An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis.

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

Expansion of Telestroke Coverage in Community Hospitals: Unifying Stroke Care and Reducing Transfer Rate.

OBJECTIVE: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. METHODS: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre- and post-TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. RESULTS: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre- and 5,051 in the post-TS expansion). In the post-TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door-to-needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. INTERPRETATION: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576-582.

Comparison of Computer-Assisted Self-Interview Versus Clinician Interview for Self-Reported Vulvovaginal Symptoms.

ABSTRACT: This secondary analysis (N = 43) compared computer-assisted self-interview (CASI) to clinician interview for self-report of 8 vulvovaginal symptoms. Concordance was moderate between interview modes (range, 70-86%) with itching and odor having highest agreement. Although prior reports suggest more responses on CASI, we found CASI did not significantly increase self-report of symptoms over clinician interview.

Pain, function, and radiographic disease in trapeziometacarpal osteoarthritis.

INTRODUCTION: Trapeziometacarpal joint osteoarthritis (OA) produces significant functional impairment due to pain and loss of strength in both power and precision grips, but few studies have related radiographic scores to functional and pain-based measures. PURPOSE: To investigate the association between markers of radiographic disease and outcomes for symptomatic and functional disease. STUDY DESIGN: This study in an exploratory analysis of baseline data from the first 100 participants in a clinical trial evaluating the efficacy of combined conservative therapies for base of thumb OA (COMBO). METHODS: Functional Index for Hand Osteoarthritis (FIHOA) scores and Visual Analogue Scale (VAS) scores for pain were recorded for the index hand. Bilateral isometric grip and tip-pinch strength measurements were taken, as well as posteroanterior and Eaton stress-view hand radiographs. Generalized estimating equations (GEEs), univariate, and multivariate analyses were used according to whether the data were bilateral or unilateral. RESULTS: A total of 79 females and 21 males were included, with a median Kellgren-Lawrence (KL) grade of 3 in the index hand. Higher KL and Eaton grades were associated with lower grip strength in the GEE analysis (B-coefficients of -1.25 and -1.16, and P-values of .002 and .010, respectively). Higher KL grade was also associated with poorer function and higher pain levels in the multivariable analysis (B-coefficients of 1.029 and 3.681, and P-values of .021 and .047, respectively). Lower radial subluxation ratios were associated with lower grip strength in the GEE analysis, and higher pain scores in the multivariable analysis (B-coefficients of 2.06 and -42.1, and P-values of .006 and .031, respectively). Greater pain scores were also associated with poorer function (B-coefficient 0.082, P-value .001). CONCLUSION: More advanced radiographic trapeziometacarpal OA severity is associated with lower grip strength and poorer self-reported functional outcomes. Lower subluxation ratios were associated with higher pain scores and lower grip strength.

Patients Follow Different Financial Hardship Trajectories in the Year after Injury.

OBJECTIVE: To determine if distinct financial trajectories exist and if they are associated with quality-of-life outcomes. SUMMARY OF BACKGROUND DATA: Financial hardship after injury measurably impacts Health-Related Quality of Life outcomes. Financial hardship, encompassing material losses, financial worry, and poor coping mechanisms, is associated with lower quality of life and increased psychological distress. However, recovery is dynamic and financial hardship may change over time. METHODS: This is a secondary analysis of a cohort of 500 moderate-to-severe nonneurologic injured patients in which financial hardship and Health-related Quality of Life outcomes were measured at 1, 2, 4, and 12 months after injury using survey instruments (Short Form-36). Enrollment occurred at an urban, academic, Level 1 trauma center in Memphis, Tennessee during January 2009 to December 2011 and follow-up completed by December 2012. RESULTS: Four hundred seventy-four patients had sufficient data for Group- Based Trajectory Analysis. Four distinct financial hardship trajectories were identified: Financially Secure patients (8.6%) had consistently low hardship over time; Financially Devastated patients had a high degree of hardship immediately after injury and never recovered (51.6%); Financially Frail patients had increasing hardship over time (33.6%); and Financially Resilient patients started with a high degree of hardship but recovered by year end (6.2%). At 12-months, all trajectories had poor Short Form-36 physical component scores and the Financial Frail and Financially Devastated trajectories had poor mental health scores compared to US population norms. CONCLUSIONS AND RELEVANCE: The Financially Resilient trajectory demonstrates financial hardship after injury can be overcome. Further research into understanding why and how this occurs is needed.

Time Heals Most Wounds - Perceptions of Thyroidectomy Scars in Patients With Thyroid Cancer.

BACKGROUND: Patients understandably have concerns about thyroidectomy scars. This study aimed to characterize patients' perceptions of their thyroidectomy scar before and up to 1-y after surgery. METHODS: Patients with papillary thyroid cancer (n = 83) completed semi-structured interviews before and at 2-wks, 6-Wk, 6-mo, and 1-y post-thyroidectomy. Interviews probed about scar concerns and appearance. Content analysis was used to identify themes. RESULTS: The majority of participants did not express concerns about scar appearance. When expressed, preoperative concerns often stemmed from previous surgery experiences or unease with neck incisions. Postoperatively, concerns about scar appearance decreased over time throughout the healing period with most patients being satisfied with their scar appearance by 6-mo after surgery. CONCLUSIONS: Patients with papillary thyroid cancer express few concerns about scar thyroidectomy appearance. Surgeons can reassure patients who have preoperative concerns that most patients are satisfied with their scar appearance by 6-mo after surgery.

Low-level laser therapy and static stretching exercises for patients with knee osteoarthritis: A randomised controlled trial.

OBJECTIVES: To investigate the laser effect associated with stretching exercise on pain and functionality in patients with knee osteoarthritis. DESIGN: A randomised controlled trial. SETTING: Special Rehabilitation Services. SUBJECTS: We enrolled 215 knee osteoarthritis patients (430 knees were treated). INTERVENTION: Group Laser + Stretch (n = 43), Placebo + Stretch (n = 43), Stretch (n = 43), Laser (n = 43) and Control (n = 43) were treated with active laser and stretching exercises; placebo laser and stretching exercises; stretching exercises; active laser, and control, respectively. Interventions were conducted 3 times a week for 8 or 11 weeks. MAIN OUTCOME MEASURES: The primary outcome was the change in knee pain and disability. Secondary outcomes included severity of osteoarthritis, mobility, knee range of motion, flexibility, activity, severity of osteoarthritis and medication intake for pain relief. RESULTS: The patients' average age was 63.52 (6.8) years. Pain scores at baseline and post treatment (p < 0.001) were 7.43 (2.10) and 2.79 (1.92) for group Laser + Stretch, 7.39 (1.98) and 4.47 (2.82) for group Placebo + Stretch, 6.83 (1.42) and 4.24 (2.43) for group Stretch, 6.61 (1.68) and 2.94 (2.65) for group Laser, 6.74 (1.75) and 6.47 (2.29) for group Control, respectively. Disability score at baseline and post treatment (p = 0.000237) were 12.36 (5.02) and 8.08 (4.64) for group Laser + Stretch, 12.71 (5.12) and 9.90 (4.95) for group Placebo + Stretch, 11.83 (2.77) and 7.20 (5.28) for group Stretch, 11.58 (5.59) and 8.21 (6.18) for group Laser, 11.23 (4.68) and 11.45 (4.83) for group Control, respectively. CONCLUSION: Laser therapy combined with stretching exercises improves pain during rest, activities of daily living, stiffness, muscle shortening and range of motion in patients with knee osteoarthritis.

High baseline pain is associated with treatment adherence in persons diagnosed with thumb base osteoarthritis: An observational study.

BACKGROUND: Thumb osteoarthritis (OA) is a common and disabling condition. Adherence to prescribed conservative interventions may affect outcomes of thumb OA trials. PURPOSE: The aim of the study was to determine whether baseline pain and hand function is associated with treatment adherence over 12 weeks in participants with thumb base OA. STUDY DESIGN: Observational cohort study nested within a randomized-controlled trial. METHODS: Ninety-four participants from the intervention group were included in the analysis. Baseline pain and function were assessed using a 100 mm Visual Analogue Scale and the Functional Index for Hand Osteoarthritis questionnaire (0-30), respectively. Participants received a combination of treatments including education, orthosis, hand exercises, and topical anti-inflammatory gel. Adherence was measured using a daily self-reported diary. Participants were classified as non-adherent, partially adherent or fully adherent if they completed none, 1 and/or 2 or all 3 of the interventions as prescribed. Ordinal logistic regression modelling was performed. RESULTS: At 12-week follow-up, half of the participants were fully adherent to the treatments (n = 46, 48.9%), 30.9% of participants were partially adherent (n = 29) and 20.2% were non-adherent (n = 19, 20.2%). High baseline pain was a significantly associated with better adherence in the unadjusted model [OR = 3.15, 95% CI (1.18, 8.42)] and adjusted model [OR = 3.20, 95% CI (1.13, 8.20)]. Baseline function was not associated with adherence [OR = 1.03, 95% CI (0.47, 2.23)]. CONCLUSION: High baseline pain was associated with better adherence in participants with thumb base OA. Higher baseline functional impairment was not associated with better adherence.

Impact of Satisfactory/Unsatisfactory Grading on Student Motivation to Learn, Academic Performance, and Well-Being.

Satisfactory/unsatisfactory (S/U) grading is often proposed to ameliorate stress by reducing the competitive nature of letter grading. Though explored considerably in human medical programs, minimal literature focuses on the veterinary school setting. The purpose of this study was to evaluate the impact of S/U grading on veterinary students' motivation to learn, academic performance, and well-being. Cornell University's COVID-19 pandemic response provided a unique opportunity to compare S/U and letter grading on the same population of students during a single pre-clinical foundation course, with the first half being graded S/U (spring semester 2020), returning to letter grades in the second half (fall semester 2020). Students were retroactively surveyed on the effect of S/U vs. letter grading on their overall educational experience and well-being, with 67.8% class participation. The majority of respondents (71.3%) stated that S/U grading had a positive impact on their overall learning experience. More than half (53.8%) perceived that they learned the same amount of information and had the same level of motivation (58.8%), even though most (61.3%) stated that they spent less time preparing for S/U assessments than letter grade assessments. Positive impact factor effects for S/U grading included decreased stress, more time for self-care, improved learning, and increased learning enjoyment. S/U grading did not negatively impact academic performance. In conclusion, this study demonstrates that, in our particular study population and setting, S/U grading conferred well-being and learning experience advantages to students without any reduction in motivation for learning or academic performance.

The NHGRI Short Course in Genomics: energizing genetics and genomics education in classrooms through direct engagement between educators and scientists.

PURPOSE: The National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) recognizes an urgent need for educator resources on cutting edge scientific topics due to increased public interest in genetics and genomics. We developed a Short Course in Genomics ("Short Course") to inspire new teaching materials through collaborative course development sessions and lectures, to expand access to cutting edge scientific information, and to provide a framework to consider when crafting new coursework related to scientific education. METHODS: We compared publicly available participant data from 2015 to 2019 with data from the National Center for Education Statistics to assess our progress in serving diverse educator and student populations. We also evaluated course agendas and interviewed participants and instructors. RESULTS: Middle school, high school, community college, and tribal college course attendees from the last five years were more likely to teach students from diverse communities underrepresented in science, technology, engineering, and mathematics (STEM). Both attendees and Short Course instructors emphasized the importance of bidirectional learning through interactive curriculum development. CONCLUSION: This course has the potential to facilitate the engagement of educators and students at all levels, recruit and maintain a diverse STEM workforce, and improve genomic literacy and future health decision-making.

The association between psychological factors and pain exacerbations in hip osteoarthritis.

OBJECTIVES: To evaluate the association between psychological factors and pain exacerbations in people with hip OA. METHODS: Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perceived they were experiencing a hip pain exacerbation. Hip pain exacerbation was defined as an increase of 2 points in pain intensity compared with baseline on an 11-point numeric rating scale (0-10). The Depression, Anxiety and Stress Scale-21 Items, Positive and Negative Affect Schedule, Pain Catastrophizing Scale and Pain Self-Efficacy Questionnaire were used to evaluate psychological factors. The associations of these with risk of hip pain exacerbation were examined by conditional logistic regression. RESULTS: Of 252 participants recruited, 131 (52.0%) contributed both case and control period data and were included in the analysis. A significant association was found between Pain Catastrophizing Scale overall score (1 point increase) with hip pain exacerbations (odds ratio: 1.07, 95% CI: 1.04, 1.11). An increase of a minimal important change (5.5 points) of Pain Self-Efficacy Questionnaire score was associated with a lower odds of pain exacerbations (odds ratio: 0.74, 95% CI: 0.65, 0.85). No significant associations were found between Depression, Anxiety and Stress Scale-21 Items or Positive and Negative Affect Schedule scores with hip pain exacerbations. CONCLUSION: Both pain catastrophizing and pain self-efficacy beliefs were associated with pain exacerbations in people with hip OA, but other psychological factors including depression, anxiety and stress or positive and negative affects, were not associated with pain exacerbations.

Carpometacarpal and metacarpophalangeal joint collapse is associated with increased pain but not functional impairment in persons with thumb carpometacarpal osteoarthritis.

INTRODUCTION: Due to the complex shape of the carpometacarpal (CMC) joint, a fixed joint collapse deformity of the thumb CMC (CMC1) and metacarpophalangeal (MCP1) joint can present in advanced stages of CMC1 osteoarthritis (OA), resulting in adduction of the first metacarpal (MC1) and hyperextension of the MCP1. PURPOSE OF THE STUDY: To determine whether joint collapse deformity is associated with worse pain and/or functional impairment. STUDY DESIGN: Cross-sectional. METHODS: This study used the baseline data from 140 patients enrolled in a longitudinal study of treatment for CMC1 OA. (efficacy of combined conservative therapies on clinical outcomes in patients with CMC1 OA). Joint collapse was determined at baseline using a pinch gauge. Pain was assessed on a visual analog scale (0-100) and function was assessed using the Functional Index for Hand Osteoarthritis questionnaire (0-30). Pain and function and the presence of joint collapse were entered in a univariate logistic regression. The final adjusted model for pain and joint collapse included age and sex. The final adjusted model for function and joint collapse included Kellgren Lawrence grade and grip strength. RESULTS: About 20% of participants demonstrated joint collapse on the tip-pinch test. The presence of joint collapse was associated with increased pain in the unadjusted [P = .047, OR = 2.45, 95% CI (1.01, 5.910)] and adjusted model [P = .049, OR = 2.45, 95% CI (1.00, 5.98)]. CONCLUSION: CMC1 patients with joint collapse reported increased pain compared with those without joint collapse. Future studies should determine the relationship between thumb hypermobility and joint collapse and how to manage these conditions effectively.

A Randomized Controlled Clinical Trial: No Clear Benefit to Prophylactic Central Neck Dissection in Patients With Clinically Node Negative Papillary Thyroid Cancer.

OBJECTIVE: The aim of this prospective randomized-controlled trial was to evaluate the risks/benefits of prophylactic central neck dissection (pCND) in patients with clinically node negative (cN0) papillary thyroid cancer (PTC). BACKGROUND: Microscopic lymph node involvement in patients with PTC is common, but the optimal management is unclear. METHODS: Sixty patients with cN0 PTC were randomized to a total thyroidectomy (TT) or a TT+ pCND. All patients received postoperative laryngoscopies and standardized radioiodine treatment. Thyroglobulin (Tg) levels and/or neck ultrasounds were performed at 6 weeks, 6 months, and 1 year. RESULTS: Tumors averaged 2.2 ±â€Š0.2 cm and 11.9% had extra-thyroidal extension. Thirty patients underwent a pCND and 27.6% had positive nodes (all ≤6 mm). Rates of postoperative PTH < 10 (33.3% vs 24.1%, P = 0.57) and transient nerve dysfunction (13.3% vs 10.3%, P = 1.00) were not significantly different between groups. Six weeks after surgery, both TT and TT + pCND were equally likely to achieve a Tg < 0.2 (54.5% vs 66.7%, P = 0.54) and/or a stimulated Tg (sTg) <1 (59.3% vs 64.0%, P = 0.78). At 1 year, rates of Tg < 0.2 (88.9% vs 90.0%, P = 1.00) and sTg < 1 (93.8% vs 92.3%, P = 1.00) remained similar between groups. Neck ultrasounds at 1 year were equally likely to be read as normal (85.7% in TT vs 85.1% in pCND, P = 1.00). CONCLUSIONS: cN0 PTC patients treated either with TT or TT + pCND had similar complication rates after surgery. Although microscopic nodes were discovered in 27.6% of pCND patients, oncologic outcomes were comparable at 1 year.

Natural history of Ollier disease and Maffucci syndrome: Patient survey and review of clinical literature.

Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg-length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS.

Design, Delivery, Maintenance, and Outcomes of Peer-to-Peer Online Support Groups for People With Chronic Musculoskeletal Disorders: Systematic Review.

BACKGROUND: Online support groups (OSGs) are one way for people with chronic diseases, their family or friends, and health professionals to communicate, gain information, and provide social support. As the number of peer-to-peer OSGs for chronic musculoskeletal conditions grows, it is important to gain insight into the different designs of groups available, who is accessing them, if and how they may be effective, and what strategies are being used to implement or increase consumer engagement. OBJECTIVE: The objectives of this systematic review of people with musculoskeletal conditions were to (1) describe the design features (functions, usage options, moderation, and expert input) of peer-to-peer OSGs, (2) describe the characteristics of the individuals using peer-to-peer OSGs, (3) synthesize the evidence on outcomes of participation, and (4) identify strategies used in the delivery and maintenance of OSGs. METHODS: A search comprising terms related to the population (people with musculoskeletal disorders) and the intervention (peer-to-peer OSGs) was conducted in 6 databases. Results were filtered from 1990 (internet inception) to February 2019. Studies identified in the search were screened according to predefined eligibility criteria using a 2-step process. Quantitative studies were appraised by 2 reviewers using the Risk Of Bias In Non-Randomized Studies of Interventions tool. Qualitative studies were appraised by 2 different reviewers using the Critical Appraisal Skills Programme checklist. Extracted data were synthesized narratively. RESULTS: We examined 21 studies with low to moderate risk of bias. Of these studies, 13 studies included OSGs hosted on public platforms, 11 studies examined OSGs that were conducted in English, and 6 studies used moderators or peer leaders to facilitate engagement. Studies either reported the number of OSG members (n=1985 across all studies) or the number of posts (range: 223-200,000). The majority of OSG members were females who were not full-time employees and with varied levels of education. There were no randomized controlled trials measuring the efficacy of OSGs. Qualitative and quantitative studies identified empowerment, social support, self-management behavior, and health literacy as primary constructs to measure OSG efficacy. Neutral or marginal improvement was reported in these constructs. Sharing experiences and a greater level of engagement appeared to have an important influence on OSGs efficacy. The extent to which members posted on the website influenced engagement. CONCLUSIONS: Across a diverse range of designs, languages, included features, and delivery platforms, peer-to-peer OSGs for chronic musculoskeletal conditions attract predominantly female participants of all ages and education levels. The level of participation of a member appears to be related to their perceived benefit, health literacy, and empowerment. Future studies are needed to identify which design and maintenance strategies have superior efficacy and whether there are concomitant improvements in health outcomes for people with chronic musculoskeletal conditions resulting from participation in OSGs. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42018090326; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018090326.

Defect in phosphoinositide signalling through a homozygous variant in PLCB3 causes a new form of spondylometaphyseal dysplasia with corneal dystrophy.

BACKGROUND: Bone dysplasias are a large group of disorders affecting the growth and structure of the skeletal system. METHODS: In the present study, we report the clinical and molecular delineation of a new form of syndromic autosomal recessive spondylometaphyseal dysplasia (SMD) in two Emirati first cousins. They displayed postnatal growth deficiency causing profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding and intellectual disability. Whole genome homozygosity mapping localised the genetic cause to 11q12.1-q13.1, a region spanning 19.32 Mb with ~490 genes. Using whole exome sequencing, we identified four novel homozygous variants within the shared block of homozygosity. Pathogenic variants in genes involved in phospholipid metabolism, such as PLCB4 and PCYT1A, are known to cause bone dysplasia with or without eye anomalies, which led us to select PLCB3 as a strong candidate. This gene encodes phospholipase C ß 3, an enzyme that converts phosphatidylinositol 4,5 bisphosphate (PIP2) to inositol 1,4,5 triphosphate (IP3) and diacylglycerol. RESULTS: The identified variant (c.2632G>T) substitutes a serine for a highly conserved alanine within the Ha2' element of the proximal C-terminal domain. This disrupts binding of the Ha2' element to the catalytic core and destabilises PLCB3. Here we show that this hypomorphic variant leads to elevated levels of PIP2 in patient fibroblasts, causing disorganisation of the F-actin cytoskeleton. CONCLUSIONS: Our results connect a homozygous loss of function variant in PLCB3 with a new SMD associated with corneal dystrophy and developmental delay (SMDCD).

Developing strategic priorities in osteoarthritis research: Proceedings and recommendations arising from the 2017 Australian Osteoarthritis Summit.

BACKGROUND: There is a pressing need to enhance osteoarthritis (OA) research to find ways of alleviating its enormous individual and societal impact due to the high prevalence, associated disability, and extensive costs. METHODS: Potential research priorities and initial rankings were pre-identified via surveys and the 1000Minds process by OA consumers and the research community. The OA Summit was held to decide key research priorities that match the strengths and expertise of the Australian OA research community and align with the needs of consumers. Facilitated breakout sessions were conducted to identify initiatives and strategies to advance OA research into agreed priority areas, and foster collaboration in OA research by forming research networks. RESULTS: From the pre-Summit activities, the three research priority areas identified were: treatment adherence and behaviour change, disease modification, and prevention of OA. Eighty-five Australian and international leading OA experts participated in the Summit, including specialists, allied health practitioners, researchers from all states of Australia representing both universities and medical research institutes; representatives from Arthritis Australia, health insurers; and persons living with OA. Through the presentations and discussions during the Summit, there was a broad consensus on the OA research priorities across stakeholders and how these can be supported across government, industry, service providers and consumers. CONCLUSION: The Australian OA Summit brought consumers, experts and opinion leaders together to identify OA research priorities, to enhance current research efforts by fostering collaboration that offer the greatest potential for alleviating the disease burden.

Musculoskeletal ultrasound in symptomatic thumb-base osteoarthritis: clinical, functional, radiological and muscle strength associations.

BACKGROUND: Thumb-base osteoarthritis (OA) is a common cause of pain and disability This study aimed to investigate the associations of musculoskeletal ultrasound OA pathologies with the extent of pain, function, radiographic scores, and muscle strength in symptomatic thumb-base osteoarthritis. METHODS: This is a cross-sectional study of an ongoing clinical trial with eligibility criteria including thumb-base pain on Visual Analogue Scale (VAS) ≥40 (0 to 100 mm), Functional Index for Hand OA (FIHOA) ≥ 6 (0 to 30) and Kellgren Lawrence (KL) grade ≥ 2. The most symptomatic side was scanned to measure synovitis and osteophyte severity using a 0-3 semi-quantitative score, power Doppler and erosion in binary score. A linear regression model was used for associations of ultrasound findings with VAS pain, FIHOA and hand grip and pinch strength tests after adjusting for age, gender, body mass index, disease duration and KL grade as appropriate. For correlation of ultrasound features with KL grade, OARSI ((Osteoarthritis Research Society International) osteophyte and JSN scores, Eaton grades, Spearman coefficients were calculated, and a significant test defined as a p-value less than 0.05. RESULTS: The study included 93 participants (mean age of 67.04 years, 78.5% females). Presence of power Doppler has a significant association with VAS pain [adjusted ß coefficient = 11.29, P = 0.02] while other ultrasound pathologies revealed no significant associations with all clinical outcomes. In comparison to radiograph, ultrasonographic osteophyte score was significantly associated with KL grade [rs = 0.44 (P < 0.001)], OARSI osteophyte grade [rs = 0.35 (P = 0.001)], OARSI JSN grade [rs = 0.43 (P < 0.001)] and Eaton grade [rs = 0.30 (P < 0.01)]. Ultrasonographic erosion was significantly related with radiographic erosion [rs = - 0.49 (P = 0.001)]. CONCLUSION: From a clinical perspective the significant relationship of power Doppler with pain severity in thumb base OA suggests this might be a useful tool in understanding pain aetiology. It is important to recognise that power Doppler activity was only detected in 14% of the study so this might be an important subgroup of persons to monitor more closely. TRIAL REGISTRATION: Registered at Australian New Zealand Clinical Trials Registry (ANZCTR), http://www.anzctr.org.au/ , ACTRN12616000353493.

Exploring the Characteristics and Preferences for Online Support Groups: Mixed Method Study.

BACKGROUND: Osteoarthritis (OA) is a chronic, disabling, and prevalent disorder. As there is no cure for OA, long-term self-management is paramount. Support groups (SGs) can facilitate self-management among people living with OA. Understanding preferences in design and features of SGs, including online SGs (OSGs), among people with OA can inform future development of SG interventions for this condition. OBJECTIVE: The objective of this study was to investigate health care- and health information-seeking behavior, digital literacy, and preferences for the design of SGs in people with OA. The study also explored the perceived barriers and enablers to being involved in OSGs. METHODS: An online survey study was conducted with a mixed method design (quantitative and qualitative). Individuals aged ≥45 years with knee, hip, or back pain for ≥3 months were recruited from an extant patient database of the Institute of Bone and Joint Research via email invitations. Quantitative elements of the survey included questions about sociodemographic background; health care- and health information-seeking behavior; digital literacy; and previous participation in, and preferences for, SGs and OSGs. Respondents were classified into 2 groups (Yes-SG and No-SG) based on previous participation or interest in an SG. Group differences were assessed with Chi-square tests (significance level set at 5%). Responses to free-text questions relating to preferences regarding OSG engagement were analyzed qualitatively using an inductive thematic analysis. RESULTS: A total of 415 people with OA completed the survey (300/415, 72.3% females; 252/415, 61.0% lived in a major city). The Yes-SG group included 307 (307/415, 73.9%) participants. Between the Yes-SG and No-SG groups, there were no differences in sociodemographic characteristics, health care- and health information-seeking behavior, and digital literacy. An online format was preferred by 126/259 (48.7%) of the Yes-SG group. Trained peer facilitators were preferred, and trustworthiness of advice and information were highly prioritized by the respondents. Qualitative analysis for OSG participation revealed 5 main themes. Lack of time and motivation were the main barriers identified. The main enablers were related to accessibility, enjoyment of the experience, and the content of the discussed information. CONCLUSIONS: These findings highlight the preferences in design features and content of SGs and OSGs and may assist in the further development of such groups.

Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes.

PURPOSE: Non-aneuploid recurrent pregnancy loss (RPL) affects approximately 100,000 pregnancies worldwide annually. Exome sequencing (ES) may help uncover the genetic etiology of RPL and, more generally, pregnancy loss as a whole. Previous studies have attempted to predict the genes that, when disrupted, may cause human embryonic lethality. However, predictions by these early studies rarely point to the same genes. Case reports of pathogenic variants identified in RPL cases offer another clue. We evaluated known genetic etiologies of RPL identified by ES. METHODS: We gathered primary research articles from PubMed and Embase involving case reports of RPL reporting variants identified by ES. Two authors independently reviewed all articles for eligibility and extracted data based on predetermined criteria. Preliminary and amended analysis isolated 380 articles; 15 met all inclusion criteria. RESULTS: These 15 articles described 74 families with 279 reported RPLs with 34 candidate pathogenic variants in 19 genes (NOP14, FOXP3, APAF1, CASP9, CHRNA1, NLRP5, MMP10, FGA, FLT1, EPAS1, IDO2, STIL, DYNC2H1, IFT122, PADI6, CAPS, MUSK, NLRP2, NLRP7) and 26 variants of unknown significance in 25 genes. These genes cluster in four essential pathways: (1) gene expression, (2) embryonic development, (3) mitosis and cell cycle progression, and (4) inflammation and immunity. CONCLUSIONS: For future studies of RPL, we recommend trio-based ES in cases with normal parental karyotypes. In vitro fertilization with preimplantation genetic diagnosis can be pursued if causative variants are found. Utilization of other sequencing technologies in concert with ES should improve understanding of the causes of early embryonic lethality in humans.