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Purpose: Loop ileostomy is a common surgical procedure but is associated with complications such as outlet obstruction (OO), parastomal hernia (PH), and high-output stoma (HOS). This study aimed to identify risk factors for these complications and their causal relationships.Methods: The study included 188 consecutive patients who underwent loop ileostomy between April 2016 and September 2021. Clinical factors and postoperative stoma-related complications (OO, HOS, and PH) were analyzed retrospectively. Stoma-related factors were evaluated by computed tomography (CT). The incidence, clinical course, and risk factors for the stoma-related complications were investigated.Results: OO was diagnosed in 28 cases (15.7%), PH in 57 (32%), and HOS in 57 (31.8%). A small longitudinal stoma diameter at the rectus abdominis level on CT and a right-sided stoma were significantly associated with OO. Creation of an ileostomy for anastomotic leakage was independently associated with HOS. Higher body weight and a large longitudinal stoma diameter at the rectus abdominis level on CT were significantly associated with PH. There was a significant relationship between occurrence of OO and occurrence of HOS; however, the association of occurrence of OO with that of PH was marginal.Conclusion: This study identified key risk factors for OO, HOS, and PH as complications of loop ileostomy and their causal relationships. Our findings may contribute to prevention and management of complications related to loop ileostomy.

Purpose Elderly people are thought to be more likely than their non-elderly counterparts to experience a decline in activities of daily living (ADL) and quality of life (QOL) due to the onset and treatment of disease. In this study, we investigated whether there was an age-related difference in changes in health-related QOL indices after surgical resection of colorectal cancer. Methods Patients who underwent elective surgery for primary colorectal cancer at our hospital between September 2017 and November 2021 were enrolled. Changes in QOL after surgery were evaluated after dividing the study population into a non-elderly (NE) group (younger than 75 years) and an elderly (E) group. A self-administered Short-Form 36-Item Health Survey was used as an index of QOL. The subscale and component summary scores before and 6 months after surgery were compared. Results There was no significant difference in clinical or demographic characteristics between the NE group (n=166) and the E group (n=47). There was also no significant difference in worsening of indices of physical function after surgery in either group. In the NE group, there were significant decreases in role physical and role component summary scores and significant increases in general health, mental health, and mental component summary scores. In the E group, there were no significant changes in the subscale or component summary scores after surgery. Conclusion There was no significant difference in QOL after surgery for colorectal cancer between elderly patients and non-elderly patients. Surgical resection for colorectal cancer should be considered even for elderly patients, while considering possible risk factors for worsening ADL and QOL.

Background Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications. Methods The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected. Results The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring. Conclusions Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections.

The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors., IRF5 is a potential target for therapy in systemic lupus erythematosus (SLE). Here the authors show using mouse SLE-like models that genetic or chemical inhibition of IRF5 after SLE onset could be more effective than, or an add on for, currently utilised type I interferon inhibition.

In diabetic pathology, insufficiency in β-cell mass, unable to meet peripheral insulin demand, and functional defects of individual β-cells in production of insulin are often concurrently observed, collectively causing hyperglycemia. Here we show that the phosphorylation of ERK1/2 is significantly decreased in the islets of db/db mice as well as in those of a cohort of subjects with type 2 diabetes. In mice with abrogation of ERK signaling in pancreatic β-cells through deletion of Mek1 and Mek2, glucose intolerance aggravates under high-fat diet–feeding conditions due to insufficient insulin production with lower β-cell proliferation and reduced β-cell mass, while in individual β-cells dampening of the number of insulin exocytosis events is observed, with the molecules involved in insulin exocytosis being less phosphorylated. These data reveal bifunctional roles for MEK/ERK signaling in β-cells for glucose homeostasis, i.e., in regulating β-cell mass as well as in controlling insulin exocytosis in individual β-cells, thus providing not only a novel perspective for the understanding of diabetes pathophysiology but also a potential clue for new drug development for diabetes treatment.

Grammar is often considered as an established convention used by all speakers of a language, while variability should be expected if using language is regarded as meaningful sociocultural as well as cognitive behavior. This paper considers the flexible and fluid nature of grammar and the language user’s knowledge of grammatical variability by examining natural discourse data of one Japanese speaker/writer in four different communicative contexts and examples of expository writing. The study finds that the pairing of meaning/function with a form has a crucial role in determining the use of a (non-) conventional construction in context, as maintained in Construction Grammar. The conventionality and variability (in time and space) of grammar can be elucidated by postulating a constellation of multiple layers of socioculturally mediated meanings/functions of a form, a “construction-based semiotic constellation (CBSC).” Some meanings/functions may acquire exclusive association with a context and become conventionalized or even normative through sociocultural beliefs and endorsement, while others remain malleable. An ideal model of grammar should reflect the flexibility and conventionality of language use and the user’s knowledge. In that spirit, this analysis offers a socioculturally informed illustration of conventionalization and flexibility in grammar.

Cross-cultural contrastive approaches motivate research that questions the universality premise of pragmatic theories by illustrating facts of local linguistic practices from diverse geographical areas. In the spirit of my earlier studies of Japanese (e.g. Matsumoto 1988, 1989), I suggest that contrastive pragmatics can lead the field of pragmatics to addressing variations in linguistic practice that go beyond the geographical diversity of cultures and encompass other types of “atypical” discourse, such as discourse of speakers with varied cognitive conditions including persons with Alzheimer’s. This paper argues for the pragmatics of understanding, i.e. the language users’ and the analysts’ efforts (i) to understand what speakers are trying to convey in verbal interaction and (ii) to understand local pragmatic principles of verbal exchange, and thereby to encourage more inclusive studies of pragmatics.

It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan.The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status.Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85-1.37) or RFS (hazard ratio 1.06; 95% CI 0.87-1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70-1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18-0.56).There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR.

SUMMARYCaloric restriction (CR) is a nutritional intervention that reduces the risk of age-related diseases in numerous species, including humans. CR’s metabolic effects, including decreased fat mass and improved insulin sensitivity, play an important role in its broader health benefits. However, the extent and basis of sex differences in CR’s health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young female mice. Females’ resistance to fat and weight loss was associated with decreased lipolysis, lower systemic energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis compared to males. Positron emission tomography-computed tomography (PET/CT) with18F-fluorodeoxyglucose (18F-FDG) showed that peripheral glucose uptake was comparable between sexes. Instead, the sex differences in glucose homeostasis were associated with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity but higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, thereby stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis to a similar extent in both sexes. Finally, in a cohort of overweight and obese humans CR-induced fat loss was also sex- and age-dependent: younger females (45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR’s metabolic benefits. These findings have important implications for understanding the interplay between diet and health and for maximising the benefits of CR in humans.HIGHLIGHTSCaloric restriction (CR) decreases fat mass and improves glucose homeostasis in young male mice, but young females resist these effects.CR females resist lipolysis, decrease energy expenditure and increase postprandial lipogenesis more than CR males, explaining how females resist fat loss.Sex differences in glucose homeostasis are associated with altered hepatic metabolism and gluconeogenesis, without marked differences in peripheral glucose uptake.CR’s effects on fat loss and glucose homeostasis are comparable in aged male and female mice, implicating oestrogen as the driver of the sexually dimorphic effects in young mice.In humans, females resist CR-induced fat loss in an age-dependent manner, further supporting the role of oestrogen in the sexually dimorphic effects of CR.

The transanal and transperineal endoscopic approaches are useful advanced surgical options for removing rectal and anorectal cancers. Intraoperative carbon dioxide (CO2 ) embolisms, however, have been increasingly reported as potentially fatal complications associated with surgery employing these approaches. We report our experience with a CO2 embolism that was detected because of a sudden drop in end-tidal CO2 with decreasing saturation of percutaneous arterial oxygen during total pelvic exenteration using the transperineal endoscopic approach under pneumopelvis/pneumoperitoneum. Transesophageal echocardiography confirmed that it was a CO2 embolus. We reversed the pneumopelvis and pneumoperitoneum, which alleviated the cardiopulmonary problems, and the surgery then proceeded to achieve R0 resection. The patient was discharged without severe complications other than the CO2 embolism.

The incidence and time of onset of acute chemotherapy-induced peripheral neuropathy (ACIPN) caused by oxaliplatin remain unclarified. Hence, we investigated the prevalence, onset time, and location of ACIPN symptoms in patients with colorectal cancer (CRC) receiving oxaliplatin without cold stimulation. The study cohort comprised patients receiving oxaliplatin for CRC at our hospital between April 2017 and August 2018. Patients were instructed not to touch and/or drink cold things and were monitored for ACIPN symptoms in the hospital for 24 h after chemotherapy. ACIPN symptoms that appeared > 24 h after chemotherapy were recorded at the next visit. Symptom appearance time was defined as the duration from the administration of chemotherapy until the appearance of paresthesia classified as grade 1 using the Common Terminology Criteria for Adverse Events. Forty-five patients received chemotherapy, comprising 23 men and 22 women, aged 67 years (29–88 years). The location of ACIPN was the fingers in 55.6% of cases, pharynx in 26.7%, perioral region in 24.4%, and feet in 6.7%. The average duration from oxaliplatin administration to symptom development was 182 min (range 62–443 min) for the fingers, 291 min (176–432 min) for the pharynx, 311 min (127–494 min) for the perioral region, and 297 min (234–355 min) for the feet. Pharyngeal symptoms were more common in patients older than 65 years than in those younger than 65 years. The incidence and time of the onset of ACIPN caused by oxaliplatin varies between the body and regions.

Total pelvic exenteration (TPE) is sometimes required for radical treatment of locally advanced or recurrent gynecologic cancer [1]. However, TPE with a transabdominal approach requires highly advanced techniques in the case of repeated surgery due to the effects of primary surgery and/or chemoradiotherapy, especially when a transabdominal approach is used. Recent technical advances in transanal/transperineal endoscopic surgery have proved beneficial for complicated surgery in the deep pelvis [2]. Here we introduce our surgical procedure for combined laparoscopic and transperineal endoscopic TPE (TpTPE) for pelvic recurrence of cervical cancer. A 42-year-old woman was diagnosed with vaginal stump recurrence of cervical cancer involving the rectum, bladder, and ureters following hysterectomy and pelvic lymph node dissection as primary surgery and chemotherapy/chemoradiotherapy for previous recurrences. We decided to perform TpTPE with a combined laparoscopic approach. The GelPOINT advanced access platform was fixed through a perineal skin incision around the tightly closed anus, external urethral orifice, and vagina. With sufficient pneumopelvic pressure (12 mmHg), TpTPE was performed under a good surgical view without any effect of the primary surgery. A ureterostomy and sigmoid colostomy were created and a right gracilis muscle flap was used to reconstruct the pelvic defect. The total operative time and estimated blood loss were 887 minutes and 497 mL, respectively. Histopathological examination revealed recurrent cervical cancer invading the rectum, bladder, and bilateral ureters with negative surgical margins. The postoperative course was uneventful except for paralytic ileus. The patient was discharged on postoperative day 18. TpTPE is a technically feasible and effective approach for locally advanced pelvic tumors.

Many studies have examined communicative and linguistic strategies helpful to the interactional inclusion of persons living with dementia (PLwD) and the promotion of an age-inclusive society (e.g., Wray, 2020; Stickle, 2020). Building on this existing body of research, our study examines question-answer sequences in conversations (Schegloff & Sacks, 1973) among younger adults and PLwD using discourse analysis methodology to illuminate effective communicative practices for facilitating more inclusive and meaningful interactions between these individuals. Findings from this methodology are complemented by analysis of post-interaction interviews. The data set for this study consists of audio-video recordings of (1) intergenerational conversations around haiku poetry in English between older adults with mild cognitive impairments (MCI) and college students, and (2) post-interaction interviews that assess participants’ feelings about the experience. The data was collected as part of a larger study designed to promote social inclusion of individuals of all ages and cognitive conditions, particularly during the pandemic, via an online intergenerational haiku-making activity. The audio-video recordings were transcribed for qualitative analysis. Findings from the analysis demonstrate the effectiveness of open and emotion-focused questions (Matsumoto, Liao, Xue, 2020; Worley, 2005) in encouraging persons with MCI to express themselves on their own terms and promoting their interactional participation. By presenting the benefits of this type of question and related linguistic strategies, this study hopes to provide a basis for developing more inclusive communicative environments for people of all ages and PLwD to help improve quality of life and well-being across all stages of life.

Animals suffering from uncontrollable stress sometimes show low effort to escape stress (learned helplessness). Changes in serotonin (5-hydroxytryptamine) signalling are thought to underlie this behaviour. Although the release of 5-hydroxytryptamine is triggered by the action potential firing of dorsal raphe nuclei 5-hydroxytryptamine neurons, the electrophysiological changes induced by uncontrollable stress are largely unclear. Herein, we examined electrophysiological differences among 5-hydroxytryptamine neurons in naïve rats, learned helplessness rats and rats resistant to inescapable stress (non-learned helplessness). Five-week-old male Sprague Dawley rats were exposed to inescapable foot shocks. After an avoidance test session, rats were classified as learned helplessness or non-learned helplessness. Activity-dependent 5-hydroxytryptamine release induced by the administration of high-potassium solution was slower in free-moving learned helplessness rats. Subthreshold electrophysiological properties of 5-hydroxytryptamine neurons were identical among the three rat groups, but the depolarization-induced spike firing was significantly attenuated in learned helplessness rats. To clarify the underlying mechanisms, potassium (K+) channels regulating the spike firing were initially examined using naïve rats. K+ channels sensitive to 500 μM tetraethylammonium caused rapid repolarization of the action potential and the small conductance calcium-activated K+ channels produced afterhyperpolarization. Additionally, dendrotoxin-I, a blocker of Kv1.1 (encoded by Kcna1), Kv1.2 (encoded by Kcna2) and Kv1.6 (encoded by Kcna6) voltage-dependent K+ channels, weakly enhanced the spike firing frequency during depolarizing current injections without changes in individual spike waveforms in naïve rats. We found that dendrotoxin-I significantly enhanced the spike firing of 5-hydroxytryptamine neurons in learned helplessness rats. Consequently, the difference in spike firing among the three rat groups was abolished in the presence of dendrotoxin-I. These results suggest that the upregulation of dendrotoxin-I-sensitive Kv1 channels underlies the firing attenuation of 5-hydroxytryptamine neurons in learned helplessness rats. We also found that the antidepressant ketamine facilitated the spike firing of 5-hydroxytryptamine neurons and abolished the firing difference between learned helplessness and non-learned helplessness by suppressing dendrotoxin-I-sensitive Kv1 channels. The dendrotoxin-I-sensitive Kv1 channel may be a potential target for developing drugs to control activity of 5-hydroxytryptamine neurons., Hashimoto et al. reported electrophysiological changes induced by learned helplessness in dorsal raphe serotonin neurons. The depolarization-induced spike firing was attenuated in rats showing learned helplessness. The firing attenuation was caused by upregulation of dendrotoxin-I-sensitive Kv1 channels. The firing attenuation was reversed by ketamine., Graphical Abstract Graphical Abstract

Accurate preoperative T staging is important when determining the treatment strategy for advanced colorectal cancer. We have previously reported the usefulness of preoperative T staging based on the spatial relationship of tumors and “bordering vessels” by computed tomography colonography (CTC) with multiplanar reconstruction (MPR). The aims of this study were to evaluate the external validity of this method and to determine whether there is a difference in the accuracy of T staging between the mesenteric and antimesenteric sides. The study subjects were 110 patients with colorectal cancer who underwent preoperative CTC and surgical resection from June 2016 to March 2018. Preoperative T stage was determined by CTC based on the relationship between the tumor and the bordering vessels and compared with the pathological T stage. The influence of tumor location, namely, whether the tumor was on the antimesenteric or mesenteric side, on preoperative T staging was assessed in 78 patients with colorectal cancer. Sensitivity, specificity, accuracy, positive, and negative predictive values were respectively, 65%, 91%, 83%, 76%, and 85% for T2 (n = 34); 76%, 82%, 81%, 50%, and 94% for T3 (n = 23); and 77%, 93%, 87%, 86%, and 88% for T4a disease (n = 39). Overall right answer rate was 83.3% (15/18) for the mesenteric side and 65% (39/60) for the antimesenteric side (n = 0.14). Diagnostic criteria based on the bordering vessels seen on CTC images with MPR are useful for T staging of colorectal cancer. However, the accuracy differs between the antimesenteric and mesenteric sides.

Transanal minimally invasive surgery is a combination of single-port surgery and transanal surgery and was initially developed as a treatment for rectal tumors. Recently, this approach has also been used for more advanced or extended pelvic surgery. We present a surgical video of combined laparoscopic and transperineal endoscopic total pelvic exenteration performed in a male patient with recurrent rectal cancer and discuss the pros and cons of this approach. The operating time was 775 min and the operative blood loss was 485 ml. The pathology was recurrent adenocarcinoma invading the prostate and urethra with negative surgical margins. The postoperative course was uneventful except for a urinary tract infection that was treated with antibiotics. The transanal/perineal endoscopic approach may have some benefits for extended pelvic surgery for recurrent rectal cancer.

BACKGROUND C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP

The patient was a 66-year-old woman. She underwent central venous port insertion as part of postoperative adjuvant chemotherapy for sigmoid colon cancer. At the beginning of the 2 cycle, she experienced discomfort in the neck, and computed tomography was performed. As a result, catheter deviation and a thrombus in the internal jugular vein were observed. It was considered that breast displacement due to gravity caused the catheter deviation and that the position of the tip of the catheter deviating to immediately above the venous valve caused thrombus formation. We examined the factors that may cause catheter deviation.

During insulin resistance, lipid uptake by the liver is promoted with peroxisome proliferator activated protein (PPAR) γ-upregulation, leading to hepatic steatosis. Insulin, however, does not directly regulate adipogenic gene expression in liver, and the mechanisms for their upregulation in obesity remains unclear. Here, we show that the Irs2locus, a critical regulator of insulin actions, encodes an antisense transcript ASIrs2, whose expression increased in obesity or after refeeding in liver, reciprocally to that of Irs2. ASIrs2 regulates hepatic Pparg-expression, and its suppression ameliorates steatosis in obese mice. The human orthologue AL162497.1 shows similar genomic organization like ASIrs2, whose expression being correlated with hepatic PPARG and severity of NASH. We also identified HARS2 as a potential binding protein for ASIrs2, functioning as a regulator of Pparg. Collectively, our data revealed a functional duality of Irs2 gene locus, where reciprocal changes of Irs2 and ASIrs2 in obesity cause insulin resistance and steatosis.