Impact of using XP-endo finisher and nanobubble water during EDTA dentin conditioning on TGF-ß1 release in regenerative endodontic procedures.

INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-ß1) plays a crucial role in the success of Regenerative Endodontic Procedures (REPs) as they directly impact the proliferation and differentiation of stem cells. TGF-ß1 is released by conditioning of the dentin matrix using 17% EDTA. EDTA was found to have deleterious effects on dentin especially in immature teeth with fragile dentin walls. Decreasing the irrigation time was reported to decrease these effects. Accordingly, enhancement and activation of the EDTA solution to maintain its efficiency in TGF-ß1 release from dentin and thus compensating the reduction in irrigation time was employed. EDTA solution was enhanced by adding Nanobubble (NB) water which contains oxygen filled cavities less than 200 nm in diameter. Additionally, EDTA was activated with XP-endo Finisher rotary file. The aim of this study was to assess the impact of NB enhancement and/or XP-endo Finisher activation of the EDTA solution on the TGF-ß1 release from dentin. METHODS: Fifty standardized root segments with open apex were allocated to two main groups according to whether EDTA was enhanced with NB water or not, and within each group whether XP-endo Finisher activation was used or not in addition to a Negative Control group. The concentration of the released TGF-ß1 in the root canal was measured using enzyme-linked immunosorbent assay (ELISA). The statistical analysis was done using the Shapiro- Wilk, Kolmogorov Smirnov, ANOVA and Post-hoc Tukey tests. RESULTS: All groups released a considerable amount of TGF-ß1 with the highest values in the EDTA/NB/XP group, followed by EDTA/NB, EDTA/DW/XP, EDTA/DW and Negative Control groups respectively. CONCLUSIONS: The results of this study suggest that NBs can promote the success of REPs since it revealed a significant increase in the TGF-ß1 release following its use in the enhancement of the EDTA solution. A comparable effect was obtained by XP-endo finisher activation of the EDTA solution. The combined use of NBs and XP-endo Finisher can be a promising addition in REPs. Accordingly, Enhancement and activation of the EDTA solution may compensate decreasing the EDTA irrigation time attempted to avoid the deleterious effect of EDTA on dentin.

Extension and Evaluation of the PROMIS Sexual Function and Satisfaction Measures for Use in Adults Living With Multiple Sclerosis.

BACKGROUND: Sexual dysfunction is a common symptom of multiple sclerosis (MS). Clinically meaningful and psychometrically sound measures of sexual function validated in people with MS are necessary to identify people with MS who experience problems with sexual function. AIM: To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) v2.0 measure in people with MS and to extend the PROMIS SexFS Brief and Full Profiles to include additional aspects of sexual function relevant to people living with MS. METHODS: A convenience sample of MS clinicians and sexually active individuals with MS ranked relevance of 26 items that listed specific factors that interfere with sexual function. Rankings were used to select items to include in the modified SexFS for Multiple Sclerosis (SexFS-MS) profiles. Sex-FS Brief and Full profiles along with the top 22 ranked interfering factor items underwent cognitive interviews (CI) to assess whether the items were understandable and meaningful. OUTCOMES: The SexFS as originally published functioned well in people with MS after minor modifications. RESULTS: Twelve MS clinicians and 26 people with MS ranked items. The 10 highest ranked questions about factors that interfere with sexual function most relevant to people with MS were added to the SexFS-MS Brief profiles and 18 to the Full profiles. Ten men and 12 women with MS participated in CIs and found most items to be clear and meaningful. However, important changes were made to the profile instructions, some response sets, and to some items to improve clarity and function. New items to assess numbness and reasons why sexually active people choose at times not to engage in sexual activity were added. CLINICAL IMPLICATIONS: Brief and Full profiles are freely available and are recommended for research and clinical practice that include people with MS. STRENGTHS & LIMITATIONS: This study is the first to provide validity evidence for the PROMIS SexFS in people living with MS. Though the PROMIS SexFS was tested in people who identify as lesbian, gay, or bisexual, only individuals who identified as heterosexual participated in this study. Results may not represent views of people with MS who identify as other sexual orientations who may have different concerns and priorities related to sexual function. CONCLUSION: This study extended the PROMIS SexFS Brief and Full profiles to create the SexFS-MS by adding items that measure most relevant issues related to sexual function in individuals living with MS. Amtmann D, Bamer AM, Salem R, et al. Extension and Evaluation of the PROMIS Sexual Function and Satisfaction Measures for Use in Adults Living With Multiple Sclerosis. J Sex Med 2022;19:719-728.

Use of Standardized Outcome Measures for People With Lower Limb Amputation: A Survey of Prosthetic Practitioners in the United States.

OBJECTIVE: To assess the clinical resources available for the assessment of health outcomes in people with lower limb amputation and to understand barriers and facilitators associated with use of standardized outcome measures in clinical practice. DESIGN: Cross-sectional survey. SETTING: General community (online). PARTICIPANTS: A volunteer sample of prosthetic practitioners was recruited through national professional organizations. Eligible participants were practitioners certified by a professional prosthetics organization and currently practicing as a prosthetist, prosthetist-orthotist, or prosthetic assistant. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A custom-designed online survey on clinical use of patient-reported and performance-based standardized outcome measures to assess patients with lower limb amputation. RESULTS: A total of 375 participants completed the survey. Most participants (79%) reported that they are encouraged or required to administer standardized outcome measures in their clinic or facility. Most participants reported that use of patient-reported and performance-based outcome measures are within their scope of practice (88%) and that they have the knowledge required for outcomes measurement (84%). Few participants agreed that outcomes measurement is standardized across the profession (30%). Most participants had access to small spaces and equipment for outcomes measurement, such as short hallways (65%-94%), stairs (69%), and tablets with wireless internet connection (83%). Most participants reported that they would be willing to spend between 5 (36% of participants) and 10 (43% of participants) minutes on self-reported surveys, and between 10 (41% of participants) and 20 (28% of participants) minutes on performance-based tests. CONCLUSIONS: Outcomes measurement is encouraged or expected in contemporary prosthetic practice. Strategies to improve standardization and efficiency of administration are needed to facilitate routine use of outcome measures in clinical care.

A Comparison of the Two-Minute Walk Test (2MWT) and Comprehensive High-level Activity Mobility Predictor (CHAMP) in People with a Leg Prosthesis.

OBJECTIVE: To determine if the two-minute walk test (2MWT) could serve as an alternative measure of high-level mobility in lower limb prosthesis users when circumstances preclude administration of the Comprehensive High-level Activity Mobility Predictor (CHAMP). DESIGN: Cross-sectional study. SETTING: Indoor recreational athletic field and gymnasium. SUBJECTS: Fifty-eight adult lower limb prosthesis users with unilateral or bilateral lower limb amputation who participate in recreational athletic activities. INTERVENTION: N/A. MAIN MEASURES: The 2MWT and CHAMP while using their preferred prosthesis(es) on an indoor artificial athletic field or hardwood gymnasium floor. RESULTS: Thirty-nine men and nineteen women with a median age of 38.3 years participated in the study. Most participants experienced amputation(s) due to trauma (62%) or tumor (10%) and were generally higher functioning (K4 (91.4%) and K3 (8.6%)). The median (range) score for the CHAMP was 23.0 points (1.5-33.5) and the mean ± standard deviation (range) 2MWT distance walked was 188.6 ± 33.9 m (100.2-254.3 m). The CHAMP demonstrated a strong positive relationship with 2MWT (r = 0.83, p < 0.001). The 2MWT distance predicted 70% of the variance in CHAMP score. CONCLUSIONS: Although the 2MWT does not test multi-directional agility like the CHAMP, they were found to be highly correlated. If space is limited, the two-minute walk test can serve as an alternative measure for assessing high-level mobility capabilities in lower limb prosthesis users.

Perceptions and Attitudes of Cancer Patients and Caregivers Towards Enrollment in Clinical Trials in Lebanon.

The rates of participation in oncology clinical trials (CTs) are relatively lower in the Middle East compared to other areas in the world. Many social and cultural factors underlie the patients' reluctance to participate. To probe the knowledge, attitudes, and perceptions of patients with cancer and their caregivers regarding participation in CTs at our tertiary referral center in Lebanon, we interviewed 210 patients and caregivers visiting the outpatient clinics in the Naef Basile Cancer Institute at the American University of Beirut. A questionnaire was derived from literature and administered in Arabic. The study was approved by the Institutional Review Board (IRB). Two hundred individuals agreed to answer the questionnaire. The majority of participants (90.5%) were Lebanese with the remaining being non-Lebanese Arabs. Eighty-nine participants (45%) were aware of the concepts of CTs. Eighty-two respondents (41%) would participate in phase I CTs. Twenty-nine individuals (14.5%) agree to be enrolled in CTs with the approval of their family members only. One hundred twenty-nine subjects (64.5%) stated that they would refuse enrollment in a CT where they might receive placebo. Eighty-eight (44%) of participants considered that medical records could be reviewed for research without consent while 54% agreed that samples collected during clinical workup could be used for research without the consent of the patient. There are several social and demographic correlates for participation in CTs. Raising awareness and overcoming barriers of misconception are keys to promote participation in CTs in Lebanon.

Do measures of depressive symptoms function differently in people with spinal cord injury versus primary care patients: the CES-D, PHQ-9, and PROMIS®-D.

PURPOSE: To evaluate whether items of three measures of depressive symptoms function differently in persons with spinal cord injury (SCI) than in persons from a primary care sample. METHODS: This study was a retrospective analysis of responses to the Patient Health Questionnaire depression scale, the Center for Epidemiological Studies Depression scale, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS®) version 1.0 eight-item depression short form 8b (PROMIS-D). The presence of differential item function (DIF) was evaluated using ordinal logistic regression. RESULTS: No items of any of the three target measures were flagged for DIF based on standard criteria. In a follow-up sensitivity analyses, the criterion was changed to make the analysis more sensitive to potential DIF. Scores were corrected for DIF flagged under this criterion. Minimal differences were found between the original scores and those corrected for DIF under the sensitivity criterion. CONCLUSIONS: The three depression screening measures evaluated in this study did not perform differently in samples of individuals with SCI compared to general and community samples. Transdiagnostic symptoms did not appear to spuriously inflate depression severity estimates when administered to people with SCI.

Cross-Sectional Assessment of Factors Related to Pain Intensity and Pain Interference in Lower Limb Prosthesis Users.

OBJECTIVE: To determine relationships between pain sites and pain intensity/interference in people with lower limb amputations (LLAs). DESIGN: Cross-sectional survey. SETTING: Community. PARTICIPANTS: Lower limb prosthesis users with unilateral or bilateral amputations (N=1296; mean time since amputation, 14.1y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity (1 item to assess average pain), PROMIS pain interference (4-item short form to assess the consequences of pain in desired activities), and questions that asked participants to rate the extent to which each of the following were a problem: residual limb pain (RLP), phantom limb pain (PLP), knee pain on the nonamputated side, back pain, and shoulder pain. RESULTS: Nearly three quarters (72.1%) of participants reported problematic pain in 1 or more of the listed sites. Problematic PLP, back pain, and RLP were reported by 48.1%, 39.2%, and 35.1% of participants, respectively. Knee pain and shoulder pain were less commonly identified as problems (27.9% and 21.7%, respectively). Participants also reported significantly (P<.0001) higher pain interference (T-score ± SD, 54.7±9.0) than the normative sample based on the U.S. population (T-score ± SD, 50.0±10.0). Participants with LLAs rated their pain intensity on average ± SD at 3.3±2.4 on a 0-to-10 scale. Pain interference (ρ=.564, P<.0001) and intensity (ρ=.603, P<.0001) were positively and significantly correlated with number of pain sites reported. CONCLUSIONS: Problematic pain symptoms, especially RLP, PLP, and back pain, affect most prosthetic limb users and have the potential to greatly restrict participation in life activities.

Construct Validity of the Prosthetic Limb Users Survey of Mobility (PLUS-M) in Adults With Lower Limb Amputation.

OBJECTIVE: To assess construct validity of the Prosthetic Limb Users Survey of Mobility (PLUS-M), a self-report mobility measure for people with lower limb amputation (LLA). DESIGN: Cross-sectional study. SETTING: Private prosthetic clinics (n=37). PARTICIPANTS: Current lower limb prosthesis users (N=199; mean age ± SD, 55.4±14.3y; 71.4% men) were assessed before receiving a replacement prosthesis, prosthetic socket, and/or prosthetic knee. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Convergent construct validity was examined using correlations between participants' PLUS-M T-scores and measures of physical function, mobility, and balance, including the Amputee Mobility Predictor (AMP), timed Up and Go (TUG), Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Prosthesis Evaluation Questionnaire-Mobility Subscale (PEQ-MS), and Activities-specific Balance Confidence (ABC) Scale. Known-groups construct validity was evaluated by comparing differences in PLUS-M T-scores among participants grouped by Medicare Functional Classification Level (MFCL). RESULTS: PLUS-M T-scores demonstrated a moderate positive relationship with AMP scores (ρ=.54, P<.001) and a moderate negative relationship with TUG times (ρ=-.56, P<.001). The PLUS-M also showed a strong positive relationship with PEQ-MS scores (ρ=.78, P<.001), ABC Scale scores (ρ=.81, P<.001), and PROMIS-PF T-scores (ρ=.81, P<.001). Significant differences (P<.05) in PLUS-M T-scores were found among groups of people classified by different MFCLs. CONCLUSIONS: Study results support the validity of the PLUS-M as a self-report measure of prosthetic mobility. Correlations between PLUS-M and measures of physical function, mobility, and balance indicate convergent construct validity. Similarly, significant differences in PLUS-M T-scores across MFCL groups provide evidence of known-groups construct validity. In summary, evidence indicates that PLUS-M has good construct validity among people with LLA.

Self-Reported Cognitive Concerns in People With Lower Limb Loss.

OBJECTIVES: To investigate differences between self-reported cognitive concerns in people with lower limb loss (LLL) and normative data derived from the U.S. general population, and secondarily to determine whether there were cognitive differences based on amputation etiology or age. DESIGN: Survey. SETTING: General community. PARTICIPANTS: A volunteer sample of persons with LLL (N=1086) resulting from trauma or dysvascular complications who regularly use a prosthetic limb. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Quality of Life in Neurological Disorders Applied Cognition-General Concerns Short Form version 1.0 (Neuro-QoL ACGC), an 8-item self-report measure of general cognitive concerns. RESULTS: People with LLL reported significantly more cognitive concerns than the Quality of Life in Neurological Disorders normative sample. Mean Neuro-QoL ACGC scores were significantly lower than normative values (P<.001) across subgroups defined by age (ie, <40, 40-49, 50-59, 60-69, and 70+ years) and subgroups defined by etiology (ie, traumatic and dysvascular LLL). However, there were no significant differences in cognitive concerns among age subgroups (P=.84) or between the etiology subgroups (P=.58). CONCLUSIONS: When compared with the Quality of Life in Neurological Disorders normative sample, individuals with LLL report greater concerns with cognitive health. Cognitive concerns were not differentially affected by age or cause of amputation. The presence of cognitive concerns in people with LLL suggests a need to assess perceived cognitive function in order to tailor education and training in prosthetic use and care.

Measuring fatigue in people with multiple sclerosis - which questionnaire should be used? A Plain Language Summary of Publication.

WHAT IS THIS SUMMARY ABOUT?: This summary explains the findings of a recent study that compared different questionnaires used by doctors to measure levels of fatigue in people with multiple sclerosis (MS). The aim of the study was to find out which questionnaire doctors should use to measure fatigue in people with MS in the future. Fatigue, which can be described as the overwhelming feeling of tiredness or exhaustion, is a very common symptom of MS. For the majority of people with MS, fatigue is one of the worst symptoms of MS, so it is essential that doctors can measure it accurately. Currently, people with MS are asked to complete questionnaires so that their care team can see the effect of fatigue on their day-to-day lives. There are many questionnaires that are used to measure fatigue in people with MS. It would be valuable to come to an agreement, based on evidence from research like this study, on which questionnaire is the most appropriate for measuring fatigue in both research and healthcare settings. This study compared a questionnaire called the PROMIS® Fatigue (MS) 8a, referred to throughout this summary as the PROMIS® MS Fatigue Short Form, with two of the most commonly used questionnaires: the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). The questionnaires were compared to see which one should be recommended to doctors for measuring fatigue in people with MS. WHAT ARE THE KEY TAKEAWAYS?: It was found that while all three questionnaires were good, the PROMIS® MS Fatigue Short Form questionnaire was better than the other two questionnaires at showing differences in levels of fatigue between people with MS. The PROMIS® MS Fatigue Short Form was also found to be better than the Fatigue Severity Scale (FSS) at showing changes in the person with MS's level of fatigue. The PROMIS® MS Fatigue Short Form questionnaire may help people with MS to better communicate challenges with their fatigue to their doctors. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: The study suggests that the PROMIS® MS Fatigue Short Form questionnaire is a helpful tool for doctors and people with MS to measure fatigue.

The impact of TK2 deficiency syndrome and its treatment by nucleoside therapy on quality of life.

TK2d is an ultrarare autosomal recessive mitochondrial DNA depletion syndrome. Nucleoside therapy improves or stabilizes disease across key outcomes including survival, ambulation, and requirement for mechanical ventilation. However, little is known about the effects of nucleoside therapy treatment of TK2d from the patient's perspective. This study sought to address this knowledge gap. Participants with TK2d and/or their parents/caregivers completed online surveys with standardized health measures and interviews. During interviews, participants rated and described TK2d's impact on 13 quality of life domains, changes since starting nucleoside therapy, and if they would recommend nucleoside therapy. Twenty-five individuals participated (17 adults with TK2d, 4 parent-participant pairs, 4 parents of children with TK2d). Adult participants with TK2d had clinically meaningfully worse scores than the general population on global physical and mental health, physical function, pain interference, fatigue, anxiety, and social function. Children's mobility and pain interference were significantly worse than the general pediatric population. Physical domains most affected by TK2d were: mobility (84%), fatigue (60%), respiratory function (56%), and hospitalizations (55%). Psychosocial domains most affected were: impact on family members (39%), mood (36%), and social life (28%). Most (77%) treated patients reported improvement; whereas, 67% in the untreated group reported worsening. All participants would recommend nucleoside therapy. In summary, TK2d has significant negative impacts on most areas of life and function. Measures of fatigue, sleep, swallowing/eating, speaking, and mood, should be considered as outcomes in clinical trials and research studies. Nucleoside therapy appears to provide meaningful improvements across many health domains affected by TK2d. SYNOPSIS: The consequences of having TK2d are devastating for both those with the disorder and their families; however, nucleoside therapy appears to provide meaningful improvements across many health domains affected by TK2d.

Fenfluramine treatment for Dravet syndrome: Caregiver- and clinician-reported benefits on the quality of life of patients, caregivers, and families living in Germany, Spain, Italy, and the United Kingdom.

OBJECTIVE: Clinical trial data and prior preliminary research indicate that fenfluramine (FFA) provides meaningful improvements in seizure-related and quality of life (QOL) outcomes for individuals with Dravet syndrome (DS), their caregivers, and their families. This study sought to replicate and extend these preliminary findings in a new sample of individuals with DS and their families who live in European countries. METHODS: Study participants were European clinicians and parents caring for individuals with DS who had participated in an EU FFA Early Access Program. Participants completed one-on-one semi-structured interviews and were asked the extent to which they noticed changes in a number of the child's seizure- and non-seizure-related QOL domains after starting FFA treatment. Participants were also asked about the benefits of FFA treatment to the caregivers' lives and for the family unit. RESULTS: 25 parent caregivers and 16 clinicians participated. The caregivers and clinicians reported improvements in both seizure-related (i.e., reductions in seizure activity, improvements in the frequency or type of seizure triggers and post-ictal recovery times, and improved post-seizure function) and non-seizure-related (e.g., cognition, focus, alertness, speech, academic performance, behavior, sleep, motor function) QOL domains after FFA treatment in individuals with DS. Caregivers also reported improved mood and more time for things they enjoyed, felt less overwhelmed, reported better sleep quality, and had less personal and family stress; clinicians corroborated most of these reports. All clinicians (100%) and most (96%) caregivers said they would "very likely" or "quite likely" recommend FFA to others with DS. CONCLUSIONS: Real-world experience in Europe with FFA treatment is associated with meaningful improvements in many QOL domains for individuals with DS and their families; replicating findings from a previous study of DS patients and their families from the USA. Caregivers and clinicians provided specific examples of the benefits of FFA for people with DS, caregivers, and their families and are very likely to recommend FFA to others with DS.

Development and initial validation of the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses.

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users' mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user's mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies.

Development of an item bank for measuring prosthetic mobility in people with lower limb amputation: The Prosthetic Limb Users Survey of Mobility (PLUS-M).

BACKGROUND: Achieving mobility with a prosthesis is a common post-amputation rehabilitation goal and primary outcome in prosthetic research studies. Patient-reported outcome measures (PROMs) available to measure prosthetic mobility have practical and psychometric limitations that inhibit their use in clinical care and research. OBJECTIVE: To develop a brief, clinically meaningful, and psychometrically robust PROM to measure prosthetic mobility. DESIGN: A cross-sectional study was conducted to administer previously developed candidate items to a national sample of lower limb prosthesis users. Items were calibrated to an item response theory model and two fixed-length short forms were created. Instruments were assessed for readability, effective range of measurement, agreement with the full item bank, ceiling and floor effects, convergent validity, and known groups validity. SETTING: Participants were recruited using flyers posted in hospitals and prosthetics clinics across the United States, magazine advertisements, notices posted to consumer websites, and direct mailings. PARTICIPANTS: Adult prosthesis users (N = 1091) with unilateral lower limb amputation due to traumatic or dysvascular causes. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Candidate items (N = 105) were administered along with the Patient Reported Outcome Measurement Information System Brief Profile, Prosthesis Evaluation Questionnaire - Mobility Subscale, and Activities-Specific Balance Confidence Scale, and questions created to characterize respondents. RESULTS: A bank of 44 calibrated self-report items, termed the Prosthetic Limb Users Survey of Mobility (PLUS-M), was produced. Clinical and statistical criteria were used to select items for 7- and 12-item short forms. PLUS-M instruments had an 8th grade reading level, measured with precision across a wide range of respondents, exhibited little-to-no ceiling or floor effects, correlated expectedly with scores from existing PROMs, and differentiated between groups of respondents expected to have different levels of mobility. CONCLUSION: The PLUS-M appears to be well suited to measuring prosthetic mobility in people with lower limb amputation. PLUS-M instruments are recommended for use in clinical and research settings.

Fenfluramine treatment for dravet syndrome: Real-world benefits on quality of life from the caregiver perspective.

OBJECTIVE: Prior research has demonstrated durable and profound reductions in seizure frequency and improvements in executive functions in individuals with Dravet syndrome (DS) who are treated with fenfluramine (FFA). This study aimed to understand the benefits of FFA from the perspective of the patients' caregivers. METHODS: Caregivers for a child with DS participated in semi-structured interviews to discuss the benefits of FFA treatment on the child with DS, the caregiver, and the family. RESULTS: 65 caregivers participated. Patients were between 2 and 33 years old and had been treated with FFA for an average of 22.7 months. The most commonly reported seizure-related benefits (> 50 % of participants) of FFA treatment included a reduction in seizure activity, fewer seizure triggers, and shorter post-ictal recovery. The most common quality of life (QOL) benefits in patients included improvements in cognitive function, alertness, and academic performance. In addition, the caregivers reported improvements in their sleep quality (74 %) and that they felt less overwhelmed (72 %) and stressed (69 %) after their children began FFA treatment. Many caregivers also reported improved relationships between the child with DS and their siblings (52 %). CONCLUSIONS: The study found that FFA treatment is associated with meaningful improvement in a large number of QOL domains both for the people with DS who received FFA and their families.

A comparison of the measurement properties of the PROMIS Fatigue (MS) 8a against legacy fatigue questionnaires.

BACKGROUND: Amidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research was to compare the validity and responsiveness of scores from the PROMIS Fatigue (MS) 8a with those of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), across US and UK MS populations. METHODS: Two observational studies were performed in MS populations as part of a PRO measure development project, including a cross-sectional study in two tertiary US MS centers (n = 340) and a 96-week longitudinal study in the UK MS Register cohort (n = 352). In post-hoc analyses, we examined  relative validity, based on ability to discriminate across patient groups with different fatigue levels or functional status at baseline (i.e., ANOVA-F PROX ÷ ANOVA-F PROMIS (MS) 8a), and relative responsiveness, based on baseline-to-Week-52 score change (effect sizes) across fatigue or functional status response groups . RESULTS: Mean ± standard deviation (SD) age was 44.6 ± 11.3/50.0 ± 9.7; and 72.9%/77.3% were female (US/UK samples). The mean PROMIS Fatigue (MS) 8a T-score ± SD at baseline was 57.7 ± 10.5/58.9 ± 9.3 (US/UK samples). Compared with the PROMIS Fatigue (MS) 8a, relative validity (anchor: Global Health Score [GHS] fatigue global question) was 85% for MFIS symptom score, 48% for MFIS total score, and 44% for the FSS. Relative to the FSS, PROMIS Fatigue (MS) 8a scores were more sensitive to worsening (effect size = -0.43 versus -0.18) as well as improvement (effect size = 0.5 versus 0.2) in fatigue (≥1-point increase/decrease in GHS fatigue global question) over 52 weeks of follow-up. A similar pattern of score changes was observed based on a second anchor. CONCLUSION: The PROMIS Fatigue (MS) 8a scores showed higher responsiveness to fatigue changes than those of the FSS. The PROMIS measure also had higher precision in differentiating levels of fatigue compared to the FSS, the MFIS physical, and MFIS total scores. These differences have practical implications for the application of these questionnaires in both clinical practice and research settings (e.g., sample size estimation in clinical trials).

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis.

Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin's (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.

The validity, responsiveness, and score interpretation of the PROMISnq Physical Function - Multiple Sclerosis 15a short form in multiple sclerosis.

BACKGROUND: A valid, sensitive patient-reported outcome (PRO) measure of physical function (PF) for people with multiple sclerosis (MS) would have substantial value in routine care and clinical research. We now describe development of the PROMISnq Short Form v2.0 PF - Multiple Sclerosis 15a [PROMISnq PF(MS)15a] for assessing PF in relapsing and progressive MS. Also, the validity, reliability, and responsiveness of the PROMISnq PF(MS)15a is evaluated, minimal important difference (MID) thresholds for score change estimated and a score interpretation guide developed. METHODS: A mixed-methods sequential design was employed. Relevant PF concepts were elicited through semi-structured interviews with people with relapsing MS, and then mapped to the PROMIS PF item bank. Measurement experts integrated results from interviews with people with MS and input from a panel of neurologists to generate a draft short form. Relevance and comprehensiveness of the draft short form were assessed in cognitive debriefing interviews with people with relapsing or progressive MS. Subsequently, item reduction and evaluation of psychometric properties were performed in two observational studies: a cross-sectional study in the US (n = 296), and a 96-week longitudinal study in the UK MS Register cohort (n = 558). The main outcomes and measures are estimates of: known-groups validity, convergent validity, reliability, responsiveness; MID for worsening. RESULTS: Factor analyses supported the unidimensionality of the newly derived 15-item short form. Cronbach's alpha (≥ 0.97) and intraclass correlation coefficient (≥ 0.97) of test-retest scores (5-27 days) indicated strong reliability. Convergent validity was demonstrated by moderate-to-strong correlations with scores on related PRO measures. Scores discriminated among patient groups classified by levels of physical health and other criteria. Score changes of 2.3-2.7 points are proposed as MID criteria for minimal worsening in PF. CONCLUSION: PROMISnq PF(MS)15a demonstrated reliability, validity and sensitivity to change. Input from patients and clinicians ensured the content is comprehensive and relevant for people with MS.

Biomedical Applications of Biomolecules Isolated from Methanotrophic Bacteria in Wastewater Treatment Systems.

Wastewater treatment plants and other remediation facilities serve important roles, both in public health, but also as dynamic research platforms for acquiring useful resources and biomolecules for various applications. An example of this is methanotrophic bacteria within anaerobic digestion processes in wastewater treatment plants. These bacteria are an important microbial source of many products including ectoine, polyhydroxyalkanoates, and methanobactins, which are invaluable to the fields of biotechnology and biomedicine. Here we provide an overview of the methanotrophs' unique metabolism and the biochemical pathways involved in biomolecule formation. We also discuss the potential biomedical applications of these biomolecules through creation of beneficial biocompatible products including vaccines, prosthetics, electronic devices, drug carriers, and heart stents. We highlight the links between molecular biology, public health, and environmental science in the advancement of biomedical research and industrial applications using methanotrophic bacteria in wastewater treatment systems.

Screening for Methane Utilizing Mixed Communities with High Polyhydroxybutyrate (PHB) Production Capacity Using Different Design Approaches.

With the adverse environmental ramifications of the use of petroleum-based plastic outweighing the challenges facing the industrialization of bioplastics, polyhydroxyalkanoate (PHA) biopolymer has gained broad interest in recent years. Thus, an efficient approach for maximizing polyhydroxybutyrate (PHB) polymer production in methanotrophic bacteria has been developed using the methane gas produced in the anaerobic digestion process in wastewater treatment plants (WWTPS) as a carbon substrate and an electron donor. A comparison study was conducted between two experimental setups using two different recycling strategies, namely new and conventional setups. The former setup aims to recycle PHB producers into the system after the PHB accumulation phase, while the latter recycles the biomass back into the system after the exponential phase of growth or the growth phase. The goal of this study was to compare both setups in terms of PHB production and other operational parameters such as growth rate, methane uptake rate, and biomass yield using two different nitrogen sources, namely nitrate and ammonia. The newly proposed setup is aimed at stimulating PHB accumulating type II methanotroph growth whilst enabling other PHB accumulators to grow simultaneously. The success of the proposed method was confirmed as it achieved highest recorded PHB accumulation percentages for a mixed culture community in both ammonia- and nitrate-enriched media of 59.4% and 54.3%, respectively, compared to 37.8% and 9.1% for the conventional setup. Finally, the sequencing of microbial samples showed a significant increase in the abundance of type II methanotrophs along with other PHB producers, confirming the success of the newly proposed technique in screening for PHB producers and achieving higher PHB accumulation.