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The Burkholderia cepacia complex (Bcc) is a group of bacteria with similar biological properties which are an important cause of opportunistic infections. Identification of the Bcc species is important to understand clinical outcomes in human patients. However, there are few studies of Bcc species infecting companion animals such as cats. This report shows for the first time an infection with B. pseudomultivorans, a member of Bcc, in veterinary medicine. A 9-year-old, FIV-positive, mixed-breed cat was subjected to immunosuppressive therapy, developed septic shock, and died. In the bone marrow specimen collected postmortem, numerous short bacilli—some of which were phagocytosed by leukocytes—were observed. By bacteriological examination, the Bcc-like bacteria were isolated from the bone marrow sample. Genetic analysis showed that the recA gene sequence detected from the present case exhibited the highest homology (98–100%) to that of B. pseudomultivorans. Based on these examinations, the present case was diagnosed as B. pseudomultivorans infection. The findings of this study highlight the need for investigation of the Bcc species in veterinary practice to help in treatment decisions and the prognostic evaluation of Bcc infections.

The identification, diagnosis, and categorisation of students who qualified for special education have created long-standing controversy. This article explores Maximilian P. E. Groszmann's measurement practices, which were intended to facilitate instruction in the early twentieth-century United States. In 1900, Groszmann established a private residential school for "atypical" children and developed his own method of measuring these children's capabilities, an alternative to the Binet scale. "Atypical" children were defined as those who deviated from the average human type but had the potential of a "normal" child. Thus, they were children who were classified between normal and abnormal. Groszmann's methods were based on his conviction that "atypical" children's development was closely and intricately related to their social environment. His holistic perception of "atypical" children's development led Groszmann to try to take a wider view of their difficulties, reactions, and experiences. Groszmann's answers to the questions of what, where, and why to measure children differed from those of advocates of intelligence testing. In short, his methods were intended to help children adapt to their social environment, not to label and sort them as "atypical" or socially incapable.

Abstract Background and Aim Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all‐in‐one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

Rett syndrome is characterized by severe global developmental impairments with autistic features and loss of purposeful hand skills. Here we show that human induced pluripotent stem cell (hiPSC) lines derived from four Japanese female patients with Rett syndrome are generated from peripheral blood mononuclear cells using Sendai virus vectors. The generated hiPSC lines showed self-renewal and pluripotency and carried heterozygous frameshift, missense, or nonsense mutations in the MECP2 gene. Since the molecular pathogenesis caused by MECP2 dysfunction remains unclear, these cell resources are useful tools to establish disease models and develop new therapies for Rett syndrome.

Palmitoylation and depalmitoylation represent dichotomic processes by which a labile posttranslational lipid modification regulates protein trafficking and degradation. The depalmitoylating enzyme, palmitoyl-protein thioesterase 1 (PPT1), is associated with the devastating pediatric neurodegenerative condition, infantile neuronal ceroid lipofuscinosis (CLN1). CLN1 is characterized by the accumulation of autofluorescent lysosomal storage material (AFSM) in neurons and robust neuroinflammation. Converging lines of evidence suggest that in addition to cellular waste accumulation, the symptomology of CLN1 corresponds with disruption of synaptic processes. Indeed, loss of Ppt1 function in cortical neurons dysregulates the synaptic incorporation of the GluA1 AMPA receptor (AMPAR) subunit during a type of synaptic plasticity called synaptic scaling. However, the mechanisms causing this aberration are unknown. Here, we used the Ppt1−/− mouse model (both sexes) to further investigate how Ppt1 regulates synaptic plasticity and how its disruption affects downstream signaling pathways. To this end, we performed a palmitoyl-proteomic screen, which provoked the discovery that Akap5 is excessively palmitoylated at Ppt1−/− synapses. Extending our previous data, in vivo induction of synaptic scaling, which is regulated by Akap5, caused an excessive upregulation of GluA1 in Ppt1−/− mice. This synaptic change was associated with exacerbated disease pathology. Furthermore, the Akap5- and inflammation-associated transcriptional regulator, nuclear factor of activated T cells (NFAT), was sensitized in Ppt1−/− cortical neurons. Suppressing the upstream regulator of NFAT activation, calcineurin, with the FDA-approved therapeutic FK506 (Tacrolimus) modestly improved neuroinflammation in Ppt1−/− mice. These findings indicate that the absence of depalmitoylation stifles synaptic protein trafficking and contributes to neuroinflammation via an Akap5-associated mechanism.

Abstract Objectives Individual treatment strategies for esophageal cancer have been investigated based on the anatomical subsite classification. Accurate subsite classification based on these anatomical landmarks is thus important. We investigated the suitability of the existing endoscopic classification and explored alternative landmarks for esophageal subsite classification. Methods Patients who received endoscopic ultrasonography (and computed tomography scans for surveillance of esophageal cancer treatment or esophageal submucosal tumors were included. Distances between anatomical landmarks, including the inferior cricoid cartilage border, superior border of the sternum, and tracheal bifurcation, were measured using a combination of endoscopic ultrasonography, computed tomography, and other information. Results The mean (standard deviation) distances from the superior incisor dentition to the pharynx–esophagus, cervical–upper thoracic esophagus, and upper–middle thoracic esophagus boundaries were 16.9 (1.7), 21.7 (1.9), and 29.0 (1.9) cm, respectively. However, variances in the differences between the mean and individual distances were large (2.8, 3.4, and 3.7, respectively), mainly because of differences in body height. However, variances in the differences between individual distances and novel endoscopic landmarks, including the lower end of the pyriform sinus and lower end of compression of the left main bronchus, were lower (1.7, 1.2, and 0.6, respectively). Conclusions Existing indicators of esophageal subsite boundaries were not consistent with anatomical boundaries. Modification of the distance from the superior incisor dentition based on average distances from anatomical landmarks or the use of alternative endoscopic landmarks is recommended to provide more suitable anatomical boundaries.

Animals display a body temperature rhythm (BTR). Little is known about the mechanisms by which a rhythmic pattern of BTR is regulated and how body temperature is set at different times of the day. As small ectotherms, Drosophila exhibit a daily temperature preference rhythm (TPR), which generates BTR. Here, we demonstrate dorsal clock networks that play essential roles in TPR. Dorsal neurons 2 (DN2s) are the main clock for TPR. We find that DN2s and posterior DN1s (DN1ps) contact and the extent of contacts increases during the day and that the silencing of DN2s or DN1ps leads to a lower temperature preference. The data suggest that temporal control of the microcircuit from DN2s to DN1ps contributes to TPR regulation. We also identify anterior DN1s (DN1as) as another important clock for TPR. Thus, we show that the DN networks predominantly control TPR and determine both a rhythmic pattern and preferred temperatures.

Objectives: Bone fragility fracture (BFF) is a serious incident in treating rheumatoid arthritis (RA). We hypothesized that pain degree during treatment RA correlated with incident BFF and validated how pain affects incident BFF (inc-BFF). Methods: Postmenopausal RA patients treated for at least 3 years were recruited. The primary endpoint was the development of inc-BFF. Follow-up began with the first bone mineral density measurement (baseline) and continued until the development of the first BFF or termination of the study. Clinical indicators at baseline, including pain score using a visual analog scale (PS-VAS), were analyzed statistically using Cox regression analysis, receiver operation characteristics (ROC), Kaplan-Meier survival curve analysis (K-M), and chi-square test. Results: A total of 239 patients were recruited. Using a multivariate Cox regression analysis, the baseline's PS-VAS and prevalent BFF (pr-BFF) demonstrated significantly higher risk ratios. For ROC, pr-BFF and PS-VAS had significant cutoff index (COI) (positive, 21.0) and an area under-curve of 0.692 (P COI had a 2.24-fold higher hazard ratio than PS-VAS ≤ COI using K-M. When these 2 conditions were combined, patients with pr-BFF-positive and PS-VAS-positive had a sensitivity of 42.3% and a specificity of 88.8% for the inc-BFF. PS-VAS > COI had no statistical significance in the subgroup without pr-BFF, whereas the existence of pr-BFF had a significantly higher risk ratio in the PS-VAS ≤ COI. Conclusions: The PS-VAS during RA treatment is a good indicator for predicting the inc-BFF in postmenopausal RA patients with pr-BFF.

Abstract Background Many studies have examined the association between oral health, care needs, and physical function, but few have focused on the association between oral health and locomotive syndrome (LS). We examined the association between LS and oral-health status, such as the number of teeth and chewing function, in an adult population. Methods The study included 2888 participants who underwent examinations of motor function and oral health. Individuals with LS stage 1 or higher were classified as having LS, while others were classified as not having it. Logistic regression analysis was performed using the presence or absence of LS as the dependent variable and age, sex, smoking status, drinking habit, exercise habit, walking speed, history of stroke, bone density, body mass index, metabolic syndrome, chewing function, and the number of teeth as independent variables to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for each independent variable. Results When the number of teeth and chewing function were included separately in multivariate analyses, the OR for LS was significantly higher for participants with 0–19 teeth than for those with 28 teeth, and for participants with poor chewing function than for those with good function (adjusted ORs, 1.47 [95% CI, 1.01–2.15] and 1.73 [95% CI, 1.37–2.18], respectively). In analyses that included tooth number and chewing function as a combined independent variable, relative to individuals with 28 teeth and good masticatory function, the adjusted ORs were 2.67 (95% CI, 1.57–4.52) for those with 28 teeth and poor chewing function, 1.63 (95% CI, 1.20–2.22) for those with 20–27 teeth and poor chewing function, and 1.83 (95% CI, 1.06–3.18) for those with 0–19 teeth and poor chewing function. Conclusion Having fewer teeth and poor chewing function may be associated with LS. The maintenance of masticatory function may be important to prevent LS in adulthood.

Abstract Background Little is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM). Methods EC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS). Results In total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P

Abstract Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1–3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1–3 positive nodes, histological grade

Abstract Background Ruptured aneurysm is a serious complication of distal pancreatectomy (DP) or pancreatoduodenectomy (PD) that can be life-threatening if not treated promptly. This study aimed to examine the efficacy of a Viabahn stent graft for stopping bleeding after pancreatectomy. Methods Between April 2016 and June 2022, we performed 245 pancreatectomies in our institution. Six patients experienced postoperative bleeding and underwent endovascular treatment. Results All six cases of bleeding occurred post-PD (3.7%). The bleeding was from gastroduodenal artery (GDA) pseudoaneurysms in three patients, and Viabahn stent grafts were inserted. All three patients did not show liver function abnormalities or hepatic blood flow disorders. One patient with a Viabahn stent graft experienced rebleeding, which required further management to obtain hemostasis. Of the six cases in which there was hemorrhage, one case of bleeding from the native hepatic artery could not be managed. Conclusions Using the Viabahn stent graft is an effective treatment option for postoperative bleeding from GDA pseudoaneurysms following PD. In most cases, using this device resulted in successful hemostasis, without observed abnormalities in hepatic function or blood flow.

This study describes Gnorimosphaeroma rivulare sp. nov. from a stream on Chichi-jima Island, Ogasawara Islands, Japan. This is the second freshwater species of Gnorimosphaeroma and the third Sphaeromatidae from oceanic islands. Gnorimosphaeroma rivulare sp. nov. is morphologically similar to G. boninense Nunomura, 2006, G. naktongense Kwon & Kim, 1987 and G. saijoense Nunomura, 2013. However, G. rivulare sp. nov. differs from these species in various morphological features, such as the shape of pleotelson and pereopod 2, relative length of antennule peduncular articles and pleopod 3 rami, number of setae on maxillula and maxilliped, and setation on pereopod 3. Phylogenetic analyses revealed that G. akanense is sister to G. saijoense, and together they are sister to G. hokurikuense. This three taxa clade is sister to G. rivulare sp. nov. with G. iriei basal to them all. Our analysis concludes that G. boninense from Haha-jima Island, Ogasawara Islands is only distantly related to G. rivulare and may represent an independent colonization event.

Abstract Background Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103+CD8+ tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (TRM), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and TRM. Methods The relationships between TRM infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, TRM infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. Results TRM-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than TRM-poor patients (6 vs 2 patients). TRM infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but TRM may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with TRM but did not impact prognosis. Conclusions TRM-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that TRM are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.