DOCK2 is involved in the host genetics and biology of severe COVID-19.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Prognostic value of initial serum sodium level in predicting disease severity in patients with COVID-19: A multicenter retrospective study.

INTRODUCTION: Early prediction of coronavirus disease (COVID-19) severity is crucial. Hyponatremia has been linked to poor outcomes in hospitalized COVID-19 patients, but its association with mild cases is unclear. This study aimed to investigate whether initial serum sodium level is a risk factor for COVID-19 severity in patients with mild-to-moderate disease. METHODS: A multicenter retrospective cohort study was conducted in 10 hospitals in Fukui City, Japan, from July 1, 2020, to October 31, 2021. The study included 1055 adult patients with asymptomatic, mild, or moderate COVID-19 confirmed by a positive RT-PCR test. The primary outcome was the need for oxygen therapy after hospitalization, and the secondary outcome was the composite of in-hospital death and critical care interventions. The association between initial serum sodium level (at the emergency department or on admission) and outcomes was examined, adjusting for age, sex, hypertension, and pneumonia presence. RESULTS: Of the 1267 patients diagnosed with COVID-19 during the study period, 1055 were eligible (median age: 45 years; 54 % male). Hyponatremia was observed in 5.2 % of patients upon admission. A lower initial serum sodium level was associated with an increased risk of the need for oxygen therapy after hospitalization (adjusted odds ratio [OR] per 1 mmol/L lower, 1.12 [95 % confidence interval {CI}, 1.05-1.19]) and the composite of critical care and in-hospital death (adjusted OR per 1 mmol/L lower, 1.09 [95 % CI, 0.99-1.20]). CONCLUSIONS: Among patients with mild COVID-19, lower initial serum sodium level was a risk factor for COVID-19 progression.

The frequency of mutations in advanced thyroid cancer in Japan: a single-center study.

We analyzed the outcomes of genetic testing to study the frequency of mutations in advanced thyroid cancer in Japan. Patients (n = 96) with unresectable or metastatic thyroid carcinoma were included for retrospective chart review. Results of gene panel testing, which was performed between May 2020 and April 2023, were analyzed. The median age of the patients was 73.5 years (range, 17-88); 59 were women, and 39 were men. Overall, 17 patients had anaplastic thyroid carcinoma (ATC), 68 had papillary thyroid carcinoma (PTC), 7 had follicular thyroid carcinoma, and 6 had poorly differentiated thyroid carcinoma (PDTC). Of the 81 patients with differentiated thyroid carcinoma (DTC) and PDTC, 88.9% were radioactive iodine-refractory, and 32.7% of all cases had previously been treated with multiple kinase inhibitors. Of ATC cases, 52.9% had BRAF mutations, and 5.9% had RET fusion. Of PTC cases, 83.1% had BRAF mutations, 9.2% had RET fusion, and 1.5% had NTRK fusion. One case each of ATC and PTC had a tumor mutation burden of ≥10. ATC cases had a significantly higher prevalence of TP53 alterations than the other cases (82.3% vs. 11.8%), whereas the frequencies of TERT promoter mutations were 88.2% in ATC cases and 64.7% in the other cases, albeit without a significant difference. In conclusion, 58.8% of ATC, 93.8% of PTC, and 42.9% of PDTC had genetic alterations linked to therapeutic agents. Active gene panel testing is required to increase treatment options.

Effect of digital game intervention on cognitive functions in older adults: a multiple baseline single case experimental design study.

BACKGROUND: Residents in nursing homes are prone to cognitive decline affecting memory, visuospatial cognition, and executive functions. Cognitive decline can lead to dementia, necessitating prioritized intervention. METHODS: The current study aimed to investigate whether an intervention using a digital game was effective for preserving and improving the cognitive function of residents in nursing homes. An intervention study was conducted using a single-case AB design with multiple baselines. The participants in the study were five older adults aged 65 and over who do not play digital games regularly. The study ran for 15 weeks, including a baseline (phase A) and an intervention phase (phase B). Phase A had five baselines (5 to 9 weeks) with random participant assignment. In phase B, participants engaged in a digital game (Space Invaders) individually. Cognitive function was assessed as the outcome, measured using the Brain Assessment (performed on a tablet through the Internet) at 16 measurement points. Four of five participants (two female and two male) were included in the analysis, using visual inspection and Bayesian statistics with multi-level modeling. RESULTS: Visual inspection of the graphs revealed cognitive function score improvements after the intervention for most layers in terms of memory of numbers, memory of words, mental rotation test (visuospatial ability), and total scores in the Brain Assessment. These effects were also significant in the analysis by multi-level modeling. CONCLUSIONS: The results suggest that the use of digital games may be effective for preserving and improving cognitive function among residents of nursing home. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000048677; public title: Effect of a Digital Game Intervention for Cognitive Functions in Older People; registration date: August 30, 2022).

ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.

Thymic MALT lymphoma associated with Sjögren's syndrome with postoperative cardiac tamponade and acute pleuritis: a case report.

BACKGROUND: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren's syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. CASE PRESENTATION: A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. CONCLUSIONS: Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications.

The role of fat indices as factors leading to sarcopenia in older adults residing in underpopulated areas.

Simplifying the diagnostic criteria for sarcopenia is key to establishing effective interventions. Herein, we aimed to clarify novel diagnostic factors. We calculated novel fat indices [total fat index (TFI) and limb fat index (LFI)] and clarified factors leading to pre-sarcopenia and sarcopenia in 594 enrolled older adults. Physical measurements [height, weight, body mass index (BMI), gait speed, grip strength, and skeletal muscle mass] were performed. Sarcopenia was determined using established diagnostic criteria (pre-sarcopenia, n = 102; sarcopenia, n = 42). Age was associated with sarcopenia status. BMI, TFI, and LFI were lower in patients with pre-sarcopenia and sarcopenia. Logistic regression analysis showed the following odds ratios (ORs) for pre-sarcopenia: BMI [OR: 0.787, 95% confidence interval (CI): 0.7-0.885], LFI (OR: 0.589, 95% CI: 0.402-0.863), and age (OR: 1.06, 95% CI: 1.02-1.1). ORs for sarcopenia (vs pre-sarcopenia) were as follows: LFI (OR: 50.6, 95% CI: 10.2-250.0), age (OR: 1.1, 95% CI: 1.0-1.2), and BMI (OR: 0.418, 95% CI: 0.28-0.608). Our findings contribute to informing medical guidelines.

Can bone mass measured via bioelectrical impedance analysis be used to diagnose sarcopenia?

The simplification of diagnostic criteria is critical to promoting interventions for sarcopenia. This study aimed to evaluate the relationship between sarcopenia and bone mass [measured by bioelectrical impedance analysis (BIA)], as well as to identify new indicators associated with this disease. Basic interviews and measurement of physical function were performed on 474 community-dwelling older adults (aged 77.1 ±â€…7.6 years), including older adult patients with sarcopenia, in Wakasa Town, Fukui Prefecture. The findings led to 363, 71, and 40 participants being classified as 'normal', 'pre-sarcopenia', and 'having sarcopenia', respectively. An Ordinal Logistic Regression Analysis showed that age, bone mass phase angle (lower limb), Fat-free Mass Index, and leg muscle score were aggravating factors for sarcopenia in both men and women. A receiver operating characteristic analysis of bone mass and sarcopenia status showed that the area under the curve and cut-off value, as well as its sensitivity and specificity, in men were 0.915 [95% confidence interval (CI): 0.853-0.977], 2.2 kg, 81%, and 87%, respectively, and 0.913 (95% CI: 0.858-0.968), 1.6 kg, 91%, and 88%, respectively, in women. This study revealed that the BIA method of measuring bone mass has excellent accuracy in detecting sarcopenia in both males and females.

A multimodal non-pharmacological intervention for persons with dementia in nursing homes: a multicentre randomised controlled trial.

BACKGROUND: Persons with dementia in nursing homes often experience cognitive decline (e.g., memory and visuospatial/construction problems), behavioural and psychological symptoms of dementia (BPSD), and impaired activities of daily living. Therefore, comprehensive interventions for this population are needed. We assessed whether a multimodal non-pharmacological intervention improved cognitive functions, BPSD, and activities of daily living in persons with dementia in nursing homes. METHODS: This was a multicentre randomised controlled trial. Participants were 40 persons with dementia (38 women) living in four nursing homes (intervention group = 21; control group = 19). The intervention was conducted for 8 weeks, followed by an 8-week follow-up. Outcome measures were scores on the Japanese version of the Neurobehavioral Cognitive Status Examination Five and the ABC Dementia Scale. In the analysis, parameters were estimated using Bayesian statistics and a mixed-effects linear regression model for the change in each outcome measure. RESULTS: There were significant between-group differences in changes in ABC Dementia Scale BPSD scores (8-week: posteriori median = 1.66, 95% Bayesian confidence interval 0.36-3.01; 16-week: median = 2.37, 95% Bayesian confidence interval 0.05-4.65). There was also a significant between-group difference in changes in Neurobehavioral Cognitive Status Examination Five constructional ability scores (16-week: median = 0.93, 95% Bayesian confidence interval 0.35-1.50). CONCLUSION: This intervention may have a maintenance and improvement effect on BPSD in persons with dementia in nursing homes, and a sustained effect on constructional ability post-intervention. The intervention may be useful and easy to apply in practice.

[The Long-term Results of Valve Sparing Aortic Root Replacement and Aortic Cusp Repair for Aortic Regurgitation].

We reported our long-term results of valve sparing aortic root replacement (VSRR) and aortic cusp repair for aortic regurgitation( AR) were satisfactory. Three hundred twenty-seven patients had VSRR, and 164 patients of them had aortic cusp repair for prolapse. At 10 years after the operation, the overall survival was 91.5%, the freedom from more than mild recurrent AR was 71.2%, and the freedom from aortic valve reoperation was 82.0%. As for the aortic cusp repair technique, there was no significant difference in the mid-term results of the recurrent AR and reoperation for the aortic valve between the central plication technique and the resuspension technique (two layers of continuous mattress sutures placed the entire length of the free margin of the aortic cusp). The resuspension technique might be useful for repairing the aortic cusp with prolapse. Furthermore, among the patients with acute aortic dissection, connective tissue disease, or aortitis, the long-term results of VSRR and aortic cusp repair were also satisfactory.

[Giant Left Ventricular Aneurysm After Double Patch Closure of Ventricular Septal Perforation Through Right Ventriculotomy].

A 66-year-old man. He had myocardial infarction due to occlusion of the left anterior descending branch, which was subsequently complicated by ventricular septal perforation. Ventricular septal perforation was repaired through right ventricle incision, applying double patches for closure, and injecting glue between the patches. The early postoperative course was good, but the infarcted left ventricular anterior wall remained because of the right ventriculotomy approach. A left ventricular aneurysm was demonstrated on postoperative follow-up echocardiography, which gradually enlarged to become giant. Since symptoms of heart failure such as respiratory distress appeared, left ventriculoplasty was performed 29 months after the perforation of the initial surgery. Since thinned left ventricular wall remains following right ventriculotomy approach, risk of postoperative left ventricular aneurysm should be taken into account.

Histological findings of thyroid cancer after lenvatinib therapy.

AIMS: Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy. METHODS AND RESULTS: We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues. CONCLUSIONS: Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.

Shared decision-making practices and patient values in pharmacist outpatient care for rheumatic disease: A multiple correspondence analysis.

Purpose: To investigate the value-to-value relationships, relationship between values and patient background, continuation rate of treatment after shared decision-making (SDM), and disease status in order to clarify the values involved in drug therapy decisions for patients with rheumatic disease. Methods: We investigated patient values (efficacy of drug therapy [effectiveness], safety, economics, daily life, and other) and the continuance rate and disease status of treatment after 6 months in 94 patients with rheumatic disease aged ≥18 years who made decisions with pharmacists and physicians in the pharmacy outpatient clinic between September 2019 and April 2021. Multiple correspondence and K-means cluster analyses were performed to show the relationship between values and basic patient information. Results: Among the selected patients, 87% and 47% selected effectiveness for multiple selections and single selection, respectively. Effectiveness was at the center of the graph; three clusters containing other values were placed around it. History of allergy or side effects caused by biologics or Janus kinase inhibitors were in the safety cluster. The non-usage history of biologics or Janus kinase inhibitors was in the economic cluster. Conclusion: Effectiveness was the most important factor for patients with rheumatic disease; the values that patients consider important may shift from effectiveness to other values based on each patient's subjective experience with the treatment and/or the stage of life in which they were treated. It is important to positively link patient values and information about the treatment plan in shared decision-making while establishing rapport with the patient.

Frequency of subclinical interstitial lung disease in COVID-19 autopsy cases: potential risk factors of severe pneumonia.

Risk factors of severe coronavirus disease 2019 (COVID-19) have been previously reported; however, histological risk factors have not been defined thus far. The aim of this study was to clarify subclinical hidden interstitial lung disease (ILD) as a risk factor of severe pneumonia associated with COVID-19. We carefully examined autopsied lungs and chest computed tomography scanning (CT) images from patients with COVID-19 for interstitial lesions and then analyzed their relationship with disease severity. Among the autopsy series, subclinical ILD was found in 13/27 cases (48%) in the COVID-19 group, and in contrast, 8/65 (12%) in the control autopsy group (p = 0.0006; Fisher's exact test). We reviewed CT images from the COVID-19 autopsy cases and verified that subclinical ILD was histologically detectable in the CT images. Then, we retrospectively examined CT images from another series of COVID-19 cases in the Yokohama, Japan area between February-August 2020 for interstitial lesions and analyzed the relationship to the severity of COVID-19 pneumonia. Interstitial lesion was more frequently found in the group with the moderate II/severe disease than in the moderate I/mild disease (severity was evaluated according to the COVID-19 severity classification system of the Ministry of Health, Labor, and Welfare [Japan]) (moderate II/severe, 11/15, 73.3% versus moderate I/mild, 108/245, 44.1%; Fisher exact test, p = 0.0333). In conclusion, it was suggested that subclinical ILD could be an important risk factor for severe COVID-19 pneumonia. A benefit of these findings could be the development of a risk assessment system using high resolution CT images for fatal COVID-19 pneumonia.

Two cases of acute pulmonary artery embolism triggered by fresh and chronic mixed-vein thrombosis with a "Blowfish sign".

Ultrasonography and computed tomography of the lower extremities revealed fresh and chronic mixed-vein thrombosis (FCMVTs) presenting the "Blowfish sign," accompanied by pulmonary embolism. FCMVTs presenting the "Blowfish sign" may increase the risk of fatal pulmonary embolism, and its detection by ultrasonography is important for preventing pulmonary embolism.

Equivalence of the top-down manoeuvre and bottom-up manoeuvre in speed and accuracy of identifying the cricothyroid membrane: a prospective randomised cross-over study.

BACKGROUND: Accurate identification of the cricothyroid membrane is crucial for successful cricothyrotomy; however, a manoeuvre that helps identify it both accurately and quickly remains unclear. The effectiveness of the so-called 'bottom-up manoeuvre' has never been investigated. This study aimed to examine whether the bottom-up manoeuvre is as rapid and accurate as the conventional 'top-down manoeuvre' at identifying the cricothyroid membrane. METHODS: This study was a prospective randomised cross-over trial conducted at an academic medical centre between 2018 and 2019. Fifth-year medical students participated. The students were trained in the use of either the top-down manoeuvre or the bottom-up manoeuvre first. Each student subsequently performed the technique once on a volunteer. The students were then taught and practiced the other manoeuvre as well. The accuracy of cricothyroid membrane identification and the time taken by successful participants only were measured and compared between the manoeuvres using equivalence tests with two one-sided tests. RESULTS: A total of 102 medical students participated in this study and there was no missing data. The accuracy of identification and time required for success were similar between the top-down manoeuvre and the bottom-up manoeuvre (65.7% vs. 70.6%, taking 13.8 s [interquartile range (IQR): 9.4-17.5] vs. 15.5 s [IQR: 11.5-19.9], respectively). The success rate was statistically equivalent (rate difference, 4.9%; 90% confidence interval [CI], -5.8 to 15.6; equivalence margin, -20.0 to 20.0). The time required for success was also statistically equivalent (median difference, 1.7 s; 90% CI, -0.2 to 3.3; equivalence margin, -4.0 to 4.0). CONCLUSION: Among students first trained in both manoeuvres for identifying the cricothyroid membrane, the speed and accuracy of identification were similar between those using the bottom-up manoeuvre and those using the top-down manoeuvre.

Anterior cutaneous nerve entrapment syndrome in children.

QUESTION: I frequently see adolescents with recurrent abdominal pain in my family medicine clinic. While the diagnosis frequently is a benign condition such as constipation, I recently heard that after 2 years of recurrent pain, an adolescent was diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES). How is this condition diagnosed? What is the recommended treatment? ANSWER: Anterior cutaneous nerve entrapment syndrome, first described almost 100 years ago, is caused by entrapment of the anterior branch of the abdominal cutaneous nerve as it pierces the anterior rectus abdominis muscle fascia. The limited awareness of the condition in North America results in misdiagnosis and delayed diagnosis. Carnett sign-in which pain worsens when using a "hook-shaped" finger to palpate a purposefully tense abdominal wall-helps to confirm if pain originates from the abdominal viscera or from the abdominal wall. Acetaminophen and nonsteroidal anti-inflammatory drugs were not found to be effective, but ultrasound-guided local anesthetic injections seem to be an effective and safe treatment for ACNES, resulting in relief of pain in most adolescents. For those with ACNES and ongoing pain, surgical cutaneous neurectomy by a pediatric surgeon should be considered.

Possible significance of degeneration and decreased expression of progesterone receptor in postmenopausal uterine leiomyoma.

BACKGROUND: The growth of uterine leiomyomas is dependent on the levels of sex steroid hormones, and they usually shrink after menopause. However, there are cases in which leiomyomas continue to grow and/or surgery is required after menopause. In addition to estrogen, progesterone has recently been implicated in leiomyoma enlargement, but its relevance to postmenopausal leiomyoma remains unknown. Therefore, we investigated whether hormone receptor expression is associated with postmenopausal leiomyoma enlargement and characterized pathological findings of postmenopausal leiomyoma, which have not been clarified yet. METHODS: Nine cases that required total hysterectomy for leiomyomas after menopause were examined. Surgeries were conducted because of pelvic pressure, pelvic pain, suspected malignancy, or growing leiomyoma. Six cases of leiomyomas being incidentally found during total hysterectomy for postmenopausal uterine prolapse, and six patients who underwent hysterectomy for leiomyomas before menopause, were examined as controls. We evaluated the expression of estrogen receptor, progesterone receptor B, and progesterone receptor AB by immunohistochemical staining among the cases. We also analyzed the pathological findings of leiomyomas. RESULTS: In postmenopausal leiomyomas, the expression of progesterone receptor was higher than that in the adjacent myometrium. Compared with premenopausal leiomyomas, the expression of progesterone receptor decreased. Postmenopausal leiomyomas that required surgery did not show elevated sex steroid hormone receptor expression, compared with the leiomyomas that did not require surgery. The degeneration frequency of leiomyomas was 92% in the group that underwent surgery for postmenopausal leiomyomas, 65% in the group that underwent surgery for reasons other than the presence of leiomyomas after menopause, and 47% in the group operated for leiomyomas before menopause. CONCLUSIONS: These results suggest that sex steroid hormones are unlikely to be associated with the growth of leiomyomas after menopause. Since leiomyoma degeneration with increased extracellular matrix is likely to occur in postmenopausal women, the degeneration of leiomyomas may be the main mechanism for the growth of postmenopausal leiomyomas.

Effect of a multimodal non-pharmacological intervention on older people with dementia: a single-case experimental design study.

BACKGROUND: Older people with dementia (PWD) in nursing homes (NHs) tend to have decreased cognitive function, which may cause behavioral and psychological symptoms of dementia (BPSDs) and hinder activities of daily living (ADLs). Therefore, taking measures against the cognitive decline of PWD in NH and, in turn, the decline of BPSDs and ADLs is crucial. The purpose of this study was to test whether a multimodal non-pharmacological intervention (MNPI) is effective in maintaining and improving global cognitive function, BPSDs, and ADLs in PWD in NHs. METHODS: An intervention study using a single-case AB design was conducted in three subjects in NHs. During the non-intervention phase, participants underwent follow-up assessments, and during the intervention phase, they participated in an MNPI. The ABC Dementia Scale (which concurrently assesses ADLs ["A"], BPSDs ["B"], and cognitive function ["C"]) was used for the assessment. RESULTS: One of the three patients showed improvement in dementia severity, global cognitive function, ADLs, and BPSDs. However, the other two participants showed no improvement following the MNPI, although the possibility of a maintenance effect remained. CONCLUSION: Although there is room for improvement of the MNPI, it may be effective in maintaining and improving cognitive function, ADLs, and BPSD, in PWD in NHs. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ , No. UMIN000045858, registration date: November 1, 2021).

Quantitative differentiation of tendon and ligament using magnetic resonance imaging ultrashort echo time T2* mapping of normal knee joint.

BACKGROUND: Ligaments and tendons are difficult to differentiate on conventional magnetic resonance imaging (MRI). Ligaments and tendons are different histologically, and tendon graft ligamentization is known to occur after anterior cruciate ligament (ACL) reconstruction. PURPOSE: To quantify and differentiate the ultrashort echo time T2* (UTE-T2*) values of normal knee ligaments and tendons using a 1.5-T MRI scanner. MATERIAL AND METHODS: The right knees of 12 healthy volunteers (6 men, 6 women; mean age = 30.8 ± 9.6 years) were scanned using a UTE-T2* sequence and the UTE-T2* values of the proximal, middle, and distal portions of the ACL, posterior cruciate ligament (PCL), and patellar tendon (PT) were evaluated. Two doctors manually drew the regions of interest four times and intra- and inter-observer reliability were evaluated by intraclass correlation coefficients. RESULTS: The UTE-T2* values of ACL at the proximal, middle, distal, and mean were 12.0 ± 2.3, 11.3 ± 2.3, 12.3 ± 2.6, and 11.9 ± 2.4 ms, respectively. The UTE-T2* values of the PCL at each site were 6.9 ± 1.5, 9.0 ± 1.8, 8.8 ± 2.4, and 8.3 ± 2.1 ms, respectively. The UTE-T2* values of the PT at each site were 7.1 ± 1.7, 4.3 ± 1.7, 4.3 ± 1.8, and 5.2 ± 2.1 ms, respectively. Both intra- and inter-observer reliability showed high agreement rates. There were significant differences among the ACL mean, PCL mean, and PT mean, with a P value <0.01 in all cases. CONCLUSION: This study confirms that UTE-T2* mapping can quantify the ACL, PCL, and PT, and tendons and ligaments can be differentiated using the UTE-T2* values in normal volunteer knee joints.