Somatic mutations in tumor-infiltrating lymphocytes impact on antitumor immunity.

Immune checkpoint inhibitors (ICIs) exert clinical efficacy against various types of cancers by reinvigorating exhausted CD8+ T cells that can expand and directly attack cancer cells (cancer-specific T cells) among tumor-infiltrating lymphocytes (TILs). Although some reports have identified somatic mutations in TILs, their effect on antitumor immunity remains unclear. In this study, we successfully established 18 cancer-specific T cell clones, which have an exhaustion phenotype, from the TILs of four patients with melanoma. We conducted whole-genome sequencing for these T cell clones and identified various somatic mutations in them with high clonality. Among the somatic mutations, an SH2D2A loss-of-function frameshift mutation and TNFAIP3 deletion could activate T cell effector functions in vitro. Furthermore, we generated CD8+ T cell-specific Tnfaip3 knockout mice and showed that Tnfaip3 function loss in CD8+ T cell increased antitumor immunity, leading to remarkable response to PD-1 blockade in vivo. In addition, we analyzed bulk CD3+ T cells from TILs in additional 12 patients and identified an SH2D2A mutation in one patient through amplicon sequencing. These findings suggest that somatic mutations in TILs can affect antitumor immunity and suggest unique biomarkers and therapeutic targets.

Menstrual Status Is Associated with the Prevalence of Irritable Bowel Syndrome in a Japanese Young Population: A Cross-Sectional Study.

INTRODUCTION: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. METHODS: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. RESULTS: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. CONCLUSION: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.

Integration of anatomy and physiology into nursing practice as perceived by undergraduate students and registered nurses: a scoping review.

OBJECTIVE: The current study aimed to determine perceptions of registered and student nurses regarding the integration of anatomy and physiology into nursing practice. METHODS: This scoping review was conducted following the checklist provided in the Reporting Items for Systematic reviews and Meta-Analysis extension for scoping reviews. Articles published in PubMed, ERIC, and CINAL from January 1, 2002 to September 30, 2022 were included. RESULTS: A literature review of 20 articles that matched the indicative criteria revealed that both undergraduate student and registered nurses recognized knowledge of anatomy and physiology as important to nursing practice. Student nurses recognized that such knowledge is related to understanding patient pathophysiology, patient observation, treatment selection, and patient safety and forms the basis for nursing practice. Registered nurses who were confident in their knowledge of anatomy and physiology also reported that they were able to explain the rationale for their nursing practice. They also reported that this knowledge is necessary for communication with multiple professions, which promotes patient/family trust in nurses and is the basis for building trusting relationships with patients and their families. CONCLUSIONS: Although undergraduate student and registered nurses recognized the importance of learning anatomy and physiology, the integration of anatomy and physiology into nursing practice was not the same for all student and registered nurses. This suggests the need to investigate the overall perceptions of nurses regarding the integration of anatomy and physiology into nursing practice and for faculty to discuss how to facilitate critical thinking among students.

Association between body mass index and irritable bowel syndrome in the young Japanese population: a cross-sectional study.

PURPOSE: The association between body mass index (BMI) and irritable bowel syndrome (IBS) has been inconsistent in the Asian population. Also, no evidence regarding this issue in the young population exists. The aim of the present study is to investigate the association between BMI and IBS based on the Rome III criteria in young Japanese people. METHODS: This study was a cross-sectional study consisted of 8923 Japanese university students. The definition of IBS was based on the Rome III criteria. BMI was divided into four categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, and overweight was BMI < 18.5 kg/m2, 18.5 ≤ BMI < 25 kg/m2 (reference), and 25 ≤ BMI kg/m2, respectively. Age, sex, drinking, smoking, exercise habit, anemia, and sports injury were selected a priori as potential confounding factors. RESULTS: The prevalence of IBS was 6.5%, with females having a significantly higher prevalence than males (6.0% vs. 7.2%, p = 0.029). In females, being overweight was independently positively associated with IBS after adjustment (adjusted odds ratio [OR]: 1.81 [95% confidence interval (CI): 1.13-2.79]). In contrast, in males, no association between being lean or overweight and IBS was found. CONCLUSIONS: Among the young Japanese population, being overweight might be independently positively associated with prevalence of IBS in females but not in males.

Frequency, Intensity, and Partner of Exercise Habit Is Inversely Associated with Functional Dyspepsia in Young Japanese Population.

BACKGROUND: Functional dyspepsia (FD) has a high prevalence worldwide and reduces patients' quality of life. The etiology of FD is likely multifactorial. Although two studies showed an inverse association between exercise habits and FD, evidence regarding the association between exercise habits and FD remains scarce. AIMS: This study aimed to investigate the association between exercise habits and FD among the young Japanese population, taking the presence or absence of an exercise partner as an additional variable. METHODS: The study subjects consisted of 8923 Japanese university students. The definition of FD was based on the Rome III criteria. Information on exercise frequency, exercise intensity, and exercise partners was obtained from a self-administered questionnaire. RESULTS: The prevalence of FD was 1.9% in this cohort. Low, moderate, and high frequency of exercise was independently inversely associated with FD (adjusted odds ratio [OR] was low: OR 0.69 [95% confidence interval (CI) 0.47-0.997], moderate: OR 0.53 [95% CI 0.34-0.81] and high: OR 0.53 [95% CI 0.30-0.88], p for trend p = 0.002). Moderate and high intensity of exercise was independently inversely associated with FD (moderate: OR 0.56 [95% CI 0.36-0.84] and high: OR 0.49 [95% CI 0.30-0.76], p for trend p = 0.001). Exercise with groups and with friends was independently inversely associated with FD whereas the association between exercising alone and FD was not significant (groups: OR 0.28 [95% CI 0.14-0.50] and friends: OR 0.44 [95% CI 0.24-0.74]). CONCLUSION: Among the young Japanese population, frequency and intensity of exercise may be independently inversely associated with FD. Additionally, exercise with groups and with friends but not by oneself was inversely associated with exercise and FD, respectively.

Positive Association Between Sleep Disturbance and Prevalence of Functional Dyspepsia in Japanese Young People.

BACKGROUND: Evidence regarding the association between sleep disturbance and functional dyspepsia (FD) remains limited in the young population. AIMS: This study aimed to investigate the association between sleep disturbance and FD including subgroups among Japanese young people. METHODS: Study subjects were 8923 university students. FD was defined according to the Rome III criteria. Subjects with FD were further categorized as having postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS). Subjects completed a self-reported questionnaire assessing self-reported sleep duration, sleep disturbance, difficulty falling asleep, deep sleep disorder, nocturnal awakening, early awakening, and daytime sleepiness. RESULTS: The prevalence of FD was 1.9%. After adjustment, all types of sleep disturbances were independently positively associated with FD (total sleep disturbance: OR 4.11 [95% CI: 2.89-5.78], difficulty falling asleep: OR 3.97 [95% CI: 2.53-6.01], deep sleep disorder: OR 4.85 [95% CI: 3.06-7.40], nocturnal awakening: OR 4.35 [95% CI: 1.90-8.67], early awakening: OR 4.50 [95% CI: 1.97-8.97], and daytime sleepiness: OR 2.83 [95% CI: 1.25-5.56]). While nocturnal awakening and daytime sleepiness were not associated with EPS, the other types of sleep disturbance were independently positively associated with EPS and PDS. No association between self-reported sleep duration and FD was found. CONCLUSIONS: Sleep disturbance may be independently positively associated with the prevalence of FD among Japanese young people. Nocturnal awakening and daytime sleepiness were not associated with EPS; the other types of sleep disturbance were independently positively associated with EPS and PDS.

A case of cutaneous variant of intravascular large B-cell lymphoma in which dermoscopy revealed telangiectasias associated with erythematous induration.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal, diffuse, large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumen of small blood vessels, with no lymphadenopathy or masses. Herein, we report a cutaneous variant of IVLBCL that is rare in Asia. A healthy 73-year-old Japanese woman presented to our hospital with painful erythematous indurations and telangiectasia of the lower extremities, which was confirmed on dermoscopy. Physical examination revealed no systemic involvement, and laboratory parameters were within normal ranges. No abnormal fluorodeoxyglucose (FDG) uptake was detected on 18FDG positron emission tomography/computed tomography. Histopathological examination revealed proliferation and dilatation of blood vessels in the subcutis layer, occluded by CD20-positive atypical lymphoid cells. Thus, the patient was diagnosed with a cutaneous variant of IVLBCL without systemic symptoms. In conclusion, it is important to confirm telangiectasia using dermoscopy and perform skin biopsies in patients presenting with sudden-onset erythematous induration.

Multimorbidity of Allergic Diseases Is Associated With Functional Gastrointestinal Disorders in a Young Japanese Population.

Background/Aims: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people. Methods: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. Results: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). Conclusion: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

Exercise habits that include exercise partners and irritable bowel syndrome in a young Japanese population: a cross-sectional study.

OBJECTIVE: Evidence regarding the association between exercise habits and irritable bowel syndrome (IBS) remains scarce in a young population. It is also unknown whether the existence of an exercise partner affects this issue. The purpose of this study was to explore the association between exercise habits that include an exercise partner and IBS in a young Japanese population. METHODS: This study enrolled 8923 Japanese university students and examined exercise frequency and intensity, and exercise partners using self-administered questionnaires. IBS and functional dyspepsia were defined according to the Rome III criteria. RESULTS: The prevalence of IBS in this survey was 6.5%. Moderate frequency exercise was inversely related with IBS [adjusted odds ratio (aOR): 0.65 (95% confidence interval, CI: 0.51-0.83), P for trend = 0.005]. Moderate and high exercise intensities were independently and inversely related with IBS, respectively [aORs were moderate: 0.76 (95% CI: 0.61-0.95) and high: 0.62 (95% CI: 0.48-0.78), P for trend = 0.001]. Exercising with a group or with friends instead of alone was independently inversely related with IBS [aOR with groups: 0.53 (95% CI: 0.40-0.70) and with friends: aOR 0.71 (95% CI: 0.54-0.93)]. After excluding subjects with overlapping IBS and functional dyspepsia, an inverse association between high intensity of exercise or exercise in a group and IBS remained significant. CONCLUSION: The frequency and intensity of exercise may be independently inversely related with IBS in a young Japanese population. Also, exercise with others may be important for preventing IBS.

The Association between Laughter and Functional Dyspepsia in a Young Japanese Population.

The potential health benefits of laughter are recognized in relation to several chronic diseases. However, no study has yet investigated the association between laughter and functional dyspepsia (FD). The purpose of this study was to investigate this issue in a young Japanese population. METHODS: This study was conducted on 8923 Japanese university students. Information on the frequency of laughter and types of laughter-inducing situations, digestive symptoms (Rome III criteria) were obtained through a self-administered, web-based questionnaire. RESULTS: The percentage of respondents who laughed out loud almost every day was 64.3%. On the other hand, 1.8% of the subjects reported that they rarely laughed. No association was found between the total frequency of laughter and FD. Laughing while talking with family and friends almost every day was significantly inversely associated with FD (adjusted odds ratio (OR): 0.47 (95% confidence interval (CI): 0.28-0.81); p for trend was 0.003). On the other hand, laughing while watching TV or videos and laughing while looking at comics or magazines independently showed a positive correlation with FD (TV or videos: adjusted OR, 1-5 times a week: 1.74 (95% CI: 1.16-2.60); comics or magazines: adjusted OR, 1-5 times a week: 1.78 (95% CI: 1.08-2.81)). CONCLUSION: In this young Japanese population, no association between laughter frequency and FD was observed although laughing while talking with friends and family was independently and inversely associated with FD.

Association Between Body Mass Index and Functional Dyspepsia in Young Japanese People.

Background/Aims: Evidence regarding the association between body mass index (BMI) and functional dyspepsia (FD) in the Asian population is limited. Further, no study has evaluated this issue in young people in Asian and Western populations. Thus, we aim to investigate this issue among young Japanese people. Methods: The study subjects comprised of 8923 Japanese university students. BMI was divided into 4 categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, overweight, and obese was BMI < 18.5 kg/m2, 18.5 ≤ BMI < 25 kg/m2 (reference), 25 kg/m2 ≤ BMI < 30 kg/m2, and 30 kg/m2 ≤ BMI, respectively. The definition of FD was based on the Rome III criteria. Results: The prevalence of FD was 1.9% in this cohort. The lowest BMI was independently associated with FD after adjustment (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.46-3.67); P for trend = 0.001). The lowest BMI was independently associated with FD in women but not in men (OR, 2.94; 95% CI, 1.59-5.77; P for trend = 0.001). Leanness was independently associated with FD in total and in women but not in men (total: adjusted OR, 2.01; 95% CI, 1.40-2.86) and women (OR, 2.19; 95% CI, 1.35-3.45). However, interaction analysis showed no significant difference for sex. Conclusions: Among young Japanese people, BMI may be independently inversely associated with FD. Leanness may be an independent associated factor for FD in the young Japanese women.

Association between menstrual pain and functional dyspepsia in a Japanese young population.

BACKGROUND: Functional dyspepsia (FD) is a very common disease worldwide. Dysmenorrhea impairs quality of life among females of reproductive age. Although dysmenorrhea is associated with irritable bowel syndrome (IBS), no study has yet evaluated the association between dysmenorrhea and FD. METHODS: This study's subjects consisted of 4693 female Japanese university students. We defined FD according to the Rome III criteria. Subjects completed a self-reported questionnaire regarding menstrual irregularity, menstrual pain, and medication for menstrual pain. Age, body mass index, drinking, smoking, exercise habit, anemia, and first-year student status were selected as potential confounding factors. RESULTS: The prevalence of FD, epigastric pain syndrome (EPS), and postprandial distress syndrome (PDS) was 2.5%, 0.6%, and 2.1%, respectively. Heavy menstrual pain was independently positively associated with FD and PDS but not EPS (adjusted ORs: FD, 3.18 [95% CI: 1.60-6.89] and PDS, 2.93 [95% CI: 1.56-7.93] for heavy menstrual pain, p for trend = 0.001 and 0.004, respectively). Using medication for menstrual pain often was independently positively associated with FD, EPS, and PDS, respectively, (adjusted ORs: FD, 2.41 [95% CI: 1.50-3.83], EPS, 2.93 [95% CI: 1.04-7.93], PDS, 2.44 [95% CI: 1.46-4.01]). Irregular menstrual cycle was not associated with FD or with subtype of FD. CONCLUSION: Among the young female Japanese population, menstrual pain might be independently positively associated with FD and PDS but not EPS. The use of medication for menstrual pain might be independently positively associated with FD including subtype of FD.

Association Between Eating Behavior, Frequency of Meals, and Functional Dyspepsia in Young Japanese Population.

Background/Aims: Functional dyspepsia (FD) may be a common digestive disease worldwide and reduces the quality of life of patients. However, only a few studies have investigated the association between eating behavior and FD. The purpose of this cross-sectional study is to examine the association between eating behavior and prevalence of FD in a young Japanese cohort. Methods: In this study, we enrolled 8923 Japanese university students. FD is diagnosed based on the Rome III criteria. Eating habits and frequency of meals were investigated using a self-administered questionnaire. Results: The FD subjects had a younger mean age, a lower body mass index, and a lower proportion of men compared to the non-FD subjects. An independent positive association between skipping breakfast and/or lunch and FD was found (adjusted ORs were 1.60 [95% CI, 1.10-2.32] for breakfast and 2.52 [95% CI, 1.04-5.18] for lunch). Skipping dinner, extra meals (snacks) or midnight snacks was not associated with FD. The prevalence of FD in subjects eating 1, 2, and 3 meals per day was 4.8%, 2.2%, and 1.7%, respectively. The frequency of meals was independently inversely associated with prevalence of FD (adjusted ORs were 1 per day: 2.72 [95% CI, 1.19-5.42], and 2 per day: 1.69 [95% CI, 1.16-2.43], P for trend = 0.001). Conclusions: In the young Japanese people, the frequency of meals may be independently inversely associated with prevalence of FD. In particular, skipping breakfast and/or lunch was associated with the prevalence of FD.

[Education of physiology in nursing school: common issues and measures with pharmacology].

Anatomy, physiology or pharmacology is the important subject in nursing education. Nursing education is established in a law since 1951. Although the law is revised many times according to social situation, the subjects like physiology have been positioned as a basic specialized subject in the law now. Physiology is educated at 1st grade in most nursing school. However, there are some problems in educating physiology. First, academic ability in nursing students tend to decline recently. For example, there are some students who cannot solve simple arithmetic. They cannot calculate how much volume (mL) they have to aspirate injection solution to the syringe, when a doctor orders an injection medicine. Thus, there are increasing number of students who are not good at calculation. Second, they do not learn the technical term exactly. There are many names of pharmaceutical drug they must learn in pharmacology, some of which have similar names of pharmaceutical drug. If students do not learn them exactly, there is the possibility of causing a medical accident. Third, students learn something or an events from restricted one side. Therefore, they cannot answer the question they are asked from a different point of view. Furthermore, student cannot relate the knowledge they have learned with other knowledge. It seems that it must be important to have students understand how to utilize the knowledge in physiology or pharmacology in nursing practice at an early stage.

Effects of footbathing on autonomic nerve and immune function.

The purpose of this study was to investigate the effects of footbathing on autonomic nerve and immune function. Eleven healthy female volunteers (aged 22-24 years) undertook footbaths at 42 degrees C for 10 min, with or without additional mechanical stimulation (air bubbles and vibration). Autonomic responses were evaluated by electrocardiography and spectral analysis of heart rate variability, and by measurement of blood flow in the sural region. White blood cell (WBC) counts, ratios of lymphocyte subsets, and natural killer (NK) cell cytotoxicity were used as indicators of immune function. Footbathing with mechanical stimulation produced (1) significant changes in the measured autonomic responses, indicating a shift to increased parasympathetic and decreased sympathetic activity and (2) significant increases in WBC count and NK cell cytotoxicity, suggesting an improved immune status. Because these physiological changes are likely to be of benefit to health, our findings support the use of footbathing in nursing practice.

Effect of local application of cold or heat for relief of pricking pain.

The present study was designed to determine the effect of the application of cold or heat on the sensation of pricking pain based on autonomic responses. Electrical stimulation was applied to the antebrachium or brachium of subjects as an artificial pricking pain, and skin blood flow (BF) and skin conductance level (SCL) at the fingertip were measured. Pain sensation was evaluated using the visual analog scale. Pain stimulation produced a significant increase in SCL and a significant decrease in BF at both the antebrachium and brachium. Application of cold to the stimulation site using an ice-water pack reduced BF and SCL responses and pain sensation. Application of heat using a hot water bottle caused a significant increase in pain sensation and enhancement of BF and SCL responses. These results suggest that application of cold promotes relief of pricking pain sensation and suppression of autonomic responses, and that application of heat has no such effect. It is important that nurses ascertain the type of pain or source of pain and take proper measures for its relief.