Mauritian Endemic Medicinal Plant Extracts Induce G2/M Phase Cell Cycle Arrest and Growth Inhibition of Oesophageal Squamous Cell Carcinoma in Vitro.

Terrestrial plants have contributed massively to the development of modern oncologic drugs. Despite the wide acceptance of Mauritian endemic flowering plants in traditional medicine, scientific evidence of their chemotherapeutic potential is lacking. This study aimed to evaluate the in vitro tumor cytotoxicity of leaf extracts from five Mauritian endemic medicinal plants, namely Acalypha integrifolia Willd (Euphorbiaceae), Labourdonnaisia glauca Bojer (Sapotaceae), Dombeya acutangula Cav. subsp. rosea Friedmann (Malvaceae), Gaertnera psychotrioides (DC.) Baker (Rubiaceae), and Eugenia tinifolia Lam (Myrtaceae). The cytotoxicities of the extracts were determined against six human cancer cell lines, including cervical adenocarcinoma, colorectal carcinoma, oesophageal adenocarcinoma, and oesophageal squamous cell carcinoma. The potent extracts were further investigated using cell cycle analysis and reverse phase protein array (RPPA) analysis. The antioxidant properties and polyphenolic profile of the potent extracts were also evaluated. Gas chromatography mass spectrometry (GC-MS) analyses revealed the presence of (+)-catechin and gallocatechin in E. tinifolia and L. glauca, while gallic acid was detected in A. integrifolia. L. glauca, A. integrifolia, and E. tinifolia were highly selective towards human oesophageal squamous cell carcinoma (KYSE-30) cells. L. glauca and E. tinifolia arrested KYSE- 30 cells in the G2/M phase, in a concentration-dependent manner. RPPA analysis indicated that the extracts may partly exert their tumor growth-inhibitory activity by upregulating the intracellular level of 5'AMP-activated kinase (AMPK). The findings highlight the potent antiproliferative activity of three Mauritian endemic leaf extracts against oesophageal squamous cell carcinoma and calls for further investigation into their chemotherapeutic application.

Readmission Rates for One Versus Two-Midnight Length of Stay for Primary Total Knee Arthroplasty: Analysis of the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) Database.

BACKGROUND: The length of stay (LOS) in the hospital for total knee arthroplasty (TKA) has been declining over recent decades. The purpose of this study was to determine if patients with an LOS for TKA that includes only 1 midnight have an increased odds of 90-day readmission compared with those with a 2-midnight LOS. We also sought to identify any predictors of 90-day hospital readmission among those readmitted during our period of analysis. METHODS: A retrospective review of the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) database was performed to identify patients with a 1-midnight or 2-midnight LOS for TKA during a 5-year period. The primary end point of this study was inpatient readmission within the 90-day postoperative period. A multiple logistic regression model and propensity score matching were used to compare the odds of 90-day readmission between 1-midnight and 2-midnight LOS. The secondary end points of this study were 90-day complications. RESULTS: There were 96,250 TKA procedures identified in the database, and 46,709 met our inclusion criteria for LOS. No difference in 90-day-readmission odds between patients with a 1-midnight LOS and those with a 2-midnight LOS for primary TKA was identified. Male sex, single marital status, age of ≥80 years, type-I diabetes, previous smoking, narcotic use prior to surgery, and a higher American Society of Anesthesiologists (ASA) scores increased the odds of 90-day readmission. Patients in the age group of ≥50 to <65 years, those with a higher preoperative hemoglobin level, and those with a positive social history of alcohol use were found to have decreased odds of readmission. CONCLUSIONS: We found no association between the LOS for primary TKA (1 midnight compared with 2 midnights) and the 90-day readmission risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Probable pulmonary embolism with repeat administration of prothrombin complex concentrate in a factor Xa inhibitor patient.

WHAT IS KNOWN AND OBJECTIVE: Prothrombin complex concentrate (PCC) is a plasma-derived concentrate used to replenish clotting factors. There are limited recommendations for treating coagulopathy induced by direct oral anticoagulants (DOAC). Data are limited regarding both total dose and repeated dosing with this population. CASE SUMMARY: We describe a case of an adult patient anticoagulated with apixaban who received two 35 unit/kg doses of PCC resulting in suspected pulmonary embolism. WHAT IS NEW AND CONCLUSION: Treatment of DOAC-induced bleeding remains an "off-label" indication for PCC. Additional doses should be given with caution if given at all and patients monitored closely.

Fermi LARGE AREA TELESCOPE OBSERVATIONS OF BLAZAR 3C 279 OCCULTATIONS BY THE SUN.

Observations of occultations of bright γ-ray sources by the Sun may reveal predicted pair halos around blazars and/or new physics, such as, e.g., hypothetical light dark matter particles-axions. We use Fermi Gamma-Ray Space Telescope (Fermi) data to analyze four occultations of blazar 3C 279 by the Sun on October 8 each year from 2008 to 2011. A combined analysis of the observations of these occultations allows a point-like source at the position of 3C 279 to be detected with significance of ≈3σ, but does not reveal any significant excess over the flux expected from the quiescent Sun. The likelihood ratio test rules out complete transparency of the Sun to the blazar γ-ray emission at a 3σ confidence level.

Alveolar rhabdomyosarcoma originating between the fourth and fifth metatarsal--case report and literature review.

We report a case of alveolar rhabdomyosarcoma arising between the fourth and fifth metatarsal. A 13-year-old boy presented to outpatients with a history of pain and swelling in the lateral aspect of his left forefoot. Plain radiographs and MRI showed a soft tissue mass displacing the fourth metatarsal. Percutaneous biopsy revealed an alveolar rhabdomyosarcoma. Staging scans showed advanced metastatic disease. The patient was treated with chemotherapy. This highly malignant lesion remains challenging to diagnose, and difficult to treat successfully.

Fiber type composition and maximum shortening velocity of muscles crossing the human shoulder.

A study of the fiber type composition of fourteen muscles spanning the human glenohumeral joint was carried out with the purpose of determining the contribution of fiber types to overall muscle cross-sectional area (CSA) and to estimate the maximum shortening velocity (V(max)) of those muscles. Muscle biopsies were procured from 4 male cadavers (mean age 50) within 24 hr of death, snap frozen, mounted, and transversely sectioned (10 microm). Slides were stained for myofibrillar ATPase after alkaline preincubation. Photoimages were taken of defined areas (100 fibers) using the Bioquant system, and fiber type and CSA were measured from these images. Staining for mATPase produced three different fiber types: slow-oxidative (SO), fast-oxidative-glycolytic (FOG), and fast-glycolytic (FG). On average, the muscle fiber type composition ranged from 22 to 40% of FG, from 17 to 51% of FOG, and from 23 to 56% of SO. Twelve out of the 14 muscles had average SO proportions ranging from 35 to 50%. V(max) was calculated from the fiber type contribution relative to CSA and shortening velocity values taken from the literature. The maximum velocities of shortening presented here provide a physiological basis for the development of human shoulder musculoskeletal models suitable for predicting muscle forces for functionally relevant tasks encompassing conditions of muscle shortening and lengthening.

Effects of glenohumeral rotations and translations on supraspinatus tendon morphology.

OBJECTIVE: The purpose of this study was to evaluate the effects of glenohumeral rotations and humeral head translations on supraspinatus tendon morphology. DESIGN: A convenience sample of cadaver shoulders was used to measure supraspinatus tendon shape and dimensions from MRI images. BACKGROUND: Epidemiological evidence has indicated that shoulder elevation and external rotation may be risk factors for rotator cuff tendon pathology, but little is known about how these postures affect tendon morphology. METHODS: Measurements of supraspinatus tendon morphology were made from three-dimensional reconstructions based on T2-weighted fast spin-echo magnetic resonance images. Seven cadaver arms were imaged at neutral, 45 degrees external and 45 degrees internal rotations at 0 degrees, 30 degrees, and 60 degrees of glenohumeral abduction. Measurements of the anterior, middle, and posterior portions of the tendon were made using ANALYZE software. RESULTS: The supraspinatus tendon was twisted at the muscle-tendon junction of the middle and posterior portions in 45 degrees external and 45 degrees internal axial rotations of the humerus, especially over 30 degrees of abduction. Abduction over 30 degrees shortened the entire supraspinatus tendon. External and internal rotation motions elongated the anterior and posterior portions, respectively. CONCLUSIONS: Arm posture affects morphology of the supraspinatus tendon. RELEVANCE: The results support the epidemiologic evidence linking external rotation and abduction to supraspinatus tendon disorders.

Altered transcription in yeast expressing expanded polyglutamine.

Expanded polyglutamine tracts are responsible for at least eight fatal neurodegenerative diseases. In mouse models, proteins with expanded polyglutamine cause transcriptional dysregulation before onset of symptoms, suggesting that this dysregulation may be an early event in polyglutamine pathogenesis. Transcriptional dysregulation and cellular toxicity may be due to interaction between expanded polyglutamine and the histone acetyltransferase CREB-binding protein. To determine whether polyglutamine-mediated transcriptional dysregulation occurs in yeast, we expressed polyglutamine tracts in Saccharomyces cerevisiae. Gene expression profiles were determined for strains expressing either a cytoplasmic or nuclear protein with 23 or 75 glutamines, and these profiles were compared to existing profiles of mutant yeast strains. Transcriptional induction of genes encoding chaperones and heat-shock factors was caused by expression of expanded polyglutamine in either the nucleus or cytoplasm. Transcriptional repression was most prominent in yeast expressing nuclear expanded polyglutamine and was similar to profiles of yeast strains deleted for components of the histone acetyltransferase complex Spt/Ada/Gcn5 acetyltransferase (SAGA). The promoter from one affected gene (PHO84) was repressed by expanded polyglutamine in a reporter gene assay, and this effect was mitigated by the histone deacetylase inhibitor, Trichostatin A. Consistent with an effect on SAGA, nuclear expanded polyglutamine enhanced the toxicity of a deletion in the SAGA component SPT3. Thus, an early component of polyglutamine toxicity, transcriptional dysregulation, is conserved in yeast and is pharmacologically antagonized by a histone deacetylase inhibitor. These results suggest a therapeutic approach for treatment of polyglutamine diseases and provide the potential for yeast-based screens for agents that reverse polyglutamine toxicity.

The relationship between Parson's tubercle and the insertion of the anterior horn of the medial meniscus.

PURPOSE: The purpose of this investigation was to correlate the anatomic characteristics of the third intercondylar tubercle of Parsons (TITP) with the insertional variations of the anterior horn of the medial meniscus using precise measurements in an anatomic cadaver study. Our hypothesis was that the height of the TITP would correlate with the degree of inferior insertion of the medial meniscus. TYPE OF STUDY: A cadaver study using a convenience sample. METHODS: Twenty unpaired proximal tibia specimens without advanced arthritis were analyzed with a coordinate measuring machine using a 0.479-mm diameter probe. A reference plane was created using 3 reproducible points on the tibial surface. Measurements from the TITP included another reference plane through its base, which was used to calculate its absolute height. The locations of the anterior- and inferior-most insertional points of the anterior horn of the medial meniscus were also determined. Correlations between the height of the TITP and age were also made. RESULTS: The overall height of the TITP was found to correlate with the degree of inferior insertion of the anterior horn of the medial meniscus (r =.52, P =.019). No correlation was found with the anterior placement of the meniscus (r =.12, P =.629) or with the age of the specimen (r =.14, P =.592). CONCLUSIONS: This absolute height of the TITP correlates with the inferior location of the insertion of the anterior horn of the medial meniscus. This association suggests a developmental relationship between 2 anatomic structures within the knee.

The effect of wearing a back belt on spine kinematics during asymmetric lifting of large and small boxes.

STUDY DESIGN: A crossover design was used to evaluate kinematic measurements collected with an infrared-based motion measurement system. OBJECTIVES: To evaluate belt effects on spine kinematics during asymmetric lifting of large and small boxes and to test for carryover effects between trials from belts. SUMMARY OF BACKGROUND DATA: Conflicting evidence in the literature exists regarding whether belts are beneficial or detrimental to manual material handlers. Studies have not examined belt effects when lifting different sized boxes, nor carryover effects from belts. METHODS: Twenty-eight subjects with manual-handling experience (17 male and 11 female) were randomly assigned to lift either a large or small box (weighing 9.4 kg), from a sagittally symmetric origin at pallet height to a 79 cm height, 60 degrees to the right. Spine flexion, lateral bending and twisting, hip and knee flexion, and angular velocity measurements of the torso with respect to the pelvis were collected for each of three lifting periods, 50 lifts each at 3 lifts per minute, with 18-minute breaks between periods. RESULTS: Belts significantly reduced maximum spine flexion, spine flexion and extension angular velocities, and torso left lateral bending angular velocity, and increased hip and knee flexion, regardless of box size. When lifting large boxes, belts significantly reduced torso right lateral bending and torso left twisting. No significant differential carryover effects were detected from belts. CONCLUSIONS: Subjects with belts lifted more slowly and used more of a squat-lift technique, regardless of box size. Belts reduced more torso motions while lifting large boxes.

Therapeutic opportunities in polyglutamine disease.

Polyglutamine diseases comprise a class of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine tracts. Great progress has been made in elucidating the molecular mechanisms contributing to polyglutamine pathology, and in identifying potential drug targets. Although much remains to be learned, these advances provide an opportunity for rational approaches to target-based drug discovery.

Prediction of muscle force involved in shoulder internal rotation.

The estimation of shoulder muscle force is important to understand the mechanism of rotator cuff injury. In general, mean parameter values are used as input for computational models. However, anatomic and biomechanical parameters vary widely among people. The purpose of this study was to evaluate shoulder muscle forces predicted by an electromyography-driven muscle model given neuromuscular parameters generated by Monte Carlo simulation. Normal distributions were used to model muscle moment arms; electromyographic and muscle physiological cross-sectional area data were modeled with log-normal distributions. Eight muscles were included in the model. Muscle force and joint moment were predicted on the basis of the simulated parameters. The results showed that the subscapularis and pectoralis major were substantial actuators for shoulder internal rotation. During maximum voluntary contraction the median of the muscle forces of the subscapularis and the pectoralis major were 1030 N and 462 N, respectively. This study demonstrated that the Monte Carlo method could be used for muscle force prediction by integrating population variability of physiological parameter into a biomechanical muscle model.

Systematic and large-scale two-hybrid screens.

The increasing rate at which complete genome sequences become available necessitates rapid and robust methods for investigating the functions of their encoded proteins. Efforts have been made to study protein function by systematically screening large sets of proteins using the two-hybrid method. Analyses of the complete proteomes of baceriophage T7, the mammalian viruses hepatitis C and vaccinia, as well as of several protein complexes including RNA splicing proteins and RNA polymerase III from yeast, have been undertaken. Saccharomyces cerevisiae has been studied extensively by two-hybrid methods, with more than 2500 protein-protein interactions described. Systematic studies on metazoan proteomes are, however, still in their infancy.

Effect of optimization criterion on spinal force estimates during asymmetric lifting.

Optimization-based muscle force prediction models of the lumbar region are used in research and ergonomic practice, usually as a subroutine of a job analysis software package. Various optimization criteria have been put forward for use in rationally selecting a set of muscle forces to satisfy moment equilibrium, including the sum of cubed muscle contraction intensities and a double linear programming procedure for minimizing the spinal compression force and maximum muscle contraction intensity. A laboratory study was conducted to determine whether these two model formulations produce significantly different estimates of spinal forces for a dynamic asymmetric lift. Although statistically significant differences were found between the predictions of the two models, the difference in peak spinal compression force was only 1.1%.

Normative values of agonist-antagonist shoulder strength ratios of adults aged 20 to 78 years.

OBJECTIVE: To determine normative values for isometric flexion/extension, abduction/adduction, and external/internal rotation strength ratios about the shoulder and to determine if these ratios are affected by age or gender. STUDY DESIGN: A cross-sectional study of 120 healthy volunteers (60 men, 60 women) aged 20 to 78 years. SETTING: Orthopedic research laboratory. METHODS: Flexion and extension strengths were measured isometrically using a Cybex II dynamometer at arm flexion angles of 30 degrees, 60 degrees, and 90 degrees. Abduction and adduction strengths were measured at 30 degrees, 60 degrees, and 90 degrees abduction. Internal and external rotation strengths were measured (1) with the arm abducted 15 degrees and neutral external/internal rotation and (2) with the arm abducted 90 degrees and externally rotated 30 degrees above the transverse plane. OUTCOME MEASURES: Isometric strength ratios for flexion/extension, abduction/adduction, and external/internal rotation. RESULTS: No statistically significant differences in agonist/antagonist strength ratios were found between dominant and nondominant sides or between genders. Age was associated with changes in strength ratios for measurements taken with the arm flexed or abducted 90 degrees. Posture was found to affect strength ratios. CONCLUSIONS: These data can serve as a normative reference for clinical use.

Identification of optimal strategies for increasing whole arm strength using Karush-Kuhn-Tucker multipliers.

OBJECTIVE: The purpose of this study was to develop a computer model for identifying muscles critical to improving functional upper extremity strength. DESIGN: A three-dimensional biomechanical model of the upper extremity was developed, and the predictions were compared to maximal arm strength data collected from healthy volunteers. BACKGROUND: Although several optimization-based mathematical models of the shoulder have been developed, none have utilized the mathematical properties of the Karush-Kuhn-Tucker multipliers to efficiently estimate the effect of strengthening individual muscles on functional strength of the whole arm. METHODS: A static three-dimensional biomechanical model of the glenohumeral, radio-humeral, ulno-humeral and wrist joints was developed for predicting maximal hand exertion forces. The model was formulated as a linear program. Constraints consisted of moment equilibrium conditions and limits on maximum and minimum allowable muscle forces. Predicted arm strengths were compared to maximal pull strength measurements made on 10 subjects (5 male; 5 female). The task involved pulling toward the mid-sagittal plane of the body with the arm flexed 45 degrees. The Karush-Kuhn-Tucker variables associated with the maximal limits on muscle force were computed to estimate the effect of altering the strength of individual muscles on functional arm strength. RESULTS: Maximum pull strengths were predicted well by the model. Karush-Kuhn-Tucker values ranged from 0 (for muscles not at their upper force limits) to 0.11 for the flexor carpi radialis and pectoralis major muscles. Karush-Kuhn-Tucker multipliers were found to be insensitive to the assumed specific tension of muscle. CONCLUSIONS: Upper extremity strength can be predicted from musculoskeletal geometry and physiology using linear programming. RELEVANCE: Karush-Kuhn-Tucker multipliers associated with the muscle force upper limits give insight into the effect of strengthening individual muscles on whole arm exertion strength. Such an analysis may provide insight into the development of optimal rehabilitation protocols.

Age-related changes in normal isometric shoulder strength.

Normative data are useful for assessing isometric shoulder strength in patients with bilateral shoulder abnormalities. The purpose of this study was to develop a normative database for shoulder strength in the clinically relevant positions and movements. Twenty combinations of exertions and postures-including flexion, extension, abduction, adduction, internal rotation, and external rotation-were tested for both the dominant and nondominant sides. Strength was measured isometrically using a modified Cybex II dynamometer. The cross-sectional study design included 120 subjects (60 women and 60 men) ranging in age from 20 to 78 years from southern Minnesota. Tables of normative strength data were constructed. Multivariate analyses were performed to assess the effect of age, sex, and weight on strength. Age was negatively associated with all strength measures, and weight was positively associated with them. Men were stronger than women when controlling for age and weight. Statistically significant differences between dominant and nondominant shoulders were found for only some of the strength measures taken. These normal data will be useful to the clinician, as they permit a standard against which to compare shoulder strength.