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International audience; The root system of a plant is composed of the primary, lateral and adventitious roots (ARs). Lateral roots always develop from roots, whereas ARs form from stem or leaf‐derived cells. AR formation is part of the normal development of the plant and occurs naturally, like in most monocotyledonous for which they constitute the main root system or in many dicotyledonous species that propagate vegetatively. Adventitious rooting is an essential step for vegetative propagation of economically important horticultural and woody species as it allows clonal propagation and rapid fixation of superior genotypes prior to their introduction into production or breeding programmes. Development of ARs is a complex process that is affected by multiple endogenous and environmental factors, including phytohormones; light; nutritional status; associated stress responses, such as wounding; and genetic characteristics.

Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin, and standard of care in cancer-associated VTE. Tinzaparin has the highest molecular weight of all LMWH, and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20ml/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20ml/min and in cancer-associated VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50ml/min with an indication for anticoagulation. Tinzaparin anti-Xa levels were tested at days 2, 7 and 14 (+/- one day) and transition to oral anticoagulants were allowed at clinician discretion. No accumulation of tinzaparin was seen into day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor), and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and BSA-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on day 2, and this effect was lost when patients with CrCl >50ml/min were excluded. Data from our cohort confirms previous pharmacokinetic studies using therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50ml/min with no signs of accumulation. Bleeding and death outcomes were also comparable to other trials using tinzaparin in cancer-associated VTE. Tinzaparin is an attractive alternative anticoagulant with once-daily administration in a range of potential indications. This article is protected by copyright. All rights reserved.

Objective: \ud To identify prognostic factors for health outcomes following an eight-week supervised exercise therapy and education program for individuals with knee and hip osteoarthritis (OA) alone or with concomitant hypertension, heart or respiratory disease, diabetes, or depression.\ud \ud Methods: \ud We included individuals with knee and/or hip OA from the Good Life with osteoArthritis in Denmark (GLA:D®). GLA:D® consists of two patient education sessions and 12 supervised exercise therapy sessions. Before GLA:D®, participants self-reported any comorbidities and were categorized in eight comorbidity groups. 21 potential prognostic factors (demographics, clinical data, and performance-based physical function) gathered from participants and clinicians before the program were included. Outcomes were physical function using the 40-m Fast-Paced Walk Test (FPWT), health-related quality of life using the EQ-5D-5L index score, and pain intensity using a visual analogue scale (0-100, VAS) assessed before and immediately after the GLA:D® program. Within each comorbidity group, associations of prognostic factors with outcomes were estimated using multivariable linear regression.\ud \ud Results: \ud Data from 35,496 (40-m FPWT) and 37,576 (EQ-5D-5L and VAS) participants were included in the analyses. Clinically relevant associations were demonstrated between age, self-efficacy, self-rated health, and pain intensity with change in 40-m FPWT, EQ-5D-5L or VAS across comorbidity groups. Furthermore, anxiety, education, physical function, and smoking were associated with outcomes among subgroups having depression or diabetes in addition to OA.\ud \ud Conclusion: \ud Age, self-efficacy, self-rated health, and pain intensity may be prognostic of change in health outcomes following an eight-week exercise therapy and patient education program for individuals with OA, irrespective of comorbidities.

Objectives To investigate whether patients with osteoarthritis (OA) are at a higher risk of developing Parkinson's disease (PD). Methods This retrospective cohort study was conducted using Taiwan's Longitudinal Health Insurance Database 2005. We enrolled 33,360 patients who were 50-64 years old and had OA in 2002-2005 to form the OA group. The comparison group consisted of 33,360 age- and sex-matched, randomly sampled subjects without OA. Then, their PD-free survival curves were generated using the Kaplan-Meier method. Multivariable Cox proportional-hazard regression analysis was employed to estimate the effect of having OA on patients' subsequent risk of PD. Results Of the two groups, the OA group had a significantly higher risk of developing PD (adjusted hazard ratio [aHR]=1.41, 95% CI, 1.16-1.70, p=0.0003). The PD-free survival rate of the OA group was also significantly lower than that of the comparison group (p=0.0004). The subgroup analysis showed that patients with knee or hip OA appeared to have a higher magnitude of PD risk (aHR 1.55, 95% CI, 1.14-2.11) than patients with non-knee and non-hip OA (aHR 1.42, 95% CI, 1.06-1.89) or with uncategorized OA (aHR 1.32, 95% CI,1.05-1.64). Conclusions Our findings suggest that OA is linked to an increased risk of developing PD.

Many parasites induce decreased host movement, known as lethargy, which can impact disease spread and the evolution of virulence. Mathematical models have investigated virulence evolution when parasites cause host death, but disease-induced decreased host movement has received relatively less attention. Here, we consider a model where, due to the within-host parasite replication rate, an infected host can become lethargic and shift from a moving to a resting state, where it can die. We find that when the lethargy and disease-induced mortality costs to the parasites are not high, then evolutionary bistability can arise, and either moderate or high virulence can evolve depending on the initial virulence and the magnitude of mutation. These results suggest, firstly, the transient coexistence of strains with different virulence, which may explain the coexistence of low- and high-pathogenic strains of avian influenza and human immunodeficiency viruses, and secondly, that medical interventions to treat the symptoms of lethargy or prevent disease-induced host deaths can result in a large jump in virulence and the rapid evolution of high virulence. In complement to existing results that show bistability when hosts are heterogeneous at the population-level, we show that evolutionary bistability may arise due to transmission heterogeneity at the individual host-level.

Background Prostate cancer (PCa) is a heavy health-threat for human worldwide. Recent studies revealed that microRNAs (miRNAs) are associated with the progression of human cancers, including PCa. However, no study has been performed to investigate the role of microNA-4286 (miR-4286) on PCa. Methods Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to analyze the expression level of miR-4286 in PCa cells. Connection of miR-4286 and spalt like transcription factor 1 (SALL1) was analyzed with bioinformatic analysis tool, dual-luciferase activity reporter assay, and western blot. Effects of miR-4286 and SALL1 on PCa cell behaviors were examined in vitro. Results We showed miR-4286 expression was significantly increased in PCa cells compared with normal cell line. Knockdown of miR-4286 could inhibit PCa cell proliferation but promote cell apoptosis via targeting SALL1. Conclusions Our study suggested that miR-4286 overexpression represents a tumor promoter role in PCa.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objective of this review will be to evaluate the efficacy and safety of administering lactoferrin for the post‐operative management of term neonates, measured by the incidence of sepsis, mortality and duration of hospital stay. We aim to evaluate benefits and harms with the use of lactoferrin in individual gastrointestinal pathologies and specific lactoferrin product, if sufficient data are available.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of exercise interventions in adults after liver transplantation.

Background Some genetic association studies tried to investigate potential associations of phosphatase and actin regulator 1 (PHACTR1) polymorphisms with coronary artery disease (CAD). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between PHACTR1 polymorphisms and CAD in a larger pooled population. Methods Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible studies. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate strength of associations. Results Totally 8 studies were included for analyses (10856 cases and 18801 controls). Pooled analyses suggested that rs9349379 polymorphism was significantly associated with CAD in overall population (dominant model: p=0.004, OR=1.39, 95%CI 1.11-1.73, I2 =91%; recessive model: p=0.002, OR=0.63, 95%CI 0.48-0.84, I2 =85%; over-dominant model: p=0.03, OR=0.89, 95%CI 0.80-0.99, I2 =59%; allele model: p=0.0002, OR=1.30, 95%CI 1.13-1.49, I2 =89%), and this significant finding was further confirmed in both Asians and Caucasians. However, no any positive findings were observed for rs2026458 polymorphism in pooled analyses. Conclusions Our meta-analysis suggested that rs9349379 polymorphism might affect individual susceptibility to CAD in both Caucasians and Asians. Future investigations need to explore the underlying molecular mechanisms of our positive findings.

Background Glucocorticoid Modulatory Element-Binding protein 1 (GMEB1) suppresses caspase-mediated cell apoptosis. microRNA-320 (miR-320a) can inhibit tumor development by arresting tumor cell invasion. To our best knowledge, no previous study focused on the role of miR-320a andGMEB1 in colorectal cancer (CRC), which deserves our exploration. Methods GMEB1 expression was detected through immunohistochemistry and compared with the pathology of 60 CRC patients. Transwell and scratch healing experiments detected cell invasion and migration. Western blot was used to observe Epithelial-Mesenchymal Transition (EMT)-related proteins expression after silencing and overexpressing GMEB1 (oe-GMEB1). Online database search and dual-luciferase reporter assay identified the target relationship between miR-320a and GMEB1. qRT-PCR was conducted to compare the differences in the expression of miR-320a between normal and tumor tissues of CRC patients. Results GMEB1 is overexpressed in CRC tissues, and its high expression levels can be correlated with lymph node invasion, TNM stage, and differentiation degrees of CRC. The si-GMEB1 group showed a significant decrease in invasion and metastatic abilities, accompanied by a decline in the expression of N-cadherin and vimentin., but the expression of E-cadherin was increased, while an opposite trend was observed in the oe-GMEB1 group. Both cell and tissue tests verified that miR-320a mimic can downregulate the expression of GMEB1. Conclusion miR-320a can promote EMT phenotype changes by silencing the expression of GMEB1, which inhibits the invasion of CRC cells. This feature is a potential basis for the diagnosis and treatment of CRC at the genetic level.

Background: Rhabdomyolysis (RM) associated acute kidney injury (AKI) is the most common systemic complication of RM. The present study aimed to assess the clinical characteristics and risk factors for intensive care unit (ICU) transfer for patients with RM-associated AKI.Methods: We included all patients who were age ≥ 18 years old with a diagnosis of RM from September 2012 to October 2018 and divided them into RM-associated AKI group and RM without AKI group. The primary outcome was transferring to ICU treatment. Regression analysis was performed to identify factors associated with ICU treatment and recovery of renal function.Results: Among the 149 patients with RM, 68 (45.6%) developed AKI. The percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% versus 12.3%, P < 0.002). Additionally, patients with AKI had higher percentage of undergoing dialysis (19.1% versus 2.5%, P < 0.01), all-cause mortality (13.2% versus 1.2%, P < 0.01), cost of hospitalization [10.8 1,000 yuan, IQR (5.5, 3.5) versus 5.9 1,000 yuan, IQR 5.9 (3.6, 9.9), P = 0.03], as well as longer length of hospital stay [8.0 (5.0, 14.0)] versus [6.0 (4.0, 11.0)], P = 0.02). Moreover, most patients with AKI achieved complete recovery (77.9%) at discharge. After adjusting for potential risk factors, RM-associated AKI remained an independent risk factor for ICU transfer (OR = 3.0, 95% CI, 1.11–8.3, P = 0.03). However, ICU transfer was not associated with recovery of renal function (OR = 0.88, 95% CI, 0.22–3.57, P = 0.856).Conclusion: RM leaded to AKI in most patients. RM-associated AKI could cause worse clinical outcome and predict ICU transfer for patients with RM.

BACKGROUND The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3-1mg/kg/day. However, recent studies reported non-inferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30mg/day or ≥40mg/day. PATIENTS-METHODS Patients with new-onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30mg/day) and high prednisone groups (≥40mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria

Objective Otolaryngologists are at increased occupational risk of Coronavirus Disease 2019 (COVID-19) infection due to exposure from respiratory droplets and aerosols generated during otologic, nasal, and oropharyngeal examinations and procedures. There have been a variety of guidelines and precautions developed to help mitigate this risk. While many reviews have focused on the personal protective equipment (PPE) and preparation guidelines for surgery in the COVID-19 era, none have focused on the more creative and unusual solutions designed to limit viral transmission. This review aims to fill that need. Data sources PubMed, Ovid/Medline, and Scopus. Methods A comprehensive review of literature was performed on September 28, 2020 using PubMed, Ovid/Medline, and Scopus databases. All English-language studies were included if they proposed or assessed novel interventions developed for Otolaryngology practice during the COVID-19 pandemic. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results A total of 41 papers met inclusion criteria and were organized into 5 categories (‘General Recommendations for Otolaryngologic Surgery’, ‘Equipment Shortage Solutions’, ‘Airway Procedures’, ‘Nasal Endoscopy and Skull Base Procedures’, and ‘Otologic Procedures’). Articles were summarized, highlighting the innovations created and evaluated during the COVID-19 pandemic. Creative solutions such as application of topical viricidal agents, make-shift mask filters, three-dimensional (3-D) printable adapters for headlights, aerosol containing separation boxes, and a variety of new draping techniques have been developed to limit the risk of COVID-19 transmission. Conclusions Persistent risk of COVID-19 exposure remains high. Thus, there is an increased need for solutions that mitigate the risk of viral transmission during office procedures and surgeries, especially given that most COVID-19 positive patients present asymptomatically. This review examines and organizes creative solutions that have been proposed and utilized in the otolaryngology. These solutions have a potential to minimize the risk of viral transmission in the current clinical environment and to create safer outpatient and operating room conditions for patients and healthcare staff.

Background and objective Functional endoscopic sinus surgery (FESS) increases the nasal volume, and thereby it can alter the nasal resonance. The objectives were to measure the percentage of nasal resonance following FESS and compare it with healthy individuals with normal nasal findings. Methods The nasometric analysis of voice was done using n/p/m consonant sounds in 72 individuals with healthy post FESS cavities (group 1) and 72 healthy individuals with normal nasal findings without any nasal pathology (group 2). The scores of nasal resonances were expressed in percentages and were compared between the two groups. Both in group 1 and group 2, 32 (44.4%) were females, and 40 (55.6%) were males. In group 1, 51 participants had bilateral FESS cavities, and 21 had unilateral FESS cavities. Kannada was the mother tongue in 30 (41.7%) participants in group 1 and 36 (50.0%) in group 2. Malayalam was the mother tongue in 42 (58.3%) participants in group 1 and 36 (50.0%) in group 2. Results In both cases and control groups, more than 80% of the participants were showing less than 20% of nasal resonance. In group 1, the mean values of /n/p/m sounds were 11.23%, 10.23% and 11.42% respectively, and in group 2 the mean values were 8.27%, 8.58% and 8.58% respectively. But the P value was not statistically significant. Individuals with unilateral FESS cavities had more nasal resonance values compared to bilateral FESS cavities. Similarly, Kannada speaking people had more values compared to Malayalam speaking individual. Conclusion Changes in nasal resonance after FESS is minimal, and it is unnoticed. But it may affect the speech quality in professional voice users, depending on their language. Though the nasometer is considered as the most validated instrument to record nasal resonance, we feel that further standardization is needed to evaluate the nasalance.

Objective To determine the incidence of tuberculous lymphadenitis (TBL) and other pathologies in cervical lymphadenopathies in Somalia and accompanying radiological findings. Methods In this hospital-based retrospective study, the demographic characteristics, pathology results and radiological findings of 263 patients who underwent ultrasound (US)-guided cervical lymph node biopsy between January 2016 and February 2020 were analyzed. Results Of 241 patients 118 men and 123 women (mean age 27.9 ± 18.1 years) included in the study, 46.1% (n = 111) were diagnosed as necrotizing granulomatous lymphadenitis (caseified, consistent with TBL) and 21.6% (n = 12, atypical lymphoid cells and n = 40, metastases) as malignancy. The most common type of metastasis was squamous cell cancer (n = 31), and the primary source of most of them was esophageal cancer (16/31, 51.6%). The age of patients with TBL was significantly lower than that of non-TBL (21.9 ± 14.6 vs. 41.9 ± 24.6, P = 0.003) and the incidence of TBL in pediatric patients was statistically higher (58.0% vs. 21.5%, P = 0.019). The rate of patients with TBL being localized at level 4 and level 5 was significantly more than non-TBL patients (18.0% vs. 10.0% and 23.4% vs. 10.8%, respectively, P = 0.01). Half of patients with TBL who have chest radiography had pathological findings; consolidation and bronchopneumonia were present in 52.6% of them. There were 2 patients with paravertebral abscess and one patient with gastrointestinal tuberculosis. Conclusion In Somalia, in the presence of cervical lymphadenopathy, after diagnosis by using US-guided biopsy; primarily considering of TBL and malignancy, thoracic involvement should be investigated, and esophageal carcinoma must be excluded in terms of metastatic lymph node.

Background Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction. Objectives The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers. Methods Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed. Results Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (

Background Allergic rhinitis (AR) is characterized by mucosal inflammation that leads to a variety of symptoms, such as nasal congestion, rhinorrhea, and sneezing. This rhinitis is triggered by inhalation of allergens, such as pollen, and this condition has a negative impact on the quality of life. AR was shown to be associated with a number of co-morbidities, including hypothyroidism, asthma, and chronic sinusitis. Objective This study aimed to assess AR-associated comorbidities in patient’s presenting symptoms and paranasal sinus computed tomography (CT) scan findings in Taif City, Saudi Arabia. Methods This cross-sectional study evaluated medical and radiological records of AR patients retrospectively from the period of December 2018 to September 2019 in Al-Hada Armed Forces Military Hospital, Taif City, Saudi Arabia. Results A total of 103 AR patients with a mean age of 39.0 ± 15.6 years with 55.3% males and 44.7% females. The three most common associated comorbidities in allergic rhinitis patients were chronic sinusitis (28.2%), hypothyroidism (21.4%), and asthma (8.7%). Nasal obstruction (30.1%) was the symptom most frequently presented by all patients. Mucosal thickening occurred most frequently in patients with associated chronic sinusitis, while bilateral osteomeatal complex obliteration was observed mostly in asthmatic patients, and bony boundary thinning was more prevalent among patients with associated hypothyroidism. Conclusion The gender distribution of AR was 10% more common among males; however, the most common three comorbidites in allergic rhinitis patients were chronic sinusitis, hypothyroidism, and asthma, and most of those patients were females. Hypothyroidism can be a hidden predisposing factor for AR, while chronic sinusitis can be caused by AR due to secretion stasis or immune system activation.

BACKGROUND We aimed to determine risk factors for incident CKD in a large population-based cohort. METHODS This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia enrolment database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely-collected databases. The primary outcome was the development of incident CKD, defined as eGFR

Background: Group B streptococcus (GBS) is a recognised perinatal and neonatal pathogen. There are reports of increasing GBS sepsis globally outside this demographic. North Queensland is part of tropical Australia, with a relatively high proportion of Indigenous Australians. Aims: This study aims to analyse the epidemiology of GBS bacteraemia and explore associated risk factors. Methods: This was a 10-year retrospective review of GBS bacteraemia in a tertiary facility in North Queensland, between 2010 and February 2020. Data variables collected included; demographics, risk factors, clinical source and outcomes. Multivariable logistic regression was performed to examine the association of Indigenous status and other relevant clinical factors with mortality from GBS bacteraemia at three months. Results: Of the 164 total cases, 123 were not pregnancy related. The rate of GBS bacteraemia for the Indigenous population was 12.48 per 100, 000 and 4.84 per 100, 000 for the non-Indigenous population. Indigenous patients were more likely to be diabetic and have chronic kidney disease compared to the non-Indigenous patients. Males [AOR = 4.34, 95% CI (1.14, 16.56), P=0.031] and immunosuppressed patients, [AOR = 11.49, 95% CI (2.73, 48.42), P

To identify discrete clusters of systemic lupus erythematosus (SLE) patients based on symptoms and investigate differences across clusters.Data were collected in the US and 5 European countries via the Adelphi Real World Lupus Disease Specific Programme, a cross-sectional survey. Rheumatologists provided data for 5 consecutively consulting adult patients with SLE, who were invited to participate. Identified SLE symptoms were reduced to factors based on commonly concurrent symptoms, using principal-component factor analysis. Factors were used as covariates in a latent-class cluster analysis to identify discrete patient clusters. Patient-reported outcomes and physician-reported data were compared across clusters.Among 1,376 patients, 87% were female and 74% were White. We identified 4 patient clusters (very mild, mild, moderate, and severe) based on 39 signs/symptoms. Physician-reported symptom burden, organ involvement, disease activity, and the number of flares increased with increasing cluster severity (P 0.0001). Patient-reported impact (health status, fatigue, work productivity impairment, anxiety/depression, and emotional impact) increased with increasing cluster severity (P 0.0001). Glucocorticoid and immunosuppressant use increased, and antimalarial use decreased, with increasing cluster severity. In all clusters,20% of patients received biologics;15% of patients not receiving biologics were considered eligible for treatment by their physician. The proportion of physicians and patients satisfied with treatment decreased with increasing cluster severity (P 0.0001).Our large, international, real-world survey of SLE patients and physicians demonstrated strong associations between increased impairment, organ involvement, and humanistic burden in SLE, highlighting an unmet need for effective treatment options in patients with high disease activity.

We aimed at determining the predictors of osteonecrosis (ON) in a longitudinal lupus cohort.Data were reviewed from the initiation of the cohort in 1987 until October 2019. In total, 2,428 patients were included in the analysis based on 224,295 person-months of follow-up. We used pooled logistic regression to assess the relationship between risk factors and rates of ON events. After identifying a set of variables related to ON incidence, we fit a final multivariable model to identify the most important risk factors for incident ON.In 18,691 person-years of follow-up after cohort entry, 122 incident ON events were observed (rate = 6.5/1,000 person-years). In the multivariable analysis, African American patients were at twice the risk for ON compared to White patients. Male patients and smokers had an increased risk for ON of ~80% and 50% compared to female patients and nonsmokers, respectively. For every 10-year increase in the age at diagnosis, there was a 20% reduced risk for ON. Patients diagnosed after the 1990s had a 50% reduced risk of ON compared to those diagnosed before the 1990s. A highest daily dosage of prednisone of 40 mg or higher, even when administered for a month or less, significantly increased the risk of ON. Use of pulse methylprednisolone or intramuscular triamcinolone was not associated with an increased risk of ON.African American patients with systemic lupus erythematosus are at double the risk of experiencing ON compared to White patients. Oral prednisone at 20-39 mg for more than 1 month, or 40 mg daily for even 1 month, at any point in the disease course, remained the most important glucocorticoid predictor of ON.

Objective We aim to predict the probability of a benefit from two contrasting exercise programs for a woman with a new diagnosis of mild knee osteoarthritis (OA). The short and long-term effects of aquatic resistance training (ART) and high-impact aerobic land training (HLT) compared with the control will be estimated. Methods Original data sets from two previously conducted randomised controlled trials (RCT) were combined and used in a Bayesian meta-analysis. Group differences in multiple response variables were estimated. Variables included cardiorespiratory fitness, dynamic maximum leg muscle power, maximal isometric knee extension and flexion force, pain, other symptoms and quality of life. The statistical model included a latent commitment variable for each female participant. Results ART has 55% - 71% probability of benefits in the outcome variables and as the main effect, the intervention outperforms the control in cardiorespiratory fitness with a probability of 71% immediately after the intervention period. HLT has 46% - 63% probability of benefits after intervention with the outcome variables, but differently from ART, the positive effects of physical performance fade away during the follow-up period. Overall, the differences between groups were small and the variation in the predictions between individuals was high. Conclusions Both interventions had benefits but ART has a slightly higher probability of long-term benefits on physical performance. Because of high individual variation and no clear advantage of one training method over the other, personal preferences should be considered in the selection of the exercise program to ensure highest commitment to training.

Objective To review current literature and experience with Gore-TexⓇ implant extrusion following medialization thyroplasty, as well as to report the unique case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Methods Review of existing literature and description of personal experience with unique case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Results Review of existing literature found no prior reported cases of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Risk factors for implant extrusion include the pressure of the implant on insertion and the inability to secure the implant. Cases of implant extrusion can be managed operatively via an endoscopic or via an external open approach. Conclusion This is the first reported case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Careful consideration should be given in revision medialization thyroplasty as additional implant material may cause increased pressure, a risk factor for implant extrusion.

Objective To investigate the risk factors for lateral lymph node metastasis (LLNM) in papillary thyroid carcinoma (PTC). Methods A retrospective analysis of 209 patients with PTC who underwent primary surgery at the Beijing Friendship Hospital affiliated with Capital Medical University from November 2014 to November 2018 was performed. The patients were divided into the LLNM group and the non-LLNM group. The clinical and pathological characteristics of the patients were analysed. The risk factors for LLNM were analysed by univariate and multivariate analyses. Results The incidence of LLNM was 13.4% in PTC patients. Univariate analysis showed that the maximum diameter of the primary tumour >2 cm (P 2 cm, ETE, and CLNM were independent risk factors for LLNM (OR values were 3.880, 5.202, and 4.474, respectively). There were 6 patients with skip lateral cervical lymph node metastasis, accounting for 21% of all LLNM patients. Conclusion This study revealed several independent risk factors for predicting LLNM in PTC patients, such as the maximum diameter of the primary tumour >2 cm, ETE and CLNM. Lateral neck dissection may be recommended in PTC patients with those risk factors. Paying attention to the occurrence of skip lateral cervical lymph node metastasis during the clinical diagnosis and treatment processes is necessary.

Objective There is an unmet need for therapies that target the underlying pathophysiology of osteoarthritis (OA). However, defining appropriate measures for clinical trials of such therapies is challenging. Our objective is to propose concept clinical endpoints that directly capture clinical benefit in this setting and evaluate the feasibility of their use. Methods This analysis used the multi-center, longitudinal, observational Osteoarthritis Initiative (OAI) database. OAI participants primarily had knee OA, with follow-up of up to nine years and assessments of joints, surgical interventions, performance outcomes, and patient-reported outcomes (PROs). We examined this dataset to identify existing outcome measures of direct clinical benefit. We evaluated the feasibility of conducting trials using these candidate endpoints by estimating incidence rates and resulting required sample sizes and study durations in time-to-event analyses. Results We identified candidate endpoints based on total knee replacement (TKR) and composite endpoints defined by TKR and conservative thresholds of PROs of pain and function. Using time to TKR as an endpoint, a study with an average follow-up time of three years requires approximately 3,000 to 18,000 subjects depending on effect size. Alternatively, a composite endpoint such as 'time to TKR or severe pain or severely impaired functioning', the required sample sizes ranged from approximately 2,000 to 11,000 for a three-year study. Conclusion The proposed concept endpoints can reliably and feasibly evaluate effectiveness of therapies for this unmet need. In particular, the composite endpoint approach can substantially reduce sample sizes (up to approximately 40%) compared to the use of TKR alone.

BACKGROUND: Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens related to type of steroid, timing of treatment initiation, duration, pulse versus continuous delivery, and cumulative dose. OBJECTIVES: To assess the effects of different corticosteroid treatment regimens on mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight infants. SEARCH METHODS: We conducted searches in September 2022 of MEDLINE, the Cochrane Library, Embase, and two trial registries, without date, language or publication- type limits. Other search methods included checking the reference lists of included studies for randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We included RCTs comparing two or more different treatment regimens of systemic postnatal corticosteroids in preterm infants at risk for BPD, as defined by the original trialists. The following comparisons of intervention were eligible: alternative corticosteroid (e.g. hydrocortisone) versus another corticosteroid (e.g. dexamethasone); lower (experimental arm) versus higher dosage (control arm); later (experimental arm) versus earlier (control arm) initiation of therapy; a pulse-dosage (experimental arm) versus continuous-dosage regimen (control arm); and individually-tailored regimens (experimental arm) based on the pulmonary response versus a standardized (predetermined administered to every infant) regimen (control arm). We excluded placebo-controlled and inhalation corticosteroid studies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility and risk of bias of trials, and extracted data on study design, participant characteristics and the relevant outcomes. We asked the original investigators to verify if data extraction was correct and, if possible, to provide any missing data. We assessed the following primary outcome: the composite outcome mortality or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes were: the components of the composite outcome; in-hospital morbidities and pulmonary outcomes, and long-term neurodevelopmental sequelae. We analyzed data using Review Manager 5 and used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 16 studies in this review; of these, 15 were included in the quantitative synthesis. Two trials investigated multiple regimens, and were therefore included in more than one comparison. Only RCTs investigating dexamethasone were identified. Eight studies enrolling a total of 306 participants investigated the cumulative dosage administered; these trials were categorized according to the cumulative dosage investigated, 'low' being < 2 mg/kg, 'moderate' being between 2 and 4 mg/kg, and 'high' > 4 mg/kg; three studies contrasted a high versus a moderate cumulative dose, and five studies a moderate versus a low cumulative dexamethasone dose. We graded the certainty of the evidence low to very low because of the small number of events, and the risk of selection, attrition and reporting bias. Overall analysis of the studies investigating a higher dose versus a lower dosage regimen showed no differences in the outcomes BPD, the composite outcome death or BPD at 36 weeks' PMA, or abnormal neurodevelopmental outcome in survivors assessed. Although there was no evidence of a subgroup difference for the higher versus lower dosage regimens comparisons (Chi2 = 2.91, df = 1 (P = 0.09), I2 = 65.7%), a larger effect was seen in the subgroup analysis of moderate-dosage regimens versus high-dosage regimens for the outcome cerebral palsy in survivors. In this subgroup analysis, there was an increased risk of cerebral palsy (RR 6.85, 95% CI 1.29 to 36.36; RD 0.23, 95% CI 0.08 to 0.37; P = 0.02; I² = 0%; NNTH 5, 95% CI 2.6 to 12.7; 2 studies, 74 infants). There was evidence of subgroup differences for higher versus lower dosage regimens comparisons for the combined outcomes death or cerebral palsy, and death and abnormal neurodevelopmental outcomes (Chi2 = 4.25, df = 1 (P = 0.04), I2 = 76.5%; and Chi2 = 7.11, df = 1 (P = 0.008), I2 = 85.9%, respectively). In the subgroup analysis comparing a high dosage regimen of dexamethasone versus a moderate cumulative-dosage regimen, there was an increased risk of death or cerebral palsy (RR 3.20, 95% CI 1.35 to 7.58; RD 0.25, 95% CI 0.09 to 0.41; P = 0.002; I² = 0%; NNTH 5, 95% CI 2.4 to 13.6; 2 studies, 84 infants; moderate-certainty evidence), and death or abnormal neurodevelopmental outcome (RR 3.41, 95% CI 1.44 to 8.07; RD 0.28, 95% CI 0.11 to 0.44; P = 0.0009; I² = 0%; NNTH 4, 95% CI 2.2 to 10.4; 2 studies, 84 infants; moderate-certainty evidence). There were no differences in outcomes between a moderate- and a low-dosage regimen. Five studies enrolling 797 infants investigated early initiation of dexamethasone therapy versus a moderately early or delayed initiation, and showed no significant differences in the overall analyses for the primary outcomes. The two RCTs investigating a continuous versus a pulse dexamethasone regimen showed an increased risk of the combined outcome death or BPD when using the pulse therapy. Finally, three trials investigating a standard regimen versus a participant-individualized course of dexamethasone showed no difference in the primary outcome and long-term neurodevelopmental outcomes. We assessed the GRADE certainty of evidence for all comparisons discussed above as moderate to very low, because the validity of all comparisons is hampered by unclear or high risk of bias, small samples of randomized infants, heterogeneity in study population and design, non-protocolized use of 'rescue' corticosteroids and lack of long-term neurodevelopmental data in most studies. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of different corticosteroid regimens on the outcomes mortality, pulmonary morbidity, and long term neurodevelopmental impairment. Despite the fact that the studies investigating higher versus lower dosage regimens showed that higher-dosage regimens may reduce the incidence of death or neurodevelopmental impairment, we cannot conclude what the optimal type, dosage, or timing of initiation is for the prevention of BPD in preterm infants, based on current level of evidence. Further high quality trials would be needed to establish the optimal systemic postnatal corticosteroid dosage regimen.

Alzheimer’s disease is a neurodegenerative disorder characterized clinically by cognitive decline and pathologically by amyloid deposition and neurofibrillary changes. These neuropathological hallmarks are accompanied by reactive events including microglial activation and astrogliosis. The inflammatory response in Alzheimer’s disease brains is distinguished by a pro-inflammatory signature involving amyloid peptides1, inflammasome signaling2 and disrupted blood brain barrier3. Inflammatory changes are observed also in the cerebrospinal fluid in Alzheimer’s disease4,5. It remains unknown, however, whether the choroid plexus which produces cerebrospinal fluid and guards the brain from peripheral inflammatory insults6,7, contributes to the inflammation and pathogenesis of Alzheimer’s disease. Here we show that the choroid plexus in Alzheimer’s disease exhibits a pro-inflammatory signature with aberrant protein accumulations, which contribute to the age-dependent inflammatory changes observed in the cerebrospinal fluid. Magnetic resonance imaging reveals that the choroid plexus in patients with Alzheimer’s disease displays pathological signal and increased volume, which inversely correlates with cognitive decline. Our findings suggest that the choroid plexus, being unable to efficiently resolve inflammatory insults over the lifetime, eventually ignites and drives the aberrant inflammatory response observed in Alzheimer’s disease. These findings advance our understanding of the pathogenesis and open new vistas in the diagnostics and therapeutics of Alzheimer’s disease.

Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long noncoding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs that sponge microRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1) in CRC. We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. miR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. Src homology 2 B adaptor protein 1 (SH2B1) was notably upregulated in CRC cell lines and was identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.

Objective: Emerging research supports the role of chronic stress in chronic disease development. This scoping review aimed to map the field of research exploring relationships between chronic stress and the development of arthritis in adult populations. Methods: Five electronic databases were systematically searched without publication limits based on three key concepts: stress, arthritis and adults. Eligible qualitative studies investigated individuals’ perceived causes of arthritis; quantitative studies investigated relationships between exposure to a chronic stressor and an arthritis presence outcome. Articles were screened by two independent reviewers and data were narratively synthesised. Results: Of 1819 unique records, 54 studies met inclusion criteria. Nine studies used qualitative methods and 45 used quantitative methods. Studies increased chronologically, with half (n = 27) published since 2010. Chronic stress exposures were heterogenous; most were categorised as adverse life events (n = 22) or adverse childhood experiences (n = 17). Self‐reported arthritis was the most frequent measure of arthritis outcome (n = 26) in quantitative studies. A majority of studies (n = 41) suggested a relationship between exposure to chronic stressors and arthritis development. Conclusion: Increasing study numbers in the past decade may reflect increasing awareness of the potential impact of chronic stress in arthritis development, consistent with a biopsychosocial approach to chronic disease aetiology and management. Further research, using precise arthritis definitions, conducted within a clearly articulated pathophysiological framework, is required to establish a causal relationship between exposure to chronic stressors and the development of specific arthritis conditions. Refereed/Peer-reviewed

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce.We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc.Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus β-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died.This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and β-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis.

As suggested by this article, considerable advances in clinical management and research have taken place during the past 20 years. Although mechanisms underlying the pain syndrome CRPS I and CRPS II remain far from one's understanding, glimpses of the pathophysiology are beginning to take shape. There is now strong evidence that these syndromes exemplify a complex neurologic disease involving the brain at several integrated levels. The changes that occur in CRPS I patients involve somatosensory, sympathetic, and somatomotor systems. The diagnostic criteria have helped to focus on aspects of these foregoing systems and whereas there is no specific laboratory test for CRPS, enough is now known about the pathophysiology to use the following tests: quantitative sensory testing (QST), autonomic testing that include quantitative sudomotor axon reflex test (QSART) for sweating abnormalities, the cold pressor test in conjunction with thermographic imaging to observe the vasoconstrictor response, and laser Doppler flowmetry to monitor background vasomotor control. Recognition of a motor disorder requires accurate documentation and may be a component of the diagnostic criteria in the future. Until a better understanding of mechanistic overtones that would help to put in place mechanism-based therapeutic strategies, current management is built around a rehabilitation model. For this to be successful, as described in the foregoing pages, different non-interventional and interventional modalities are applied in a time-restricted manner to facilitate those modalities that favor progress in the treatment algorithm. As has been described, it is important when using physiotherapeutic maneuvers to minimize joint movement in the affected region to reduce the mechanorecpetor barrage and its increase in perceived pain to encourage and maintain a patient's compliance with their rehabilitation. Finally, of greater significance is the understanding that sympatholysis per se is not a "diagnostic" test for CRPS, but rather a useful procedure that may facilitate treatment for pain that is sympathetically maintained.

Background Clinical characteristics of women with different obstructive sleep apnoea (OSA) severity and adherence to Continuous Positive Airway Pressure (CPAP) therapy have not been previously explored. Therefore, in this retrospective study we assessed OSA prevalence. predictors, clinical and polysomnographic (PSG) characteristics and adherence to CPAP therapy among adult Australian women. Methods All female patients who underwent a diagnostic PSG between 2014/2015 were included. CPAP adherence was assessed during the study period between 2018/2019 using multiple regression model. Results Among a total of 591 females included in this study (Aboriginal n=86), OSA was diagnosed in 458/591 (78%) patients; mild, moderate and severe OSA was present in 44%, 27% and 29% respectively. Older age, higher BMI and hypertension predicted the presence and severity of OSA. The Epworth Sleepiness Scale (ESS) score was not significantly different with [10 (5, 13)] or without [8 (5, 12)] OSA. PSG showed rapid eye movement (REM) sleep associated apnoea hypopnea index (AHI) was higher with all severity of OSA. Adherence to CPAP therapy was noted in 171 (57%) patients; 47% mild, 57% moderate and 63% with severe OSA respectively. Three multiple regression models [clinical, PSG parameters, OSA severity, combined (clinical and PSG)] showed combined model had strongest predictive value and demonstrated that higher ESS and more severe oxygen desaturation were associated with CPAP adherence irrespective of OSA severity. Conclusion Older age, higher BMI and presence of hypertension predicted the presence of OSA. REM sleep related AHI was higher. Adherence to CPAP was associated with symptomatic OSA and severe oxygen desaturation. This article is protected by copyright. All rights reserved.

We developed and validated a set of composite scores that combine quantitative magnetic resonance imaging (MRI)-based measurements of hyaline cartilage damage, bone marrow lesions (BMLs), and effusion-synovitis into composite scores.We selected 300 participants (n = 100 for development cohort; n = 200 for validation cohort) from the Osteoarthritis Initiative with complete clinical, radiographic, and MRI data at baseline and 24 months. We used semiautomated programs to quantify tibiofemoral and patellar cartilage damage, BML volume, and whole-knee effusion-synovitis volume. The candidate composite scores were formed by summing changes from baseline to 24 months based on prespecified methods. We evaluated the candidate composite scores for 1) the ability to differentiate groups with and without knee osteoarthritis progression (17 radiographic and patient-reported definitions), 2) sensitivity to change (standardized response means), and 3) relative performance relating to legacy outcome measures of knee osteoarthritis progression.Three of 13 developed composite scores qualified for testing in the validation cohort (ranked by sensitivity to change): whole-knee cumulative cartilage damage, unweighted total knee score, and BML plus effusion-synovitis volume. Change in cumulative cartilage damage associated with radiographic progression (Kellgren/Lawrence grade: odds ratio [OR] 1.84; joint space width progression: OR 2.11). Changes in the unweighted total knee score (OR 1.97) and BML plus effusion-synovitis score (OR 1.92) associated with Western Ontario and McMaster Universities Osteoarthritis Index knee pain progression.Two composite scores emerged, reflecting discrete domains of knee osteoarthritis progression. First, cumulative damage, which is measured by a whole-knee cartilage damage score, reflects the damage accrued over time. Second, dynamic disease activity, which is measured by a BML plus effusion-synovitis score, relates to changes in a patient's state of disease and symptoms.

Background: The primary goal of COPD management is to optimize a patient's functional status and quality of life. By encouraging effective patient self-management within primary health care, unplanned and potentially avoidable COPD admissions to the emergency department can be avoided. Aim: The aim of this study is to examine whether distance to hospital influences the rate of ED presentation, hospital admission and hospital length of stay for COPD patients. Methods: The 2016 to 2018 resulted in a total of 5253 patient presentations with a primary medical diagnosis code of J44 (COPD). These were at the main hospitals of three Queensland Hospital and Health Services: Toowoomba, Ipswich and Gold Coast. To examine the variations in patient characteristics based on distance a one-way ANOVA (Analysis of Variance) test was conducted. The Kruskal-Wallis (KW) test indicated that there were group differences. Results: This study identified significant variation in COPD-related hospital length of stay and distance to hospital among COPD patients within three hospitals in South East Queensland, Australia. These results confirm that distance plays an important role in determining duration of hospital stay (in number of days) among COPD patients, with clear evidence of the distance 'decay phenomenon'. It appears from the findings of the current study that distance to the hospital is not associated with the greater likelihood of ED presentation but may influence length of stay. Conclusions: Several distance-specific studies have concluded that lower utilisation of hospital care is associated with distance to hospital. This article is protected by copyright. All rights reserved.

Background Inflammatory bowel disease (IBD) patients living in regional or remote Queensland are often disadvantaged by limited access to IBD specialist care. Telehealth clinics could potentially address this disparity and improve patient outcomes. Aim We report the impact of the Royal Brisbane and Women's Hospital (RBWH) IBD telehealth clinics from March 2011 to December 2017 including patient satisfaction and healthcare activity. Methods Patient satisfaction surveys were collected prospectively between March 2011 and March 2012. Healthcare activity was assessed through occasions of service (OOS), number of enrolled patients on biologics and IBD related admissions to RBWH. Results Overall, 3764 OOS were completed including 576 new patient and 3188 follow up visits. Mean age at first telehealth visit was 44 years (range:16-87). The IBD telehealth clinics were well accepted with 99% of the first 153 patients surveyed choosing to continue with telehealth and 94% rated the telehealth experience as very good or excellent. The net number of patients under active review increased from 125 patients in 2011 to 345 patients in 2017. Enrolled patients on biologics also increased from 9 patients in 2011 to 63 patients in 2017. There was an initial dip in annual IBD related admissions to RBWH in 2011 but these have progressively increased over time although the average length of inpatient stay annually has remained stable. Conclusion The RBWH IBD telehealth clinics have shown that telemedicine is well received and can be used successfully to deliver IBD specialist care to patients living in regional or remote areas. This article is protected by copyright. All rights reserved.

Rural and remote patients with rheumatoid arthritis (RA) are at risk for inequities in health outcomes based on differences in physical environments and health care access potential compared to urban populations. The aim of this systematic review was to synthesize epidemiology, clinical outcomes, and health service use reported for global populations with RA residing in rural and remote locations.Medline, Embase, HealthStar, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library were searched from inception to June 2019 using librarian-developed search terms for RA and rural and remote populations. Peer-reviewed published manuscripts were included if they reported on epidemiologic, clinical, or health service use outcomes.Fifty-four articles were included for data synthesis, representing studies from all continents. In 11 studies in which there was an appropriate urban population comparator, rural and remote populations were not at increased risk for RA; 1 study reported increased prevalence, and 5 studies reported decreased prevalence in rural and remote populations. Clinical characteristics of rural and remote populations in studies with an appropriate urban comparator showed no significant differences in disease activity measures or disability, but 1 study reported worse physical function and health-related quality of life in rural and remote populations. Studies reporting on health service use provided evidence that rural and remote residence adversely impacts diagnostic time, ongoing follow-up, access to RA-care-related practitioners and services, and variation in medication access and use, with prominent heterogeneity noted between countries.RA epidemiology and clinical outcomes are not necessarily different between rural/remote and urban populations within countries. Rural and remote patients face greater barriers to care, which increases the risk for inequities in outcomes.

Studies on the impact of ocean acidification on marine organisms involve exposing organisms to future acidification scenarios as projected for open ocean, which has limited relevance for coastal calcifiers. Characterization of reaction norms across a range of pH and identification of tipping points beyond which detrimental effects are observed has been limited and focus on only a few macro-physiological traits. Here we filled this knowledge gap by developing a framework to analyze the broad macro-physiological and molecular responses over a wide pH range of juvenile Pacific oyster, a model species for which the tolerance threshold to acidification remains unknown. We identify low tipping points for physiological traits at pH 7.3-6.9 that coincide with a major reshuffling in membrane lipids and transcriptome. In contrast, shell parameters exhibit effects with pH drop well before tipping points, likely impacting animal fitness. These findings were made possible by the development of an innovative methodology to synthesize and identify the main patterns of variations in large -omic datasets, fit them to pH and identify molecular tipping-points. We propose the application of our framework broadly to the assessment of effects of global change on other organisms.

International audience; Tree architecture shows large genotypic variability, but how this affects water-deficit responses is poorly understood. To assess the possibility of reaching ideotypes with adequate combinations of architectural and functional traits in the face of climate change, we combined high-throughput field phenotyping and genome-wide association studies (GWAS) on an apple tree (Malus domestica) core-collection. We used terrestrial light detection and ranging (T-LiDAR) scanning and airborne multispectral and thermal imagery to monitor tree architecture, canopy shape, light interception, vegetation indices and transpiration on 241 apple cultivars submitted to progressive field soil drying. GWAS was performed with single nucleotide polymorphism (SNP)-by-SNP and multi-SNP methods. Large phenotypic and genetic variability was observed for all traits examined within the collection, especially canopy surface temperature in both well-watered and water deficit conditions, suggesting control of water loss was largely genotype-dependent. Robust genomic associations revealed independent genetic control for the architectural and functional traits. Screening associated genomic regions revealed candidate genes involved in relevant pathways for each trait. We show that multiple allelic combinations exist for all studied traits within this collection. This opens promising avenues to jointly optimize tree architecture, light interception and water use in breeding strategies. Genotypes carrying favourable alleles depending on environmental scenarios and production objectives could thus be targeted.

To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer.Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation).Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively).This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Background A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim To describe the association between SES and time to THR and TKR. Methods 1072 older-adults residing in Tasmania, Australia were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined by the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD), from the Australian Bureau of Statistics' 2001 census data. IRSAD was analysed in two ways; 1) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group, 2) the cohort dichotomised at the quartile 1 cut-point. Results The mean age was 63.0 (±7.5) years, and 51% were women. Over the median follow-up of 12.9 (Interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR, and 79 (7%) had a TKR. Compared to the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR) (HR: 0.56, 95% CI 0.32, 1.00) but not TKR (HR: 0.90, 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions This study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. This article is protected by copyright. All rights reserved.

A growing literature demonstrates the impact of helminths on their host gut microbiome. We investigated whether the stickleback host microbiome depends on ecoevolutionary variables by testing the impact of exposure to the cestode parasite Schistocephalus solidus with respect to infection success, host genotype, parasite genotype, and parasite microbiome composition. We observed constitutive differences in the microbiome of sticklebacks of different origin, and those differences increased when sticklebacks exposed to the parasite resisted infection. In contrast, the microbiome of successfully infected sticklebacks varied with parasite genotype. More specifically, we revealed that the association between microbiome and immune gene expression increased in infected individuals and varied with parasite genotype. In addition, we showed that S. solidus hosts a complex endomicrobiome and that bacterial abundance in the parasite correlates with expression of host immune genes. Within this comprehensive analysis we demonstrated that (i) parasites contribute to modulating the host microbiome through both successful and unsuccessful infection, (ii) when infection is successful, the host microbiome varies with parasite genotype due to genotype-dependent variation in parasite immunomodulation, and (iii) the parasite-associated microbiome is distinct from its host and impacts the host immune response to infection.

To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti-modified protein antibodies (AMPAs) and affect the risk of developing RA.Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite/cmSubjects at risk of developing RA (n = 75) who had broad-spectrum AMPAs (6-8 reactivities) had significantly more severe microstructural changes, including a higher mean ± SD number of cortical microchannels per joint (95 ± 3) and lower total volumetric BMD (vBMD; 265 ± 45), trabecular vBMD (176 ± 42), and cortical vBMD (585 ± 138), than those with moderate AMPA reactivity (3-5 reactivities) (number of cortical microchannels, 79 ± 30; total vBMD, 293 ± 33; trabecular vBMD, 195 ± 32; and cortical vBMD, 627 ± 91) and those with narrow AMPA reactivity (1-2 reactivities) (number of cortical microchannels, 47 ± 20; total vBMD, 311 ± 34; trabecular vBMD, 211 ± 30; and cortical vBMD, 674 ± 56). Progressors to RA had significantly higher numbers of cortical microchannels (103 ± 30 versus 71 ± 35) and lower bone volume (258 ± 37 versus 295 ± 34) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%).Microstructural changes in individuals at risk of RA are associated with broad-spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.

OBJECTIVES To determine 1) whether patients with inflammatory joint disease (IJD) meet current guidelines on physical activity; 2) which factors influence physical activity levels and sedentary behaviour in patients with IJD. METHOD Cross-sectional study of 137 patients with medical diagnosis of an IJD prior to commencing a NHS-run inflammatory Arthritis Exercise Programme. Physical activity and sedentary behaviour (SB) were measured objectively using a thigh worn physical activity monitor for seven consecutive days. Activity levels were subdivided into low physical activity (LPA) and moderate-vigorous activity (MVPA). Firstly, activity levels were analysed against current guidelines of 150minutes of MVPA a week. Secondly time spent in SB, LPA and MVPA were analysed against possible determinants. RESULTS 29% of patients with IJD met current physical activity guidelines. Patients on average spend 10 hours a day in SB. Poor physical fitness measured by 6-minute walk test was the only significant predictor (p=0.019) of high SB (R2 = 4.7%). Attending an exercise facility in the community (p=0.034) and low role limitations due to physical health (p=0.008) predicted high LPA following a backward multiple regression (R2 = 8.0%). Low role limitations due to emotional problems (p=0.031), higher physical fitness (p=0.002) and healthier exercise attitudes and beliefs (p=0.021) predicted meeting current physical activity guidelines following a backward conditional logistic regression explaining between 22.2% and 31.7% of variance. CONCLUSIONS Patients with IJD are inactive and spent a lot of time in SB. Good general health predicts high activity levels. No disease-specific factors were found to determine SB, LPA or MVPA.

To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes.The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-βThe 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-βOur study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

Objective The objective of this study was to examine the association of quadriceps strength symmetry and surgical status (ACL reconstruction or nonoperative management) with early clinical knee OA 5 years after ACL injury or reconstruction. Methods 204/300 athletes were analyzed 5 years after ACL injury or reconstruction (ACLR). Quadriceps strength was measured and reported as a limb symmetry index. We identified participants with early clinical knee OA using criteria that two of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales score ≤85% (Luyten et al. 2018). We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression, adjusted for age, sex, meniscal injury, and BMI, to examine the associations between quadriceps strength and surgical status with clinical knee OA. Results 21% of participants met KOOS criteria for clinical knee OA (Luyten et al. 2018). For every 1% increase in quadriceps limb symmetry index, there was 4% lower odds of clinical OA (adjusted OR 0.96, 95% CI 0.93-0.99) at 5 years. Surgical status was not associated with clinical knee OA (adjusted OR 0.58, 95% CI 0.23, 1.50). Conclusions More symmetrical quadriceps strength, but not surgical status, 5 years after ACL injury or reconstruction was associated with lower odds of clinical knee OA.