Search

The present study aimed to identify the HCO3--dependent mechanisms contributing to the homeostasis of the intracellular pH (pHi) in ruminal epithelial cells of sheep. Therefore, pHi was measured spectrofluorometrically in primary cultured ruminal epithelial cells loaded with the pH-sensitive fluorescent dye, 2′,7′-bis(carboxyethyl)-5(6′)-carboxyfluorescein acetoxymethyl ester. Switching from a HEPES-buffered to a CO2/HCO3--buffered solution caused a rapid intracellular acidification followed by a counter-regulation towards alkaline levels. The counter-regulation was totally dependent upon extracellular Na+, but independent of intracellular Cl-. Adding 30 μM EIPA to the solutions did not affect the pHi counter-regulation following the acidification. Presence of 500 M H2DIDS inhibited the counter-regulation of pHi by 67%. These results pointed to a Na+–HCO3--cotransporter (NBC) as the main pHi regulatory mechanism in the presence of HCO3-. Existence of an NBC in both cultured ruminal epithelial cells and intact ruminal epithelium was verified by reverse transcription polymerase chain reaction (RT-PCR) studies. RT-PCR yielded a band of the expected molecular size of 333 bp in both cultured cells and intact epithelium. The mRNA sequences were identical and shared a homology of 62% with human kidney NBC (Genebank accession number AF007216), of 66% with rat kidney NBC (AF004017) and of 65% with mouse duodenal NBC (AF141934). [ABSTRACT FROM AUTHOR]

Aminofunctional siloxanes are important auxiliary chemicals for softening in a broad class of finishing applications. They provide "supersoft" hand in premium grade fabrics in addition to other important benefits. Their chief drawback is yellowing with loss of water absorbency. The structure activity relationship between the arrangement of pendant aminofunctional side chains and important finish responses such as whiteness, hand, water absorbency and soil release is explored. Surprisingly, dramatic effects are observed which suggest that optimization of the structure of the aminofunctional side chain could lead to substantial finish Improvement. [ABSTRACT FROM AUTHOR]

Introduction: Doctor of Physical Therapy (DPT) students have reported learning new behaviors, enhanced self-awareness, and personal and professional growth during their first year of DPT school. The purpose of this study was to explore in greater depth, through semistructured interviews, the student perceptions of self-identity and social identity., Subjects: Seventeen early second-year DPT students from 3 universities., Methods: This investigation is an extension of a larger multisite study. Qualitative interviews were employed to enable the use of a constructivist lens to explore the importance of personal context in participants' experiences during the first year of DPT school., Results: Students across programs shared similar characteristics and experiences. Three themes emerged: DPT students share common perceptions of themselves and classmates; sociocultural experiences shaped their actions and perceptions of self; and students recognized the need to change to be successful. The voices of the older second-career students and racially minoritized students were uniquely different from other participants., Discussion and Conclusion: Doctor of Physical Therapy student experiences are similar across programs except for older students and racially minoritized students. Early professional identity formation was noted as well. A richer understanding of the personal characteristics, influential sociocultural factors, and student perceptions of self and classmates could enable educators to customize supports and educational strategies to help students understand the role their past and present experiences play in shaping their professional identities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Academy of Physical Therapy Education, APTA.)

Background: The Association of American Medical Colleges suggests an Experiences-Attributes-Metrics framework for holistic review, but there is minimal research on demographic and personal characteristic attributes and the interplay between these Attributes subcategories. Understanding how personal attributes may vary among students considered represented and those considered underrepresented in one or more categories is critical to avoid unintentionally perpetuating practices that favor represented groups. This study explored differences in six personal characteristics either consistently related to academic performance or deemed positive professional traits based on diversity characteristics (categories of underrepresentation), age, and sex., Methods: Three cohorts of first-year Doctor of Physical Therapy students at a single institution were invited to participate in this prospective, observational study. Participants completed six surveys: PROMIS® General Self-efficacy, PROMIS® Anxiety, 12-item Grit Scale, Perceived Stress Scale-10 (PSS-10), Brief Resilience Scale (BRS), and PROMIS® Positive Affect. T-tests and ANOVAs (or nonparametric equivalents) were used to examine differences in these measures by number of diversity characteristics, age, and sex. Multivariate linear regression was used to determine if diversity characteristics explained additional variance in each of the personal attribute scores after controlling for age and sex., Results: One Hundred and Forty Five students participated (80.7% female, 77.9% < 25 years old, 51% 0 diversity characteristics). Students with more diversity characteristics and males reported higher self-efficacy and resilience (p's < 0.05). Females reported higher anxiety (p's < 0.01). Diversity characteristics explained additional variance in self-efficacy (3.3%, p = 0.02) and resilience (2.5%, p = 0.05) after controlling for age and sex. Grit, perceived stress, and positive affect did not show any group differences., Conclusions: Underrepresented students demonstrated higher self-efficacy and resilience than their represented peers, qualities that may be important to overcome challenges prior to and during graduate school. Males exhibited higher self-efficacy and resilience, but lower anxiety than females which is generally consistent across higher education. Grit, perceived stress, and positive affect were similar across all students and may be less useful to create a diverse learning environment. Further studies should investigate differences in attributes among admitted and unadmitted students and the relationship to future performance for admitted students., (© 2024. The Author(s).)

Objective: The purpose of this study was to explore how physical therapists use movement as a component of their clinical reasoning. Additionally, this research explored whether movement as a component of clinical reasoning aligns with the proposed signature pedagogy for physical therapist education, human body as teacher., Methods: The study utilized qualitative, descriptive methods in a multiple case studies design (each practice setting represented a different case for analysis purposes) with cross-case comparisons. Researchers conducted 8 focus groups across practice settings including acute care, inpatient neurological, outpatient orthopedics, and pediatrics. Each focus group had 4 to 6 participants. Through an iterative, interactive process of coding and discussion among all researchers, a final coding scheme was developed., Results: Through exploration of the research aims, 3 themes emerged from the data. These primary themes are: (1) movement drives clinical reasoning to optimize function; (2) reasoning about movement is multisensory and embodied; and (3) reasoning about movement relies on communication., Conclusions: This research supports a description of movement as the lens used by physical therapists in clinical reasoning and the integral role of movement in clinical reasoning and in learning from and through movement of the human body while learning from clinical reasoning experiences in practice., Impact: As the understanding of the ways physical therapists use and learn from movement in clinical reasoning and practice continues to emerge, it is important to continue exploring ways to best make this expanded, embodied conception of clinical reasoning explicit in the education of future generations of physical therapists., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of this work was to evaluate the influence of residual quadrupolar interaction on the determination of human brain apparent tissue sodium concentrations (aTSCs) using quantitative sodium magnetic resonance imaging ( 23 Na MRI) in healthy controls (HCs) and patients with multiple sclerosis (MS). Especially, it was investigated if the more detailed examination of residual quadrupolar interaction effects enables further analysis of the observed 23 Na MRI signal increase in MS patients., Materials and Methods: 23 Na MRI with a 7 T MR system was performed on 21 HC and 50 MS patients covering all MS subtypes (25 patients with relapsing-remitting MS, 14 patients with secondary progressive MS, and 11 patients with primary progressive MS) using 2 different 23 Na pulse sequences for quantification: a commonly used standard sequence (aTSC Std ) as well as a sequence with shorter excitation pulse length and lower flip angle for minimizing signal loss resulting from residual quadrupolar interactions (aTSC SP ). Apparent tissue sodium concentration was determined using the same postprocessing pipeline including correction of the receive profile of the radiofrequency coil, partial volume correction, and relaxation correction. Spin dynamic simulations of spin-3/2 nuclei were performed to aid in the understanding of the measurement results and to get deeper insight in the underlying mechanisms., Results: In normal-appearing white matter (NAWM) of HC and all MS subtypes, the aTSC SP values were approximately 20% higher than the aTSC Std values ( P < 0.001). In addition, the ratio aTSC SP /aTSC Std was significantly higher in NAWM than in normal-appearing gray matter (NAGM) for all subject cohorts ( P < 0.002). In NAWM, aTSC Std values were significantly higher in primary progressive MS compared with HC ( P = 0.01) as well as relapsing-remitting MS ( P = 0.03). However, in contrast, no significant differences between the subject cohorts were found for aTSC SP . Spin simulations assuming the occurrence of residual quadrupolar interaction in NAWM were in good accordance with the measurement results, in particular, the ratio aTSC SP /aTSC Std in NAWM and NAGM., Conclusions: Our results showed that residual quadrupolar interactions in white matter regions of the human brain have an influence on aTSC quantification and therefore must be considered, especially in pathologies with expected microstructural changes such as loss of myelin in MS. Furthermore, the more detailed examination of residual quadrupolar interactions may lead to a better understanding of the pathologies themselves., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Doctor of physical therapy (PT) (DPT) programs are rigorous, and students report facing overwhelming challenges. Faculty may not be cognizant of the extent of these challenges and miss opportunities to support student learning. The purpose of this article is to describe factors affecting student coping abilities and the lessons they learned from managing their self-identified challenges., Review of Literature: Given the growing body of evidence surrounding mental health issues in DPT students, educators are exploring ways to support student well-being and promote their professional development., Subjects: This study is a component of a larger multisite study of first-year DPT students from 3 private universities., Methods: Participants submitted written narratives in response to a critical incident questionnaire designed to better understand first-year challenges. Responses were deidentified, researchers were blinded to participation, and confidentiality was maintained throughout. A consensus-driven interpretivist approach to qualitative data analysis was used. Strategies to ensure trustworthiness included triangulation of researchers, peer review, prolonged engagement, and use of thick rich descriptions., Results: Seventy responses were analyzed. Two major themes are presented: (1) students described factors internal and external to the learning environment that inhibited and facilitated their ability to cope with challenges and (2) students shared academic successes and lessons learned from overcoming challenges, including the development of new behaviors, enhanced self-awareness, and personal and professional growth., Discussion and Conclusion: Building on previous work, analysis of the lived experiences of first-year DPT students revealed a process of transformational learning through challenge. This process highlights the importance of recognizing and supporting the significant incidental learning that occurs in our students during their journey through PT school. Faculty focusing solely on content knowledge, skills, and even critical thinking may not recognize and support the incidental learning occurring and may be missing significant transformational learning opportunities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Academy of Physical Therapy Education, APTA.)

Background: Many female people with multiple sclerosis (pwMS) are in childbearing age; however, only few data exist about the situation of breastfeeding in pwMS. Objective: Our study analyzed breastfeeding rate and duration, reasons for weaning, and the impact of disease severity on successful breastfeeding in pwMS. Methods: The study included pwMS giving birth within 3 years before study participation. Data were collected by structured questionnaire. Results: Compared to published data, we found a significant difference ( p  = 0.0007) between the nursing rate in the general population (96.6%) and females with MS (85.9%). However, a higher rate of exclusive breastfeeding could be observed in our study population for 5-6 months in 40.6% of pwMS versus 9% for 6 months in the general population. In contrast, total breastfeeding duration in our study population was shorter (18.8% for 11-12 months) than in the general population (41.1% for 12 months). Reasons for weaning were predominantly (68.7%) related to breastfeeding barriers based on MS. No significant impact of prepartum or postpartum education on the breastfeeding rate could be observed. Prepartum relapse rate and prepartum disease-modifying drugs had no effect on breastfeeding success. Conclusion: Our survey provides an insight into the situation of breastfeeding in pwMS in Germany.

Apparent tissue sodium concentrations (aTSCs) determined by 23 Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23 Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23 Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23 Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23 Na/ 1 H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23 Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23 Na brain MRI as a biomarker in diseases such as MS., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Evolutionary change following gene duplication can lead to functionally divergent paralogous proteins. If comprising identical subunits their random assortment would also form potentially detrimental heteromeric proteins. In Arabidopsis, the ARF GTPase guanine-nucleotide exchange factor GNOM is essential for polar recycling of auxin-efflux transporter PIN1 from endosomes to the basal plasma membrane whereas its paralog GNL1 mediates retrograde Golgi-endoplasmic reticulum traffic. Here we show that both GNOM and GNL1 form homodimers but no heterodimers. To assess the biological significance of this, we generated transgenic plants expressing engineered heterodimer-compatible GNOM variants. Those plants showed developmental defects such as the failure to produce lateral roots. To identify mechanisms underlying heterodimer prevention, we analyzed interactions of the N-terminal dimerization and cyclophilin-binding (DCB) domain. Each DCB domain interacted with the complementary fragment (ΔDCB) both of their own and of the paralogous protein. However, only DCB GNOM interacted with itself whereas DCB GNL1 failed to interact with itself and with DCB GNOM . GNOM variants in which the DCB domain was removed or replaced by DCB GNL1 revealed a role for DCB-DCB interaction in the prevention of GNOM-GNL1 heterodimers whereas DCB-ΔDCB interaction was essential for dimer formation and GNOM function. Our data suggest a model of early DCB-DCB interaction that facilitates GNOM homodimer formation, indirectly precluding formation of detrimental heterodimers., (© 2022 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Purpose: To demonstrate direct imaging of the white matter ultrashort T 2 ∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol., Material and Methods: The IR UTE technique suppresses long T 2 ∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T 2 ∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T 2 ∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed., Results: A frequency shift of -1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T 2 ∗ time of (147 ± 58) μs was quantified with a chemical shift of (-3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T 2 ∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed., Conclusions: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T 2 ∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions., Purpose: To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS relapse and during recovery., Study Type: Prospective., Subjects: Twenty-nine relapsing-remitting MS patients with an acute relapse were included., Field Strength/sequence: A 3D density-adapted radial sodium sequence at 3 T using a dual-tuned ( 23 Na/ 1 H) head coil., Assessment: Full-brain images of the tissue sodium concentration (TSC1, n = 29) and a sodium inversion recovery sequence (SIR1, n = 20) at the beginning of the anti-inflammatory therapy and on medium-term follow-up visits (days 27-99, n = 12 [TSC], n = 5 [SIR]) were measured. Regions of interest (RoIs) with contrast enhancement (T 1 CE+) and without change in T1-weighted imaging (FL + T1n) were normalized (nTSC and nSIR). To gain insight on the origin of the TSC enhancement at time point 1, it is investigated whether the nTSC enhancement of the lesions is accompanied by a change of the respective nSIR. Potential prognostic value of nSIR1 is examined referring to the nTSC progression. STATISTICAL TESTS: nTSC and nSIR were compared regarding the type of lesion and the time point using a one-way ANOVA. Pearson's correlation coefficient was calculated for nTSC over nSIR and for nTSC1-nTSC2 over nSIR1. A P-value <0.05 was considered statistically significant., Results: At the first measurement, all lesion types showed increased nTSC, while nSIR was decreased in the FL + T 1 n and the T 1 CE+ lesions in comparison to the normal-appearing white matter. For acute lesions, the difference between nTSC at baseline and nTSC at time point 2 showed a significant correlation with the baseline nSIR., Data Conclusion: At time point 1, nTSC is increased, while nSIR is unchanged or decreased in the lesions. The mean sodium IR signal at baseline correlates with recovery or progression of an acute lesion., Evidence Level: 2 TECHNICAL EFFICACY: Stage 4., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Novel MRI techniques allow a noninvasive quantification of tissue sodium and reveal the skin as a prominent compartment of sodium storage in health and disease. Since multiple sclerosis (MS) immunopathology is initiated in the periphery and increased sodium concentrations induce proinflammatory immune cells, the skin represents a promising compartment linking high sodium concentrations and MS immunopathology. We used a 7-T sodium MRI ( 23 Na-MRI) and inductively coupled plasma mass spectrometry to investigate the skin sodium content in two mouse models of MS. We additionally performed 3-T 23 Na-MRI of calf skin and muscles in 29 male relapsing-remitting MS (RRMS) patients and 29 matched healthy controls. Demographic and clinical information was collected from interviews, and disease activity was assessed by expanded disability status scale scoring. 23 Na-MRI and chemical analysis demonstrated a significantly increased sodium content in the skin during experimental autoimmune encephalomyelitis independent of active immunization. In male patients with RRMS, 23 Na-MRI demonstrated a higher sodium signal in the area of the skin compared to age- and biological sex-matched healthy controls with higher sodium, predicting future disease activity in cranial MRI. In both studies, the sodium enrichment was specific to the skin, as we found no alterations of sodium signals in the muscle or other tissues. Our data add to the recently identified importance of the skin as a storage compartment of sodium and may further represent an important organ for future investigations on salt as a proinflammatory agent driving autoimmune neuroinflammation such as that in MS., Competing Interests: The authors declare no competing interest.

As perceivers, we need to understand context to make social judgments about emotion, such as judging whether emotion is appropriate. We propose a graphic novel-like method, the emotion storyboard, for use in research on social judgments of emotion. Across two studies, participants were randomly assigned to read emotion storyboards or written vignettes to compare the efficacy of the emotion storyboard to that of vignettes in studies on social judgments of emotion. In Study 1, undergraduates (N = 194) answered comprehension questions and rated story clarity and immersion. Participants also made social judgments of emotion by rating main character emotion control and appropriateness of intensity. To further compare the efficacy of the methods, in Study 2, Amazon Mechanical Turk workers (N = 213) answered comprehension questions while response times were recorded, rated clarity, answered a race manipulation check, and rated main character emotion type appropriateness. Overall, emotion storyboards resulted in greater clarity ratings, greater race manipulation check accuracy, and in some instances, enhanced comprehension and comprehension response times relative to vignettes. In emotion storyboards, main character emotion was rated more controlled and more appropriate in intensity, but not different in emotion type appropriateness, than in vignettes. Overall, the method offers a new method of examining social elements of emotion that enhances comprehension and maximizes experimental efficiency., Competing Interests: The authors have declared that no competing interests exist.

Researchers investigating gender and anger have consistently found that White women, but not White men, are evaluated unfavorably when experiencing anger in the workplace. Our project originally aimed to extend findings on White women's, Black women's, and White men's workplace anger by examining whether evaluations are exacerbated or buffered by invalidating or affirming comments from others. In stark contrast to previous research on gender stereotyping and anger evaluations, however, results across four studies ( N = 1,095) showed that both Black and White women portrayed as experiencing anger in the workplace were evaluated more favorably than White men doing so. After Study 1's initial failure to conceptually replicate, we investigated whether perceivers' evaluations of women's workplace anger could have been affected by the contemporaneous cultural event of #MeToo. Supporting this possibility, we found evaluations were moderated by news engagement and beliefs that workplace opportunities are gendered. Additionally, we found invalidating comments rarely affected evaluations of a protagonist yet affirming comments tended to favorably affect evaluations. Overall, findings suggest the need for psychologists to consider the temporary, or perhaps lasting, effects of cultural events on research outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McCormick-Huhn and Shields.)

Background: Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a "real-world" setting., Methods: In this retrospective cohort study, data of 128 (86 relapsing-remitting, 42 progressive) MS patients at initiation of ocrelizumab were analyzed at the MS center of the University of Erlangen, Germany. Additionally, follow-up data of 68 patients at 6-months retreatment were analyzed. Structured phone interviews were applied after ocrelizumab initiation to report undocumented side effects., Results: Patients predominantly switched from monoclonal antibodies (46%), orals (20%), injectables (10%), steroids or immunosuppressants (each 8%), with a mean interval of 9.0 months after the last application of the previous immunotherapy. Applying a combined premedication with steroids, antihistamines and antipyretics for >90% of patients, ocrelizumab treatment was well tolerated and mainly comprised mild (n = 59/128 at initiation, n = 5/68 at 6 months retreatment) and rarely moderate (n = 7/128 at initiation, n = 2/68 at 6 months) side effects. Predominantly mild infusion related reactions (IRR) were reported with a declining percentage over the follow-up applications. Infections occurred rarely. No severe side effects were observed. Secondary, treatment appeared efficient when looking at clinical surrogates of stable disease., Discussion: Our study delineates good short-term tolerability of ocrelizumab in a miscellaneous "real-world" MS cohort. Additional studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Physical therapy, along with most health professions, struggles to describe clinical reasoning, despite it being a vital skill in effective patient care. This lack of a unified conceptualization of clinical reasoning leads to variable and inconsistent teaching, assessment, and research., Objective: The objective was to conceptualize a broad description of physical therapists' clinical reasoning grounded in the published literature and to unify understanding for future work related to teaching, assessment, and research., Design/methods: The design included a systematic concept analysis using Rodgers' evolutionary methodology. A concept analysis is a research methodology in which a concept's characteristics and the relation between features of the concept are clarified., Results: Based on findings in the literature, clinical reasoning in physical therapy was conceptualized as integrating cognitive, psychomotor, and affective skills. It is contextual in nature and involves both therapist and client perspectives. It is adaptive, iterative, and collaborative with the intended outcome being a biopsychosocial approach to patient/client management., Limitations: Although a comprehensive approach was intended, it is possible that the search methods or reduction of the literature were incomplete or key sources were mistakenly excluded., Conclusions: A description of clinical reasoning in physical therapy was conceptualized, as it currently exists in representative literature. The intent is for it to contribute to the unification of an understanding of how clinical reasoning has been conceptualized to date by practitioners, academicians, and clinical educators. Substantial work remains to further develop the concept of clinical reasoning for physical therapy, including the role of movement in our reasoning in practice., (© 2018 American Physical Therapy Association.)

Background and Purpose: Bowel incontinence in multiple sclerosis might be associated with specific lesion sites. This study intended to determine associations between bowel incontinence and cerebral multiple sclerosis lesions using a voxel-wise lesion symptom mapping analysis., Methods: We conducted a retrospective study of multiple sclerosis patients with self-reported bowel incontinence and matched controls. Lesions were manually outlined on T2-weighted MRI scans and transformed into stereotaxic space. We performed a voxel-wise subtraction analysis subtracting the lesion overlap of patients without from patients with bowel incontinence. Finally, we compared the absence or presence of bowel incontinence between patients with and without lesions in a given voxel using the Liebermeister test., Results: A total of 51 patients were included in the study. The analysis yielded associations between bowel incontinence and lesions in the supramarginal gyrus of the left secondary somatosensory cortex and another lesion cluster in the right parahippocampal gyrus and amygdala., Conclusions: Our analysis indicates associations between bowel incontinence and lesions in the left supramarginal gyral area contributing to integrating anorectal-visceral sensation and in the right parahippocampal gyrus and amygdala contributing to generating visceral autonomic arousal states. Moreover, our results suggest left hemispheric dominance of sensory visceral integration, while limbic areas of the right hemisphere seem to contribute to the autonomic component of the defecation process. A limitation of our study is the retrospective evaluation of the bowel incontinence status based on medical records. Further research should evaluate the bowel incontinence status in multiple sclerosis patients prospectively to overcome the limitations of the current study., (© 2018 by the American Society of Neuroimaging.)

In multiple sclerosis (MS), experimental and ex vivo studies indicate that pathologic intra- and extracellular sodium accumulation may play a pivotal role in inflammatory as well as neurodegenerative processes. Yet, in vivo assessment of sodium in the microenvironment is hard to achieve. Here, sodium magnetic resonance imaging ( 23 NaMRI) with its non-invasive properties offers a unique opportunity to further elucidate the effects of sodium disequilibrium in MS pathology in vivo in addition to regular proton based MRI. However, unfavorable physical properties and low in vivo concentrations of sodium ions resulting in low signal-to-noise-ratio (SNR) as well as low spatial resolution resulting in partial volume effects limited the application of 23 NaMRI. With the recent advent of high-field MRI scanners and more sophisticated sodium MRI acquisition techniques enabling better resolution and higher SNR, 23 NaMRI revived. These studies revealed pathologic total sodium concentrations in MS brains now even allowing for the (partial) differentiation of intra- and extracellular sodium accumulation. Within this review we (1) demonstrate the physical basis and imaging techniques of 23 NaMRI and (2) analyze the present and future clinical application of 23 NaMRI focusing on the field of MS thus highlighting its potential as biomarker for neuroinflammation and -degeneration.

Background: Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at "no evidence of disease activity" (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in "real-world" clinical settings. Hence, our study aims at investigation of NEDA in a heterogeneous cohort of relapsing MS patients., Methods: This is a retrospective single-center study at the Department of Neurology of the University Hospital Erlangen, Germany, including data of 306 patients with relapsing forms of MS (RMS) or clinical isolated syndrome (CIS) from 2009 to 2016. Inclusion required sufficient clinical information and in house cranial MRI follow-up data sets at baseline and at follow-up after one year with a potential extension to two and three year follow-up, if possible. NEDA-3 status, its correlation to clinical features, associated medication and NEDA failure (EDA) were analyzed., Results: In a cohort of RMS patients at the early stages of the disease (median EDSS 1.5, mean disease duration 30 months) at baseline, 45% retained NEDA-3 status after one year. This percentage decreased in year two (29%) and three (21%) of follow-up. MRI criteria were responsible for loss of NEDA status in 64% of cases and CIS patients were more likely to sustain NEDA status. Therapy with monoclonal antibodies appeared superior in sustaining NEDA status as compared to injectables or oral treatment options., Discussion: In our real-world analysis, we confirm the potential of NEDA for the evaluation and surveillance of MS disease activity, progression and therapy efficacy. Despite highly efficient immunomodulatory treatment, NEDA-3 was only preserved in a minority of patients. Monoclonal antibodies may yield best NEDA rates. Further studies are warranted to evaluate the value of the NEDA concept in real-world settings beyond standardized clinical studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Secondary paroxysmal dyskinesia is a rare but life-quality-compromising symptom in multiple sclerosis (MS) and might be associated with particular MS lesions. The present study intended to determine associations between paroxysmal dyskinesia and the MS-associated lesion site using a voxelwise lesion analysis. We conducted a retrospective study and sought MS patients with documented paroxysmal dyskinesia and controls without paroxysmal dyskinesia matched for age, disease severity, and disease duration in a local database. The MS lesions were analysed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T), manually outlined, and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of paroxysmal dyskinesia voxelwise between patients with and without lesions in a given voxel using the Liebermeister test with 4000 permutations. From 15,869 MS patient records screened, we identified 25 patients with paroxysmal dyskinesia. The voxelwise analysis in 22 subjects yielded associations between paroxysmal dyskinesia and MS lesions in the internal capsule, the basal ganglia, and another prominent lesion cluster in the posterior periventricular white matter. Our voxelwise analysis shows associations between paroxysmal dyskinesia and MS lesions in the internal capsule and basal ganglia, areas contributing to motor sequence programming. This association in another lesion site located in the posterior thalamic radiation suggests that lesions in subcortical sensory pathways may also contribute to paroxysmal dyskinesia in MS.

Background: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice., Methods: Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics., Results: On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia., Discussion: Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.

Background: Chronic inflammatory demyelinating diseases of the CNS typically show a limited lesion size. However, extended lesions may appear with an atypical configuration. Large lesions with a diameter>2cm accompanied by tumor-like edema are entitled "tumefactive" and may occur in multiple sclerosis (MS) and other demyelinating diseases. Historically, differential diagnosis often requires histological analysis. Therefore, advanced imaging techniques are warranted to allow for a precise non-invasive diagnosis. Cerebral sodium ( 23 Na) MRI was recently described as a new method to investigate in vivo sodium accumulation. Indicating extended sodium levels in MS lesions, 23 Na MRI is a promising differential diagnostic tool further elucidating the role of sodium in demyelinating lesions., Methods: Repetitive 23 Na MRI measurements in a MS patient with a tumefactive demyelinating lesion providing insight into the medium-term course of cerebral sodium levels., Results and Conclusion: 23 Na MRI depicts persistent lesional sodium accumulation after anti-inflammatory treatment and provides the opportunity of a non-invasive, in vivo analysis of sodium levels in inflammatory CNS lesions without need for contrast enhancing media. As a result of the extended dimension, tumefactive lesions may have an appropriate size for the analysis of inflammatory demyelination by 23 Na MRI with sufficient resolution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Fingolimod is an oral sphingosine-1-phosphate-receptor modulator which reduces the recirculation of immune cells and may also directly target glial cells. Here we investigate effects of fingolimod on expression of astroglial glutamate transporters under pro-inflammatory conditions. In astrocyte cell culture, the addition of pro-inflammatory cytokines led to a significant downregulation of glutamate transporters glutamate transporter-1 (slc1a2/SLC1A2) and glutamate aspartate transporter (slc1a3/SLC1A3) expression on the mRNA or protein level. In this setting, the direct application of fingolimod-1 phosphate (F1P) on astrocytes did not change expression levels of slc1a2 and slc1a3 mRNA. The analysis of both transporters on the protein level by Western Blot and immunocytochemistry did also not reveal any effect of F1P. On a functional level, the addition of conditioned supernatants from F1P treated astrocytes to neuronal cell culture did not result in increased neurite growth. In experimental autoimmune encephalomyelitis as a model of multiple sclerosis, fingolimod treatment reduced T cell and macrophages/microglia mediated inflammation and also diminished astrocyte activation. At the same time, fingolimod restored the reduced expression of slc1a2 and slc1a3 in the inflamed spinal cord on the mRNA level and of SLC1A2 and SLC1A3 on the protein level, presumably via indirect, anti-inflammatory mechanisms. These findings provide further evidence for a predominantly peripheral effect of the compound in neuroinflammation.

Background: Although clinical reasoning abilities are important learning outcomes of physical therapist entry-level education, best practice standards have not been established to guide clinical reasoning curricular design and learning assessment., Objective: This research explored how clinical reasoning is currently defined, taught, and assessed in physical therapist entry-level education programs., Design: A descriptive, cross-sectional survey was administered to physical therapist program representatives., Methods: An electronic 24-question survey was distributed to the directors of 207 programs accredited by the Commission on Accreditation in Physical Therapy Education. Descriptive statistical analysis and qualitative content analysis were performed. Post hoc demographic and wave analyses revealed no evidence of nonresponse bias., Results: A response rate of 46.4% (n=96) was achieved. All respondents reported that their programs incorporated clinical reasoning into their curricula. Only 25% of respondents reported a common definition of clinical reasoning in their programs. Most respondents (90.6%) reported that clinical reasoning was explicit in their curricula, and 94.8% indicated that multiple methods of curricular integration were used. Instructor-designed materials were most commonly used to teach clinical reasoning (83.3%). Assessment of clinical reasoning included practical examinations (99%), clinical coursework (94.8%), written examinations (87.5%), and written assignments (83.3%). Curricular integration of clinical reasoning-related self-reflection skills was reported by 91%., Limitations: A large number of incomplete surveys affected the response rate, and the program directors to whom the survey was sent may not have consulted the faculty members who were most knowledgeable about clinical reasoning in their curricula. The survey construction limited some responses and application of the results., Conclusions: Although clinical reasoning was explicitly integrated into program curricula, it was not consistently defined, taught, or assessed within or between the programs surveyed-resulting in significant variability in clinical reasoning education. These findings support the need for the development of best educational practices for clinical reasoning curricula and learning assessment., (© 2017 American Physical Therapy Association)

Background: Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS typically affecting younger adults and resulting in neuro-axonal degeneration already at early stages of the disease. Less is known about the effects of a later disease onset (LOMS, onset >50years of age). Analysis of retinal layers by optical coherence tomography (OCT) is a non-invasive method to investigate retinal and neuro-axonal degeneration. We applied OCT to detect differences in retinal damage depending on a later disease manifestation., Methods: 14 LOMS patients, 14 age- and 14 disease duration-matched normal onset (NOMS) patients with a relapsing remitting disease course and 15 healthy controls (HC) were included. OCT measurement of peripapillary retinal nerve fiber layer (RNFL), total macular volume (TMV), combined ganglion cell/inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer retinal layers (ORL) was conducted. Furthermore, analysis of clinical features and of effects of previous optic neuritis (ON) was performed RESULTS: In a GEE based analysis of age- and disease duration matched NOMS, LOMS patients show no significant differences in retinal layer thickness whereas ON significantly reduced thickness of retinal layers. All MS groups display lower retinal layer thickness as compared to HC independently of type of onset., Discussion: Our LOMS findings are well in line with published OCT data of normal onset MS. As the degree of retinal layer thinning was similar in MS subgroups, retinal neurodegeneration in MS may occur independently of time of disease onset., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome., Purpose: To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity., Methods: Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days., Results: Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02)., Conclusion: Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.

As sessile organisms, plants have to continuously adjust growth and development to ever-changing environmental conditions. At the end of the growing season, annual plants induce leaf senescence to reallocate nutrients and energy-rich substances from the leaves to the maturing seeds. Thus, leaf senescence is a means with which to increase reproductive success and is therefore tightly coupled to the developmental age of the plant. However, senescence can also be induced in response to sub-optimal growth conditions as an exit strategy, which is accompanied by severely reduced yield. Here, we show that class III homeodomain leucine zipper (HD-ZIPIII) transcription factors, which are known to be involved in basic pattern formation, have an additional role in controlling the onset of leaf senescence in Arabidopsis. Several potential direct downstream genes of the HD-ZIPIII protein REVOLUTA (REV) have known roles in environment-controlled physiological processes. We report that REV acts as a redox-sensitive transcription factor, and directly and positively regulates the expression of WRKY53, a master regulator of age-induced leaf senescence. HD-ZIPIII proteins are required for the full induction of WRKY53 in response to oxidative stress, and mutations in HD-ZIPIII genes strongly delay the onset of senescence. Thus, a crosstalk between early and late stages of leaf development appears to contribute to reproductive success., (© 2014. Published by The Company of Biologists Ltd.)

Introduction: Unvaccinated patients with history of splenectomy are prone to fulminant courses of Streptococcus pneumoniae-associated bacterial meningitis. Besides direct brain damage those patients may additionally suffer from parainfectious syndromes, notably vasculitis and acute disseminated encephalomyelitis (ADEM). Differentiation and treatment of these immunological reactions is challenging., Methods: Case report., Results: A 61 year-old woman with history of splenectomy without vaccination for S. pneumoniae presented with progressive headache and meningism. CSF-analysis revealed pleocytosis with microbiological evidence for pneumococcal meningitis. After unsuspicious initial cranial CT imaging and initiation of appropriate antibiotic therapy, MRI two days later showed widespread FLAIR- and T2-hyperintense white matter lesions that further progressed upon follow-up MRI and that fulfilled imaging criteria of ADEM. Meanwhile the patient deteriorated and required mechanical ventilation. Cranial angiography showed no signs of vasculitis or vasospasms. Screening for autoimmune diseases remained negative, however oligoclonal bands turned positive. Brain biopsy mainly revealed perivascular CD4+ T-cells and demyelinated areas. Despite ongoing acute meningitis, a 10-day corticosteroid-pulse was initiated followed by steroid-tapering. Within 4 weeks, clinical and MRI findings ameliorated. In an one-year follow-up visit, the patient significantly recovered, MRI lesions were markedly reduced and no further relapses occurred., Conclusion: Acute pneumococcal meningitis in unvaccinated splenectomized patients may be complicated by a monophasic course of parainfectious ADEM that can be controlled with high-dose corticosteroids. Parainfectious vasculitis or cerebritis are important differential diagnoses and exact differentiation of these entities is important to initiate early appropriate immunotherapy.

Unlabelled: The aim of this study was to evaluate the construct validity of the Health Science Reasoning Test (HSRT) by determining if the test could discriminate between expert and novice physical therapists' critical-thinking skills., Methods: Experts identified from a random list of certified clinical specialists and students in the first year of their physical therapy education from two physical therapy programs completed the HSRT., Results: Experts (n = 73) had a higher total HSRT score (mean 24.06, SD 3.92) than the novices (n = 79) (mean 22.49, SD 3.2), with the difference being statistically significant t (148) = 2.67, p = 0.008., Conclusion: The HSRT total score discriminated between expert and novice critical-thinking skills, therefore establishing construct validity. To our knowledge, this is the first study to compare expert and novice performance on a standardized test. The opportunity to have a tool that provides evidence of students' critical thinking skills could be helpful for educators and students. The test results could aid in identifying areas of students' strengths and weaknesses, thereby enabling targeted remediation to improve critical thinking skills, which are key factors in clinical reasoning, a necessary skill for effective physical therapy practice.

Background and Purpose: The purpose of this retrospective and prospective case report is to describe the feasibility and outcomes of using a low-cost, commercially available gaming system (Wii) to augment the rehabilitation of an adolescent with cerebral palsy., Patient and Setting: The patient was an adolescent with spastic diplegic cerebral palsy classified as GMFCS level III who was treated during a summer session in a school-based setting., Intervention: The patient participated in 11 training sessions, 2 of which included other players. Sessions were between 60 and 90 minutes in duration. Training was performed using the Wii sports games software, including boxing, tennis, bowling, and golf. He trained in both standing and sitting positions., Outcomes: Three main outcome measures were used: (1) visual-perceptual processing, using a motor-free perceptual test (Test of Visual Perceptual Skills, third edition); (2) postural control, using weight distribution and sway measures; and (3) functional mobility, using gait distance. Improvements in visual-perceptual processing, postural control, and functional mobility were measured after training., Discussion and Conclusion: The feasibility of using the system in the school-based setting during the summer session was supported. For this patient whose rehabilitation was augmented with the Wii, there were positive outcomes at the impairment and functional levels. Multiple hypotheses were proposed for the findings that may be the springboard for additional research. To the authors' knowledge, this is the first published report on using this particular low-cost, commercially available gaming technology for rehabilitation of a person with cerebral palsy.

The term 'Langerhans cell microgranuloma' (LCM) was introduced a decade ago to draw attention to focal collections of these cells within the epidermal layer that develops during certain immune reactions. In spite of a growing awareness of this phenomenon during the past decade, few reports have focused on the development and phenotype of LCM. In this commentary, we review the historical development of the concept of LCM, demonstrate the salient immunomorphologic characteristics of LCM, and advance a hypothesis to explain their sequential evolution and formation.

Calciphylaxis is a rare, often fatal disease characterized clinically by progressive cutaneous necrosis and ulceration, and histologically by vascular calcification and thrombosis. It has been described in association with end-stage renal disease, after initiation of dialysis, following renal transplantation, and in patients with hyperparathyroidism. We present the first case of calciphylaxis occurring in a patient with both normal renal function and parathyroid hormone level and discuss the possible aetiological role of chemotherapy-induced functional protein C and protein S deficiency.

Pemphigus herpetiformis is a rare pemphigus variant with light microscopic features that have historically been described as either "acantholytic dermatitis herpetiformis" or as "eosinophilic spongiosis in pemphigus". The clinical features of this form of pemphigus are reminiscent of dermatitis herpetiformis; however, the direct immunofluorescence finding of epidermal inter-cellular IgG deposition is that of the pemphigus group. We report two patients with clinical presentations suggestive of dermatitis herpetiformis in whom the histopathologic features were those of a neutrophilic intraepidermal blistering disorder. Biopsies showed marked epidermal spongiosis with midepidermal acantholytic vesicles containing predominantly neutrophils and a few eosinophils. Direct immunofluorescence was positive for epidermal intercellular IgG; IgA deposition was not present. Neutrophilic spongiosis, in the absence of a prominent eosinophilic infiltrate, should be recognized as an early finding in some cases of pemphigus, and immunofluorescence studies are justified when this histologic feature is encountered in a skin biopsy.

The authors report the case of a man 49 years of age with near-fatal ethylene glycol poisoning. Detection of calcium oxalate monohydrate crystals in the urine was the only real-time confirmation of the diagnosis. The case illustrates that, if the toxin has already been metabolized, familiarity with the appearance and significance of this unusual form of calcium oxalate crystal may be the key to an accurate diagnosis.