Quality of Life in Children and Adolescents with Neurofibromatosis Type 1: A Single-Center Observational Study.

This article obtains an overview of the health status of children and adolescents with neurofibromatosis type 1 (NF1) with a focus on the clinical course of the disease, neuropsychodiagnostic findings, and their impact on quality of life (QoL). In this observational study, data were collected from 24 children and adolescents with NF1 who were cared for at the University Hospital in Innsbruck, Austria, from 2008 to 2022. Data were collected every 6 to 12 months from routine check-ups, including clinical features and imaging findings. Results of neuropsychodiagnostic tests and the KINDL questionnaire to assess QoL were included. Of 24 patients, 15 underwent a neuropsychological examination. Attention performance was examined in 11 of them. Eight of 11 (72%) showed an attention deficit. Assessment for specific developmental disorders showed visual-spatial difficulties in 12/15 (80%) patients. The KINDL questionnaire values ranged from 58.22 to 97.92 (0 stands for reduced QoL, 100 for very good QoL). Patients with scoliosis had a lower range of QoL (56.33-73.96). No trend in QoL was observed in children and adolescents with plexiform neurofibromas, below-average intelligence or optic gliomas. NF1 patients show very different clinical courses. Regular neuropsychological assessment especially with regard to visual-spatial skills and attention deficits is necessary to offer appropriate support, promote children's development, and thus improve their QoL.

Veterans with Traumatic Brain Injury-related Ocular Injury and Vision Dysfunction: Vision Rehabilitation Utilization.

SIGNIFICANCE: Visual dysfunction is frequently associated with traumatic brain injury (TBI). Although evidence regarding the prevalence of symptoms of this population has been published, little is known about health care utilization. A retrospective review of the data derived from the Department of Veterans Affairs (VA)-mandated "Traumatic Brain Injury Specific Ocular Health and Visual Functioning Examination for Polytrauma Rehabilitation Center Patients" provided a unique opportunity to investigate vision rehabilitation utilization. PURPOSE: The purpose of this study was to understand (a) the frequency of vision rehabilitation follow-up visits at 6, 12, and 24 months; (b) the association between follow-up and demographic, comorbidity, and severity of TBI covariates as well as ocular and visual symptoms, geographic access, and evaluating facility; and (c) why some veterans did not follow up with recommendations. METHODS: Retrospective and survey designs were used. The sample included 2458 veterans who served in the Operation Enduring Freedom/Operation Iraqi Freedom conflicts and received care at one of the five VA Polytrauma Rehabilitation Centers between January 1, 2008, and December 31, 2017. Quantitative and qualitative descriptive analyses and stepwise logistic regression were performed. RESULTS: About 60% of veterans followed up with recommended vision rehabilitation with visits equally split between VA Polytrauma Rehabilitation Centers and community VA facilities. For each 10-year increase in age, there was a corresponding reduction of 12% in the odds of follow-up. Veterans with decreased visual field had 50% greater odds of follow-up than those who did not. Veterans with difficulty reading had 59% greater odds of follow-up than those who did not. Those who had a double vision had 45% greater odds of follow-up than those who did not. CONCLUSIONS: Our findings suggest that the need for vision rehabilitation may extend as long as 2 years after TBI. Access to vision rehabilitation is complicated by the paucity of available neuro-optometric services.

Veterans with Traumatic Brain Injury-related Ocular Injury and Vision Dysfunction: Recommendations for Rehabilitation.

SIGNIFICANCE: We know the prevalence of traumatic brain injury (TBI)-related vision impairment and ocular injury symptoms. Lacking is an understanding of health care utilization to treat these symptoms. Utilization knowledge is important to structuring access to treatment, identifying clinical training needs, and providing evidence of the effectiveness of treatment. PURPOSE: This article reports rehabilitation, glasses/contacts, and imaging/photography/video recommendations made by optometrists and ophthalmologists as part of the Department of Veterans Affairs-mandated Performance of Traumatic Brain Injury Specific Ocular Health and Visual Functioning Examination administered to veterans with TBI at Department of Veterans Affairs polytrauma specialty facilities. METHODS: Using a retrospective design, natural language processing, and descriptive and regression statistics, data were analyzed for 2458 Operation Enduring Freedom/Operation Iraqi Freedom veterans who were administered the mandated examination between 2008 and 2017. RESULTS: Of the 2458 veterans, vision rehabilitation was recommended for 24%, glasses/contacts were recommended for 57%, and further imaging/photography/video testing was recommended for 58%. Using key words in the referral, we determined that 37% of veterans were referred to blind rehabilitation, 16% to occupational therapy, and 3% to low-vision clinics. More than 50% of the referrals could have been treated by blind rehabilitation, occupational therapy, or low-vision clinics. Rehabilitation referrals were significantly associated with younger age, floaters, photosensitivity, double vision, visual field and balance deficits, dizziness, and difficulty reading. In comparison, prescriptions for glasses and contacts were associated with older age, photosensitivity, blurred vision, decreased visual field and night vision, difficulty reading, and dry eye. Imaging/photography/video testing was associated with floaters, photosensitivity, and headache. CONCLUSIONS: Findings delineate service delivery models available to veterans with TBI-related vision impairment. The challenge these data address is the lack of clear paths from diagnosis of TBI to identification of vision dysfunction deficits to specialized vision rehabilitation, and finally to community reintegration and community based-vision rehabilitation.

Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3.

Here, we report the fragment-based discovery of BI-9321, a potent, selective and cellular active antagonist of the NSD3-PWWP1 domain. The human NSD3 protein is encoded by the WHSC1L1 gene located in the 8p11-p12 amplicon, frequently amplified in breast and squamous lung cancer. Recently, it was demonstrated that the PWWP1 domain of NSD3 is required for the viability of acute myeloid leukemia cells. To further elucidate the relevance of NSD3 in cancer biology, we developed a chemical probe, BI-9321, targeting the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 µM. As a single agent, BI-9321 downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells. This first-in-class chemical probe BI-9321, together with the negative control BI-9466, will greatly facilitate the elucidation of the underexplored biological function of PWWP domains.

China Electricity Generation Greenhouse Gas Emission Intensity in 2030: Implications for Electric Vehicles.

Electrification of transportation offers clear national energy security benefits but unclear climate benefits. With the current heterogeneity of grid electricity mix in China, greenhouse gas (GHG) benefits of battery electric vehicles (BEVs) vary dramatically with location. Currently, compared to baseline conventional gasoline vehicles, BEVs in north and northeastern Chinese provinces have very modest (∼10-20%) well-to-wheel (WTW) GHG benefits, whereas BEVs in southern provinces have substantial benefits (∼50%). With the expected transition to a more renewable electricity mix documented here, regional effects will largely disappear and the benefits of BEVs will be substantial (∼60-70% lower than current internal combustion engine vehicles (ICEVs) and ∼10-40% lower than 2030 advanced hybrid electric vehicles (HEVs)) across the whole of China by 2030. GHG emissions from BEVs in Chinese cities (Beijing, Shanghai, Chongqing, and Pearl River Delta) and United States cities and regions (New York; Washington, DC; Chicago; New England; Texas; and California) in 2015 and 2030 are evaluated and compared. BEVs in Chinese cities will still have substantially higher WTW GHG emissions than those in New York, New England, and California in 2030.

Assessment of the hepatocytic differentiation ability of human skin-derived ABCB5+ stem cells.

The continuously decreasing willingness for liver donation aggravates treatment of end-stage liver diseases requiring organ transplantation as the only curative strategy. Cell therapy approaches using human hepatocytes or stem cell-derived hepatocyte-like cells may be a therapeutic option out of this dilemma. ABCB5-positive mesenchymal stromal cells from human skin featured promising potential to treat immune-mediated diseases. Since most of chronic liver diseases involve exaggerating immune mechanisms, it was the aim to demonstrate in this study, whether ABCB5+ stem cells may serve as a resource to generate hepatocytic cells for application in liver cell transplantation. Using an established single-step protocol, which had been successfully applied to differentiate mesenchymal stromal cells into the hepatocytic lineage, ABCB5+ skin-derived stem cells did not gain significant characteristics of hepatocytes. Yet, upon culture in hepatocytic differentiation medium, ABCB5+ stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others. Hepatic transplantation of ABCB5+ stem cells, which had been prior cultured in hepatocytic differentiation medium, did not cause any obvious deterioration of liver architecture suggesting their safe application. Thus, human ABCB5+ skin-derived stem cells secreted putative hepatotropic factors after culture in hepatocytic differentiation medium.

Mammalian MSC from selected species: Features and applications.

Mesenchymal stromal/stem cells (MSC) are promising candidates for cellular therapy of different diseases in humans and in animals. Following the guidelines of the International Society for Cell Therapy, human MSC may be identified by expression of a specific panel of cell surface markers (CD105+, CD73+, CD90+, CD34-, CD14-, or CD11b-, CD79- or CD19-, HLA-DR-). In addition, multiple differentiation potential into at least the osteogenic, adipogenic, and chondrogenic lineage is a main criterion for MSC definition. Human MSC and MSC of a variety of mammals isolated from different tissues meet these criteria. In addition to the abovementioned, they express many more cell surface markers. Yet, these are not uniquely expressed by MSC. The gross phenotypic appearance like marker expression and differentiation potential is similar albeit not identical for MSC from different tissues and species. Similarly, MSC may feature different biological characteristics depending on the tissue source and the isolation and culture procedures. Their versatile biological qualities comprising immunomodulatory, anti-inflammatory, and proregenerative capacities rely largely on the migratory and secretory capabilities of MSC. They are attracted to sites of tissue lesion and secrete factors to promote self-repair of the injured tissue. This is a big perspective for clinical MSC applications in both veterinary and human medicine. Phase I/II clinical trials have been initiated to assess safety and feasibility of MSC therapies in acute and chronic disease settings. Yet, since the mode of MSC action in a specific disease environment is still unknown at large, it is mandatory to unravel the response of MSC from a given source onto a specific disease environment in suitable animal models prior to clinical applications. © 2017 International Society for Advancement of Cytometry.

Vehicle emissions of short-lived and long-lived climate forcers: trends and tradeoffs.

Evaluating technology options to mitigate the climate impacts of road transportation can be challenging, particularly when they involve a tradeoff between long-lived emissions (e.g., carbon dioxide) and short-lived emissions (e.g., methane or black carbon). Here we present trends in short- and long-lived emissions for light- and heavy-duty transport globally and in the U.S., EU, and China over the period 2000-2030, and we discuss past and future changes to vehicle technologies to reduce these emissions. We model the tradeoffs between short- and long-lived emission reductions across a range of technology options, life cycle emission intensities, and equivalency metrics. While short-lived vehicle emissions have decreased globally over the past two decades, significant reductions in CO2 will be required by mid-century to meet climate change mitigation targets. This is true regardless of the time horizon used to compare long- and short-lived emissions. The short-lived emission intensities of some low-CO2 technologies are higher than others, and thus their suitability for meeting climate targets depends sensitively on the evaluation time horizon. Other technologies offer low intensities of both short-lived emissions and CO2.

Family Caregiver Training Program (FCTP): A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to examine the effectiveness of the Family Caregiver Training Program (FCTP) for caregivers of people with dementia. METHOD: A random assignment control group research design with a 3-mo follow-up was implemented. RESULTS: Thirty-six family caregivers of people with dementia demonstrated an increase in activity of daily living (ADL) knowledge (p < .001) and maintenance of that knowledge 3 mo posttest. Caregiver confidence, regardless of group assignment, improved; however, it was not maintained. Burden, depression, and occupational performance and satisfaction remained unchanged for the intervention group; however, physical health as it pertained to quality of life improved 3 mo posttest (p < .001). CONCLUSION: Findings demonstrate that the FCTP can effectively provide knowledge to family caregivers on how to assist people with dementia with ADLs. Even when standard care was provided, there was limited information on ADLs that family caregivers faced daily.

Attenuation of Postoperative Acute Liver Failure by Mesenchymal Stem Cell Treatment Due to Metabolic Implications.

OBJECTIVE: To prevent posthepatectomy acute liver failure after extended resection by treatment with mesenchymal stem cells (MSCs). BACKGROUND: Liver tumors often require extended liver resection, overburdening metabolic and regenerative capacities of the remnant organ. Resulting dysfunction and failure may be improved by the proregenerative characteristics of MSCs. METHODS: Extended liver resection was performed in (DPPIV)-deficient F344-Fischer rats. Wild-type animals served as donors of peritoneal adipose-derived MSCs. These were predifferentiated in vitro into hepatocytic cells and delivered to the liver by splenic application. Liver-related blood parameters (international normalized ratio, bilirubin, aspartate aminotransferase, alanine aminotransferase) and liver histology (hematoxylin-eosin, Sudan III) were determined to monitor liver function. Metabolic changes were assessed by metabolomic analyses in the remnant liver and the serum. Liver damage and regeneration were quantified by determination of the apoptotic and proliferation rates. RESULTS: MSCs supported survival after partial hepatectomy. They decreased liver-related blood parameters indicative for the improvement of liver function. The extensive lipid accumulation in hepatocytes illustrating the metabolic overload after resection was attenuated. Treatment with MSCs normalized imbalance of amino acids, acylcarnitines, sphingolipids, and glycerophospholipids in the liver and blood. Furthermore, MSCs decreased the apoptotic rate and increased the proliferation rate. The experimental time period (48 hours) was too short to allow for integration of MSCs into the host liver. Thus, the mode of action was probably indirect. CONCLUSIONS: MSCs ameliorated hepatic dysfunction and improved liver regeneration after extended resection by paracrine mechanisms. They may represent a new therapeutic option to treat posthepatectomy acute liver failure.

Pathological implications of cadherin zonation in mouse liver.

Both acute and chronic liver diseases are associated with ample re-modeling of the liver parenchyma leading to functional impairment, which is thus obviously the cause or the consequence of the disruption of the epithelial integrity. It was, therefore, the aim of this study to investigate the distribution of the adherens junction components E- and N-cadherin, which are important determinants of tissue cohesion. E-cadherin was expressed in periportal but not in perivenous hepatocytes. In contrast, N-cadherin was more enriched towards the perivenous hepatocytes. In agreement, ß-catenin, which links both cadherins via α-catenin to the actin cytoskeleton, was expressed ubiquitously. This zonal expression of cadherins was preserved in acute liver injury after treatment with acetaminophen or partial hepatectomy, but disrupted in chronic liver damage like in non-alcoholic steatohepatitis (NASH) or α1-antitrypsin deficiency. Hepatocyte proliferation during acetaminophen-induced liver damage was predominant at the boundary between the damaged perivenous and the intact periportal parenchyma indicating a minor contribution of periportal hepatocytes to liver regeneration. In NASH livers, an oval cell reaction was observed pointing to massive tissue damage coinciding with the gross impairment of hepatocyte proliferation. In the liver parenchyma, metabolic functions are distributed heterogeneously. For example, the expression of phosphoenolpyruvate carboxykinase and E-cadherin overlapped in periportal hepatocytes. Thus, during liver regeneration after acute damage, the intact periportal parenchyma might sustain essential metabolic support like glucose supply or ammonia detoxification. However, disruption of epithelial integrity during chronic challenges may increase susceptibility to metabolic liver diseases such as NASH or vice versa. This might suggest the regulatory integration of tissue cohesion and metabolic functions in the liver.

Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells.

BACKGROUND: The beneficial impact of mesenchymal stem cells (MSC) on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. METHODS: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. RESULTS: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1) increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM) decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT) and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor) signalling pathways as relevant networks. Relationships to transforming growth factor ß (TGF-ß) and hypoxia-inducible factor 1-α (HIF1-α) signalling seemed also relevant. CONCLUSION: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.

Understanding the Provision of Assistive Mobility and Daily Living Devices and Service Delivery to Veterans After Stroke.

OBJECTIVE: The objective of this study was to determine whether facility-level, structural factors affect the provision of assistive devices and services. DESIGN: A retrospective design was used. Activities of daily living and mobility-related devices were categorized into 11 types. Logistic regression models were performed for each type of device, controlling for patient-level and facility-level covariates. RESULTS: Non-veteran-level factors significantly affect the provision of assistive devices, even after covariate adjustment. Increased rehabilitation clinician staffing by 1 full-time equivalent position was associated with increased provision odds of 1%-5% for 5 of 11 types of devices. Lower facility complexity was significantly associated with increased provision odds of 35%-59% for 3 types of devices and with decreased provision odds of 16%-69% for 3 types of devices. CONCLUSION: System-level factors, in addition to patient need, significantly affect the provision of assistive devices. Provision guidelines could assist clinicians in making decisions about device provision.

Innovative Power Wheelchair Control Interface: A Proof-of-Concept Study.

Some people without independent mobility are candidates for powered mobility but are unable to use a traditional power wheelchair joystick. This proof-of-concept study tested and further developed an innovative method of driving power wheelchairs for people whose impairments prevent them from operating commercial wheelchair controls. Our concept, Self-referenced Personal Orthotic Omni-purpose Control Interface (SPOOCI), is distinguished by referencing the control sensor not to the wheelchair frame but instead to the adjacent proximal lower-extremity segment via a custom-formed orthosis. Using a descriptive case-series design, we compared the pre-post functional power wheelchair driving skill data of 4 participants, measured by the Power Mobility Program, using descriptive analyses. The intervention consisted of standard-care power wheelchair training during 12 outpatient occupational or physical therapy sessions. All 4 participants who completed the 12-wk intervention improved their functional power wheelchair driving skills using SPOOCI, but only 3 were deemed safe to continue with power wheelchair driving.

A fat option for the pig: hepatocytic differentiated mesenchymal stem cells for translational research.

STUDY BACKGROUND: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. METHODS: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. RESULTS: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. CONCLUSION: The hepatocyte differentiation of porcine adipose tissue-derived MSC was shown for the first time yielding hepatocyte-like cells with specific functions similar in bone marrow and subcutaneous adipose tissue-derived MSC. That makes them good pre-clinical candidates for supportive approaches after liver resection in the pig.

Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model.

Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver.

Light-duty vehicle CO2 targets consistent with 450 ppm CO2 stabilization.

We present a global analysis of CO2 emission reductions from the light-duty vehicle (LDV) fleet consistent with stabilization of atmospheric CO2 concentration at 450 ppm. The CO2 emission reductions are described by g CO2/km emission targets for average new light-duty vehicles on a tank-to-wheel basis between 2010 and 2050 that we call CO2 glide paths. The analysis accounts for growth of the vehicle fleet, changing patterns in driving distance, regional availability of biofuels, and the changing composition of fossil fuels. New light-duty vehicle fuel economy and CO2 regulations in the U.S. through 2025 and in the EU through 2020 are broadly consistent with the CO2 glide paths. The glide path is at the upper end of the discussed 2025 EU range of 68-78 g CO2/km. The proposed China regulation for 2020 is more stringent than the glide path, while the 2017 Brazil regulation is less stringent. Existing regulations through 2025 are broadly consistent with the light-duty vehicle sector contributing to stabilizing CO2 at approximately 450 ppm. The glide paths provide long-term guidance for LDV powertrain/fuel development.

Human bone marrow mesenchymal stem cell-derived hepatocytes improve the mouse liver after acute acetaminophen intoxication by preventing progress of injury.

Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC) and transplanted into livers of immunodeficient Pfp/Rag2⁻/⁻ mice treated with a sublethal dose of acetaminophen (APAP) to induce acute liver injury. APAP induced a time- and dose-dependent damage of perivenous areas of the liver lobule. Serum levels of aspartate aminotransferase (AST) increased to similar levels irrespective of hMSC-HC transplantation. Yet, hMSC-HC resided in the damaged perivenous areas of the liver lobules short-term preventing apoptosis and thus progress of organ destruction. Disturbance of metabolic protein expression was lower in the livers receiving hMSC-HC. Seven weeks after APAP treatment, hepatic injury had completely recovered in groups both with and without hMSC-HC. Clusters of transplanted cells appeared predominantly in the periportal portion of the liver lobule and secreted human albumin featuring a prominent quality of differentiated hepatocytes. Thus, hMSC-HC attenuated the inflammatory response and supported liver regeneration after acute injury induced by acetaminophen. They hence may serve as a novel source of hepatocyte-like cells suitable for cell therapy of acute liver diseases.

Retrospective Analysis of Vision Rehabilitation for Veterans With Traumatic Brain Injury-Related Vision Dysfunction.

INTRODUCTION: Traumatic brain injury (TBI) can trigger vision-based sequelae such as oculomotor and accommodative abnormalities, visual-vestibular integrative dysfunction, visual field loss, and photosensitivity. The need for diagnosis and management of TBI-related vision impairment has increased because of the increasing frequencies of combat warfighters returning from Iraq and Afghanistan with TBIs. The purpose of this research was to learn the sequelae of rehabilitation service delivery to veterans with TBI-related visual dysfunction after they are diagnosed. To accomplish this, we investigated vision rehabilitation assessments and interventions provided to veterans with TBI-related visual dysfunction at the Department of Veterans Affairs (VA) specialty polytrauma facilities for the 2 years following their injury. The research questions asked what assessments, interventions, and prescribed assistive devices were provided by VA specialty clinics (e.g., occupational therapy, polytrauma, and blind rehabilitation) and how service delivery was affected by demographic and clinical variables. MATERIALS AND METHODS: A retrospective design was used to analyze VA data using natural language processing of unstructured clinician notes and logistic regression of structured data. Participants included 350 veterans with TBI who received rehabilitation at one of the five VA Polytrauma Rehabilitation Centers (Tampa, FL; Richmond, VA; Minneapolis, MN; San Antonio, TX; and Palo Alto, CA) between 2008 and 2017 and who were administered the 2008 congressionally mandated "Traumatic Brain Injury Specific Ocular Health and Visual Functioning Exam." The outcome variables were vision assessments, interventions, and prescribed assistive technology discovered via natural language processing of clinician notes as well as the vision rehabilitation specialty clinics providing the clinical care (polytrauma, occupational therapy, outpatient blind rehabilitation, inpatient blind rehabilitation, optometry, and low vision) extracted from VA structured administrative data. RESULTS: Veterans receiving rehabilitation for TBI-related vision dysfunction were most frequently assessed for saccades, accommodation, visual field, and convergence. Intervention was provided most frequently for eye-hand coordination, saccades, accommodation, vergence, and binocular dysfunction. Technology provided included eyeglasses, wheelchair/scooter, walker/cane, aids for the blind, and computer. There was an overlap in the services provided by specialty clinics. Services available and delivered were significantly associated with the comorbidities of each patient and the specialty clinics available at each VA Polytrauma Rehabilitation Center. CONCLUSIONS: The delivery of patient services should be driven by the needs of veterans and not by system-level factors such as the availability of specific vision rehabilitation services at specific locations. Traditional low vision and blind rehabilitation programs were not designed to treat the comorbidities and symptoms associated with TBI. To address this challenge, blind rehabilitation and neurologic recovery cross training is needed. Our findings document how five VA Polytrauma Rehabilitation Centers implemented this training in 2008. The next step is to extend and standardize this new paradigm to community care, where these post-deployment patients now reside.

Sustained acoustic medicine for the treatment of musculoskeletal injuries: a systematic review and meta-analysis.

BACKGROUND: Musculoskeletal injuries account for 10 million work-limited days per year and often lead to both acute and/or chronic pain, and increased chances of re-injury or permanent disability. Conservative treatment options include various modalities, nonsteroidal anti-inflammatory drugs, and physical rehabilitation programs. Sustained Acoustic Medicine is an emerging prescription home-use mechanotransductive device to stimulate cellular proliferation, increase microstreaming and cavitation in situ, and to increase tissue profusion and permeability. This research aims to summarize the clinical evidence on Sustained Acoustic Medicine and measurable outcomes in the literature. METHODS: A systematic literature review was conducted using PubMed, EBSCOhost, Academic Search Complete, Google Scholar and ClinicalTrials.gov to identify studies evaluating the effects of Sustained Acoustic Medicine on the musculoskeletal system of humans. Articles identified were selected based on inclusion criteria and scored on the Downs and Black checklist. Study design, clinical outcomes and primary findings were extracted from included studies for synthesis and meta-analysis statistics. RESULTS: A total of three hundred and seventy-two participants (372) were included in the thirteen clinical research studies reviewed including five (5) level I, four (4) level II and four (4) level IV studies. Sixty-seven (67) participants with neck and back myofascial pain and injury, one hundred and fifty-six (156) participants with moderate to severe knee pain and radiographically confirmed knee osteoarthritis (Kellgren-Lawrence grade II/III), and one hundred forty-nine (149) participants with generalized soft-tissue injury of the elbow, shoulder, back and ankle with limited function. Primary outcomes included daily change in pain intensity, change in Western Ontario McMaster Osteoarthritis Questionnaire, change in Global Rate of Change, and functional outcome measures including dynamometry, grip strength, range-of-motion, and diathermic heating (temperature measurement). CONCLUSION: Sustained Acoustic Medicine treatment provides tissue heating and tissue recovery, improved patient function and reduction of pain. When patients failed to respond to physical therapy, Sustained Acoustic Medicine proved to be a useful adjunct to facilitate healing and return to work. As a non-invasive and non-narcotic treatment option with an excellent safety profile, Sustained Acoustic Medicine may be considered a good therapeutic option for practitioners.