Diatom-inspired silicification process for development of green flexible silica composite aerogels.

In this study, we have developed novel biomimetic silica composite aerogels and cryogels for the first time, drawing inspiration from the natural diatom's silicification process. Our biomimetic approach involved the modification of tyrosinase-mediated oxidized silk fibroin (SFO) surfaces with polyethyleneimine (PEI). This modification introduced ample amine groups onto the SF polymer, which catalyzed the silicification of the SFO-PEI gel surface with silicic acid. This process emulates the catalytic function of long-chain polyamines and silaffin proteins found in diatoms, resulting in a silica network structure on the primary SFO-PEI network gel's surface. The SFO-PEI gel matrix played a dual role in this process: (1) It provided numerous amine functional groups that directly catalyzed the silicification of silicic acid on the porous structure's exterior surface, without encapsulating the created silica network in the gel. (2) It served as a flexible mechanical support facilitating the creation of the silica network. As a result, the final ceramic composite exhibits a mechanically flexible nature (e.g., cyclic compressibility up to 80% strain), distinguishing it from conventional composite aerogels. By mimicking the diatom's silicification process, we were able to simplify the development of silica-polymer composite aerogels. It eliminates the need for surfactants, multi-step procedures involving solvent exchange, and gel washing. Instead, the reaction occurs under mild conditions, streamlining the composite aerogels fabrication process.

Exploration of the advanced preparation nurse-mother role in care of children with chronic disease: A narrative inquiry.

AIM: To explore the lived experience of advanced preparation nurses (APNs) who are mothers (APN-mothers) as they seek care in the Emergency Department for a child with a chronic disease. DESIGN: Qualitative, Narrative Inquiry. METHODS: Narrative Inquiry was used to examine critical self-reflections of four (n = 4) APN-mothers. Directed by a question guide, participants engaged in the Narrative Reflective Process through metaphoric and artistic means. RESULTS: Participants identified salient challenges associated with their experiences. Narrative threads that emerged include feelings around being discovered, unfair expectations by healthcare providers, feelings of guilt and the tension from competing roles: APN and mother. CONCLUSION: APN-mothers represent a unique population with enhanced knowledge, skills and judgement; however, they indicate that there is insufficient communication and interprofessional collaboration between parents and Emergency Department staff. Further research is needed to foster and improve therapeutic relationships between APN-mothers and healthcare providers. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Findings can inform the development of family centred care guidelines for healthcare professional parents and their children. IMPACT: This study explores the experiences of an understudied population. This research will impact APN-mothers, healthcare professionals in the Emergency Department as well as nursing students and researchers. REPORTING METHOD: EQUATOR guidelines and SRQR reporting method used. PATIENT OR PUBLIC CONTRIBUTION: APN-mothers, caregivers and support persons of children with chronic disease enacted investigator-participant roles and were involved in each step of the study process. In addition, some patients (participants' children with chronic diseases) were included in data collected.

The detection and prediction of surgical site infections using multi-modal sensors and machine learning: Results in an animal model.

Introduction: Surgical Site Infection (SSI) is a common healthcare-associated infection that imposes a considerable clinical and economic burden on healthcare systems. Advances in wearable sensors and digital technologies have unlocked the potential for the early detection and diagnosis of SSI, which can help reduce this healthcare burden and lower SSI-associated mortality rates. Methods: In this study, we evaluated the ability of a multi-modal bio-signal system to predict current and developing superficial incisional infection in a porcine model infected with Methicillin Susceptible Staphylococcus Aureus (MSSA) using a bagged, stacked, and balanced ensemble logistic regression machine learning model. Results: Results demonstrated that the expression levels of individual biomarkers (i.e., peri-wound tissue oxygen saturation, temperature, and bioimpedance) differed between non-infected and infected wounds across the study period, with cross-correlation analysis indicating that a change in bio-signal expression occurred 24 to 31 hours before this change was reflected by clinical wound scoring methods employed by trained veterinarians. Moreover, the multi-modal ensemble model indicated acceptable discriminability to detect the presence of a current superficial incisional SSI (AUC = 0.77), to predict an SSI 24 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.80), and to predict an SSI 48 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.74). Discussion: In sum, the results of the current study indicate that non-invasive multi-modal sensor and signal analysis systems have the potential to detect and predict superficial incisional SSIs in porcine subjects under experimental conditions.

Conceptualization of Biomimicry in Engineering Context among Undergraduate and High School Students: An International Interdisciplinary Exploration.

Biomimicry is an interdisciplinary design approach that provides solutions to engineering problems by taking inspiration from nature. Given the established importance of biomimicry for building a sustainable world, there is a need to develop effective curricula on this topic. In this study, a workshop was conducted twice in Singapore: once with 14 students from a local high school in Singapore, and once with 11 undergraduate students in engineering from the United States. The workshop aimed to better understand how students conceptualize biomimicry following the bottom-up and top-down biomimetic methods. The workshop contained a lecture and laboratory session, and data were collected via questionnaires, field observation, and participant presentations at the end of the laboratory session. A qualitative analysis revealed that the top-down biomimetic approach was initially understood using vague and generic terms. In contrast, the students described the bottom-up approach using precise and technical vocabulary. By naming the themes highlighting the students' conceptualizations, it was concluded that strengthening the principle that makes the natural object unique and increasing interdisciplinary knowledge are needed to help them perform the top-down approach. The results from this work should be confirmed with a more significant number of participants, and they could help develop a curriculum to teach the two approaches effectively by providing tools to help the students generalize their ideas and abstract meaning from systems.

Challenges encountered by pharmacy staff in using prescription medication labels during medication counselling with older adults and solutions employed: A mixed-methods study.

Background: Prescription medication labels (PMLs) predominantly dispensed in English, are an important adjunct to medication counselling. PMLs are routinely used by pharmacy staff to counsel older adults about their medications. This study sought to identify challenges that pharmacy staff observe older adults face in using their PMLs, and to identify and quantify solutions employed by pharmacy staff during medication counselling to address such challenges. Methods: Ten in-depth interviews were done with primary care pharmacy staff to gather the range of challenges and solutions. Subsequently, a quantitative survey, informed by the qualitative findings, was administered to 121 pharmacy staff to assess if the reported solutions were commonly used. Results: The two main challenges were incongruity between PML language (English) and older adults' language proficiency, and poor PML legibility. The solutions, classified under three themes, were simplifying medication information on PMLs, supplementing PMLs with additional medication information and mitigating poor readability. Conclusions: Pharmacy staff observed challenges faced by older adults in using PMLs during medication counselling. Ad-hoc improvisations by pharmacy staff to PMLs were pervasive. System-level PML improvements, such as provision of legible bilingual medication instructions, pharmaceutical pictograms and additional medication information, through patient information leaflets or using quick response (QR) codes on PMLs, should be considered. This will facilitate patient-provider communication, especially in settings with language dissonance between PMLs and patients.

RhoA signaling increases mitophagy and protects cardiomyocytes against ischemia by stabilizing PINK1 protein and recruiting Parkin to mitochondria.

Mitophagy, a mitochondria-specific form of autophagy, removes dysfunctional mitochondria and is hence an essential process contributing to mitochondrial quality control. PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin are critical molecules involved in stress-induced mitophagy, but the intracellular signaling mechanisms by which this pathway is regulated are unclear. We tested the hypothesis that signaling through RhoA, a small GTPase, induces mitophagy via modulation of the PINK1/Parkin pathway as a protective mechanism against ischemic stress. We demonstrate that expression of constitutively active RhoA as well as sphingosine-1-phosphate induced activation of endogenous RhoA in cardiomyocytes result in an accumulation of PINK1 at mitochondria. This is accompanied by translocation of Parkin to mitochondria and ubiquitination of mitochondrial proteins leading to recognition of mitochondria by autophagosomes and their lysosomal degradation. Expression of RhoA in cardiomyocytes confers protection against ischemia, and this cardioprotection is attenuated by siRNA-mediated PINK1 knockdown. In vivo myocardial infarction elicits increases in mitochondrial PINK1, Parkin, and ubiquitinated mitochondrial proteins. AAV9-mediated RhoA expression potentiates these responses and a concurrent decrease in infarct size is observed. Interestingly, induction of mitochondrial PINK1 accumulation in response to RhoA signaling is neither mediated through its transcriptional upregulation nor dependent on depolarization of the mitochondrial membrane, the canonical mechanism for PINK1 accumulation. Instead, our results reveal that RhoA signaling inhibits PINK1 cleavage, thereby stabilizing PINK1 protein at mitochondria. We further show that active RhoA localizes at mitochondria and interacts with PINK1, and that the mitochondrial localization of RhoA is regulated by its downstream effector protein kinase D. These findings demonstrate that RhoA activation engages a unique mechanism to regulate PINK1 accumulation, induce mitophagy and protect against ischemic stress, and implicates regulation of RhoA signaling as a potential strategy to enhance mitophagy and confer protection under stress conditions.

Validation of pharmaceutical pictograms among older adults with limited English proficiency.

OBJECTIVE: Pictograms on prescription medication labels enhance medication literacy and medication adherence. However, pictograms need to be contextually validated. We assessed the validity of 52 International Pharmaceutical Federation pictograms among 250 older Singaporeans with limited English proficiency. METHODS: Participants were randomly assigned 11 pictograms each. For each pictogram, participants were first asked its intended meaning. Then, they were told the intended meaning and asked to rate how well the pictogram represented the meaning, on a scale of 1-7. Pictograms were classified as valid (≥66% participants assigned the pictogram interpreted its intended meaning correctly [transparency criterion] and ≥85% participants rated its representativeness as ≥5 [translucency criterion]), partially valid (only transparency criterion was fulfilled) or not valid. Open-ended questions gathered feedback to improve pictograms. RESULTS: 14 pictograms (26.9%) achieved validity and 6 pictograms (11.5%) achieved partial validity. A greater proportion of pictograms for dose and route of administration, and dosage frequency achieved validity or partial validity versus those depicting precautions, indications or side effects. CONCLUSION: Majority (61.5%) of the assessed pictograms did not achieve validity or partial validity, highlighting the importance of contextual validation. PRACTICE IMPLICATIONS: Low pictogram comprehension emphasizes the importance of facilitating pictogram understanding during medication counseling.

Integrating case-finding and initial management for osteoarthritis, anxiety, and depression into primary care long-term condition reviews: results from the ENHANCE pilot trial.

BACKGROUND: Multimorbidity is increasingly the norm; however, primary care remains focused on single diseases. Osteoarthritis, anxiety, and depression are frequently comorbid with other long-term conditions (LTCs), but rarely prioritized by clinicians. OBJECTIVES: To test the feasibility of a randomized controlled trial (RCT) of an intervention integrating case-finding and management for osteoarthritis, anxiety, and depression within LTC reviews. METHODS: A pilot stepped-wedge RCT across 4 general practices recruited patients aged ≥45 years attending routine LTC reviews. General practice nurses provided usual LTC reviews (control period), then, following training, delivered the ENHANCE LTC review (intervention period). Questionnaires, an ENHANCE EMIS-embedded template and consultation audio-recordings, were used in the evaluation. RESULTS: General practice recruitment and training attendance reached prespecified success criteria. Three hundred and eighteen of 466 (68%) of patients invited responded; however, more patients were recruited during the control period (206 control, 112 intervention). Eighty-two percent and 78% returned their 6-week and 6-month questionnaires, respectively. Integration of the ENHANCE LTC review into routine LTC reviews varied. Case-finding questions were generally used as intended for joint pain, but to a lesser extent for anxiety and depression. Initial management through referrals and signposting were lacking, and advice was more frequently provided for joint pain. The stepped-wedge design meant timing of the training was challenging and yielded differential recruitment. CONCLUSION: This pilot trial suggests that it is feasible to deliver a fully powered trial in primary care. Areas to optimize include improving the training and reconsidering the stepped-wedge design and the approach to recruitment by targeting those with greatest need. TRIAL REGISTRATION: ISRCTN registry (ISRCTN: 12154418). Date registered: 6 August 15. Date first participant was enrolled: 13 July 2015. https://www.isrctn.com/ISRCTN12154418?q=depression%20schizophrenia&filters=conditionCategory:Not%20Applicable&sort=&offset=5&totalResults=9&page=1&pageSize=20&searchType=basic-search.

Lentivirus-Mediated Expression of Human Secreted Amyloid Precursor Protein-Alpha Promotes Long-Term Induction of Neuroprotective Genes and Pathways in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-ß toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer's disease (AD), we demonstrated that long-term overexpression of human sAPPα (for 8 months) in a mouse model of amyloidosis (APP/PS1) could prevent the behavioral and electrophysiological deficits that develop in these mice. OBJECTIVE: To explore the underlying molecular mechanisms responsible for the significant physiological and behavioral improvements observed in sAPPα-treated APP/PS1 mice. METHODS: We assessed the long-term effects on the hippocampal transcriptome following continuous lentiviral delivery of sAPPα or empty-vector to male APP/PS1 mice and wild-type controls using Affymetrix Mouse Transcriptome Assays. Data analysis was carried out within the Affymetrix Transcriptome Analysis Console and an integrated analysis of the resulting transcriptomic data was performed with Ingenuity Pathway analysis (IPA). RESULTS: Mouse transcriptome assays revealed expected AD-associated gene expression changes in empty-vector APP/PS1 mice, providing validation of the assays used for the analysis. By contrast, there were specific sAPPα-associated gene expression profiles which included increases in key neuroprotective genes such as Decorin, betaine-GABA transporter and protocadherin beta-5, subsequently validated by qRT-PCR. An integrated biological pathways analysis highlighted regulation of GABA receptor signaling, cell survival and inflammatory responses. Furthermore, upstream gene regulatory analysis implicated sAPPα activation of Interleukin-4, which can counteract inflammatory changes in AD. CONCLUSION: This study identified key molecular processes that likely underpin the long-term neuroprotective and therapeutic effects of increasing sAPPα levels in vivo.

Dissociation of mitochondrial HK-II elicits mitophagy and confers cardioprotection against ischemia.

Preservation of mitochondrial integrity is critical for maintaining cellular homeostasis. Mitophagy is a mitochondria-specific type of autophagy which eliminates damaged mitochondria thereby contributing to mitochondrial quality control. Depolarization of the mitochondrial membrane potential is an established mechanism for inducing mitophagy, mediated through PINK1 stabilization and Parkin recruitment to mitochondria. Hexokinase-II (HK-II) which catalyzes the first step in glucose metabolism, also functions as a signaling molecule to regulate cell survival, and a significant fraction of cellular HK-II is associated with mitochondria (mitoHK-II). We demonstrate here that pharmacological interventions and adenoviral expression of a mitoHK-II dissociating peptide which reduce mitoHK-II levels lead to robust increases in mitochondrial Parkin and ubiquitination of mitochondrial proteins in cardiomyocytes and in a human glioblastoma cell line 1321N1, independent of mitochondrial membrane depolarization or PINK1 accumulation. MitoHK-II dissociation-induced mitophagy was demonstrated using Mito-Keima in cardiomyocytes and in 1321N1 cells. Subjecting cardiomyocytes or the in vivo heart to ischemia leads to modest dissociation of mitoHK-II. This response is potentiated by expression of the mitoHK-II dissociating peptide, which increases Parkin recruitment to mitochondria and, importantly, provides cardioprotection against ischemic stress. These results suggest that mitoHK-II dissociation is a physiologically relevant cellular event that is induced by ischemic stress, the enhancement of which protects against ischemic damage. The mechanism which underlies the effects of mitoHK-II dissociation can be attributed to the ability of Bcl2-associated athanogene 5 (BAG5), an inhibitor of Parkin, to localize to mitochondria and form a molecular complex with HK-II. Overexpression of BAG5 attenuates while knockdown of BAG5 sensitizes the effect of mitoHK-II dissociation on mitophagy. We suggest that HK-II, a glycolytic molecule, can function as a sensor for metabolic derangements at mitochondria to trigger mitophagy, and modulating the intracellular localization of HK-II could be a novel way of regulating mitophagy to prevent cell death induced by ischemic stress.

Development and validation of prediction models to estimate risk of primary total hip and knee replacements using data from the UK: two prospective open cohorts using the UK Clinical Practice Research Datalink.

OBJECTIVES: The ability to efficiently and accurately predict future risk of primary total hip and knee replacement (THR/TKR) in earlier stages of osteoarthritis (OA) has potentially important applications. We aimed to develop and validate two models to estimate an individual's risk of primary THR and TKR in patients newly presenting to primary care. METHODS: We identified two cohorts of patients aged ≥40 years newly consulting hip pain/OA and knee pain/OA in the Clinical Practice Research Datalink. Candidate predictors were identified by systematic review, novel hypothesis-free 'Record-Wide Association Study' with replication, and panel consensus. Cox proportional hazards models accounting for competing risk of death were applied to derive risk algorithms for THR and TKR. Internal-external cross-validation (IECV) was then applied over geographical regions to validate two models. RESULTS: 45 predictors for THR and 53 for TKR were identified, reviewed and selected by the panel. 301 052 and 416 030 patients newly consulting between 1992 and 2015 were identified in the hip and knee cohorts, respectively (median follow-up 6 years). The resultant model C-statistics is 0.73 (0.72, 0.73) and 0.79 (0.78, 0.79) for THR (with 20 predictors) and TKR model (with 24 predictors), respectively. The IECV C-statistics ranged between 0.70-0.74 (THR model) and 0.76-0.82 (TKR model); the IECV calibration slope ranged between 0.93-1.07 (THR model) and 0.92-1.12 (TKR model). CONCLUSIONS: Two prediction models with good discrimination and calibration that estimate individuals' risk of THR and TKR have been developed and validated in large-scale, nationally representative data, and are readily automated in electronic patient records.

Simultaneous Phrenic and Intercostal Nerves Transfer for Elbow Flexion and Extension in Total Brachial Plexus Root Avulsion Injury.

BACKGROUND: To report the results of restoring the elbow flexion and extension in patients with total brachial root avulsion injuries by simultaneous transfer of the phrenic nerve to the nerve to the biceps and three intercostal nerves to the nerve of the long head of the triceps. METHODS: Ten patients with total brachial root avulsion injuries underwent the spinal accessory nerve transfer to the suprascapular nerve for shoulder reconstruction. Simultaneous transfer of the phrenic nerve to the nerve to the biceps via the sural nerve graft and three intercostal nerves to the nerve of the long head of the triceps was done for restoration of the elbow flexion and extension. Trunk flexion exercise program was used for all patients postoperatively. The mean follow up period was 36 months. RESULTS: For elbow flexion, there were two M4, seven M3, and one M1. For elbow extension, there were three M4, four M3, two M2, and one M1. No patient demonstrated a respiratory problem clinically postoperatively. The average FVC% decreased to 61% of the predicted value at 24 months after surgery. CONCLUSIONS: The simultaneous nerve transfer using the phrenic nerve to the nerve to the biceps and 3 intercostal nerves to the nerve of the long head of the triceps with postoperative trunk flexion exercise provide a comparable result for restoration of elbow function in total brachial plexus root avulsion injury. The patients who appear to have a respiratory problem and are unable to comply with the post-operative respiratory muscles training should be contraindicated for this simultaneous transfer.

RhoA regulates Drp1 mediated mitochondrial fission through ROCK to protect cardiomyocytes.

Cardiac ischemia/reperfusion, loss of blood flow and its subsequent restoration, causes damage to the heart. Oxidative stress from ischemia/reperfusion leads to dysfunction and death of cardiomyocytes, increasing the risk of progression to heart failure. Alterations in mitochondrial dynamics, in particular mitochondrial fission, have been suggested to play a role in cardioprotection from oxidative stress. We tested the hypothesis that activation of RhoA regulates mitochondrial fission in cardiomyocytes. Our studies show that expression of constitutively active RhoA in cardiomyocytes increases phosphorylation of Dynamin-related protein 1 (Drp1) at serine-616, and leads to localization of Drp1 at mitochondria. Both responses are blocked by inhibition of Rho-associated Protein Kinase (ROCK). Endogenous RhoA activation by the GPCR agonist sphingosine-1-phosphate (S1P) also increases Drp1 phosphorylation and its mitochondrial translocation in a RhoA and ROCK dependent manner. Consistent with the role of mitochondrial Drp1 in fission, RhoA activation in cardiomyocytes leads to formation of smaller mitochondria and this is attenuated by inhibition of ROCK, by siRNA knockdown of Drp1 or by expression of a phosphorylation-deficient Drp1 S616A mutant. In addition, activation of RhoA prevents cell death in cardiomyocytes challenged by oxidative stress and this protection is blocked by siRNA knockdown of Drp1 or by Drp1 S616A expression. Taken together our findings demonstrate that RhoA activation can regulate Drp1 to induce mitochondrial fission and subsequent cellular protection, implicating regulation of fission as a novel mechanism contributing to RhoA-mediated cardioprotection.

Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease driven in large part by accumulated deposits in the brain of the amyloid precursor protein (APP) cleavage product amyloid-ß peptide (Aß). However, AD is also characterised by reductions in secreted amyloid precursor protein-alpha (sAPPα), an alternative cleavage product of APP. In contrast to the neurotoxicity of accumulated Αß, sAPPα has many neuroprotective and neurotrophic properties. Increasing sAPPα levels has the potential to serve as a therapeutic treatment that mitigates the effects of Aß and rescue cognitive function. Here we tested the hypothesis that lentivirus-mediated expression of a human sAPPα construct in a mouse model of AD (APPswe/PS1dE9), begun before the onset of plaque pathology, could prevent later behavioural and electrophysiological deficits. Male mice were given bilateral intra-hippocampal injections at 4 months of age and tested 8-10 months later. Transgenic mice expressing sAPPα performed significantly better than untreated littermates in all aspects of the spatial water maze task. Expression of sAPPα also resulted in partial rescue of long-term potentiation (LTP), tested in vitro. These improvements occurred in the absence of changes in amyloid pathology. Supporting these findings on LTP, lentiviral-mediated expression of sAPPα for 3 months from 10 months of age, or acute sAPPα treatment in hippocampal slices from 18 to 20 months old transgenic mice, completely reversed the deficits in LTP. Together these findings suggest that sAPPα has wide potential to act as either a preventative or restorative therapeutic treatment in AD by mitigating the effects of Aß toxicity and enhancing cognitive reserve.

Treatment preferences for decompression illness amongst Singapore dive physicians.

INTRODUCTION: Owing to the scarcity of randomized controlled trials to guide treatment for decompression illness (DCI), there are many unanswered questions about its management. Apart from reviews and expert opinion, surveys that report practice patterns provide information about useful management strategies. Hence, this study aimed to identify current treatment preferences for DCI amongst diving physicians in Singapore. METHODS: An anonymous web-based questionnaire was sent to known diving physicians in Singapore. The demographics of the respondents were captured. Respondents were asked about their preferred management for five different DCI scenarios. RESULTS: The response rate was 74% (17 of 23 responses). All respondents chose to recompress patients described in the five scenarios. Regarding the number of recompression sessions, "one additional session after no further improvement in signs and symptoms" was the most common end point of treatment across all the scenarios (47 of 85 responses). Analgesics would be used by five physicians, three would use lidocaine and two steroids as adjuvant therapies. CONCLUSIONS: Apart from the general agreement that recompression is indicated for DCI, there was no strong consensus regarding other aspects of management. This survey reinforces the need for robust RCTs to validate the existing recommendations for DCI treatment.

Relation of Lateral Antebrachial Cutaneous Nerve to the Volar Approach to Distal Radius.

BACKGROUND: The anatomy of the lateral antebrachial cutaneous nerve (LABCN) in relation to volar approaches to the distal radius is not well visited. With the increasing popularity of distal radius fracture fixation with volar locking plates, it is prudent to study the innervation pattern of the LABCN to minimize the risk of nerve injury. METHODS: Ten cadaveric distal radial forearms were dissected to study the relationship between the LABCN, flexor carpi radialis (FCR), superficial branch of radial nerve (SBRN), and scaphoid tubercle (ST). RESULTS: The LABCN coursed closer to the FCR than the SBRN, with branches traversing the tendon in two specimens. The LABCN was also noted to be intimately related to the radial artery, with an average distance of the LABCN from the lateral border of FCR was 6.4mm distally and 9.6mm proximally. CONCLUSIONS: There is a sparsely innervated corridor between the radial border of the FCR and terminal branches of the LABCN that provides safe access for volar approach to the distal radius.

Nutrient-sensing mTORC1: Integration of metabolic and autophagic signals.

The ability of adult cardiomyocytes to regenerate is limited, and irreversible loss by cell death plays a crucial role in heart diseases. Autophagy is an evolutionarily conserved cellular catabolic process through which long-lived proteins and damaged organelles are targeted for lysosomal degradation. Autophagy is important in cardiac homeostasis and can serve as a protective mechanism by providing an energy source, especially in the face of sustained starvation. Cellular metabolism is closely associated with cell survival, and recent evidence suggests that metabolic and autophagic signaling pathways exhibit a high degree of crosstalk and are functionally interdependent. In this review, we discuss recent progress in our understanding of regulation of autophagy and its crosstalk with metabolic signaling, with a focus on the nutrient-sensing mTOR complex 1 (mTORC1) pathway.

The triple whammy anxiety depression and osteoarthritis in long-term conditions.

Improving the management of people with long-term conditions is a key priority of the UK National Health Service. Whilst the coexistence of two or more long-term conditions in one person is increasingly the norm in primary care, guidelines and delivery of care remain focused on single disease management.Anxiety, depression and osteoarthritis are frequently comorbid with other long-term conditions and with each other, with up to 70 % of people with anxiety and depression also suffering from chronic pain. The relationships between anxiety, depression and pain are reciprocal, with each predicting and worsening the outcome of the others. Where these conditions occur in the context of other long-term conditions, further reduction in health-related quality of life and poorer clinical outcomes for all comorbid conditions is observed. It therefore follows that optimising the management of one comorbid condition should confer benefit to the other/s. Yet despite this, anxiety, depression and chronic pain are seldom prioritised by either patient or clinician, therefore remaining under-recognised and under-treated.Case-finding aims to identify and offer timely treatment to individuals with a given disease in a population at risk, therefore offering one possible solution. Yet case-finding is not without its problems, with well-recognised barriers including lack of time, cultural difficulties and inadequate resources and practitioner skills. So whilst the merits of why to actively seek these conditions is clear, how this may be best achieved is not. We explore the potential role of case-finding for anxiety, depression and osteoarthritis-related joint pain in individuals with comorbid long-term conditions, assessing whether adopting an integrated approach to care may allow opportunistic case-finding therefore promoting identification and timely management of these deleterious conditions.

Risk of Major Abdominal Surgery in an Asian Population-based Crohn's Disease Cohort.

BACKGROUND: Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. METHODS: This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. RESULTS: The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). CONCLUSIONS: Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection.

Hexokinases (HKs) catalyze the first step of glucose metabolism, phosphorylating glucose to glucose 6-phosphate (G6P). HK2/hexokinase-II is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues and is also upregulated in many types of tumors associated with enhanced aerobic glycolysis (the Warburg effect). Accumulating evidence indicates that HK2 plays an important role not only in glycolysis but also in cell survival. Although there is increasing recognition that cellular metabolism and cell survival are closely related, the molecular link between metabolism and autophagic pathways has not been fully elucidated. We recently discovered that HK2 facilitates autophagy in response to glucose deprivation (HK substrate deprivation) to protect cardiomyocytes, and suggest that HK2 functions as a molecular switch from glycolysis to autophagy to ensure cellular energy homeostasis under starvation conditions.