primary lung SCC and the multiple LNMs almost disappeared completely, while the ureteral and right lung metastases showed progression. The ureteral metastasis was resected by left open nephroureterectomy. Histology of the ureteral tumor revealed features consistent with CCC. Histological examination of the multiple right lung metastases that were resected by partial lobectomy via a small thoracic incision also revealed features consistent with CCC. Two months after nephroureterectomy, a solitary left lung metastasis was treated by nivolumab and ipilimumab. Six months after nephroureterectomy, the patient died of RCC. Further studies of specimens revealed that the tumor cells in the primary RCC and the ureteral and lung metastases showed negative results of IHC for PD-L1. Conclusions The responses to ICI therapy of concomitant RCC and NSCLC were quite different. The PD-L1 expression status in individual tumors in cases of multiple primary malignancies (MPMs) may directly predict the response of each malignancy to ICI therapy, because the host immune system, which may affect the response to ICI therapy, could be the same in MPMs.

Abstract Background Renal cell carcinoma rarely metastasizes to the bladder, and its biological behavior is not yet fully understood. Case presentation In our case (54-year-old Japanese woman), computed tomography evaluation suggested the presence of a bladder metastasis, associated with additional metastases in the lungs, mediastinal lymph nodes, ribs, and renal bed, 4 years after radical nephrectomy for renal cell carcinoma. The histological findings of the metastatic bladder tumor were consistent with those of clear cell carcinoma. The mediastinal lymph node, rib, and renal bed metastases responded to treatment with an immune checkpoint inhibitor administered for 12 months after surgery for the bladder and lung metastases. In patients with bladder metastasis, absence of metastases in other organs and an interval of more than 1 year after nephrectomy are known to be favorable prognostic factors. Interestingly, in our case, the bladder metastasis was detected more than 1 year after nephrectomy, which was a favorable factor, but there were also metastases in other organs, which was an unfavorable factor. Therefore, we reviewed the literature, including that pertaining to targeted therapy and immune checkpoint inhibitor therapy published in the last two decades, to analyze the clinical significance of the presence of additional metastasis in other organs in renal cell carcinoma (clear cell type, which is the predominant subtype) patients with bladder metastasis. Conclusions Patients with bladder metastasis after nephrectomy for renal cell carcinoma also having metastases in other organs may respond to targeted therapy and immune checkpoint inhibitor therapy. This may suggest that the interval to relapse in the bladder after nephrectomy may be a more important prognostic factor than the presence of synchronous metastases in other organs.

The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. These outbreaks have emphasized the need for the development of rapid diagnostic tests for this disease. Using monoclonal antibodies specific to the viral nucleoprotein, we developed an immunochromatography (IC) assay for the rapid diagnosis of MVD. The IC assay was found to be capable of detecting approximately 102−4 50% tissue culture infectious dose (TCID50)/test of MARV and RAVV in the infected culture supernatants. We further confirmed that the IC assay could detect the MARV and RAVV antigens in the serum samples from experimentally infected nonhuman primates. These results indicate that the IC assay to detect MARV can be a useful tool for the rapid point-of-care diagnosis of MVD.

Summary: The relationships between tissue-resident microglia and early macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding in situ and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated or genetic labeling, we find that intraventricular CD206+ macrophages, which are abundantly observed along the inner surface of the mouse cerebral wall, frequently enter the pallium at embryonic day 12. Immunofluorescence of the tracked cells show that postinfiltrative macrophages in the pallium acquire microglial properties while losing the CD206+ macrophage phenotype. We also find that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the “roof plate→ventricle→pallium” route is an essential path for microglial colonization into the embryonic mouse brain.

5-fluorouracil (5-FU), which is widely used as an anticancer drug, causes enteritis due to disruption of mucosal tissue, resulting in diarrhoea and body weight loss. Ginsenoside Rd (GRd) and ginsenoside Re (GRe) are two of the saponins contained in carrots. Their anti-inflammatory effects on the digestive system have been reported, but their effects on small intestinal mucositis have not been studied much. This study investigated the effect of GRd and GRe on 5-FU-induced mucoenteritis. GRd and GRe did not affect weight loss or exacerbation of diarrhoea due to 5-FU administration in mice. Histopathological observations showed that 5-FU reduced the shortening of intestinal villi and the number of crypts and cells compared to the vehicle group. However, co-administration of GRd and GRe, significantly suppressed the decrease in the number of small intestinal crypts and cells in the crypt by 5-FU treatment. It indicates that 5-FU-induced enteritis is attenuated by the co-administration of GRd and GRe. The expression of NF-κB was increased by 5-FU administration and this increase was clearly suppressed in the group that was co-administered GRd. Although the anti-inflammatory effects of GRd and GRe have been reported based on various mechanisms in many models, the mechanism of their enteritis-suppressing action in anticancer drug-induced enteritis has not been clarified. It was reported that the anti-inflammatory effect of GRd was due to the suppression of NF-κB expression; we concluded that NF-κB may be one of the molecules involved in the suppression of 5-FU-incuced enteritis.

Abstract Background Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). Methods Patients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire – Disability Index [HAQ-DI], and Subject’s Global Assessment of Pain [SGAP]), and Physician’s Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET). Results Data from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p

Abstract The clinical utility of antigen test using anterior nasal samples has not been well evaluated. We conducted a prospective study in a drive-through testing site located at a PCR center to evaluate the diagnostic performance of the antigen test QuickNavi-COVID19 Ag using anterior nasal samples and to compare the degrees of coughs or sneezes induction and the severity of pain between anterior nasal collection and nasopharyngeal collection. The study included a total of 862 participants, of which 91.6% were symptomatic. The median duration from symptom onset to sample collection was 2.0 days. Fifty-one participants tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription PCR (RT-PCR) with nasopharyngeal samples, and all of them were symptomatic. In comparison to the findings of RT-PCR, the antigen test using anterior nasal samples showed 72.5% sensitivity (95% confidence interval [CI] 58.3–84.1%) and 100% specificity (95% CI 99.3–100%). Anterior nasal collection was associated with a significantly lower degree of coughs or sneezes induction and the severity of pain in comparison to nasopharyngeal collection (p

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer’s disease and Lewy body dementia.

Abstract Maternal infection or inflammation causes abnormalities in brain development associated with subsequent cognitive impairment and in an increased susceptibility to schizophrenia and autism spectrum disorders. Maternal immune activation (MIA) and increases in serum cytokine levels mediates this association via effects on the fetal brain, and microglia can respond to maternal immune status, but consensus on how microglia may respond is lacking and no-one has yet examined if microglial process motility is impaired. In this study we investigated how MIA induced at two different gestational ages affected microglial properties at different developmental stages. Immune activation in mid-pregnancy increased IL-6 expression in embryonic microglia, but failed to cause any marked changes in morphology either at E18 or postnatally. In contrast MIA, particularly when induced earlier (at E12), caused sustained alterations in the patterns of microglial process motility and behavioral deficits. Our research has identified an important microglial property that is altered by MIA and which may contribute to the underlying pathophysiological mechanisms linking maternal immune status to subsequent risks for cognitive disease.

Although immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that Krüppel-like factor 15 (KLF15) and IL-6 are upregulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca2+ bioimaging revealed that the cytosolic Ca2+ concentration ([Ca2+]i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the downregulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies against IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobility-induced muscle atrophy was validated in human samples. Our results thus uncover a paradigm for Ca2+ signaling in that a decrease in [Ca2+]i from the basal level triggers a defined biological event.

Abstract Background The value of medical education in the community has been increasingly and globally recognized. In 2015, the World Federation for Medical Education emphasized the importance of medical education in various settings in their standard. Similarly, in Japan, the Model Core Curriculum for Medical Education in Japan (MCCMEJ) is revised in 2016. However, both the learning objectives of such clerkships and their concrete strategies in Japan are not clearly established. In this study, the authors identified the learning objectives of clinical clerkship in community health reflecting the perspectives of medical professionals and community inhabitants. Methods They held six focus groups that included physicians, other medical professionals, and inhabitants (n = 35) who were involved in a clinical clerkship in community health at three prefectures in Japan from 2017 to 2018. Further, they recorded, transcribed, and thematically analyzed the discussion using MCCMEJ as conceptual frameworks. Results The learning objectives comprised of 13 domains. The following four domains were not found in “Basic Qualities and Capacities for Physicians” in MCCMEJ: “future‐oriented systematic view,” “organic integration of knowledge/skill,” “understanding of the community,” and “awareness as an individual physician.” Conclusion With the community inhabitants' participation, the study results reflect the community needs in Japan. The authors hope that the outcome of this study will be useful to further improve clinical clerkship in community health.

Isolation during critical periods of development prevents development of normal social behaviours in mice, and this is thought to involve the prefrontal cortex. Here, the authors identify an activation pattern in parvalbumin-positive interneurons in the dorsal medial prefrontal cortex that when activated promotes sociability behaviours in mice.

BackgroundTo prevent recurrence of medical accidents, the Medical Accident Investigating System was implemented in October 2015 by the Japan Medical Safety Research Organization (Medsafe Japan) to target deaths from medical care that were unforeseen by the administrator. Medsafe Japan analyzed the 10 cases of central venous catheterization-related deaths reported in the system and published recommendations in March 2017. However, the particular emphasis for the prevention of central venous catheterization-related deaths is unclear.MethodsThis study aimed to identify the recommendation points that should be emphasized to prevent recurrence of central venous catheterization-related deaths. We assessed central venous catheterization in 8530 closed-claim cases between January 2002 and December 2016 covered by the medical insurer Sompo-Japan. Moreover, we compared central venous catheterization-related death in closed-claim cases with death in reported cases.ResultsThe background, error type, anatomic insertion site, and fatal complication data were evaluated for 37 closed-claim cases, of which 12 (32.4%) were death cases. Of the 12 closed-claim cases and 10 reported cases, 9 (75.0%) closed-claim cases and 9 (90.0%) reported cases were related to vascular access. Among these, 5 closed-claim cases (41.7%) and 7 reported cases (77.8%) were related to internal jugular vein catheterization (p = 0.28). Coagulopathy was observed in 3 (60.0%) of 5 closed-claim cases and 6 (85.7%) of 7 reported cases.ConclusionsThe risk of internal jugular catheterization in patients with coagulopathy must be carefully considered.

Although it is known that microglia respond to injury and systemic disease in the brain, it is unclear if they modulate blood–brain barrier (BBB) integrity, which is critical for regulating neuroinflammatory responses. Here authors demonstrate that microglia respond to inflammation by migrating towards and accumulating around cerebral vessels, where they initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 before switching, during sustained inflammation, to phagocytically remove astrocytic end-feet resulting in impaired BBB function

The detailed mechanism underlying diabetic chorea remains uncertain. We present a male patient with recurrent diabetic hemichorea with late-onset reduced arm swing. We explored the association between hyperglycemia, changes in neurological manifestations, and brain magnetic resonance imaging findings. Hyperglycemic control did not prevent the following progressive structural changes in the putamen. Slow progressive structural changes in the putamen may lead to the recurrence of chorea and the appearance of late-onset reduced arm swing. We speculated that hyperglycemia-related vasculopathy and subsequent structural changes in the putamen may play a crucial role in diabetic chorea.

Objectives There are limitations to defining multimorbidity (MM) based on a simple count of diseases. To address these limitations, the concept of complex MM (CMM) focuses on how many body systems are affected in a single patient, rather than counting comorbid conditions. This study compared the prediction of mortality among older Japanese adults between CMM and conventional MM.Design A population-based prospective cohort study.Setting The Japan Gerontological Evaluation Study, a nationwide longitudinal cohort study, which ran from 2010 to 2016.Participants Functionally independent individuals who were older than 65 and had complete illness data at the time of baseline survey were eligible.Outcomes measure CMM was defined as the coexistence of 3 or more body system disorders at baseline. We calculated the propensity for each individual to develop CMM based on a wide array of characteristics, including socioeconomic status and health behaviours. Individuals with and without CMM were then matched on their propensity scores before we estimated overall survival using a log-rank test.Results Our 6-year follow-up included 38 889 older adults: 20 233 (52.0%) and 7565 (19.5%) adults with MM and CMM, respectively. In the MM-matched cohort (n=15 666 pairs), the presence of MM was significantly associated with increased mortality (HR 1.07; 95% CI 1.01 to 1.14; p=0.02 by the log-rank test). A similar mortality association was found in the CMM-matched cohort (n=7524 pairs, HR, 1.07; 95% CI 0.99 to 1.16; p=0.08 by the log-rank test).Conclusion This is the first study to report the association between CMM and mortality among older adults in Japan. MM and CMM predict mortality in older adults to a similar degree. This finding needs to be replicated with more precision in larger samples.

Abstract Japan's health system is well known for achieving one of the world's highest life expectancy with universal health coverage. However, the country now faces challenges of a rapidly aging population and changes in patterns and burden of disease. Primary care is an important component of a well‐functioning health system. In Japan, primary care services are provided in both the community and hospital settings. The distinction between primary and secondary care may not always be clear. This review is based on the framework from the 2015 WHO publication on primary care systems in Europe. Our aim is to describe the journey of primary care in Japan, with its past, present, and future as a valuable addition to the academic English literature. We also hope that this article would inspire readers outside of Japan who might face similar issues in their respective countries.

Immunochromatographic kits and RT-PCR are widely used as diagnostic tools for influenza detection in clinical and hygiene fields. Immunochromatographic kits are useful for differential typing of influenza A and influenza B but cannot show if the detected virus strains have acquired drug resistance against neuraminidase inhibitors that target sialidase activity of viral neuraminidase. Although RT-PCR enables determination of drug-resistant mutants, its efficacy is limited to viruses carrying a known substitution in their neuraminidase genome sequence. In the present study, an easy, rapid and sensitive method for detection of drug-resistant influenza viruses regardless of major antigenic changes or genomic mutations was developed. By using the method in combination with virus-concentrated membranes in centrifugal filter units and a sialidase imaging probe, 2-(benzothiazol-2-yl)-4-bromophenyl-N-acetylneuraminic acid (BTP3-Neu5Ac), sialidase activity of influenza neuraminidase was visualized on membranes by the green fluorescence of produced hydrophobic BTP3 under UV irradiation with a handheld UV flashlight. Fluorescence images in the presence or absence of neuraminidase inhibitors clearly discriminated drug-resistant influenza viruses from drug-sensitive ones. The assay can be done within 15 min. The detection sensitivity was shown to be equal to or higher than the sensitivities of commercial immunochromatographic kits. The assay will be a powerful tool for screening and monitoring of emerging drug-resistant influenza viruses and would help clinicians decide effective antiviral treatment strategies when such mutants have become prevalent.

Despite having pathological changes in the brain associated with Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous reports have demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through β2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-β (Aβ) oligomers. The cholinergic network from the medial septal nucleus (MSN) is also a main modulating system for hippocampal glutamatergic neural activation through nicotinergic and/or muscarinergic acetylcholine receptors. Previously, we reported the importance of a cholinergic regulator gene in the MSN, hippocampal cholinergic neurostimulating peptide (HCNP). By using hippocampal sections from mice, we here demonstrated that the cholinergic neural activation from the MSN enhanced the glutamatergic neuronal activity during unsaturated LTP but not during saturated LTP. Synthetic Aβ oligomers suppressed the hippocampal glutamatergic activity in a concentration-dependent manner. Furthermore, HCNP, as well as a cholinergic agonist acting through the muscarinic M1 receptor, prevented the suppression of hippocampal glutamatergic neuronal activity induced by synthetic Aβ oligomers. This result suggests that the persisting cholinergic activation might be a potential explanation for the individual differences in cognitive effects of AD pathological changes.

The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei. HCNP is processed from the N-terminal region of a 186 amino acid, 21 kD HCNP precursor protein called HCNP-pp (also known as Raf kinase inhibitory protein (RKIP) and phosphatidylethanolamine-binding protein 1 (PEBP1)). In this study, we generated HCNP-pp knockout (KO) mice and assessed their cholinergic septo-hippocampal projection, local field potentials in CA1, and behavioral phenotypes. No significant behavioral phenotype was observed in HCNP-pp KO mice. However, theta power in the CA1 of HCNP-pp KO mice was significantly reduced because of fewer cholineacetyltransferase-positive axons in the CA1 stratum oriens. These observations indicated disruption of cholinergic activity in the septo-hippocampal network. Our study demonstrates that HCNP may be a cholinergic regulator in the septo-hippocampal network.

The recent large outbreaks of Ebola virus disease (EVD) in West Africa and the Democratic Republic of the Congo (DRC) have highlighted the need for rapid diagnostic tests to control this disease. In this study, we clinically evaluated a previously developed immunochromatography-based kit, QuickNaviTM-Ebola. During the 2018 outbreaks in DRC, 928 blood samples from EVD-suspected cases were tested with QuickNaviTM-Ebola and the WHO-approved GeneXpert. The sensitivity and specificity of QuickNaviTM-Ebola, estimated by comparing it to GeneXpert-confirmed cases, were 85% (68/80) and 99.8% (846/848), respectively. These results indicate the practical reliability of QuickNaviTM-Ebola for point-of-care diagnosis of EVD.

Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote differentiation of septohippocampal cholinergic neurons. The HCNP precursor protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein, a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding protein, as well as a precursor for HCNP. This study therefore aimed to elucidate the involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic–ischemic (HI) rat model of brain ischemia. The specific neural lineages in the hippocampus were investigated 14 days after ischemia. Some bromodeoxyuridine (BrdU) + neural progenitor cells in the hippocampus of hypoxic, HI, or sham-operated rats expressed HCNP-pp. Almost half of the BrdU + /HCNP-pp + cells also expressed the oligodendrocyte lineage marker 2′,3′-cyclic nucleotide 3′-phosphodiesterase, whereas only a few BrdU + /HCNP-pp + cells in the hippocampus in HI brains expressed the neuronal lineage marker, doublecortin (DCX). Interestingly, no BrdU + /HCNP-pp + progenitor cells in hypoxic, HI, or sham-operated brains expressed the astrocyte lineage marker, glial fibrillary acidic protein. Together with previous in vitro data, the results of this study suggest that the expression level of HCNP-pp regulates the differentiation of neural progenitor cells into specific neural lineages in the HI hippocampus, indicating that neural stem cell fate can be controlled via the HCNP-pp mediating pathway.

Microglial processes survey the brain parenchyma, but it is unknown whether this process is influenced by the cell activity of nearby microglia under physiological conditions. Herein, we showed that microglial process dynamics differ when facilitated by astrocytic activity and pre-synaptic activity. The results revealed distinct microglial process dynamics associated with the activity of other brain cells. [ABSTRACT FROM AUTHOR]