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Background: Rituximab (RTX) and eculizumab (ECU) are treatment options for refractory myasthenia gravis (MG), but comparative clinical data derived from real‐world experience are limited. Here, we describe the baseline characteristics, treatment, and safety outcomes of patients with antiacetylcholine receptor antibody‐positive (AChR+) generalized myasthenia gravis (gMG) treated with ECU and/or RTX in our clinic. Methods: Patients with refractory AChR+ gMG who received ECU or/and RTX treatment for more than 1 year at the Department of Neurology, Istanbul Faculty of Medicine were included in this observational study. After obtaining written patient consent, data were collected retrospectively from medical records. Results: Twelve patients treated with ECU and 25 patients treated with RTX were included in the analysis. Groups were comparable with regard to demographic and clinical characteristics, including age at onset of MG, disease duration, and history of thymoma. ECU was associated with significantly better outcomes compared with RTX, as measured by decreases in the mean MG activities of daily living score at 1 (p = 0.024), 3 (p < 0.001), 6 (p < 0.001), and 12 (p < 0.001) months of treatment; steroid‐sparing effect after 1 year of treatment (decrease in mean [standard deviation] daily prednisolone dose of −21.8 mg [13.5] vs. −6.6 mg [9.4] with RTX; p < 0.001); and need for rescue treatment and number of myasthenic crisis episodes during treatment (p < 0.001). No new safety signals were observed with either treatment. Conclusion: Our data provide real‐world evidence supporting ECU over RTX to treat patients with refractory AChR+ gMG. [ABSTRACT FROM AUTHOR]

Objective: To investigate differences in electromyography (EMG), muscle activity, and scapular kinematics during elevation in the scapular plane between healthy controls, participants with multidirectional shoulder laxity (MDL), and patients with multidirectional shoulder instability (MDI) who are diagnosed with hypermobile Ehlers‐Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Methods: Twenty‐seven women with hEDS/HSD and MDI, 27 female healthy control subjects, and 28 female subjects with MDL participated in this study. Scapular 3‐dimensional kinematic data were obtained using 8 Oqus Qualisys cameras. Simultaneously, surface EMG was used to measure muscle activity of the upper, middle, and lower trapezius, infraspinatus, latissimus dorsi, serratus anterior, posterior deltoid, and pectoralis major during arm elevation in the scapular plane. Group differences were assessed using statistical parametric mapping. Results: Regarding scapular kinematics, significantly less upward rotation was observed in hEDS/HSD patients with MDI compared to both healthy controls and MDL subjects. Significantly less posterior tilt was seen in hEDS/HSD patients compared to MDL subjects. Furthermore, significantly higher EMG activity of the infraspinatus, middle trapezius, and posterior deltoid was found in hEDS/HSD patients with MDI. Conclusion: hEDS/HSD patients with MDI demonstrate altered scapular kinematics and increased EMG muscle activity compared to subjects without MDI. These findings could serve as a stepping stone for future research regarding treatment strategies in patients whose conditions belong to the hypermobility spectrum. [ABSTRACT FROM AUTHOR]

Background: Shoulder pain is one of the most common musculoskeletal concerns in manual wheelchair users including among athletes. However, there is a paucity of research characterizing both shoulder pain and shoulder pathology in this population. Objective: To characterize and compare the prevalence of current shoulder pain and ultrasound metrics of shoulder pathology between wheelchair athletes, nonathletic wheelchair users, and nonwheelchair users. Design: Cross-sectional. Setting: Chicago-area adaptive sport teams/programs and musculoskeletal clinics. Participants: Thirty-four wheelchair athletes, six nonathletic wheelchair users, and 12 nonwheelchair users. Methods: Self-reported shoulder pain was assessed by questionnaire and Wheelchair User Shoulder Pain Index (WUSPI). Shoulder physiology and pathology were assessed by physical and ultrasound evaluation of both shoulders by a sports medicine physician. Main Outcome Measures: Questionnaire outcomes: Prevalence of current shoulder pain, total WUSPI score. Physical examination outcomes: total Physical Examination of Shoulder Scale (PESS) score. Sonographic outcomes: Acromiohumeral distance (AHD) and presence of shoulder pathology. Results: The majority of wheelchair athletes (68%) and nonathletic wheelchair users (67%) experienced shoulder pain since using a manual wheelchair. Wheelchair basketball players had a mean WUPSI score of 17.2 (SD = 21.8), and athletes participating in handcycling, sled hockey, and quad rugby had mean scores of 4.91 (SD = 8.32), 7.76 (SD = 13.1), and 4.29 (SD = 7.75), respectively. Shoulder pathology was observed in 14 of 31 (45%) wheelchair athletes and 4 of 6 (67%) nonathletic wheelchair users (p = .41). Conclusions: Although wheelchair use is a risk factor for shoulder pain, participation in amateur wheelchair sports may not be associated with increased risk of shoulder pain. It is possible that overhead sports such as wheelchair basketball may define a unique high-risk group. Further study is needed to examine this relationship and to determine whether there are differences between specific wheelchair sports. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent cancer and a major cause of death in women worldwide. Although early diagnosis and therapeutic intervention significantly improve patient survival rate, metastasis still accounts for most deaths. Here it is reported that, in a cohort of more than 2000 patients with breast cancer, overexpression of PI3KC2α occurs in 52% of cases and correlates with high tumor grade as well as increased probability of distant metastatic events, irrespective of the subtype. Mechanistically, it is demonstrated that PI3KC2α synthetizes a pool of PI(3,4)P2 at focal adhesions that lowers their stability and directs breast cancer cell migration, invasion, and metastasis. PI(3,4)P2 locally produced by PI3KC2α at focal adhesions recruits the Ras GTPase activating protein 3 (RASA3), which inactivates R‐RAS, leading to increased focal adhesion turnover, migration, and invasion both in vitro and in vivo. Proof‐of‐concept is eventually provided that inhibiting PI3KC2α or lowering RASA3 activity at focal adhesions significantly reduces the metastatic burden in PI3KC2α‐overexpressing breast cancer, thereby suggesting a novel strategy for anti‐breast cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives. This study is aimed at elucidating the prevalence of depression in patients with myasthenia gravis (MG) and examining the risk factors associated with depression. Methods. We evaluated adult patients with MG who were recruited from two tertiary hospitals in the central region (Riyadh) of Saudi Arabia. Data were collected with a two-part standardized questionnaire: the first part included data on sociodemographic and clinical features of MG including disease type and duration, therapies, prednisolone dose, time of the last relapse, previous critical care unit admissions, MG status (controlled, partially controlled, or uncontrolled), and comorbid diseases; the second part included items from the previously validated Arabic version of the Patient Health Questionnaire-9 (PHQ-9). Results. In total, 104/150 (69.3%) patients participated (72 females) with a mean age of 38.0±16.0 years. The mean PHQ-9 score was 7.02±6.1. Among all the participants, 27 (26.0%) patients had depression (PHQ‐9≥10). Multiple logistic regression analysis revealed that uncontrolled MG status (OR=12.31, 95%CI=1.13‐133.8, P=0.04) was the only factor independently associated with depression. Collectively, the prevalence of depression among patients of the primary care clinics (PCC) as reported by 5 previous studies across multiple regions of the country was 15.8%. The odds of depression among MG patients were twofold higher than those among PCC patients (OR=2.05, 95%CI=1.30‐3.22, P=0.002). Conclusions. Approximately a quarter of MG patients have depression. Achieving a minimal manifestation or better MG status may decrease the depression rate in these patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that neck pain patients feel increased symptoms following upper limb activities, and altered axioscapular muscle function has been proposed as a contributing factor.Methods: Pain sensitivity and muscle activity, during arm movements, were assessed in neck pain patients and controls. Patients with ongoing insidious-onset neck pain (IONP, N = 16) and whiplash-associated disorders (WAD, N = 9) were included along with sex- and age-matched controls (N = 25). Six series of repeated arm abductions were performed during electromyographic (EMG) recordings from eight bilateral muscles. The first and last three series were separated by 8 min and 42 s, respectively. Each series consisted of three slow and three fast movements. Pressure pain thresholds (PPTs) were recorded bilaterally from neck, head and arm at baseline, after the third and sixth movement series. Pain intensity was recorded on an electronic visual analogue scale (VAS).Results: Larger pain areas and higher VAS scores were found in patients compared with controls (p < 0.001), and in patients, the VAS scores increased in the course of movements (p < 0.02). PPTs were lower in patients compared with controls at all sites (p < 0.03), and these decreased during arm movements in the IONP group (p < 0.03), while increasing at head and neck sites in controls (p < 0.04). During the slow movements, increasing serratus anterior EMG activity was found in the series with short breaks in-between for the WAD group compared with IONP and controls (p < 0.001).Conclusion: Axioscapular movement caused different responses in pain sensitivity and muscle activity between neck pain patient groups compared with controls.Significance: Neck pain patients report increased symptoms following upper limb activities. This study shows that repeated arm movements caused differentiated responses in pain sensitivity and muscle activity between subgroups of neck pain patient and asymptomatic controls. Such findings may be of great clinical significance when planning rehabilitation for this patient population. [ABSTRACT FROM AUTHOR]

The aim of the study was to quantify the activation of arm and shoulder muscles during a static therapeutic climbing exercise and to investigate the possibility of altering the muscle activation through arm position (Jug, Undercling, Sidepull internal rotated, Sidepull external rotated), hand support (one-handed, double-handed) and wall inclination (0°, 12°). Electromyographic (EMG) activity of 14 healthy, climbing unexperienced males for the right m. biceps brachii (BB), m. serratus anterior (SA), m. upper, middle and lower trapezius (UT, MT, LT) showed mainly low to moderate EMG activation levels (BB: 4.1–40.1% maximum voluntary isometric contraction (MVIC), SA: 4.5–24.5% MVIC, UT: 1.3–28.0% MVIC, MT: 8.6–47.1% MVIC, LT: 3.8–47.3% MVIC). Significant differences occurred between the four arm positions for the UT and LT. The one-handed support revealed significant higher muscle activation than the double-handed support in every condition except for SA in Undercling arm position at 12° wall inclination. Increasing the wall inclination (from 0° to 12° overhang) led to a significant increase in muscle activation in nearly every exercise variation and muscle. These findings suggest that arm position, hand support and wall inclination are appropriate possibilities of altering muscle activation patterns in therapeutic climbing. [ABSTRACT FROM PUBLISHER]

Background: Scapular orientation may be influenced by static body posture (sitting and standing) and contribute to the development of shoulder pain. Therefore, a consistent body posture should be considered when assessing scapular orientation as well as enhancing optimal scapular positioning.Objective: To determine whether there are differences in scapular orientation between standing, neutral sitting, and habitual sitting, while adjusting for spinal posture.Design: A single group randomized repeated measures study.Setting: University laboratory.Participants: Twenty-eight participants with shoulder pain were recruited from the community.Methods: Scapular orientation between standing and seated positions was compared, with the arm by the side and at 120° of glenohumeral scaption. Thoracic kyphosis and lumbar lordosis angles were used as covariates.Main Outcome Measurements: Scapular elevation, lateral translation, upward rotation, and posterior tilt.Results: Scapular orientation was marginally but significantly different between sitting postures for lateral translation (mean 0.5 cm; 95% confidence interval [95% CI] 0.2-0.7 cm); P < .001), upward rotation (mean 3°; 95% CI 1.1-5.0°; P < .001), and posterior tilt (mean 2.3°; 95% CI 0.2-4.3°; P = .009) in the arm by side position. A small-but-significant difference between standing and neutral sitting was found for upward rotation (mean 1.8°; 95% CI 0-3.7°; P = .02), and between standing and habitual sitting for lateral translation (mean 0.6 cm; 95% CI 0-1.1 cm; P =.02) in the arm by side position.Conclusions: The results of this study suggest that scapular orientation can be slightly affected by body posture, although the clinical relevance is uncertain. To enhance scapular upward rotation or posterior tilt, it may be preferable to place the patient in neutral sitting.Level Of Evidence: Not applicable. [ABSTRACT FROM AUTHOR]

Enzymes have been used in organic chemistry and biotechnology for 100 years, but their widespread application has been prevented by a number of limitations, including the often-observed limited thermostability, narrow substrate scope, and low or wrong stereo- and/or regioselectivity. Directed evolution provides a means to address and generally solve these problems, especially since recent methodology development has made this protein engineering method faster, more efficient, and more reliable than in the past. This Darwinian approach to asymmetric catalysis has led to a number of industrial applications. Metabolic-pathway engineering, mutasynthesis, and fermentation are likewise enzyme-based techniques that enrich chemistry. This account outlines the scope, and particularly, the limitations, of biocatalysis. The complementary nature of enzymes and man-made catalysts is emphasized. [ABSTRACT FROM AUTHOR]

ABSTRACT Rotator cuff and scapular muscle strengthening exercises are an essential part of shoulder rehabilitation and sports training. Although the effect of exercise training on pain and function have been widely investigated, few studies have focused on the changes in shoulder kinematics and muscle activity after exercise training. Therefore, the purpose of the present study was to investigate the effect of rotator cuff and scapular strengthening exercises on shoulder kinematics and the activation of rotator cuff and scapular muscles in healthy subjects. Thirty-six healthy subjects were recruited and randomly assigned into either a training or control group. Subjects in the training group were trained with rotator cuff and scapular strengthening exercises for 4 weeks. Scapular kinematics and shoulder muscle activity during arm elevation were measured before and after exercise training. After the 4-week training protocol, there was an increase in strength and a decrease in upper trapezius activation in the training group, which is consistent with previous studies. However, no difference was found in scapular kinematics and activation of rotator cuff muscles between the control and training groups after the training protocol. Although the exercise protocol resulted in strength gains for the rotator cuff, these gains did not transfer to an increase in muscle activation during motion. These results demonstrate the difficulty in changing activation patterns of the rotator cuff muscles. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2079-2088, 2016. [ABSTRACT FROM AUTHOR]

Background: Biomechanical studies have demonstrated that the lower trapezius (LT) facilitates normal shoulder function, and given its potential role in causing and/or perpetuating dysfunction, clinicians have begun to evaluate and rehabilitate the LT in the context of comprehensive shoulder rehabilitation programs. Although some studies have compared side-to-side differences in LT thickness among nonthrowers, no studies have been performed to examine the normal ultrasound appearance of the LT in the adolescent throwing population.Objectives: To examine whether LT thickness and cross-sectional area (CSA) differ between dominant and nondominant sides in adolescent baseball pitchers and to determine the inter-rater and intrarater reliability of the sonographically measured parameters.Study Design: Observational, repeated measures study.Setting: Hospital-based outpatient practice.Participants: Thirty asymptomatic male baseball pitchers aged 13-18 years with at least 3 years of pitching experience from a convenience sample in the Rochester, Minnesota, area.Methods: LT thickness and CSA were measured at the T8 and T5 vertebral levels at rest, and thickness was measured again in active prone T- and Y-pose positions by multiple investigators. Side-to-side differences in thickness and CSA were examined, and inter-rater and intrarater measurement reliability coefficients were estimated.Main Outcome Measurements: Thickness and cross-sectional area were measured. For reliability, we calculated intraclass correlation coefficients along with the standard error of measurement and the minimal detectable change.Results: Resting LT thickness was 0.064 cm greater on the dominant side than on the nondominant side (P = .001). During contraction, LT thickness was 0.084 and 0.097 cm greater on the dominant side in the T and Y poses (P = .036 and P = .001, respectively). The CSA at the T5 level was 0.36 cm(2) greater on the dominant side than on the nondominant side (P < .001). Inter-rater and intrarater reliability coefficients exceeded 0.898 across all levels of measurement.Conclusion: Asymptomatic adolescent pitchers have greater resting and contracted LT thickness and resting CSA on the dominant versus the nondominant side, although the quantitative differences are small. These differences suggest that structural changes and asymmetry can manifest at young ages; however, clinically, the nondominant arm can be used as a control in the adolescent pitching population. Ultrasound provides a noninvasive way to reliably evaluate LT thickness and CSA in adolescent pitchers. [ABSTRACT FROM AUTHOR]

Chiral polyesters in general can be employed for versatile biomedical purposes, but in vitro enzyme catalyzed biocatalytic routes by a multiple-step cascade to make these functional biodegradable chiral polyesters have been hardly investigated. Recently, we developed an artificial three-step enzymatic cascade synthesis by combining an alcohol dehydrogenase (ADH), a Baeyer-Villiger monooxygenase (BVMO) and a lipase (CAL-A). Here, we extended this cascade for the synthesis of chiral methyl-substituted oligo-e-caprolactone derivatives to achieve both, the generation of chirality in a monomer and the subsequent polymerization. Several substrates were examined and provided access to functionalized chiral compounds in high yields (up to >99%) and optical purities (up to >99% ee). By subsequent enzymatic enantioselective ring opening of the enantiopure monomers, oligomeric lactones were successfully synthesized. [ABSTRACT FROM AUTHOR]

Enoate reductases are versatile enzymes for the enantio- and regioselective addition of hydrogen to double bonds. We identified three EREDs (XenA, XenB, NemA) from Pseudomonas putida ATCC 17453 through a sequence motif search. In addition to cloning, functional expression, and biochemical characterization of these enzymes, the enoate reductases were also applied in enzyme cascade reactions in combination with a Baeyer-Villiger monooxygenase and an alcohol dehydrogenase to produce lactones. [ABSTRACT FROM AUTHOR]

Joined forces: Alcohol dehydrogenase, enoate reductase, and Baeyer–Villiger monooxygenase are combined in a cascade reaction by coexpression in E. coli to have a recombinant whole‐cell biocatalyst. Such an artificial metabolic “mini”‐pathway provides access to functionalized chiral compounds in high yields and optical purities as exemplified for kinetic resolutions, desymmetrizations, and regiodivergent biotransformations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Farmers are being called to use plant protection products (PPPs) more consciously and adopt more sustainable crop protection strategies. Indicators will help farmers to monitor their progress towards sustainability and will support their learning process. Talking the indicators through in farmers' discussion groups and the resulting peer encouragement will foster knowledge acquirement and can lead to changes in attitudes, norms, perception and behaviour. RESULTS: Using a participatory approach, a conceptual framework for on-farm sustainable crop protection practices was created. The same participatory approach was used to design a dual indicator set, which pairs a pesticide impact assessment system (PIAS) with a farm inquiry. The PIAS measures the risk for human health and the environment exerted by chemical crop protection. The inquiry reveals the farmers' response to this risk, both in terms of the actions they take and their knowledge, awareness and attitude. CONCLUSIONS: The dual indicator set allows for implementation in four tiers, each representing increased potential for monitoring and social learning. The indicator set can be adjusted on the basis of new findings, and the participatory approach can be extrapolated to other situations. Copyright © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Second harmonic generating (SHG) nanoprobes have recently emerged as versatile and durable labels suitable for in vivo imaging, circumventing many of the inherent drawbacks encountered with classical fluorescent probes. Since their nanocrystalline structure lacks a central point of symmetry, they are capable of generating second harmonic signal under intense illumination - converting two photons into one photon of half the incident wavelength - and can be detected by conventional two-photon microscopy. Because the optical signal of SHG nanoprobes is based on scattering, rather than absorption as in the case of fluorescent probes, they neither bleach nor blink, and the signal does not saturate with increasing illumination intensity. When SHG nanoprobes are used to image live tissue, the SHG signal can be detected with little background signal, and they are physiologically inert, showing excellent long-term photostability. Because of their photophysical properties, SHG nanoprobes provide unique advantages for molecular imaging of living cells and tissues with unmatched sensitivity and temporal resolution. [ABSTRACT FROM AUTHOR]

This study reports on the experience of women in four community breast cancer self-help groups in Ontario, Canada. Semi-structured interviews were conducted with 24 women, asking them about benefits and limitations of their group involvement, and about their perspectives on group processes and structures. Overall, participants reported their group involvement to be extremely helpful for navigating the short and long-term impact of breast cancer. Emotional support benefits included connecting with other breast cancer survivors, feeling understood and sharing experiences, providing hope, and sharing healing laughter. Informational and practical support benefits included sharing of important information and learning how to get what you want. Even where there were concerns about limitations or tensions of group experience, these occurred against a backdrop of appreciation and commitment. From the discussion of group processes and structures, a number of issues were identified as problematic. Most notable were how to deal with deaths of group members and how to balance the group's primary purpose of providing mutual support with secondary goals of dealing with group business and engaging in meaningful advocacy. © 1997 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Careless or confused use of terms such as information giving, teaching and counselling may lead to inadequate understanding and practice. In view of the progress made in this area, designed to help patients cope with illness and treatment, this paper aims to clarify and identify similarities and differences between these activities and discuss their relevance for those in most need of these types of care. Having recognised the complexity and persistence of such needs, patients, their relatives and nurses should perhaps decide their respective roles and work towards improving the quality of and opportunities for such interventions. [ABSTRACT FROM AUTHOR]