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An 11-year-old girl presented with pain in the sinus tarsi and a foot deformity after spraining her left foot. She had flat foot due to spasticity of the peroneal tendon, which was difficult to correct manually. An imaging study revealed an accessory anterolateral talar facet (AALTF) and bone marrow oedema at the lateral aspect of the posterior talocalcaneal joint. We diagnosed peroneal spastic flat foot with possible involvement of sinus tarsi syndrome and AALTF. When conservative therapy failed, we applied a cast with the foot in full plantar flexion and an inverted position. After 4 weeks, the patient had a normal range of motion in the foot, the pain had resolved completely and the peroneal spasticity had disappeared. Orthopaedic treatment with a cast may be worth attempting before surgery in such cases.

The optimal management of patients with appendiceal endometriosis has not been determined because of the difficulty of establishing a preoperative diagnosis. There are no reports of preoperative hormone therapy for a patient with appendiceal endometriosis. We report a patient who underwent resection of appendiceal endometriosis after hormone therapy. A 40-year-old woman with history of recurrent pelvic abscesses presented to the emergency department with lower abdominal pain. The recurrent pelvic abscesses were synchronised with her menstrual cycle. CT scan demonstrated a 25 mm contrast-enhanced luminal structure adjacent to the cecum, which was thought to be a mucocele of the appendix. Considering the recurrent symptoms during menstruation, endometriosis was suspected. Treatment with a gonadotropin-releasing hormone agonist was started for appendiceal endometriosis, which alleviated the symptoms. After 3 months, elective laparoscopic appendectomy was performed. Preoperative hormonal therapy is an option for patients with appendiceal endometriosis, especially when there is concern for dense adhesions.

We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R

The heart contains a population of resident macrophages that markedly expands following injury through recruitment of monocytes and through proliferation of macrophages. In myocardial infarction, macrophages have been implicated in both injurious and reparative responses. In coronary atherosclerotic lesions, macrophages have been implicated in disease progression and in the pathogenesis of plaque rupture. Following myocardial infarction, resident macrophages contribute to initiation and regulation of the inflammatory response. Phagocytosis and efferocytosis are major functions of macrophages during the inflammatory phase of infarct healing, and mediate phenotypic changes, leading to acquisition of an anti-inflammatory macrophage phenotype. Infarct macrophages respond to changes in the cytokine content and extracellular matrix composition of their environment and secrete fibrogenic and angiogenic mediators, playing a central role in repair of the infarcted heart. Macrophages may also play a role in scar maturation and may contribute to chronic adverse remodeling of noninfarcted segments. Single cell studies have revealed a remarkable heterogeneity of macrophage populations in infarcted hearts; however, the relations between transcriptomic profiles and functional properties remain poorly defined. This review manuscript discusses the fate, mechanisms of expansion and activation, and role of macrophages in the infarcted heart. Considering their critical role in injury, repair, and remodeling, macrophages are important, but challenging, targets for therapeutic interventions in myocardial infarction.

Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy.We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68 ± 11 years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1 year after percutaneous coronary intervention (PCI). The stents (n = 106) were divided into three groups according to the lesion status at the previous PCI: CTO (n = 17), acute coronary syndrome (ACS) (n = 35), and stable coronary artery disease without CTO or non-CTO (n = 54).The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4 ± 0.5, 0.9 ± 0.8, and 1.4 ± 0.8, respectively, p 0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71 %, 51 %, and 15 %, respectively, p 0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5 ± 0.7, 1.4 ± 0.6, and 0.9 ± 0.7, respectively, p = 0.007).Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (

50 Pág., In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratifcation vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV, This work was supported in part through Laulima Govern ment Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Gov ernment Solutions, LLC under Contract No. HHSN272201800013C. This work was also funded in part by Contract No. HSHQDC 15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges support from the Mississippi Agri cultural and Forestry Experiment Station (MAFES), USDA-ARS pro ject 58-6066-9-033 and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project, under Accession Num ber 1021494.

Appendicolith causes acute appendicitis. However, surgical indications for appendicolith-related acute appendicitis have not been established. We aimed to clarify the clinical features of appendicolith-associated appendicitis and determine an appropriate treatment strategy based on the initial presentation.We retrospectively reviewed the records of 479 consecutive patients with acute appendicitis and verified the therapeutic strategy as per the appendicolith and clinical status.Appendicoliths were identified in 214 of 479 patients (44.6%) using computed tomography. Surgery was more frequently required in patients with appendicolith than in patients without appendicolith (82.7 versus 64.9%; P 0.001). The stones were smaller and serum C-reactive protein (CRP) concentration was lower among patients with appendicoliths treated with medication alone than among those surgically treated (both P 0.001). An appendicolith measuring ≤5 mm in diameter and CRP concentration ≤5.36 mg/dL were predictive of completion of nonsurgical therapy. CRP concentration10 mg/dL and stone diameter of 10 mm were significantly associated with appendiceal perforation.Nonsurgical therapy could be considered for patients with appendicoliths measuring ≤5 mm in diameter and in cases where the serum CRP concentration is ≤5 mg/dL. An appendicolith measuring10 mm in diameter or CRP concentration10 mg/dL is an indication for surgery.

The elderly are particularly susceptible to infectious and neoplastic diseases of the lung and it is unclear how lifelong exposure to environmental pollutants affects respiratory immune function. In an analysis of human lymph nodes (LNs) from 84 organ donors aged 11-93years, we found a specific age-related decline in lung-associated, but not gut-associated, LN immune function linked to the accumulation of inhaled atmospheric particulate matter. Increasing densities of particulates were found in lung-associated LNs with age, but not in the corresponding gut-associated LNs. Particulates were specifically contained within CD68(+)CD169(−) macrophages, which exhibited reduced activation, phagocytic capacity, and altered cytokine production compared to non-particulate-containing macrophages. The structures of B cell follicles and lymphatic drainage were disrupted in lung-associated LN with particulates. Our results reveal that the cumulative effects of environmental exposure with age may compromise immune surveillance of the lung via direct effects on immune cell function and lymphoid architecture.

Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma., 神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

A lack of practical resources in Japan has limited preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes. Here, we established 57 patient-derived xenografts (PDXs) in NOD.Cg-Prkdcscidll2rgtm1Sug/ShiJic (NOG) mice and created a biobank by preserving PDX cells including three extramedullary relapsed ALL PDXs. We demonstrated that our PDX mice and PDX cells mimicked the biological features of relapsed ALL and that PDX models reproduced treatment-mediated clonal selection. Our PDX biobank is a useful scientific resource for capturing drug sensitivity features of pediatric patients with ALL, providing an essential tool for the development of targeted therapies.

Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked recessive developmental disorder characterized by initially marked truncal hypotonia, later athetotic posturing, and severe intellectual disability caused by mutations in SLC16A2, which is responsible for the transport of triiodothyronine (T3) into neurons. We conducted a nationwide survey of patients with MCT8 deficiency to clarify their current status.Primary survey: In 2016-2017, we assessed the number of patients diagnosed with MCT8 deficiency from 1027 hospitals. Secondary survey: in 2017-2018, we sent case surveys to 31 hospitals (45 cases of genetic diagnosis), who responded in the primary survey. We asked for: 1) perinatal history, 2) developmental history, 3) head MRI findings, 4) neurophysiological findings, 5) thyroid function tests, and 5) genetic test findings.We estimated the prevalence of MCT8 deficiency to be 1 in 1,890,000 and the incidence of MCT8 deficiency per million births to be 2.12 (95 % CI: 0.99-3.25). All patients showed severe psychomotor retardation, and none were able to walk or speak. The significantly higher value of the free T3/free T4 (fT3/fT4) ratio found in our study can be a simple and useful diagnostic biomarker (Our value 11.60 ± 4.14 vs control 3.03 ± 0.38). Initial white matter signal abnormalities on head MRI showed recovery, but somatosensory evoked potentials (SEP) showed no improvement, suggesting that the patient remained dysfunctional.For early diagnosis, including in mild cases, it might be important to consider the clinical course, early head MRI, SEP, and fT3/fT4 ratio.

Detailed data on clinical characteristics in children with the omicron strain of SARS-COV-2 are limited.We conducted a retrospective observational study of children with COVID-19 at the National Center for Child Health and Development to evaluate the clinical manifestations during and before the emergence of the omicron variant. Only symptomatic patients without underlying diseases were included. Participants were divided into two temporal groups: the "omicron era" (1/2022-2/2022) and the "pre-omicron era," where the delta variant predominated (7/2021-11/2021). The patients were subclassified into an older vaccine-eligible group (aged 12-17 years), a younger vaccine-eligible group (aged 5-11 years), and a vaccine-ineligible group (aged 0-4 years).We compared 113 patients in the omicron era with 106 in the pre-omicron era. Most patients in both eras had non-severe disease, and no patients required mechanical ventilation or died. Among patients aged 0-4 years, sore throat and hoarseness were more common during the omicron era than the pre-omicron era (11.1% vs. 0.0% and 11.1% vs. 1.5%, respectively). Croup syndrome was diagnosed in all patients with hoarseness. Among patients aged 5-11 years, vomiting was more frequent during the omicron era (47.2%) than during the pre-omicron era (21.7%). Cough and rhinorrhea were less common during the omicron era in patients aged 0-4 and 5-11 years, respectively, than during the pre-omicron era.In children with COVID-19, clinical manifestations differed between the omicron and pre-omicron eras. In the Omicron era, croup syndrome was more frequent in vaccine-ineligible children.

Broader genetic screening has led to the growing recognition of the role of germline variants associated with adult bone marrow failure (BMF) and myeloid neoplasia (MN) not exclusively in children and young adults. In this study, we applied a germline variant panel to 3008 adult BMF and MN cases to assess the importance of germline genetics and its impact on disease phenotype and prognosis. In our cohort, up to 9.7% of BMF and 5.3% of MN cases carried germline variants. Our cohort also included heterozygous carriers of recessive traits, suggesting they contribute to the risk of BMF and MN. By gene category, variants of Fanconi anemia gene family represented the highest-frequency category for both BMF and MN cases, found in 4.9% and 1.7% cases, respectively. In addition, about 1.4% of BMF and 0.19% of MN cases harbored multiple germline variants affecting often functionally related genes as compound heterozygous. The burden of germline variants in BMF and MN was clearly associated with acquisition of monosomy 7. While BMF cases carrying germline variants showed similar overall survival as compared to the wild-type (WT) cases, MN cases with germline variants experienced a significantly shorter overall survival as compared to WT cases.

A 66-year-old Japanese woman had been diagnosed with a neuroendocrine tumor of the pancreatic head (G2) 3 years previously and undergone pancreaticoduodenectomy. Nine months postoperatively, recurrence with multiple liver metastases developed and she was referred to our department. A regimen of 10 mg of everolimus for 2 weeks plus 1-week washout was instituted, and no adverse events were observed. Fourteen months after treatment initiation, she developed severe generalized erythema multiforme (EM). Skin biopsy revealed spongiosis in the epidermis and interface change and edema in the superficial dermis. Mast cells were observed from the dermis to the subcutaneous tissue, as well as perivascular eosinophilic infiltration, leading to EM being diagnosed. Oral everolimus was discontinued, and the EM was relieved by treatment including steroid therapy. Everolimus is an inhibitor of the mammalian target of rapamycin, and its indications include neuroendocrine tumors. Skin disorders are commonly seen in the early stages of everolimus treatment, but their severity is almost always mild and never severe. This is the first report on a patient who presented with severe generalized EM more than 1 year after everolimus treatment initiation. Patients on everolimus therapy should be monitored for skin disorders on a long-term basis.

Aims: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence-practice- gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'. Methods: To establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared. Result: IFS points vary and ranged from 0 to100. The average pre-admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge. Conclusions: We developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia.

Mutations in the SCN4A gene encoding a voltage-gated sodium channel (Nav1.4) cause hyperkalemic periodic paralysis (HyperPP) and hypokalemic periodic paralysis (HypoPP). Typically, both HyperPP and HypoPP are considered as monogenic disorders caused by a missense mutation with a large functional effect. However, a few cases with atypical periodic paralysis phenotype have been caused by multiple mutations in ion-channel genes expressed in skeletal muscles. In this study we investigated the underlying pathogenic mechanisms in such cases.We clinically assessed two families: proband 1 with HyperPP and proband 2 with atypical periodic paralysis with hypokalemia. Genetic analyses were performed by next-generation sequencing and conventional Sanger sequencing, followed by electrophysiological analyses of the mutant Nav1.4 channels expressed in human embryonic kidney 293T (HEK293T) cells using the whole-cell patch-clamp technique.In proband 1, K880del was identified in the SCN4A gene. In proband 2, K880del and a novel mutation, R1639H, were identified in the same allele of the SCN4A gene. Functional analyses revealed that the K880del in SCN4A has a weak functional effect on hNav1.4, increasing the excitability of the sarcolemma, which could represent a potential pathogenic factor. Although R1639H alone did not reveal functional changes strong enough to be pathogenic, Nav1.4 with both K880del and R1639H showed enhanced activation compared with K880del alone, indicating that R1639H may modify the hNav1.4 channel function.A cumulative effect of variants with small functional alterations may be considered as the underpinning oligogenic pathogenic mechanisms for the unusual phenotype of periodic paralysis.

HDM SLIT is one of the disease-modifying treatment for allergic asthma, and has demonstrated efficacy in clinical trials. Dupilumab, blocks IL-4 and IL-13 signaling, key drivers of type 2 inflammation, and is approved for patients with uncontrolled, moderate-to-severe asthma. The aim of this study was to evaluate outcomes after HDM SLIT initiation in asthma with rhinitis not optimally controlled with dupilumab in a real-world setting.At baseline and 48 weeks after treatment, asthma control questionnaire (ACQ)-5, asthma quality of life questionnaire (AQLQ) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were assessed. Spirometry, type 2 inflammatory biomarkers and quantitative computed tomographic parameters of airway remodeling were also collected.Of 47 patients received HDM SLIT and 41 completed the study. Combined HDM SLIT and dupilumab improved ACQ-5 (p 0.05), AQLQ (p 0.05), RQLQ (p 0.05), and increased lung function and reduced FeNO (p 0.05) and airway percentage wall area, and wall thickness (each, p 0.05). The change in ACQ-5 and AQLQ score correlated with both changes in FeNO and FEVThese results support the benefits of adding HDM SLIT to pharmacotherapy plus dupilumab in uncontrolled asthma with rhinitis.

Background: Some patients with a wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with a wheat allergy is due to cross-antigenicity between wheat and barley. In our study, we aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. Methods: We compared the results of barley oral food challenges (OFCs) before oral immunotherapy (OIT) for wheat with those after OIT in nine patients with a wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. Results: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. Conclusion: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat was one of the promising options for barley allergy.

Lead (Pb) causes developmental neurotoxicity. Developmental exposure to Pb acetate (PbAc) induces aberrant hippocampal neurogenesis by increasing or decreasing neural progenitor cell (NPC) subpopulations in the dentate gyrus (DG) of rats. To investigate whether hippocampal neurogenesis is similarly affected by PbAc exposure in a general toxicity study, 5-week-old Sprague-Dawley rats were orally administered PbAc at 0, 4000, and 8000 ppm (w/v) in drinking water for 28 days. After exposure to 4000 or 8000 ppm PbAc, Pb had accumulated in the brains. Neurogenesis was suppressed by 8000 ppm PbAc, which was related to decreased number of type-2b NPCs, although number of mature granule cells were increased by both PbAc doses. Gene expression in the 8000 ppm PbAc group suggested suppressed NPC proliferation and increased apoptosis resulting in suppressed neurogenesis. PbAc exposure increased numbers of metallothionein-I/II

Insulin therapy using insulin purified from porcine or bovine pancreas revolutionized diabetes therapy in the 1920s. A series of advances including cloning human insulin cDNA enabled the development of recombinant human insulin with improved features. Insulin treatment for diabetes may well be upended by β-cell replacement therapy in the coming decades.

Laparoscopic liver resection (LLR) for tumors located in posterosuperior (PS) region of the liver (segment 7 or 8) is extremely challenging. Several techniques have been proposed; however, no standard procedure has yet been established. The aim of this study was to present and discuss the usefulness of the right kidney position as a unique idea of surgical position in LLR for tumors located in the PS region.For the right kidney position, the patient lay on the operating table in the left lateral decubitus position with the body bent so that the kidney rest (approximately the level of the twelfth rib) was elevated to extend the surgical area. The surgeon was positioned on the right or left side of the patient according to the situation during operation. An intercostal port was not used in any of the cases. The operating table was liberally rotated as per the surgeon's preference. The liver was mobilized by dividing the right triangular and coronary ligaments. Full mobilization of the right liver was not routinely performed. Liver transection was performed under intermittent inflow occlusion in all cases.Thirteen patients with tumors located in the PS region underwent LLR in the right kidney position at Shinshu University Hospital between June 2019 and May 2021. Of the 13 patients, 11 patients underwent limited liver resection and two underwent anatomic liver resection of segment 8. The right kidney position enables the surgeon to secure a wider surgical field under the dome and prevent the camera and forceps from hitting the ilium and interfering with the operation, and the surgical device can easily reach the lesion under the dome because of the migration to the caudal side of the liver. No patients required blood transfusion or conversion to open liver resection. The median surgical margin was 6 mm (range 0 to 9 mm).The right kidney position is useful, especially for the resection of tumors located in the PS region of the liver.

Using the reliable change index (RCI), we aimed to examine the effect of a multicomponent exercise program on the individual level.Overall, 270 adults (mean age, 78 years) completed a multicomponent physical exercise program (strength, aerobic, gait, and balance) for 40 min, 1-2 times per week, continued up to 1 year at a daycare center. Effectiveness was assessed using grip, ankle, knee, and hip strength; Timed UpGo (TUG); Berg Balance Scale (BBS); gait speed; and 6-min walking distance. These were measured at baseline and every 3 months thereafter. We calculated the RCI using the data between two-time points (baseline and at 3, 6, 9, or 12 months) in each participant and then calculated the mean RCI value across the participants. A paired t-test was also employed to evaluate the effect of the intervention as an average-based statistics.The highest mean RCI values were on ankle plantar-flexion strength, followed by gait speed, hip abduction strength, BBS, knee extensor strength, 6-min walk distance, grip strength, and finally TUG. Paired t-test also revealed significant improvement with moderate effect sizes for ankle plantar-flexion strength (0.504), gait speed (0.413), hip abduction strength (0.374), BBS (0.334), knee extensor strength (0.264), and 6-min walk distance (0.248). Significant but small effect size was seen on TUG (0.183).The RCI is a convenient method of comparing the effect between different assessments, especially at an individual level. This index can be applied to the use of personal feedback.

Malignancy of medulloblastoma depends on its molecular classification. Sonic Hedgehog (SHH)-type medulloblastoma with p53 mutation was recognized as one of the most aggressive types of tumors. We developed a novel drug, chlorambucil-conjugated PI-polyamides (Chb-M'), which was designed to compete with the RUNX consensus DNA-binding site. Chb-M' specifically recognizes this consensus sequence and alkylates it to inhibit the RUNX transcriptional activity. In-silico analysis showed all the RUNX families were upregulated in the SHH-type medulloblastoma. Thus, we tested the anti-tumor effects of Chb-M' in vitro and in vivo using Daoy cell lines, which belong to SHH with p53 mutation. Chb-M' inhibited tumor growth of Daoy cells by inducing apoptosis. The same inhibitory effect was also observed by knocking down of RUNX1 or RUNX2, but not RUNX3. Apoptosis array analysis showed that Chb-M' treatment induced phosphorylation of p53 serine 15 residues. In a subcutaneous tumor model, intratumoral injection of Chb-M' induced tumor growth retardation. Chb-M' mediated inhibition of RUNX1 and RUNX2 can be a novel therapeutic strategy for SHH-type medulloblastoma with p53 mutation.

Background and study aims: The gastrointestinal (GI) tract is the most common site of extra-nodal involvement for non-Hodgkin’s lymphoma (NHL). The features of GI NHLs remain unclear. The aim of this study was to clarify endoscopic characteristics of GI NHLs. Patients and methods: We retrospectively analyzed the morphological characteristics of 63 GI malignant lymphomas other than mucosa-associated lymphoid tissue lymphoma. Lesions were diagnosed between 2005 and 2020. Macroscopic findings were classified into five subtypes: superficial (S); protruding without ulcer (P); protruding with ulcer (PU); fungating (F); and multiple nodules (MN). Results: Thirty-one lesions in the stomach were classified as S type in 3 cases (9.6%), P type in 6 (19%), PU type in 13 (42%), and F type in 9 (29%). In the stomach, the ulcerated phenotype was more frequent for diffuse large B-cell lymphoma (DLBCL) (89.5%) than for other histological types (41.7%; P = 0.01). In the intestine, 23 tumors were classified as S type in 4 cases (17%), P type in 1 (4%), PU type in 6 (26%), F type in 1 (4%), and MN in 11 (48%). Eleven of the 14 cases (78.6%) of intestinal follicular lymphoma lesions showed MN type. In the colon, eight tumors were classified as S type in 2 cases (25%), P type in 2 (25%), PU type in 1 (13%), and F type in 3 (38%). Conclusion: We have clarified the endoscopic features of GI NHL using macroscopic classifications. The ulcerated phenotype was the most frequent endoscopic finding for DLBCL.

Mothers in urban Japan are at high risk for postpartum depression. Previous research indicates that parents who understand their baby's behavior may have lower risks for postpartum depression. HUG Your Baby helps parents understand their baby's behavior.The purpose of this longitudinal study was to determine whether mothers receiving prenatal HUG Your Baby teaching would have better outcomes than a control group with respect to postpartum depression and related factors.Pregnant women, after thirty weeks' gestation, were recruited to either the intervention or the control group. The intervention group received HUG Your Baby education, which teaches how to recognize and respond to a baby's behavior. The control group received a leaflet and regular, prenatal treatment. Participants completed the Edinburgh Postnatal Depression Scale, Karitane Parenting Confidence Scale, and three other scales at one and three months, postpartum. Questions about knowledge of baby's behavior was administered prenatally, and at one and three months, postpartum.Data derived from 221 mothers (Control 100, Intervention 121) were included in the analysis. Researchers found significant differences regarding postpartum depression at one and three months and parenting confidence at one month. Scores were favorable for the intervention group.The HUG Your Baby program has a positive impact on preventing postpartum depression and increasing parenting confidence. It warrants wider implementation and evaluation in prenatal programs.

In this single-center retrospective observational study, we report that the incidence of seizures in febrile children with COVID-19 was significantly higher in the Omicron era than in the pre-Omicron era (14.6% vs 1.7%, P

In the present study, we aimed to determine the changes in the administration rate of benzodiazepines for pediatric patients with suspected nonconvulsive status epilepticus (NCSE) before and after the introduction of simplified electroencephalography (sEEG) in the emergency department.This retrospective cohort study included patients who were younger than 18 years and were admitted to the emergency department from August 1, 2009, to July 31, 2017, with altered level of consciousness and nonpurposeful movement of eyes or extremities after the cessation of convulsive status epilepticus. Patients with apparent persistent convulsions, those who were fully conscious on arrival, and those who were transferred from another hospital were excluded. The patients were categorized into pre and post groups based on the introduction of sEEG, and benzodiazepine administration was compared between the 2 groups.During the study period, 464 patients with status epilepticus visited our emergency department and 69 and 93 patients fulfilling the study criteria were categorized into the pre and post groups, respectively. There were no significant differences in patient background characteristics between the 2 groups. Simplified electroencephalography was recorded in 52 patients in the post group. Benzodiazepines were administered in 44 of 69 patients (63.8%) in the pre group and 44 of 93 (47.3%) in the post group, and the benzodiazepine administration rate was significantly decreased after the introduction of sEEG ( P = 0.04). The hospitalization rate was significantly lower in the post group, but there were no significant differences in the rates of intensive care unit admission, reconvulsion after discharge, and final diagnoses between the 2 groups.Simplified electroencephalography might aid in determining the need for anticonvulsant treatment for suspected NCSE in pediatric patients. Albeit not a definitive diagnostic tool, sEEG might be a reliable choice in the evaluation of pediatric patients with suspected NCSE.

The anti-fibroblast growth factor 23 monoclonal antibody burosumab corrects hypophosphatemia in adults with X-linked hypophosphatemia (XLH) and improves pain, stiffness, physical function, and fatigue. This post hoc subgroup analysis used data from the 24-week placebo-controlled period of a phase 3 study in 134 adults with XLH (ClinicalTrials.gov NCT02526160), to assess whether the benefits of burosumab are evident in 14 clinically relevant subgroups defined by baseline demographic and functional criteria, including sex, Brief Pain Inventory-short form (BPI-SF) Average And Worst Pain, region, race, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Stiffness, Physical Function and Pain domains and total score, use of opioid/other pain medication, active fractures/pseudo-fractures, and 6-min walk test distance. There were no statistically significant interactions between any of the subgroups and treatment arm for any endpoint. Higher proportions of subjects achieved mean serum phosphate concentration above the lower limit of normal (the primary endpoint) with burosumab than with placebo in all subgroups. For the key secondary endpoints (WOMAC Stiffness and Physical Function; BPI-SF Worst Pain) individual subgroup categories showed improvements with burosumab relative to placebo. For additional efficacy endpoints, burosumab was favored in some subgroups but differences were not significant and confidence intervals were wide. For some endpoints the treatment effect is small at 24 weeks in all subjects. This subgroup analysis shows that burosumab was largely superior to placebo across endpoints in the 14 clinically relevant subgroup variables at 24 weeks and is likely to benefit all symptomatic adults with active XLH.