An Operationally Simple Approach to Indole Derivatives from 2-Alkenylanilines Utilizing an Oxidation-Intramolecular Cyclization-Elimination Sequence.

Herein we describe a novel route to indole derivatives from a variety of N-substituted 2-alkenylanilines. This route features three operationally simple steps: (1) oxidation to convert N-substituted 2-alkenylanilines into epoxide intermediates, (2) intramolecular cyclization, and (3) the acid-catalyzed elimination of water.

Cholinergic Stimulation Modulates the Functional Composition of CA3 Cell Types in the Hippocampus.

The functional heterogeneity of hippocampal CA3 pyramidal neurons has emerged as a key aspect of circuit function. Here, we explored the effects of long-term cholinergic activity on the functional heterogeneity of CA3 pyramidal neurons in organotypic slices obtained from male rat brains. Application of agonists to either AChRs generally, or mAChRs specifically, induced robust increases in network activity in the low-gamma range. Prolonged AChR stimulation for 48 h uncovered a population of hyperadapting CA3 pyramidal neurons that typically fired a single, early action potential in response to current injection. Although these neurons were present in control networks, their proportions were dramatically increased following long-term cholinergic activity. Characterized by the presence of a strong M-current, the hyperadaptation phenotype was abolished by acute application of either M-channel antagonists or the reapplication of AChR agonists. We conclude that long-term mAChR activation modulates the intrinsic excitability of a subset of CA3 pyramidal cells, uncovering a highly plastic cohort of neurons that are sensitive to chronic ACh modulation. Our findings provide evidence for the activity-dependent plasticity of functional heterogeneity in the hippocampus.SIGNIFICANCE STATEMENT The large heterogeneity of neuron types in the brain, each with its own specific functional properties, provides the rich cellular tapestry needed to account for the vast diversity of behaviors. By studying the functional properties of neurons in the hippocampus, a region of the brain involved in learning and memory, we find that exposure to the neuromodulator acetylcholine can alter the relative number of functionally defined neuron types. Our findings suggest that the heterogeneity of neurons in the brain is not a static feature but can be modified by the ongoing activity of the circuits to which they belong.

Does a shorter residual first metatarsal length after first ray amputation in diabetic patients leads to poorer outcomes - A risk factor study.

BACKGROUND: The first ray plays a vital role in the normal function of the foot and the gait cycle where in its absence can lead to abnormal changes in weight distribution to the residual first metatarsal stump and lesser metatarsals with predisposition to developing lesser toe deformities reulcerations and reamputations particularly in diabetic patients. This study aims to characterise the outcomes after first ray amputation and its associated risk factors with focus on the impact of residual first metatarsal length. METHODS: All diabetic patients with first ray amputations from January 2012 to December 2016 were reviewed. Residual first metatarsal length was measured using postoperative radiographs. Risk factors for outcomes such as readmission, reulceration and/or reamputation, transfer ulceration and/or amputation of lesser toes, proximal amputations, ulcer-free duration (UFD) and mortality were analysed using bivariate logistic/linear regression followed by multiple logistic/linear regression models adjusting for confounding factors. RESULTS: Among 89 patients with first ray amputations, 65.3 % needed readmission for further treatment. Although only 10.1 % had reulceration at the first ray which all led to reamputation, there were 56.2 % with transfer ulceration and 40.4 % with transfer amputation of the lesser toes in this cohort. The prevalence of transmetatarsal amputation was 18 % and proximal amputations at 12.4 % while the average UFD was 27 months. Mortality rate was 31.5 % with an average of 3-year survival. Preservation of the first metatarsal length via metatarsophalangeal joint disarticulation independently reduced likelihood of readmissions and residual metatarsal length of > one third when compared to < one third after first ray amputations had lower likelihood of transfer amputation of lesser toes. CONCLUSION: First ray amputation in diabetic patients leads to significant morbidities and mortality. Preservation of the residual first metatarsal length independently reduced the likelihood of readmissions and transfer amputation to the lesser toes.

Morbidities and prognostic factors after tibial pilon fracture: impact on patients.

INTRODUCTION: This study aims primarily to characterize the sequelae and morbidity associated with tibial pilon injuries from the patients' perspectives in terms of multiple surgical interventions, duration of hospital stay, downtime from work, loss of productivity and impact on patients' lives. The secondary aim is to review the associated risk factors for these morbidities. MATERIALS AND METHODS: All patients with surgically treated tibial pilon fractures from 1st July 2007 to 30th June 2017 were included. The morbidities reviewed focused on delay to surgery, numbers of surgeries, limb amputation, length of stay (LOS), readmissions, duration of medical leave (ML), follow-up and number of outpatient visits. RESULTS: There were 102 patients included in the review and up to 70% of them had an average 7 days delay to definitive surgery. They also required an average hospital LOS of at least 2 weeks extending up to 3 more weeks if soft tissue reconstruction was necessitated. Up to a third of patients were readmitted with 15% of them needing further treatment. These patients required a notable period of downtime from work as shown in the long ML (mean 152.6 days [S.D. = 110.7]). Multiple conditional regression models showed AO/OTA classification (B and C) and open fracture as independent predictors of delay to surgery. Predictors for increased LOS were high velocity mechanism of injury at 4 days longer and patients who needed soft tissue reconstruction at 21 days longer. In terms of downtime from work, only work injury has been identified as an independent predictor of ML at 88.5 days longer. CONCLUSION: Tibial pilon fractures leads to significant morbidities with profound negative impact on patients' lives in terms of multiple surgical interventions required, prolonged hospital stay, need for readmissions and prolonged downtime from work. These morbidities from patients' perspective should be emphasized to patients and employers to manage their expectations and potential limitations.

Supporting person-centred dementia care following the COVID-19 pandemic.

In recent years, nurses have experienced increased workplace pressures in part due to the coronavirus disease 2019 (COVID-19) pandemic, which exacerbated challenges in the delivery of person-centred dementia care. This article examines how people with dementia were affected by the COVID-19 pandemic, as well as exploring the ongoing effects on nurses and the care they provide for people with dementia. The author discusses the importance of dementia awareness and education for nurses that supports them to promote the needs of people with the condition. The article also outlines how nurse leaders can promote person-centred care for people with dementia through reflection and clinical supervision.

Biomechanical Comparison of a Novel 3-Screw Fixation vs Conventional 2-Screw Fixation of Calcaneal Tuberosity Avulsion Fractures.

BACKGROUND: Calcaneal tuberosity avulsion fractures are challenging to treat because of the poor bone stock and high risk of fixation failure secondary to the strong Achilles tendon pull. The purpose of this study is to compare the tensile force to failure of 2 different types of screw fixation construct in a cadaveric model of calcaneal tuberosity avulsion fracture. METHODS: An oblique osteotomy was created in the calcanei of 7 matched pairs of cadaveric specimens to simulate a tuberosity avulsion fracture and one specimen from each pair randomized into one of the 2 groups for comparison. Two cancellous screws were inserted perpendicular to the fracture line at the posteromedial and posterolateral corners of the avulsed fragment for the 2-screw construct. For the second group, an additional stab incision was made at the midline of the Achilles insertional region for a screw placed between the initial 2 screws with a trajectory toward the calcaneocuboid joint in the 3-screw construct. These specimens were then mounted and loaded to failure. RESULTS: The mean force to a predefined failure at 3.0-mm gap for the 3-screw construct was 468.7 ± 267.9 N vs 278.9 ± 164.0 N for the 2-screw construct (P < .001). The addition of a central nonparallel screw in the 3-screw construct significantly increased the force required for fracture gap displacement at all cut-off points (1.0-8.0 mm) when compared to the 2-screw construct (P < .001). Notably, the mean peak tensile force for the 3-screw construct was 499.4 ± 255.4 N occurred at the gap displacement of 4.1 mm for the 3-screw construct whereas the mean peak tensile force for the 2-screw construct was 315.9 ± 162.4 N displacing the gap at 4.3 mm. CONCLUSION: This study showed that an additional central nonparallel screw in the 3-screw construct provided significant mechanical superiority compared to a 2-screw construct. CLINICAL RELEVANCE: The present study supported the use of augmented fixation with an additional central off-axis screw to reduce risk of fixation failure in calcaneal tuberosity avulsion fractures.

Outcomes of operatively treated calcaneal tuberosity avulsion fractures.

BACKGROUND: Calcaneal tuberosity avulsion fractures are uncommon but when present should be treated emergently due to the high risk of skin compromise. Multiple fixation techniques have been reported in the literature but there are little data regarding the ideal fixation construct and outcomes. We aimed to characterize the clinical presentation, focussing on soft tissue compromise and outcomes of operatively treated calcaneal tuberosity avulsion fractures with its associated complications. METHODS: A retrospective review of all surgically treated calcaneus fracture in our institution from Jun 2008 to Jun 2017 was done. We reviewed patients' demographics, types of avulsion fracture, presence of preoperative skin compromise, age of fracture, time to operation, types of fixation construct, postoperative weight bearing regime, union rates, complications and revision surgeries if present. RESULTS: We found 9 patients from our database who met the inclusion criteria. They had an average age of 55.6 (range: 43 - 90) years with 5 (55.6%) of them aged 60 years and older. Seven (77.8%) patients were female. Four out of 9 patients (44.4%) presented with soft tissue compromise (3 cases of skin tenting and 1 case of blistering). None of them required soft tissue reconstructive surgery for skin defects postoperatively. However, 2 patients (22.2%) had wound complications after surgery requiring prolonged wound care for up to 4 months. There were 2 patients with fixation failure whereby both were allowed weight bearing prematurely. All of them were able to ambulate independently at their last review. CONCLUSION: Calcaneal tuberosity avulsion fractures have a high prevalence of soft tissue compromise and warrant early attention. This condition should be treated as both a bony and soft tissue injury rather than just a bony fracture alone. Management of this injury should take into account fracture reduction and stable fixation with neutralization of the Achilles tendon forces.

Should the location of distal tibial plating be influenced by the varus or valgus fracture pattern of tibial pilon fracture?

INTRODUCTION: Operative treatment of tibial pilon fracture is challenging. There is a lack of consensus and only one clinical study on the optimal location of distal tibial plating for fixation of pilon fractures based on varus or valgus fracture patterns. We hypothesize that complications rates, specifically mechanical complications, are not influenced by the location of the tibial plating in the fixation of pilon fractures with respect to varus or valgus fracture patterns. MATERIALS AND METHODS: Sixty-nine patients who had single plating for tibial pilon from 2007 to 2017 were recruited. They were divided into two groups, transverse fibular fracture (varus fracture pattern) and comminuted fibular fracture (valgus fracture pattern). Our primary outcome measure was any mechanical complications as a result of the location of plating (medial vs lateral) on varus or valgus fracture patterns. RESULTS: There were 38 (55.1%) patients with varus fracture pattern and 31 (44.9%) patients with valgus fracture pattern tibial pilon fractures. In the varus fracture pattern group, mechanical complications were not significantly different between the two plating locations (27.3 vs 33.3%, p > 0.05). Notably, there were more fibula fixations performed in patients with medial plating (74.1 vs 45.5%, p = 0.092) when compared those with lateral plating in the varus fracture pattern group. There were also no statistically significant differences found although 10 (40%) out of 25 patients had mechanical complications in the medial plating group compared to 1 (16.7%) out of 6 patients with lateral plating (p = 0.383) in the valgus fracture pattern group. CONCLUSION: There were no differences in mechanical complications for medial vs lateral plating in tibial pilon fracture based on varus or valgus deforming forces. As much as we should consider the fracture patterns and deforming forces when deciding on plating location, other factors such as careful soft tissue management and fragment-specific fixation should be prioritized.

Fibula fixation in the treatment of tibial pilon fractures - Is it really necessary?

BACKGROUND: There is a lack of consensus about the role of fibula fixation in these complex fractures, with only two clinical studies in the literature. We hypothesize that the fibula fracture need not be fixed in the tibial pilon fractures if primary stability can be achieved with tibial fixation alone. METHODS: We reviewed 79 patients with operatively treated tibial pilon with associated fibula fractures from 2007 to 2017 and divided them into two groups; patients with fibula fracture fixation and those without fixation. The primary outcome measure was any mechanical complications. Secondary outcomes were wound complications and other morbidities. RESULTS: There were 54 (68.4%) patients with fibula fixation and 25 (31.6%) patients without fixation. There were no statistically significant differences in mechanical complications between the two groups. However, patients without fibula fixation were noted to have more wound complications (44% vs 25.9%, p = 0.108) although this was not statistically significant. In terms of removal of implant (ROI), there were no differences noted in patients with or without fibula fixation (33.3% vs 28%, p = 0.796). There were also no significant differences in ROI for those fixed with plate and screws when compared to those fixed with Rush rod and K wire within the group with fibula fixation. CONCLUSION: Fibula fixation in the treatment of tibial pilon fractures is not routinely necessary and does not result in decreased mechanical complications such as malunion, delayed union, nonunion and implant failure. Fibula fracture fixation should be reserved for cases where it may aid reduction or provide additional stability.

Adequacy of measures of informed consent in medical practice: A systematic review.

As a critical component of medical practice, it is alarming that patient informed consent does not always reflect (1) adequate information provision, (2) comprehension of provided information, and (3) a voluntary decision. Consequences of poor informed consent include low patient satisfaction, compromised treatment adherence, and litigation against medical practitioners. To ensure a well-informed, well-comprehended, and voluntary consent process, the objective and replicable measurement of these domains via psychometrically sound self-report measures is critical. This systematic review aimed to evaluate the adequacy of existing measures in terms of the extent to which they assess the three domains of informed consent, are psychometrically sound and acceptable for use by patients. Extensive searching of multiple databases (PsychINFO, PubMed, Sociological Abstracts, CINAHL, AMED) yielded 10,000 potential studies, with 16 relevant scales identified. No existing scale was found to measure all three consent domains, with most only narrowly assessing aspects of any one domain. Information provision was the most frequently assessed domain, followed by comprehension, and then voluntariness. None of the identified scales were found to have adequate evidence for either high quality psychometric properties or patient user acceptability. No existing scale is fit for purpose in comprehensively assessing all domains of informed consent. In the absence of any existing measure meeting the necessary criteria relating to information, comprehension and voluntariness, there is an urgent need for a new measure of medical consent to be developed that is psychometrically sound, spans all three domains and is acceptable to patients and clinicians alike. These findings provide the impetus and justification for the redesign of the informed consent process, with the aim to provide a robust, reliable and replicable process that will in turn improve the quality of the patient experience and care provided.

How do you think about stress? A qualitative analysis of beliefs about stress.

This qualitative study aimed to identify common stress beliefs. Undergraduate psychology students (N = 35) completed semi-structured interviews discussing the sensations, causes, purpose, valence, consequences, control, and timeline of stress. Interviews were analysed via double-coded thematic analysis employing a latent, inductive, and realist framework. Five themes (cognition, emotion, physical health, interpersonal relations, and behaviour) and 17 subthemes were identified. Themes and subthemes were validated in a Delphi study of experts in stress research (N = 14). Many of these identified beliefs have not been incorporated into current measures of stress beliefs, suggesting the need for new approaches to measuring this construct.

Short-term clinical outcomes of arthroscopic fixation of displaced posterior cruciate ligament avulsion fractures with the use of an adjustable loop suspensory device.

INTRODUCTION: To describe the clinical outcomes of arthroscopic fixation of displaced posterior cruciate ligament (PCL) avulsion fractures with/without associated tibia plateau fractures using an adjustable loop suspensory fixation device. METHODS: Four male patients who have sustained PCL tibia avulsion fractures with/without associated tibia plateau fractures were operated on in a single centre using an arthroscopic adjustable loop suspensory device technique. After arthroscopic evaluation and reduction of the fracture using a probe and PCL drill guide, a proximal medial tibial mini incision was used to drill a bone tunnel through the fracture fragment. An adjustable loop suspensory device was relayed through the bone tunnel via a transtibial manner, and the button device was flipped onto the bony fragment for fixation. The associated tibial plateau fractures were then fixed if present. Knee function at the last follow-up was evaluated by International Knee Documentation Committee (IKDC), Knee Injury And Osteoarthritis Outcome Score (KOOS), Lysholm scores. Range of motion and knee stability were assessed, and fracture union was evaluated by plain radiographs. RESULTS: All patients underwent the operation successfully with no major complications encountered. All were followed up for a minimum of 6 months. There was no instability reported by the patients or found during objective evaluation using posterior drawer test and reverse pivot shift test. All fractures achieved union. Mean post-operative Lysholm score was 91.5 (range 85-95), IKDC score was 85.1 (range 74.7-89.7) and KOOS was 89.3 (range 81.5-94.6). All patients returned to their pre-injury activities of daily living and work. Radiographic evaluation showed union at the fracture site in all four patients at the last follow-up. CONCLUSION: This arthroscopic procedure is a viable minimally invasive technique that is appropriate in minimally displaced avulsion fractures of the PCL with associated tibia plateau fractures. LEVEL OF EVIDENCE: Case Series, IV.

Enhancing self-compassion in individuals with visible skin conditions: randomised pilot of the 'My Changed Body' self-compassion writing intervention.

Background: Abnormalities in the appearance of skin are commonly associated with compromised self-body perceptions, arising from physical manifestations of the skin condition that deviate from the individual's idealised body image. These body image concerns are associated with a range of psychological issues including anxiety, depression, fear of negative evaluation, and suicidal ideation. Unfortunately, stigma and embarrassment associated with these body image concerns mean that these issues are rarely discussed in clinical medical consultations. There is thus a need for highly accessible and acceptable interventions to address skin-related body image concerns. We have previously demonstrated that a web-based self-compassion focused therapeutic writing approach, the 'My Changed Body' intervention, is efficacious in addressing body image concerns of women in the breast cancer context. The aim of this experimental pilot study was to investigate the feasibility of applying the My Changed Body intervention to address visible skin-related body image concerns. Methods: Participants (N = 50) with a range of visible skin conditions provided online informed consent, then completed measures of demographic and medical history, body image disturbance, self-compassion and positive and negative affect. They were then randomly allocated either to an active control expressive writing condition (n = 25) or to the My Changed Body writing condition (n = 25). Participants were blind to their condition allocation. Immediately after completing their allocated writing exercise, participants completed self-compassion and affect measures. Results: Controlling for pre-writing body image disturbance, repeated measures ANCOVAs with fixed effects revealed that self-compassion and negative affect significantly improved after the My Changed Body writing exercise, compared to the control condition. There was no between groups difference at follow-up in positive affect. Conclusions: This study suggests that the My Changed Body writing intervention may provide benefit to individuals with visible skin conditions. A randomised controlled trial is needed to further confirm these results.

Reducing Body Image-Related Distress in Women With Breast Cancer Using a Structured Online Writing Exercise: Results From the My Changed Body Randomized Controlled Trial.

Purpose Breast cancer treatment adverse effects result in one in three survivors experiencing body image-related distress (BID) that negatively impacts on a woman's ability to recover after cancer and into survivorship. My Changed Body (MyCB) is a Web-based psychological intervention to alleviate BID and improve body appreciation in survivors of breast cancer (BCSs) through a single-session, self-compassion focused writing activity. This randomized controlled trial evaluated the impact of MyCB on BID and body appreciation in BCSs. The moderating effect of lymphedema status (affected or unaffected) and appearance investment (self-importance placed on personal appearance) and the mediating effect of self-compassion were evaluated. Patients and Methods Women (disease-free stage I to III BCSs who had experienced at least one negative event related to bodily changes after breast cancer) were randomly assigned to MyCB (n = 149) or an expressive writing control arm (n = 155). Primary outcomes were reduction in BID and improvement in body appreciation 1 week after intervention. Secondary outcomes included psychological distress (depression and anxiety) and self-compassion. Follow-up assessments occurred 1 week, 1 month, and 3 months after writing. Results Compliance with the MyCB intervention was 88%, and attrition was 9.2%. Intent-to-treat linear mixed models indicated that participants who received MyCB reported significantly less BID ( P = .035) and greater body appreciation ( P = .004) and self-compassion ( P < .001) than expressive writing participants. Intervention effects on BID were moderated by lymphedema status ( P = .007) and appearance investment ( P = .042). Self-compassion mediated effects on both primary outcomes. Therapeutic effects were maintained at 1 month (BID and body appreciation) and 3 months (body appreciation) after intervention. Significant reductions in psychological distress (1-month depression, P = .001; 1-week and 1-month anxiety, P = .007) were evident for MyCB participants with lymphedema. Conclusion This study supports the efficacy of MyCB for reducing BID and enhancing body appreciation among BCSs.

Outcome of Patellar Tendon Versus 4-Strand Hamstring Tendon Autografts for Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Prospective Randomized Trials.

PURPOSE: To compare clinical outcomes of anterior cruciate ligament (ACL) reconstruction and investigate whether the clinical results of 4-strand hamstring tendon (HT) reconstruction are still inferior to that of the patellar tendon (PT). METHODS: We performed a comprehensive systematic review and meta-analysis of the English literature on PubMed, Scopus, Web of Science, and the Cochrane register for papers that compared clinical outcomes of PT versus HT for ACL reconstruction. Outcome measures analyzed included rate of rerupture, KT-1000, International Knee Documentation Committee grade, Lachman, pivot shift, Lysholm score, Tegner Activity Scale, anterior knee pain, and discomfort on kneeling. RESULTS: We included 19 studies from an initial 1,168 abstracts for the systematic review, and, eventually, 19 studies were included in the meta-analysis. The study population consisted of a total of 1784 patients. The average follow-up duration was 58.8 months. We found significant differences in favor of the HT technique in the domains of anterior knee pain, kneeling pain, and restriction in the range of active extension ("extension deficit"). We found no differences between the PT and HT technique in terms of rerupture rate. There were no clinically significant differences for the outcomes of Lysholm score and Tegner Activity Scale as well as the KT-1000 side-to-side at maximum manual force. CONCLUSIONS: Contemporary 4-strand HT ACL reconstruction is comparable with the PT technique in terms of clinical stability and postoperative functional status across most parameters studied. The HT technique carries lower risk of postoperative complications such as anterior knee pain, kneeling discomfort, and extension deficit. Primary ACL reconstruction using the 4-strand HT technique achieves clinical results that are comparable with the PT technique with significantly less postoperative complications. LEVEL OF EVIDENCE: Level I, systemic review and meta-analysis of Level I studies.

A double button adjustable loop device is biomechanically equivalent to tension band wire in the fixation of transverse patellar fractures-A cadaveric study.

INTRODUCTION: Tension-band wire fixation of patellar fractures is associated with significant hardware-related complications and infection. Braided polyester suture fixation is an alternative option. However, these suture fixations have higher failure rates due to the difficulty in achieving rigid suture knot fixation. The Arthrex syndesmotic TightRope, which is a double-button adjustable loop fixation device utilizing a 4-point locking system using FibreWire, may not only offer stiff rigid fixation using a knotless system, but may also obviate the need for implant removal due to hardware related problems. The aim of our study is to compare the fixation rigidity of patella fractures using Tightrope versus conventional tension-band wiring (TBW) in a cadaveric model. MATERIALS AND METHODS: TBW fixation was compared to TightRope fixation of transverse patella fractures in 5 matched pairs of cadaveric knees. The knees were cyclically brought through 0-90° of motion for a total of 500 cycles. Fracture gapping was measured before the start of the cycling, and at 50, 100, 200 and 500 cycles using an extensometer. The mean maximum fracture gapping was derived. Failure of the construct was defined as a displacement of more than 3mm, patella fracture or implant breakage. RESULTS: All but one knee from each group survived 500 cycles. The two failures were due to a fracture gap of more than 3mm during cycling. There was no significant difference in the mean number of cycles tolerated. There was no implant breakage. There was no statistical significant difference in mean maximum fracture gap between the TBW and TightRope group at all cyclical milestones after 500 cycles (0.3026±0.4091mm vs 0.3558±0.7173mm, p=0.388). CONCLUSIONS: We found no difference between the TBW and Tightrope fixation in terms of fracture gapping and failure. With possible lower risk of complications such as implant migration and soft tissue irritation, we believe tightrope fixation is a feasible alternative in fracture management of transverse patella fractures.