Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range

Polycystin-2 is required for chondrocyte mechanotransduction and traffics to the primary cilium in response to mechanical stimulation

Primary cilia and associated intraflagellar transport are essential for skeletal development, joint homeostasis, and the response to mechanical stimuli, although the mechanisms remain unclear. Polycystin-2 (PC2) is a member of the transient receptor potential polycystic (TRPP) family of cation channels, and together with Polycystin-1 (PC1), it has been implicated in cilia-mediated mechanotransduction in epithelial cells. The current study investigates the effect of mechanical stimulation on the localization of ciliary polycystins in chondrocytes and tests the hypothesis that they are required in chondrocyte mechanosignaling. Isolated chondrocytes were subjected to mechanical stimulation in the form of uniaxial cyclic tensile strain (CTS) in order to examine the effects on PC2 ciliary localization and matrix gene expression. In the absence of strain, PC2 localizes to the chondrocyte ciliary membrane and neither PC1 nor PC2 are required for ciliogenesis. Cartilage matrix gene expression (Acan, Col2a) is increased in response to 10% CTS. This response is inhibited by siRNA-mediated loss of PC1 or PC2 expression. PC2 ciliary localization requires PC1 and is increased in response to CTS. Increased PC2 cilia trafficking is dependent on the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4) activation. Together, these findings demonstrate for the first time that polycystins are required for chondrocyte mechanotransduction and highlight the mechanosensitive cilia trafficking of PC2 as an important component of cilia-mediated mechanotransduction

Serum concentrations of the biomarkers CA125, CA15-3, CA72-4, tPSA and PAPP-A in natural and stimulated ovarian cycles

Objective Biomarkers associated with cancer screening (CA125, CA15‐3, CA72‐4, total prostate specific antigen [tPSA]) and the monitoring of pregnancy (pregnancy associated plasma protein‐A [PAPP‐A]) were measured during natural and stimulated ovarian cycles in disease‐free non-pregnant women to determine if they could reflect normal events relating to ovulation and/or endometrial changes. Methods A total of 73 blood samples (10 women) collected throughout the natural menstrual cycle, and 64 blood samples (11 women) taken during stimulated ovarian cycles, were analysed on the Roche Cobas e411 automated analyser. Results Detectable levels of tPSA were measured in at least one point in the cycle in 6/10 of women in the natural cycle and 10/11 of women in stimulated cycles, and CA72-4 was detected in only 12/21 women tested. Concentrations of CA125, tPSA, CA15‐3 and CA72‐4 showed no significant difference between the natural and stimulated ovarian cycle groups. On average the mean PAPP‐A of the natural group was (2.41±0.58) mIU/L higher than the stimulated group (t=4.10, P< 0.001). CA125 and CA15‐3 results were both significantly influenced by the stage of the cycle (P<0.0001), whereas tPSA and PAPP‐A concentrations revealed no significant changes (P≥0.65). CA72‐4 was not affected by the stage of the cycle nor ovarian stimulation. Conclusion Ovarian stimulation reduced serum PAPP‐A levels, CA125 and CA15‐3 levels were generally unaffected by ovarian stimulation but displayed cyclical changes throughout both natural and stimulated cycles, whilst tPSA and CA72-4 were not affected by the stage of the cycle or ovarian stimulation

Onset of action of the beta 3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder

Purpose Long-term persistence with pharmacotherapy for overactive bladder (OAB) requires a drug with an early onset of action and good efficacy and tolerability profile. Although antimuscarinics improve OAB symptoms within 1–2 weeks of initiating treatment, adherence after 3 months is relatively poor due to bothersome side effects (e.g., dry mouth and constipation). Mirabegron, a b3-adrenoceptor agonist, has demonstrated significant improvements in key symptoms of OAB and good tolerability after 12 weeks in Phase III studies. Methods This was a prespecified pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies, and a Phase II study, to evaluate efficacy and tolerability of mirabegron 25 and 50 mg versus placebo. The main efficacy endpoints were change from baseline to week 1 (Phase II only), week 4, and final visit in mean number of incontinence episodes/24 h, micturitions/24 h, and mean volume voided/micturition (MVV). Results A significant benefit for mirabegron 25 and 50 mg versus placebo was evident at the first assessment point, 4 weeks after initiation of therapy, in Phase III studies for incontinence, micturitions, and MVV. The earliest measured benefit was after 1 week, in the Phase II study. Quality-of-life parameters also significantly improved with mirabegron 25 and 50 mg as early as week 4. Significant benefits continued throughout the studies. Mirabegron was well tolerated. Conclusions The early onset of action and good overall efficacy and tolerability balance that mirabegron offers may lead to high rates of persistence with mirabegron in the long-term treatment of OAB

Perioperative supplementation with a fruit and vegetable juice powder concentrate and postsurgical morbidity: a double-blind, randomised, placebo controlled clinical trial

Aims Surgical trauma leads to an inflammatory response that causes surgical morbidity. Reduced antioxidant micronutrient (AM)a levels and/or excessive levels of Reactive Oxygen Species (ROS)b have previously been linked to delayed wound healing and presence of chronic wounds. We aimed to evaluate the effect of pre-operative supplementation with encapsulated fruit and vegetable juice powder concentrate (JuicePlus+®) on postoperative morbidity and Quality of Life (QoL)c. Methods We conducted a randomised, double-blind, placebo-controlled two-arm parallel clinical trial evaluating postoperative morbidity following lower third molar surgery. Patients aged between 18 and 65 years were randomised to take verum or placebo for 10 weeks prior to surgery and during the first postoperative week. The primary endpoint was the between-group difference in QoL over the first postoperative week, with secondary endpoints being related to other measures of postoperative morbidity (pain and trismus). Results One-hundred and eighty-three out of 238 randomised patients received surgery (Intention-To-Treat population). Postoperative QoL tended to be higher in the active compared to the placebo group (p=0.059). Furthermore, reduction in mouth opening 2 days after surgery was 3.1 mm smaller (p=0.042), the mean pain score over the postoperative week was 9.4 mm lower (p=0.007) and patients were less likely to experience moderate to severe pain on postoperative day 2 (RR 0.58, p=0.030), comparing verum to placebo groups. Conclusion Pre-operative supplementation with a fruit and vegetable supplement rich in AM may improve postoperative QoL and reduce surgical morbidity and post-operative complications after surgery

Why Should ACT Work When CBT Has Failed? a Study Assessing Acceptability and Feasibility of Acceptance and Commitment Therapy (ACT) for Paediatric Patients With Chronic Fatigue Syndrome/myalgic Encephalomyelitis (CFS/ME)

AIMS: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) effects 0.5–3.28% of children. NICE guidance recommends Activity Management, Graded Exercise Therapy or Cognitive Behavioural Therapy for fatigue (CBT-f). Approximately 15% of patients do not achieve full recovery within one year with current treatments. Acceptance and Commitment Therapy (ACT) is an effective treatment in many chronic illnesses. There are no studies investigating ACT for paediatric CFS/ME. This feasability study aimed to assess if ACT is a feasible and acceptable alternative treatment when current treatment has not led to recovery. METHODS: This feasability cohort study aimed to enrol a minimum of 12 participants aged 11–18 yearswith CFS/ME attending the Royal United Hospitals Bath NHS Foundation Trust Specialist Paediatric CFS/ME Service, who were still symptomatic after 12 months or 12 sessions of standard treatment and were offered six to 12 sessions of ACT. Retention and recruitment data were analysed. Participants were asked to complete questionnaires before, during and after treatment. A selection of participants and their parents were interviewed about their experience of the study. Interviews were analysed using thematic analysis. RESULTS: 19 participants (95% of those approached) were recruited. Only 4 participants of this hard-to-reach group did not complete treatment. In almost all sessions participants reported that they felt ‘totally’ listened to in post session questionnaires (31/33 sessions). Preliminary interviews (n = 12) indicate acceptability of ACT, with all young people and their parents stating that they thought ACT should be offered to this population. Participants particularly commented that the absence of thought challenging (used in CBT-f) was a positive element of ACT. Participant's openness to try new approaches and altruistic desire to be in a study was noted. CONCLUSION: Recruitment data indicate that it is feasible to recruit and retain 11–18-year-olds with CFS/ME to a study offering ACT. Interviews with participants and parents were broadly positive suggesting ACT is an acceptable treatment in this population. Results indicated that it is both feasible and acceptable to offer ACT to 11–18-year-olds with CFS/ME using this protocol, supporting the prospect of an RCT in this area

Attitudes towards Oral Health in Patients with Rheumatoid Arthritis: A Qualitative Study Nested within a Randomized Controlled Trial

Introduction: Patients with rheumatoid arthritis (RA) present a higher incidence and severity of periodontitis than the general population. Our study, Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA), was a randomized waiting-list controlled trial using mixed methods. Patients randomized to the intervention arm received intensive periodontal treatment, and those in the control arm received the same treatment with a 6-mo delay. Aim: The nested qualitative component aimed to explore patients’ experiences and priorities concerning oral health and barriers and facilitators for trial participation. Methods: Using purposive sampling until thematic saturation was reached, we conducted 21 one-to-one semistructured interviews with randomized patients in either of the 2 treatment arms as well as with patients who did not consent for trial participation. Results: The patients described their experiences about RA, oral health, and study participation. Previous experiences with dental care professionals shaped patients’ current perceptions about oral health and the place of oral health on their list of priorities compared with other conditions. Patients also highlighted some of the barriers and facilitators for study participation and for compliance with oral health maintenance. The patients, in the control arm, presented their views regarding the acceptable length of waiting time for the intervention. Conclusion: The associations between periodontal and systemic health are increasingly recognized by the literature. Our study provided an insight into RA patients’ experiences and perceptions about oral health. It also highlighted some of the barriers and facilitators for participating in a periodontal interventional study for this group. We hope that our findings will support the design of larger interventional periodontal studies in patients with RA. The complex challenges faced by the burden of RA and the associated multimorbidities in this patient group might highlight opportunities to improve access to oral health services in this patient population. Knowledge Transfer Statement: This article provided insights into the experiences and perceptions of rheumatoid arthritis patients about their oral health to improve patient participation in a definitive clinical trial

A Digital Health Solution for Child Growth Monitoring at Home: Testing the Accuracy of a Novel “GrowthMonitor” Smartphone Application to Detect Abnormal Height and Body Mass Indices

Objective To develop and evaluate a smartphone application that accurately measures height and provides notifications when abnormalities are detected. Patients and Methods A total of 145 (75 boys) participants with a mean age ± SD of 8.7±4.5 years (range, 1.0-17.0 years), from the Children’s Hospital at Barts Health Trust, London, United Kingdom, were enrolled in the study. “GrowthMonitor” (UCL Creatives) iPhone application (GMA) measures height using augmented reality. Using population-based (UK-WHO) references, algorithms calculated height SD score (HSDS), distance from target height (THSDSDEV), and HSDS change over time (ΔHSDS). Pre-established thresholds discriminated normal/abnormal growth. The GMA and a stadiometer (Harpenden; gold standard) measured standing heights of children at routine clinic visits. A subset of parents used GMA to measure their child’s height at home. Outcome targets were 95% of GMA measurements within ±0.5 SDS of the stadiometer and the correct identification of abnormal HSDS, THSDSDEV, and ΔHSDS. Results Bland-Altman plots revealed no appreciable bias in differences between paired study team GMA and stadiometer height measurements, with a mean of the differences of 0.11 cm with 95% limits of agreement of −2.21 to 2.42 cm. There was no evidence of greater bias occurring for either shorter/younger children or taller/older children. The 2 methods of measurements were highly correlated (R=0.999). GrowthMonitor iPhone application measurements performed by parents in clinic and at home were slightly less accurate. The κ coefficient indicated reliable and consistent agreement of flag alerts for HSDS (κ=0.74) and THSDSDEV (κ=0.88) between 83 paired GMA and stadiometer measurements. GrowthMonitor iPhone application yielded a detection rate of 96% and 97% for HSDS-based and THSDSDEV-based red flags, respectively. Forty-two (18 boys) participants had GMA calculated ΔHSDS using an additional height measurement 6-16 months later, and no abnormal flag alerts were triggered for ΔHSDS values. Conclusion GrowthMonitor iPhone application provides the potential for parents/carers and health care professionals to capture serial height measurements at home and without specialized equipment. Reliable interpretation and flagging of abnormal measurements indicate the potential of this technology to transform childhood growth monitoring