Phenotype-genotype relationships in Xenopus sox9 crispants provide insights into campomelic dysplasia and vertebrate jaw evolution.

Since CRISPR-based genome editing technology works effectively in the diploid frog Xenopus tropicalis, a growing number of studies have successfully modeled human genetic diseases in this species. However, most of their targets were limited to non-syndromic diseases that exhibit abnormalities in a small fraction of tissues or organs in the body. This is likely because of the complexity of interpreting the phenotypic variations resulting from somatic mosaic mutations generated in the founder animals (crispants). In this study, we attempted to model the syndromic disease campomelic dysplasia (CD) by generating sox9 crispants in X. tropicalis. The resulting crispants failed to form neural crest cells at neurula stages and exhibited various combinations of jaw, gill, ear, heart, and gut defects at tadpole stages, recapitulating part of the syndromic phenotype of CD patients. Genotyping of the crispants with a variety of allelic series of mutations suggested that the heart and gut defects depend primarily on frame-shift mutations expected to be null, whereas the jaw, gill, and ear defects could be induced not only by such mutations but also by in-frame deletion mutations expected to delete part of the jawed vertebrate-specific domain from the encoded Sox9 protein. These results demonstrate that Xenopus crispants are useful for investigating the phenotype-genotype relationships behind syndromic diseases and examining the tissue-specific role of each functional domain within a single protein, providing novel insights into vertebrate jaw evolution.

Impact of skeletal muscle mass on functional prognosis in acute stroke: A cohort study.

INTRODUCTION: Changes in skeletal muscle mass affect physical performance in chronic stroke survivors. The skeletal muscle mass index is thus an important assessment factor in stroke; however, its value in the acute phase is unclear. OBJECTIVE: This study investigated the association between skeletal muscle mass and acute stroke outcome. DESIGN: This was a single-center cohort study design. PARTICIPANTS: A total of 189 consecutively hospitalized patients with acute stroke were included in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The main outcome of the study was a good modified Rankin Scale (mRS) score at hospital discharge. We divided the participants into good (mRS score 0-2) and poor (mRS score 3-6) function groups. Logistic regression was performed to identify the factors associated with functional prognosis. RESULTS: Atrial fibrillation (odds ratio [OR], 14.95; 95% confidence interval [CI], 2.45-91.39; P = 0.003), pre-mRS (OR, 2.22; 95% CI, 1.05-4.68; P = 0.036), National Institutes of Health Stroke Scale (OR, 1.32; 95% CI, 01.12-1.56; P = 0.001), skeletal muscle mass index (OR, 0.31; 95% CI, 0.11-0.87; P = 0.027), and Lower Extremity Fugl-Meyer Assessment (OR, 0.68; 95% CI, 0.56-0.82; P = 0.000) were all independently associated with the functional prognosis of the patients included in the study. CONCLUSION: This study confirmed that skeletal muscle mass is a strong prognostic factor in acute stroke. Thus, prestroke skeletal muscle mass, along with stroke severity and lower limb paralysis, needs to be assessed to more accurately determine the prognosis of patients with stroke.

Constraint-induced Aphasia Therapy Improves the Use of Spoken Language and Word-finding Ability in Chronic Subcortical Aphasia: A Case Report.

Background: Constraint-induced aphasia therapy (CIAT) has been reported as a short-term, intensive language training program for improving language function in patients with chronic aphasia. We report the recovery of language function in a patient with chronic aphasia who was evaluated in the baseline assessment as having reached a plateau. Case: The patient with subcortical aphasia was a 62-year-old, right-handed man. At 192 days after left putamen hemorrhage, he visited our hospital to begin CIAT. The patient's language and speech abilities were evaluated 1 month before and immediately before the start of CIAT. To evaluate the training effect, language function was assessed immediately after, 1 month after, 3 months after, and 6 months after the end of CIAT. The Western Aphasia Battery (WAB), the single-word-naming task in the Test of Lexical Processing in Aphasia (TLPA), and the Verbal Activity Log (VAL) were used to assess his language function and the amount of spoken language. From 1 month before CIAT to 6 months after CIAT, the WAB Aphasia Quotient increased by 6.1 points. Compared with before therapy, the errors of apraxia of speech in the TLPA disappeared from immediately after to 6 months after CIAT. Although the VAL score at 3 months after CIAT was higher than that before the start of CIAT, the score decreased after 6 months because of reduced opportunities for communication with friends. Discussion: CIAT improved the word-naming ability and amount of spontaneous, real-world spoken language in a patient with chronic aphasia.

Relationship between Rate of Force Development of Tongue Pressure and Physical Performance.

In the assessment of skeletal muscle strength, rate of force development (RFD) is clinically identified as a functional index that reflects the effects of aging, but there are few reports on RFD of the tongue. The purpose of this study was to examine the relationship between RFD of tongue pressure (RFD-TP) and oral and whole-body physical performance in older adults, and to clarify its characteristics. We enrolled adults aged ≥65 years with pathological occlusal contact in premolar and molar regions of teeth in the Tamba-Sasayama area, Japan, from 2017 to 2018. Maximum tongue pressure (MTP) and the speed to reach the maximum tongue pressure (RFD-TP) were evaluated as measures of tongue function. Oral functions related to objective measures of tongue function, such as repetitive saliva swallowing test, oral diadochokinesis, and physical status or performance, such as mini mental state examination, body mass index, skeletal mass index, knee extension force, one-leg standing time, grip strength, walking speed, timed up-and-go test, and five-time chair stand speed was evaluated. No significant correlation was found between MTP and age, but RFD-TP had a significant negative correlation with age. Neither RFD-TP nor MTP showed a significant correlation with oral function. RFD-TP was associated with physical performance, such as knee extension force and one-leg standing time. RFD-TP is more sensitive to aging than MTP. In addition, RFD-TP is related to physical performance and may be useful for the early detection of frailty.

Impact of Thickened Liquids on Laryngeal Movement Velocity in Patients with Dysphagia.

Considering that thickened liquids are frequently used for patients with dysphagia, elucidating their impact on laryngeal dynamics is important. Although studies have investigated the impact of thickened liquids on laryngeal movement velocity among healthy young adults, no study has examined the same among patients with dysphagia. We aimed to elucidate the influence of bolus consistency on laryngeal movement velocity and surface electromyographic activity of the suprahyoid muscles in patients with dysphagia. Participants included 18 male, poststroke patients with dysphagia, whereas patients with true bulbar paralysis, head and neck cancer, neuromuscular disease, or recurrent nerve paralysis were excluded. A video fluoroscopic swallowing study (VFSS) was performed while swallowing 3 mL of moderately thick and thin liquids. Quantitative VFSS analysis, including factors such as laryngeal peak velocity, laryngeal mean velocity, laryngeal movement distance, duration of the laryngeal elevation movement, and the temporal location of laryngeal vestibule closure within the laryngeal elevation movement was performed. Muscle activity was evaluated using integrated muscles activity values obtained from electromyography (iEMG) of the suprahyoid muscle during swallowing. VFSS analysis showed that laryngeal peak velocity and laryngeal mean velocity were significantly faster while swallowing moderately thick than while swallowing thin liquids. Laryngeal movement distance was significantly greater while swallowing moderately thick than while swallowing thin liquids. iEMG was significantly higher while swallowing moderately thick liquids than while swallowing thin liquids. Compared to thin liquids, moderately thick induced an increase in laryngeal movement velocity and in suprahyoid muscle activity among patients with dysphagia, a finding consistent with that of a previous study among healthy adults.

Effects of the internal syringe shape on the International Dysphagia Diet Standardization Initiative flow test.

The International Dysphagia Diet Standardization Initiative (IDDSI) proposed the flow test (FT) as a simple method for measuring the viscosity of thickened liquids. However, the FT specifies the use of a particular syringe type (BD-Slip), which is unfortunately not easily available in Japan. Therefore, the current study primarily aimed to investigate the effects of the internal syringe shape on IDDSI FT and identify the most suitable syringe available in Japan for xanthan gum-based thickened liquids. Accordingly, four syringes, namely, Luer slip tip, Luer-Lok tip, TERUMO, and NIPRO syringes, were used to examine FT value with water and nine different water viscosity levels. The correlation and systematic errors on residual FT values between the BD-Slip syringe and the other three syringes were analyzed. The two-dimensional internal shapes of the four syringes were measured using industrial computed tomography (CT) scanning. Based on the results of our FT, TERUMO had the smallest error range among the three syringes, without systematic errors. On a CT scan, three of five tip-shape parameters showed the smallest difference between BD-Slip and TERUMO syringe. Therefore, TERUMO had the smallest FT error range compared with that in BD-Slip tip syringe, indicating that TERUMO could be used as a substitute for BD-Slip when performing IDDSI FT with xanthan gum-based thickened water in Japan.

Tongue pressure waveform analysis for ascertaining the influence of tongue muscle composition on articulation.

BACKGROUND: Rate force development is associated with performance and muscle composition in whole-body muscle. Although rate force development on tongue muscle can be examined using tongue pressure waveform, there have been only few investigations on this topic. OBJECTIVES: This study's main purpose was to investigate the reliability of tongue pressure waveform analysis and its relationship with articulation and tongue muscle composition. In addition, we also investigated the association between tongue muscle composition and articulation. METHODS: Forty-five community-dwelling individuals aged >20 years participated. We analysed tongue pressure waveform, including maximum tongue pressure (MTP), time to peak, mean rate of tongue force development and peak rate of tongue force development (PRTFD). We also assessed oral diadochokinesis. Magnetic resonance imaging of the tongue provided data on tongue muscle composition, including tongue volume, fat mass, lean muscle mass and fat percentage. We evaluated the reliability of tongue pressure waveform analysis. Moreover, we examined the coefficients between tongue pressure waveform analysis, oral diadochokinesis and tongue composition. RESULTS: We detected a high reliability of MTP and PRTFD. MTP and PRTFD were significantly correlated with tongue muscle composition. MTP was not significantly correlated with oral diadochokinesis. PRTFD was significantly positively correlated with oral diadochokinesis. Tongue fat mass and fat percentage were negatively correlated with oral diadochokinesis of /ta/ and /ka/. CONCLUSIONS: Peak rate of tongue force development is a highly reliable method for tongue pressure analysis and is useful for elucidating the functional importance of tongue muscle function on articulation. We speculated that fatty infiltration of the tongue adversely affects articulation.

Change in Nutritional Status and Dysphagia after Resection of Head and Neck Cancer.

Nutritional status is well-known to influence patient recovery after resection of head and neck cancer (HNC). The influence of preoperative nutritional status on dysphagia was assessed in patients who underwent surgical resection of HNC along with the assessment of nutritional status during the acute and subacute phases. Eighty-six patients underwent surgical resection and dysphagia assessments (repetitive saliva-swallowing test, water-swallowing test, and functional oral intake scale) and had their tongue pressure assessed five times (before surgery, after 1-2 weeks, and 1, 2, and 3 months after surgery). The nutritional status was assessed according to the body mass index, total protein, and albumin. The prognostic nutritional index was calculated from preoperative data, and the subjects were classified into three groups: Low-risk, Attention and High-risk groups. After surgery, the nutritional status index values were low, and the High-risk group showed significantly lower values in comparison to the other two groups. The water-swallowing test and functional oral intake scale findings were worse than they had been preoperatively until 2 months after surgery, and a significant correlation was noted between the postoperative nutritional status and the presence of dysphagia. The results indicated that the preoperative nutritional status of HNC patients influenced their ability to ingest/swallow, which in turn influenced their nutritional status after HNC resection.

Age-related composition changes in swallowing-related muscles: a Dixon MRI study.

BACKGROUND: Dysphagia is considered a social problem in the super-aging society. However, age-related changes in swallowing-related muscles have not been fully deciphered. AIMS: We aimed to identify intramuscular fatty infiltration and muscle atrophy in multiple swallowing-related muscles on magnetic resonance imaging (MRI). Moreover, an appropriate muscle strength parameter for the evaluation of swallowing-related muscle mass was examined. METHODS: We analyzed the Dixon MRI results of 20 elderly and 20 young adults without head and neck cancer, stroke, neuromuscular disease, or whole-body sarcopenia to evaluate intramuscular fatty infiltration (IMF) and lean muscle mass (LMM) in the tongue, geniohyoid, and pharyngeal muscles. The pharyngeal lumen size was also assessed. Tongue pressure, jaw-opening strength, occlusal force, and head-lifting strength were evaluated within a week before and after MRI. RESULTS: Aging significantly affected the IMF of the swallowing-related muscles, and the tongue muscle was most affected, followed by the pharyngeal muscle and then the geniohyoid muscle. Only the LMM of the geniohyoid muscle significantly decreased with aging. The pharyngeal lumen size did not significantly differ between the elderly and young participants, and only tongue pressure was significantly correlated with tongue, geniohyoid, and pharyngeal muscle mass. CONCLUSIONS: IMF is primarily associated with age-related composition changes in swallowing-related muscles, and it is commonly observed in the tongue and pharyngeal muscles. The geniohyoid muscle is more at risk of muscle atrophy rather than fatty infiltration. In addition, tongue pressure can be a parameter for the evaluation of swallowing-related muscle mass.

Slow decay of infection in the inhomogeneous susceptible-infected-recovered model.

The susceptible-infected-recovered (SIR) model with spatially inhomogeneous infection rate is studied with numerical simulations in one, two, and three dimensions, considering the case that the infection spreads inhomogeneously in densely populated regions or hot spots. We find that the total population of infection decays very slowly in the inhomogeneous systems in some cases, in contrast to the exponential decay of the infected population I(t) in the SIR model of the ordinary differential equation. The slow decay of the infected population suggests that the infection is locally maintained for long and it is difficult for the disease to disappear completely.

Validity of a dysphagia screening test following resection for head and neck cancer.

BACKGROUND: The aim of this study was to evaluate the validity of a dysphagia screening test (DST) in patients who have undergone resection for head and neck cancer (HNC). In addition, we examined whether or not combined effects of DSTs improve the detection accuracy of penetration/aspiration. METHODS: Thirty-six HNC patients were participated. The DST consisted of the repetitive saliva swallowing test (RSST), the water swallowing test (WST), the modified water swallowing test (MWST), the food test (FT), and tongue pressure. A videofluoroscopic swallowing study was conducted, and the penetration-aspiration scale was used for scoring. For statistical analyses, we used the receiver operating characteristic (ROC) analysis. Furthermore, the accuracy of the determination of penetration/aspiration was evaluated by combining two or three DSTs. RESULTS: The penetration/aspiration could be predicted with moderate accuracy based on MWST and FT. The area under the ROC curve (AUC) values of the MWST and FT were 0.76 (p = 0.03) and 0.80 (p = 0.050), and the sensitivity/specificity was 0.9/0.61 (MWST) and 0.8/0.8 (FT), respectively. As a result of combining 2 or 3 DSTs, the combination of "MWST and FT" was the most accurate, with an AUC of 0.87 (p = 0.02). The combination of three tests had lower accuracy than the combination of two tests. CONCLUSION: Based on our results, it is recommended that MWST or FT be used when only one type of DST is performed. In addition, the combination of two DSTs may detect aspiration patients more accurately than one alone.

Association Among Age-Related Tongue Muscle Abnormality, Tongue Pressure, and Presbyphagia: A 3D MRI Study.

Muscle aging such as sarcopenia adversely affects motor activities. However, few studies have elucidated the aging physiological mechanism of tongue concerted with the changes muscle composition. The present study aimed to examine the tongue composition changes to detect the effect of tongue fat mass on tongue pressure and swallowing function with aging. Twenty community-dwelling elderly without head and neck cancer, stroke, or neuromuscular disease and 20 healthy young were included. Tongue volume, tongue fat mass, tongue lean muscle mass, and tongue fat percentage were evaluated with 3D magnetic resonance imaging (MRI) and Dixon MRI. Tongue pressure was also measured. Swallowing function among elderly individuals was assessed via videofluorography, which was evaluated using the penetration-aspiration scale (PAS) and normalized residue ratio scale (NRRS). Tongue fat mass and tongue fat percentage significantly increased with aging. The tongue fat percentage of elderly participants was 20%, which was two times greater than that of young participants. No significant difference was observed in tongue volume and tongue lean muscle mass. A significantly negative correlation was observed between tongue fat mass and tongue fat percentage as well as tongue pressure. Conversely, tongue volume was not significantly correlated with tongue pressure. Tongue muscle composition exhibited no effect in the PAS and NRRS. Increase of fat mass is a major change in tongue composition with aging, which is associated with low tongue pressure. Thus, attention must be paid not only to tongue quantity but also to the quality of tongue muscles.

Synthetic Study on Pactamycin: Stereoselective Synthesis of the Cyclopentane Core Framework.

The cyclopentane core framework 23 of pactamycin (1) was synthesized in 14 steps from symmetric cyclohexadiene 11. Our synthetic strategy features Rh-mediated catalytic desymmetrization of 10 via aziridination and then regioselective ring-opening reaction of sulfonylaziridine 9 with NaN3, ring-contraction of cyclohexene 14 by ozonolysis followed by intramolecular aldol reaction, and stereoselective construction of the sequential tetrasubstituted carbons by dihydroxylation and methylation reaction. Stereospecific incorporation of amine on tetrasubstituted carbon was achieved by Curtius rearrangement and subsequent carbamide formation.

Change in tongue pressure in patients with head and neck cancer after surgical resection.

Tongue pressure is reportedly associated with dysphagia. This study investigated relationships among characteristics of head and neck cancer, tongue pressure and dysphagia screening tests performed in patients with head and neck cancer during the acute phase after surgical resection. Fifty-seven patients (36 men, 21 women; age range 26-95 years) underwent surgical resection and dysphagia screening tests (Repetitive Saliva Swallowing Test, Water Swallowing Test, Modified Water Swallowing Test and Food Test) and pre- and postoperative measurement of tongue pressure at 5 time points (preoperatively, and 1-2 weeks and 1, 2, and 3 months postoperatively). Progression of cancer (stage), tracheotomy, surgical reconstruction, chemotherapy, radiotherapy and neck dissection were factors associated with postoperative tongue pressure. Data were analyzed by linear mixed-effect model, Spearman correlation coefficient and receiver operating characteristic (ROC) curve. Tongue pressure was significantly reduced 1-2 weeks after surgery, and recovered over time. Changes in tongue pressure were significantly associated with stage, radiotherapy and reconstruction. All screening tests showed a significant relationship with tongue pressure. Analysis of ROC and area under the effect curve suggested that a tongue pressure of 15 kPa can be used as a cut-off value to detect dysphagia after surgery for head and neck cancer. Our results suggest that tongue pressure evaluation might offer a safe, useful and objective tool to assess dysphagia immediately postoperatively in patients with head and neck cancer.

[A case of exogenous lipoid pneumonia with marked elevation of serum KL-6 and interstitial lung shadows due to aspiration of liquid paraffin].

A 64-year-old man who ingested liquid paraffin as a laxative for over two years, was admitted to our hospital with a persistent interstitial lung shadow and marked elevation of serum KL-6. He had no overt symptoms although his chest radiograph revealed ground glass opacities in the left lower lung field and right middle and lower lung fields. We performed fiberoptic bronchoscopy. Exogenous lipoid pneumonia was diagnosed based on microscopic analysis of the bronchoalveolar lavage fluid that revealed the presence of lipid-laden alveolar macrophages. We instructed the patient to discontinue liquid paraffin ingestion and observed his clinical course. The chest radiograph and thoracic computed tomography revealed a tendency to improve and serum KL-6 decreased with time. Serum KL-6 may be an important index of the severity of exogenous lipoid pneumonia.

[Case of Heerfordt's syndrome with prolonged peripheral nerve involvement].

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.

Pulmonary sarcoidosis and antiphospholipid syndrome.

Various autoimmune diseases have been reported to occur in patients with sarcoidosis. However, coexistence of sarcoidosis and antiphospholipid syndrome (APS) is extremely rare. We describe a 59-year-old female patient with pulmonary sarcoidosis who had preceding APS. Her previous medical history consisted of a miscarriage and ischemic colitis. She was diagnosed as APS during the onset of a brainstem infarction with positive reaction to beta2-glycoprotein I-dependent anticardiolipin antibody. Two years later, chest CT revealed enlargement of the hilar and mediastinal lymph nodes and small nodules in the lung fields. Transbronchial lung biopsy demonstrated non-caseating epithelioid cell granuloma leading to the diagnosis of definite pulmonary sarcoidosis. This is the first APS case where pulmonary involvement with sarcoidosis has been confirmed through lung biopsy. Our case report suggests that APS should be recognized as an accompanying disorder of sarcoidosis.