Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet.

Coordinated beating of cilia in the trachea generates a directional flow of mucus required to clear the airways. Each cilium originates from a barrel-shaped basal body, from the side of which protrudes a structure known as the basal foot. We generated mice in which exons 6 and 7 of Odf2, encoding a basal body and centrosome-associated protein Odf2/cenexin, are disrupted. Although Odf2(ΔEx6,7/ΔEx6,7) mice form cilia, ciliary beating is uncoordinated, and the mice display a coughing/sneezing phenotype. Whereas residual expression of the C-terminal region of Odf2 in these mice is sufficient for ciliogenesis, the resulting basal bodies lack basal feet. Loss of basal feet in ciliated epithelia disrupted the polarized organization of apical microtubule lattice without affecting planar cell polarity. The requirement for Odf2 in basal foot formation, therefore, reveals a crucial role of this structure in the polarized alignment of basal bodies and coordinated ciliary beating.

Association between DNA methylation levels of thioredoxin-interacting protein (TXNIP) and changes in glycemic traits: a longitudinal population-based study.

Thioredoxin-interacting protein (TXNIP) plays an important role in glucose metabolism, and its expression is regulated by DNA methylation (DNAm). Although the association between TXNIP DNAm and type 2 diabetes mellitus has been demonstrated in studies with a cross-sectional design, prospective studies are needed. We therefore examined the association between TXNIP DNAm levels and longitudinal changes in glycemic traits by conducting a longitudinal study involving 169 subjects who underwent two health checkups in 2015 and 2019. We used a pyrosequencing assay to determine TXNIP DNAm levels in leukocytes (cg19693031). Logistic regression analyses were performed to assess the associations between dichotomized TXNIP DNAm levels and marked increases in glycemic traits. At four years, the TXNIP DNA hypomethylation group had a higher percentage of changes in fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared to those in the hypermethylation group. The adjusted odds ratios for FPG and HbA1c levels were significantly higher in the TXNIP DNA hypomethylation group than in the hypermethylation group. We found that TXNIP DNA hypomethylation at baseline was associated with a marked increase in glycemic traits. Leukocyte TXNIP DNAm status could potentially be used as an early biomarker for impaired glucose homeostasis.

The influence of a single 30-pitch session on elbow laxity in adolescent and collegiate baseball pitchers.

BACKGROUND: Ulnar collateral ligament (UCL) injuries are a source of significant injury among baseball players, and are increasingly evaluated under ultrasound. The purpose of this study is to determine the effect of a single session of pitching upon UCL thickness and laxity via a cross sectional, controlled ultrasonographic study. We hypothesize that a single session of pitching will cause the ulnar collateral ligament to thicken and become more lax. METHODS: This was a cross sectional comparative study of collegiate and high school pitchers. Pitchers underwent an ultrasonographic assessment of the UCL before and after a thirty-pitch bullpen warm-up. Laxity was measured as the change in the distance between the ulna and the trochlea with and without a 5-pound weight held in hand with the elbow at 30° of flexion. Pre- and post-throwing UCL thickness and medial laxity were statistically compared with paired tests. RESULTS: Our study included 15 pitchers, 8 collegiate and 7 high school level athletes. All played baseball at least 6 days a week, and nearly all played for at least 10 months a year. Pitchers reported a peak velocity of 89 ± 6 (77 to 98) miles per hour. In the prior season, these pitchers pitched 56 ± 33 (10 to 120) games, throwing 62 ± 34 (25-140) pitches per game on average. After throwing, there was significantly less UCL laxity (P = .013). Post-throwing laxity was significantly positively correlated with both peak pitch velocity (P = .009) and an average number of pitches thrown per game (P = .10). CONCLUSION: Throwing 30 pitches significantly decreases medial elbow laxity with stress, possibly due to flexor-pronator activation. Post-throwing medial laxity is correlated with both peak pitch velocity and average number of pitches thrown per game. Future studies should be conducted to determine the number of throws at which laxity begins to increase, as this may provide a workload management guideline for injury prevention.

The Effect of Lateralization and Distalization After Grammont-Style Reverse Total Shoulder Arthroplasty.

BACKGROUND: The purpose of this study is to evaluate the relationship between multiple radiographic measures of lateralization and distalization and clinical outcome scores after reverse total shoulder arthroplasty (RTSA). METHODS: We retrospectively evaluated all RTSAs performed by the senior author between January 1, 2007, and November 1, 2017. We then evaluated the visual analog scale for pain (VAS pain), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) scores and complication and reoperation rates at a minimum of 2-year follow-up. We measured preoperative and postoperative (2-week) radiographs for the lateralization shoulder angle (LSA), the distalization shoulder angle (DSA), lateral humeral offset (LHO), and distance from glenoid to lateral aspect of the greater tuberosity (GLAGT). A multivariable analysis was performed evaluating the effect of the postoperative radiographic measurements on final patient reported outcomes (ASES scores, SST, VAS pain). RESULTS: The cohort included 216 shoulders from unique patients who had patient reported outcome scores available at a minimum of 2-year follow-up (average, 4.0±1.9 years) for a total follow-up rate of 70%. In the multivariable models, more lateralization (LSA) was associated with worse final ASES scores -0.52 (95% CI: -0.88 to -0.17; p=0.004), and more distalization (DSA) was associated with better final ASES scores 0.40 (95% CI: 0.11, 0.69; p=0.007). More lateralization (LSA) was associated with worse final SST scores -0.06 (95% CI: -0.11, -0.003; p=0.039). Finally, greater distalization (DSA) was associated with lower final VAS pain scores, Ratio = 0.98 (95% CI: 0.96, 1.00; p=0.021). CONCLUSION: Greater distalization and less lateralization are associated with better function and less pain after Grammont-style RTSA. If utilizing a Grammont-style implant, remaining consistent with Grammont's principles of implant placement will afford better final clinical outcomes.

Ciliogenesis: building the cell's antenna.

The cilium is a complex organelle, the assembly of which requires the coordination of motor-driven intraflagellar transport (IFT), membrane trafficking and selective import of cilium-specific proteins through a barrier at the ciliary transition zone. Recent findings provide insights into how cilia assemble and disassemble in synchrony with the cell cycle and how the balance of ciliary assembly and disassembly determines the steady-state ciliary length, with the inherent length-dependence of IFT rendering the ciliary assembly rate a decreasing function of length. As cilia are important in sensing and processing developmental signals and directing the flow of fluids such as mucus, defects in ciliogenesis and length control are likely to underlie a range of cilium-related human diseases.

Serum carotenoid levels are positively associated with DNA methylation of thioredoxin-interacting protein.

Background: Carotenoids have been reported to exert protective effects against age-related diseases via changes in DNA methylation. Although lower thioredoxin-interacting protein (TXNIP) DNA methylation is associated with age-related diseases, only a few studies have investigated the factors influencing TXNIP DNA methylation. Carotenoids may be a factor linking TXNIP to specific pathophysiological functions. The aim of this study was to examine whether serum carotenoid levels are associated with TXNIP DNA methylation levels. Methods: We conducted a cross-sectional study using 376 health examination participants (169 men). DNA methylation levels were determined using a pyrosequencing assay. Serum carotenoid levels were determined by high-performance liquid chromatography. Multivariable regression analyses were performed to examine the associations between TXNIP DNA methylation levels and serum carotenoid levels with adjustment for age, BMI, HbA1c, CRP, smoking habits, alcohol consumption, exercise habits, and percentage of neutrophils. Results: Multiple linear regression analyses showed that TXNIP DNA methylation levels were positively associated with serum levels of zeaxanthin/lutein (ß [95%CI]: 1.935 [0.184, 3.685]), ß-cryptoxanthin (1.447 [0.324, 2.570]), α-carotene (1.061 [0.044, 2.077]), ß-carotene (1.272 [0.319, 2.226]), total carotenes (1.255 [0.040, 2.469]), total xanthophylls (2.133 [0.315, 3.951]), provitamin A (1.460 [0.402, 2.519]), and total carotenoids (1.972 [0.261, 3.683]) in men (all p<0.05). Of these, provitamin A showed the stronger association (standardized ß=0.216). No significant association of TXNIP DNA methylation and serum carotenoid was observed in women. Conclusions: The findings of this study suggest that carotenoid intake may protect against age-related diseases by altering TXNIP DNA methylation status in men.

A stabilizing role of the glenoid labrum: the suction cup effect.

BACKGROUND: The glenoid labrum acts as a bumper, deepening glenoid concavity and amplifying the concavity-compression mechanism, and serves as the scapular attachment for glenohumeral ligaments. The role of the posterosuperior labrum in anteroinferior glenohumeral stability, and the role of the anterior labrum in posterior stability has been debated. The purpose of this study was to quantify the contribution of anteroinferior and posterosuperior labral tears to loss of glenohumeral stability in multiple directions. METHODS: Fourteen fresh-frozen cadaveric shoulders were tested on a custom stability ratio measurement apparatus. The peak force that was required to translate the humeral head in anterior, anteroinferior, posterior, and posteroinferior directions was measured under 5 conditions: intact labrum (n = 14), anteroinferior labral tear (n = 7), posterosuperior labral tear (n = 7), combined labral tear (n = 14), and no labrum (n = 14). The stability ratio was defined as the peak translational force divided by the compressive force. Within force-translation curves, we defined the suction cup effect as the force required to release the negative pressure created by an intact labrum. RESULTS: The suction cup effect was usually present with the intact labrum and always disappeared after removal of the labrum for anterior (100% vs. 0%) and posterior (86% vs. 0%) translations (P < .001). After creation of an anteroinferior labral tear, the stability ratio for posterior direction decreased (P < .001) and the suction cup effect disappeared (P < .001). After creation of a posterosuperior labral tear, stability ratios in the anterior and anteroinferior directions decreased (P ≤ .006) and the suction cup effect disappeared (P ≤ .015). The stability ratio for anterior and anteroinferior testing was more diminished by posterosuperior labral tears than anteroinferior labral tears, and the stability ratio for posterior testing was more diminished by anteroinferior labral tears than posterosuperior labral tears. CONCLUSION: Anteroinferior labral tears decreased posterior stability and posterosuperior labral tears decreased anterior and anteroinferior stability, largely because of loss of the suction cup effect.

Rotator cuff muscle imbalance associates with shoulder instability direction.

BACKGROUND: Although muscle weakness and/or imbalance of the rotator cuff are thought to contribute to the development of shoulder instability, the association between muscular dysfunction and shoulder instability is not completely understood. The purpose of this study was to evaluate rotator cuff and deltoid muscle cross-sectional areas in different types of shoulder instability (anterior, posterior, and multidirectional instability [MDI]) and to determine the associations between muscular imbalance and shoulder instability direction. METHODS: Preoperative magnetic resonance images of patients with shoulder instability who subsequently underwent arthroscopic glenohumeral labral repair or capsular plication were evaluated. Shoulder instability was classified into 3 categories by direction: (1) anterior, (2) posterior, and (3) MDI. The rotator cuff (supraspinatus, subscapularis, and infraspinatus + teres minor) and deltoid (anterior and posterior portions, and total) muscle areas were measured on T1 sagittal and axial slices, respectively. The ratios of the subscapularis to infraspinatus + teres minor area and the anterior deltoid to posterior deltoid area were calculated to quantify the transverse force couple imbalance. RESULTS: A total of 189 patients were included, where each group consisted of 63 patients. The infraspinatus + teres minor muscle area was smaller than the subscapularis muscle area in the anterior instability group (P = .007). The subscapularis muscle area was smaller than the infraspinatus + teres minor muscle area in the posterior instability and MDI groups (P ≤ .003). The anterior deltoid muscle area was smaller than the posterior deltoid muscle area in all groups (P ≤ .001). The subscapularis-to-infraspinatus + teres minor area ratio in the anterior instability group (1.18 ± 0.40) was higher than that in the posterior instability and MDI groups (0.79 ± 0.31 and 0.93 ± 0.33, respectively; P < .001). There was no difference in the anterior deltoid-to-posterior deltoid area ratio among the 3 groups. CONCLUSION: Patients with anterior instability have smaller muscle area of the posterior rotator cuff as compared with the anterior rotator cuff. In contrast, patients with posterior instability and MDI have smaller muscle area of the anterior rotator cuff as compared with the posterior rotator cuff. Thus, the direction of shoulder instability is associated with rotator cuff muscle area.

A simple method to generate human airway epithelial organoids with externally orientated apical membranes.

Organoids, which are self-organizing three-dimensional cultures, provide models that replicate specific cellular components of native tissues or facets of organ complexity. We describe a simple method to generate organoid cultures using isolated human tracheobronchial epithelial cells grown in mixed matrix components and supplemented at day 14 with the Wnt pathway agonist R-spondin 2 (RSPO2) and the bone morphogenic protein antagonist Noggin. In contrast to previous reports, our method produces differentiated tracheobronchospheres with externally orientated apical membranes without pretreatments, providing an epithelial model to study cilia formation and function, disease pathogenesis, and interaction of pathogens with the respiratory mucosa. Starting from 3 × 105 cells, organoid yield at day 28 was 1,720 ± 302. Immunocytochemistry confirmed the cellular localization of airway epithelial markers, including CFTR, Na+/K+ ATPase, acetylated-α-tubulin, E-cadherin, and ZO-1. Compared to native tissues, expression of genes related to bronchial differentiation and ion transport were similar in organoid and air-liquid interface (ALI) cultures. In matched primary cultures, mean organoid cilia length was 6.1 ± 0.2 µm, similar to that of 5.7 ± 0.1 µm in ALI cultures, and ciliary beating was vigorous and coordinated with frequencies of 7.7 ± 0.3 Hz in organoid cultures and 5.3 ± 0.8 Hz in ALI cultures. Functional measurement of osmotically induced volume changes in organoids showed low water permeability. The generation of numerous single testable units from minimal starting material complements prior techniques. This culture system may be useful for studying airway biology and pathophysiology, aiding diagnosis of ciliopathies, and potentially for high-throughput drug screening.

Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming.

Given that fructose consumption has increased by more than 10-fold in recent decades, it is possible that excess maternal fructose consumption causes harmful effects in the next generation. This study attempted to elucidate the mechanism of the harmful effects of excessive maternal fructose intake from the perspective of offspring liver function. Female rats during gestation and lactation were fed water containing fructose, and their offspring were fed normal water. We attempted to elucidate the mechanism of fructose-induced transgenerational toxicity by conducting a longitudinal study focusing on hepatic programming prior to disease onset. Impaired Insulin resistance and decreased high-density lipoprotein-cholesterol levels were observed at 160 days of age. However, metabolic disorders were not observed in 60-day-old offspring. Microarray analysis of 60-day-old offspring livers showed the reduction of hepatic insulin-like growth factor-1 (Igf1) mRNA expression. This reduction continued until the rats were aged 160 days and attenuated Igf1 signaling. Hepatic microRNA-29 (miR-29a) and miR-130a, which target Igf1 mRNA, were also found to be upregulated. Interestingly, these miRNAs were upregulated in the absence of metabolic disorder. In this study, we found that maternal fructose intake resulted in dysregulated expression of Igf1 and its target miRNAs in the offspring liver, and that these offspring were more likely to develop metabolic disorders. Abnormal hepatic programming induced by an imbalanced maternal nutritional environment is maintained throughout life, implying that it may contribute to metabolic disorders.

Circulating microRNA-27a and -133a are negatively associated with incident hypertension: a five-year longitudinal population-based study.

BACKGROUND: Previous cross-sectional studies have shown that several circulating microRNA levels are associated with hypertension, but there are no prospective studies among general populations. OBJECTIVE: We evaluated the impact of circulating inflammatory- and oxidative stress-responsive microRNAs on changes in blood pressure and the development of hypertension in normotensive Japanese. METHOD: The study subjects were 84 normotensive participants (33 men and 51 women) who were given a health examination in both 2012 and 2017. In five years, 29 participants developed hypertension. Serum levels of miRNAs (miR-21, miR-27a, and miR-133a) were measured using qRT-PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident hypertension were estimated by logistic regression analysis. RESULTS: Serum miR-27a and -133a levels were lower in newly hypertensive subjects compared with normotensive subjects. With 1-unit lower serum miR-27a and -133a, the confounders adjusted ORs and 95% CI for incident hypertension were 0.84 (0.72-0.96) and 0.75 (0.58-0.91), respectively. The group with high levels of serum miR-27a and -133a had lower ORs than the group with low levels of these miRNAs (OR and 95% CI of miR-27a: 0.29, 0.08-0.91; miR-133a: 0.08, 0.01-0.37, respectively). CONCLUSIONS: Circulating miR-27a and -133a are potential biomarkers for the prediction and prevention of hypertension.

Increased brain-derived neurotrophic factor in the serum of persons with nonalcoholic fatty liver disease.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global health problem. In recent years, the inhibitory effect of brain-derived neurotrophic factor (BDNF) on diabetes mellitus and fatty liver has been clarified. The purpose of this study was to analyze the relationship between serum BDNF and NAFLD which caused by abnormal metabolism of glucose and lipids. This cross-sectional study involved 429 participants (mean age, 63.5 years: men, 38.5%) with low alcohol intake. Of the participants, those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 88), and the others were classified as the normal (n = 341) group. The NAFLD group was further classified into a mild group (n = 60) and a severe group (n = 28) based on the intensity of echogenicity and visualization of the hepatic vessels and diaphragm. Median BDNF levels were higher in the NAFLD group than the normal group (35.5 vs. 42.3 ng/mL, p < 0.01). Furthermore, BDNF levels tended to be associated with the severity of NAFLD (p < 0.01). In addition to the univariate analysis, in the sex- and age-adjusted model, there was a significant association between the BDNF levels and NAFLD severity (p < 0.01). The fully adjusted regression analysis also showed a positive association between the serum BDNF level and NAFLD (p < 0.01). These results suggest that NAFLD patients have a compensatory increase in circulating BDNF levels.

DNA methylation level of the gene encoding thioredoxin-interacting protein in peripheral blood cells is associated with metabolic syndrome in the Japanese general population.

Metabolic syndrome (MetS) is cluster of metabolic diseases, including abdominal obesity, hyperglycemia, high blood pressure, and dyslipidemia, that directly escalate the risk of type 2 diabetes, heart disease, and stroke. Thioredoxin-interacting protein (TXNIP) is a binding protein for thioredoxin, a molecule that is a key inhibitor of cellular oxidation, and thus regulates the cellular redox state. Epigenetic alteration of the TXNIP-encoding locus has been associated with components of MetS. In the present study, we sought to determine whether the level of TXNIP methylation in blood is associated with MetS in the general Japanese population. DNA was extracted from the peripheral blood cells of 37 subjects with and 392 subjects without MetS. The level of TXNIP methylation at cg19693031 was assessed by the bisulfite-pyrosequencing method. We observed that TXNIP methylation levels were lower in MetS subjects (median 74.9%, range 71.7-78.4%) than in non-MetS subjects (median 77.7%, range 74.4-80.5%; p = 0.0024). Calculation of the confounding factor-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hypomethylation revealed that subjects with MetS exhibited significantly higher ORs for hypomethylation than did those without MetS (OR, 2.92; 95% CI, 1.33-6.62; p = 0.009). Our findings indicated that lower levels of TXNIP methylation are associated with MetS in the general Japanese population. Altered levels of DNA methylation in TXNIP at cg19693031 might play an important role in the pathogenesis of MetS.

Association between the Extent of Peripheral Blood DNA Methylation of HIF3A and Accumulation of Adiposity in community-dwelling Women: The Yakumo Study.

INTRODUCTION: DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index (BMI). This cross-sectional study investigated correlations between DNA methylation of HIF3A and BMI or adiposity parameters in the Japanese population. METHOD: DNA methylation of HIF3A was quantified via pyrosequencing. RESULT: DNA methylation of HIF3A differed only in women; DNA methylation level at cg27146050 was associated with visceral adipose tissue thickness and correlated with BMI and percent (%) body fat after excluding smokers. CONCLUSION: Peripheral blood DNA methylation at the CpG site (cg27146050) of HIF3A correlated with VAT thickness in Japanese women.

Association of drinking behaviors with TXNIP DNA methylation levels in leukocytes among the general Japanese population.

Background: Thioredoxin-interacting protein (TXNIP) controls the cellular redox balance by binding to and inhibiting the expression and function of thioredoxin. DNA methylation of the TXNIP gene is involved in the regulation of TXNIP mRNA expression. Changes in TXNIP DNA methylation levels are associated with the development of various diseases such as type 2 diabetes mellitus (T2DM). However, few studies have focused on the influence of lifestyle factors such as alcohol intake on TXNIP DNA methylation.Objectives: This research examines the association of drinking behaviors with TXNIP DNA methylation levels in the general Japanese population.Methods: We conducted a cross-sectional study of 404 subjects (176 males and 228 females) who were divided into non-, moderate and heavy drinkers based on self-reported drinking behaviors. TXNIP DNA methylation levels in leukocytes were determined using a pyrosequencing assay.Results: The mean TXNIP DNA methylation level in heavy drinkers (74.2%) was significantly lower than that in non- and moderate drinkers (non: 77.7%, p < .001; moderate: 76.6%, p = .011). Multivariable linear regression analysis showed that log-transformed values of daily (b = -1.34; p < .001) and cumulative (b = -1.06; p = .001) alcohol consumption were associated with decreased TXNIP DNA methylation levels.Conclusion: TXNIP DNA methylation levels in heavy drinkers was lower than in non- and- moderate drinkers. Decreased TXNIP DNA methylation level increases the expression of TXNIP and elevates the risk of developing of diseases such as T2DM. Therefore, decreasing alcohol use in heavy drinkers may lessen the likelihood of some alcohol-related illnesses moderated through TXNIP DNA methylation.

Increased external rotation related to the soft tissues is associated with pathologic internal impingement in high-school baseball players.

BACKGROUND: Changes in soft-tissue structures such as anterior laxity and posterior tightness are thought to contribute to the development of pathologic internal impingement in baseball players. Although side-to-side differences in shoulder rotational range of motion (ROM) is commonly used in clinical practice to quantify the soft-tissue changes, the ROM does not accurately reflect the soft-tissue changes because the ROM is affected not only by the soft tissues, but also by the bone. Increased retroversion of the humeral head is often observed in the dominant shoulder of throwing athletes. The purpose of this study was to determine the relationship between the soft-tissue-related (STR) ROM and pathologic internal impingement in baseball players. METHODS: Bilateral humeral retroversion and ranges of glenohumeral external rotation (ER) and internal rotation (IR) were investigated in 81 high-school baseball players. The players were divided into two groups: the internal impingement group (19 players) and the control group (62 players). Humeral retroversion was measured using the ultrasound-assisted technique to assess the bone-related ER and IR. The STR ER and IR were defined as subtracting the amount of humeral retroversion from the measured ER and IR. RESULTS: The side-to-side difference (throwing shoulder - nonthrowing shoulder) in humeral retroversion showed no significant difference between the internal impingement group (6° ± 10°) and control group (11° ± 11°) (P = .064). The side-to-side difference in STR ER was significantly greater in the internal impingement group (12° ± 12°) than that in the control group (1° ± 14°) (P = .002). No significant difference was observed in the side-to-side difference in STR IR between the internal impingement group (-7° ± 16°) and control group (-5° ± 15°) (P = .696). Pathologic internal impingement was significantly associated with the side-to-side difference of STR ER (odds ratio, 1.06 for increase of 1°; 95% confidence interval, 1.02-1.11; P = .008). CONCLUSION: In high-school baseball players, the increased STR ER in the throwing shoulder may be associated with pathologic internal impingement. An increase of 10° in side-to-side difference in STR ER would increase the risk of pathologic internal impingement by 1.8 times.

Changes in shoulder muscle activities and glenohumeral motion after rotator cuff repair: an assessment using ultrasound real-time tissue elastography.

BACKGROUND: Although rotator cuff repair is performed to restore the function of the rotator cuff muscles and glenohumeral (GH) joint motion, little has been known regarding the recovery process. The purpose of this study was (1) to investigate changes over time in activities of the supraspinatus and deltoid muscles assessed by ultrasound real-time tissue elastography (RTE) after rotator cuff repair and (2) to determine contributions of the activities of these muscles to the GH joint motion. METHODS: Twenty patients after rotator cuff repair and 13 control participants were enrolled in this study. Elasticity of the supraspinatus and middle deltoid muscles were measured at rest and 30° of humerothoracic elevation in the scapular plane (scaption) by using RTE. The elasticity at 30° of scaption was normalized to that at rest in each muscle to quantify their muscle activities. In addition, the supraspinatus-to-middle deltoid (SSP/MD) ratio for the normalized elasticity was calculated. The GH elevation angle was measured with a digital inclinometer, which was calculated by subtracting the scapular upward rotation angle from 30° of scaption. For patients after rotator cuff repair, all measurements were performed at 6 weeks, 8 weeks, 3 months, and 6 months after surgery. Rotator cuff integrity was examined with magnetic resonance imaging at 6 months after surgery. RESULTS: Fifteen of 20 patients who remained intact at 6 months after surgery completed this study. The supraspinatus activity at 6 weeks was significantly smaller than that at 3 months (P = .006) and 6 months (P = .010). There was no significant difference in the supraspinatus activity between the patients at 3 months and the control participants (P = .586). The middle deltoid activity at 6 weeks was significantly greater than that at 6 months (P = .003). There was positive correlation between GH elevation angle and the activity of the supraspinatus relative to the deltoid at 6 weeks (r = 0.75, P = .001) and 8 weeks (r = 0.53, P = .041). CONCLUSION: The supraspinatus activity increased from 6 weeks to 3 months after surgery. The supraspinatus activity at 3 months after surgery was the same level as that in healthy individuals. On the other hand, the deltoid activity decreased from 6 weeks to 6 months after surgery. The increase in activity of the supraspinatus relative to the deltoid was likely to be related to the increase in GH elevation during postoperative at 8 weeks.

Orally administered octacosanol improves some features of high fructose-induced metabolic syndrome in rats.

We examined whether orally administered octacosanol, a long-chain aliphatic saturated alcohol, improves the features of high fructose-induced metabolic syndrome in rats. Five-week-old rats were fed a high fructose diet containing 60% fructose for 3 weeks. Then, the high fructose fed rats received a daily single oral administration of octacosanol (10 or 100 mg/kg body weight) with high fructose feeding for one week. Three- or four-week high fructose feeding increased insulin resistance, serum insulin, triglyceride, total cholesterol, free fatty acids, uric acid, and lipid peroxide concentrations, and hepatic triglyceride and cholesterol contents significantly and decreased serum high-density lipoprotein cholesterol and adiponectin concentrations significantly but did not affect blood pressure and hepatic lipid peroxide and reduced glutathione contents. Four-week high fructose feeding decreased hepatic ascorbic acid content significantly. Oral administration of octacosanol (10 or 50 mg/kg body weight) to high fructose-fed rats for the last 1-week fructose diet feeding attenuated these changes except serum insulin level and insulin resistance significantly and increased hepatic reduced glutathione content significantly. The higher dose of Oct decreased hepatic lipid peroxide content significantly. These results indicate that orally administered octacosanol improves dyslipidemia, hyperuricemia, hypoadiponectinemia, and oxidative stress associated with the features of high fructose-induced metabolic syndrome rats.

Maternal fructose-induced oxidative stress occurs viaTfam and Ucp5 epigenetic regulation in offspring hippocampi.

Fructose consumption is rising globally, but maternal high fructose intake might adversely affect offspring. Our previous report demonstrated that excess maternal fructose intake impairs hippocampal function in offspring, indicating that the hippocampi of offspring are highly sensitive to maternal fructose. Here, we examined the effect of maternal high fructose on mitochondrial physiology and uncoupling protein (UCP) expression. Rat dams received a 20% fructose solution during gestation and lactation. Immediately after weaning, offspring hippocampi were isolated. Maternal high fructose consumption attenuated the mitochondrial O2 consumption rate and stimulated lipid hydroperoxide production in the hippocampi of offspring. Reduced Ucp5 and mitochondrial transcription factor A (Tfam) mRNA levels were also observed after maternal exposure to fructose. We assessed the promoter regions of both genes and found that this treatment enhanced DNA methylation levels. In addition, luciferase assays showed that this DNA methylation could reduce the transcription of both genes. Chromatin immunoprecipitation analysis demonstrated that specificity protein 1 binding to the Ucp5 promoter regions was reduced by DNA methylation. In addition, Ucp5 knockdown induced the up-regulation of reactive oxygen species levels in a rat brain glioma cell line, whereas reduced O2 consumption was observed with Tfam knockdown. Maternal high fructose intake thus induces reduced O2 oxygen consumption and increases oxidative stress in offspring, at least partly through epigenetic mechanisms involving Ucp5 and Tfam.-Yamada, H., Munetsuna, E., Yamazaki, M., Mizuno, G., Sadamoto, N., Ando, Y., Fujii, R., Shiogama, K., Ishikawa, H., Suzuki, K., Shimono, Y., Ohashi, K., Hashimoto, S. Maternal fructose-induced oxidative stress occurs viaTfam and Ucp5 epigenetic regulation in offspring hippocampi.

Visual Hallucinations and Impaired Conscious Visual Perception in Parkinson Disease.

Visual hallucinations (VHs) are common in patients with Parkinson disease (PD), especially those with dementia, whereas auditory hallucinations are quite rare. Recent studies have revealed the involvement of several regions along the visual information-processing system that contribute to the pathophysiological mechanism of VHs: the eyes and retina, retinofugal projection, lateral geniculate nucleus, striate cortex, ventral pathways in the temporal cortices, and frontal and parietal cortices. In addition, the concurrent involvement of other systems in the brainstem and basal forebrain further modify VHs in PD. In this review, we discuss the pathophysiological association between the regional involvement of these areas and VHs.