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ABSTRACT IMPACT: Our data demonstrate that VC2 oncolytic virotherapy has significant clinical potential. OBJECTIVES/GOALS: Use our novel oncolytic herpes simplex virus type I (HSV-1), VC2, to understand how oncolytic virotherapy affects the immunosuppressive tumor microenvironment as a mechanism of efficacy. METHODS/STUDY POPULATION: We tested the efficacy of VC2 as an oncolytic virotherapy (OVT) in a syngeneic B16F10-derived mouse model of melanoma. We modified the B16F10 to express nectin-1 (B16F10n-1), the major receptor for HSV-1. Engrafted B16F10n-1 tumors were intratumorally treated with either phosphate-buffered saline (PBS) or 1x10^6 pfu VC2. At indicated time points, treated tumors were excised and processed for immunohistochemistry or flow cytometry analysis. For our experimental metastasis studies, mice were intravenously challenged with B16F10n-1 cells. For our depletion studies, CD4+ and CD8+ T cells were depleted in mice by treatment with mouse anti-CD4 and anti-CD8 monoclonal antibodies respectively, while the control mice were given Rat IgG2b isotype. RESULTS/ANTICIPATED RESULTS: We found that VC2 slowed tumor growth rates and significantly enhanced survival times over control treated mice. VC2-treated mice that survived initial tumor engraftment were able to reject a second tumor challenge and were also resistant to lung colonization (experimental metastasis) of tumor cells. Furthermore, VC2 treatment promoted increased intratumoral T cell infiltration and induced a strong antitumor effect that decreased growth rates of distant, untreated tumors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our data demonstrate that VC2 OVT has significant clinical potential. Furthermore, due to the increased survival rates and CD8+ T cells dependence, our model will enable study of the immunological correlates of protection for VC2 OVT and OVT in general, as well as to inform the rational design of future OVs with improved therapeutic potentials.

Background: A quarter of people with diabetes develop foot ulcer in their lifetime and are six times more likely to require a major lower limb amputation compared to the general population. Risk stratification tools can reliably identify those at the highest risk of ulceration, but it remains unclear if screening for foot complications can prevent limb loss in people with diabetes., Aims: The aim of this systematic review was to determine whether population-based foot screening in people with diabetes reduces lower limb complications as assessed by development of foot ulceration, minor and major lower limb amputations, hospitalisation, or death., Methods: MEDLINE, Embase, Emcare and CINAHL databases were searched to identify randomised and non-randomised controlled trials and observational studies (cohort, case-control and cross-sectional surveys). The screening process, study quality assessment and data extraction were performed by two independent reviewers., Results: Following abstract screening and assessment for eligibility, five out of 10,771 identified studies were included in the analysis. Of these studies, one demonstrated 24 % reduction in development of new ulceration following introduction of screening. Major amputations decreased by between 17 and 96 % in three studies. Hospitalisation rates were contradictory, with one study showing doubling in hospital admissions and another one reduction by 33 %. One study demonstrated no impact of screening on minor or major amputation rates. None of the studies addressed the effect of foot screening on all-cause mortality., Conclusions: The number and quality of studies to support population-based foot screening to prevent lower limb complications in people with diabetes is low. Current evidence suggests variable impact of screening on important clinical outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Obstructive sleep apnoea (OSA) is highly prevalent in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The gold standard treatment for OSA is continuous positive airway pressure (CPAP). Long-term, well-powered efficacy trials are required to understand whether CPAP could slow cognitive decline in individuals with MCI/AD, but its tolerability in this group remains uncertain. The present review investigates CPAP adherence among individuals with OSA and MCI/AD. Electronic searches were performed on 8 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Six independent studies and four secondary analyses included 278 unique participants (mean age = 72.1 years). In five of the retained studies, around half of participants (45% N = 85 MCI, 56% N = 22 AD) were adherent to CPAP, where ≥4 h use per night was considered adherent. Three of the retained studies also reported average CPAP use to range between 3.2 and 6.3 h/night. CPAP adherence in individuals with MCI and AD is low, albeit similar to the general elderly population. Reporting adherence in future studies as both average duration as well as using a binary cut-off would improve our understanding of the optimum CPAP use in dementia clinical trials and care., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tobacco smoking is associated with a substantially increased risk of postoperative complications. The peri-operative period offers a unique opportunity to support patients to stop tobacco smoking, avoid complications and improve long-term health. This systematic review provides an up-to-date summary of the evidence for tobacco cessation interventions in surgical patients. We conducted a systematic search of randomised controlled trials of tobacco cessation interventions in the peri-operative period. Quantitative synthesis of the abstinence outcomes data was by random-effects meta-analysis. The primary outcome of the meta-analysis was abstinence at the time of surgery, and the secondary outcome was abstinence at 12 months. Thirty-eight studies are included in the review (7310 randomised participants) and 26 studies are included in the meta-analysis (5969 randomised participants). Studies were pooled for subgroup analysis in two ways: by the timing of intervention delivery within the peri-operative period and by the intensity of the intervention protocol. We judged the quality of evidence as moderate, reflecting the degree of heterogeneity and the high risk of bias. Overall, peri-operative tobacco cessation interventions increased successful abstinence both at the time of surgery, risk ratio (95%CI) 1.48 (1.20-1.83), number needed to treat 7; and 12 months after surgery, risk ratio (95%CI) 1.62 (1.29-2.03), number needed to treat 9. More work is needed to inform the design and optimal delivery of interventions that are acceptable to patients and that can be incorporated into contemporary elective and urgent surgical pathways. Future trials should use standardised outcome measures., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Lower back pain is an extremely common medical issue in populations worldwide. One of the main contributors to lower back pain is intervertebral disc (IVD) degeneration. An ideal animal model of IVD degeneration is essential to study the pathophysiology of lower back pain and investigate potential therapeutic strategies. Rabbit models are reliable, economical, and easily established animal models. The retroperitoneal approach has been widely used to induce IVD degeneration in rabbit models. However, there are reported complications associated with this technique, such as the avulsion of segmental arteries and nerve root injury. In this paper, we aim to show a surgical protocol using needle puncture to establish rabbit lumbar disc degeneration via a transabdominal approach. Consequently, radiological checks and histological analyses indicated that lumbar disc degeneration was successfully established in rabbits. This surgical protocol presents the precise location of target discs and high reproducibility of IVD degeneration models with fewer complications.

In the context of an ageing population, the demographic sands of trauma are shifting. Increasingly, trauma units are serving older adults who have sustained injuries in low-energy falls from a standing height. Older age is commonly associated with changes in physiology, as well as an increased prevalence of frailty and multimorbidity, including cardiac, renal and liver disease. These factors can complicate the safe and effective administration of analgesia in the older trauma patient. Trauma services therefore need to adapt to meet this demographic shift and ensure that trauma clinicians are sufficiently skilled in treating pain in complex older people. This article is dedicated to the management of acute trauma pain in older adults. It aims to highlight the notable clinical challenges of managing older trauma patients compared with their younger counterparts. It offers an overview of the evidence and practical opinion on the merits and drawbacks of commonly used analgesics, as well as more novel and emerging analgesic adjuncts. A search of Medline (Ovid, from inception to 7 November 2022) was conducted by a medical librarian to identify relevant articles using keyword and subject heading terms for trauma, pain, older adults and analgesics. Results were limited to articles published in the last 10 years and English language. Relevant articles' references were hand-screened to identify other relevant articles. There is paucity of dedicated high-quality evidence to guide management of trauma-related pain in older adults. Ageing-related changes in physiology, the accumulation of multimorbidity, frailty and the risk of inducing delirium secondary to analgesic medication present a suite of challenges in the older trauma patient. An important nuance of treating pain in older trauma patients is the challenge of balancing iatrogenic adverse effects of analgesia against the harms of undertreated pain, the complications and consequences of which include immobility, pneumonia, sarcopenia, pressure ulcers, long-term functional decline, increased long-term care needs and mortality. In this article, the role of non-opioid agents including short-course non-steroidal anti-inflammatory drugs (NSAIDs) is discussed. Opioid selection and dosing are reviewed for older adults suffering from acute trauma pain in the context of kidney and liver disease. The evidence base and limitations of other adjuncts such as topical and intravenous lidocaine, ketamine and regional anaesthesia in acute geriatric trauma are discussed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Tobacco smoking is associated with a substantially increased risk of perioperative complications. The perioperative period is an opportunity to introduce tobacco-cessation strategies. A previous systematic review provided evidence that perioperative interventions increase short-term abstinence and may reduce postoperative complications. The evidence base has since expanded, with the subsequent publication of numerous randomised studies. This protocol outlines a systematic review examining the impact of perioperative tobacco-cessation interventions on successful abstinence from tobacco smoking, and on the incidence of perioperative complications., Methods and Analysis: A systematic search of the literature will be run across EMBASE (Ovid), MEDLINE (Ovid), CINAHL (Ebsco) and PsycInfo (ProQuest), from inception to present, using text words and subject headings. Randomised controlled trials published in English, examining adults in the perioperative period and reporting the outcomes from tobacco-cessation interventions will be included.Abstract screening and data extraction will be performed by five reviewers. Each abstract will be screened by two blinded reviewers, with discrepancies resolved by group consensus. The primary outcome will be point prevalence abstinence from tobacco-use at the time of surgery. Secondary outcomes are prolonged abstinence from tobacco use at 6 months and 12 months, and postoperative complications. Any other reported outcomes will be documented in the descriptive analysis. The review will also describe details of the investigated perioperative tobacco-cessation interventions. If sufficient studies report relevant data, meta-analysis of the primary and secondary outcomes will be undertaken. Results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement., Ethics and Dissemination: No ethical approval is required. Results will be disseminated by open-access, peer-reviewed journal publication and conference presentations. Results will underpin future work to modify perioperative tobacco-cessation interventions to enhance engagement and accessibility, and to develop trials aiming to facilitate abstinence from tobacco-use in patients presenting for surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Smart materials that are energy efficient and take up less space are crucial in the development of new technologies. Electrochromic polymers (ECPs) are one such class of materials that actively change their optical behavior in both visible and infrared parts of the electromagnetic spectrum. They show promise in a wide range of applications, from active camouflage to smart displays/windows. The full capabilities of ECPs are still yet to be explored, for while their electrochromic properties are well established, their Infrared (IR) modulation is less reported on. This study addresses the potential of ECPs in active IR modulating devices by optimization of Vapor Phase Polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) thin films via the substitution of its dopant anion. Dynamic ranges denoting emissivity changes between reduced and oxidized states of PEDOT are found across dopants of tosylate, bromide, sulfate, chloride, perchlorate, and nitrate. Relative to the emissivity of reduced (neutral) PEDOT, a range of ±15% is achieved from the doped PEDOT films, and a maximum dynamic range of 0.11 across a 34% change is recorded for PEDOT doped with perchlorate., (© 2023 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Cervical spondylotic myelopathy (CSM) is a common disease resulting from intervertebral disc herniation, ossification of the posterior longitudinal ligament, and other pathological changes that cause spinal cord compression. CSM progresses insidiously with mild upper-limb numbness, which patients tend to ignore. As the condition worsens, the patients may experience a limp, limited fine motor activity, and eventually, a loss of daily activity. Conservative treatments, such as physical therapy and medication, are frequently ineffective for CSM. Once surgery is deemed to be required, decompression surgery is the best option. So far, both anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) have been commonly used to treat CSM. In addition, a type of hybrid procedure that combines ACDF with ACCF has been used to treat some CSM cases and achieved satisfying results. Thus, this study aims to introduce this hybrid surgical technique and advocate for it based on its patient success.

Low back pain is the leading cause of disability, producing a substantial socio-economic burden on healthcare systems worldwide. Intervertebral disc (IVD) degeneration is a primary cause of lower back pain, and while regenerative therapies aimed at full functional recovery of the disc have been developed in recent years, no commercially available, approved devices or therapies for the regeneration of the IVD currently exist. In the development of these new approaches, numerous models for mechanical stimulation and preclinical assessment, including in vitro cell studies using microfluidics, ex vivo organ studies coupled with bioreactors and mechanical testing rigs, and in vivo testing in a variety of large and small animals, have emerged. These approaches have provided different capabilities, certainly improving the preclinical evaluation of these regenerative therapies, but challenges within the research environment, and compromises relating to non-representative mechanical stimulation and unrealistic test conditions, remain to be resolved. In this review, insights into the ideal characteristics of a disc model for the testing of IVD regenerative approaches are first assessed. Key learnings from in vivo , ex vivo , and in vitro IVD models under mechanical loading stimulation to date are presented alongside the merits and limitations of each model based on the physiological resemblance to the human IVD environment (biological and mechanical) as well as the possible feedback and output measurements for each approach. When moving from simplified in vitro models to ex vivo and in vivo approaches, the complexity increases resulting in less controllable models but providing a better representation of the physiological environment. Although cost, time, and ethical constraints are dependent on each approach, they escalate with the model complexity. These constraints are discussed and weighted as part of the characteristics of each model., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Objective: The prevalence of lower limb chronic venous insufficiency (CVI) of the deep veins is increasing and presents a significant burden to patients and health care services. To improve the evaluation of interventions it is necessary to standardise their reporting. The aim of this study was to perform a systematic review of the outcomes of interventions delivered to people with CVI of the deep veins as part of the development of a novel core outcome set (COS)., Methods: Following the Core Outcome Measures in Effectiveness Trials (COMET) framework for COS development, a systematic review was conducted to PRISMA guidance. The protocol was preregistered on PROSPERO (CRD42021236795). MEDLINE, Embase, Emcare, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched from January 2018 to January 2021. Clinical trials and observational studies involving more than 20 participants, reporting outcomes for patients with CVI of the deep veins were eligible. Outcomes were extracted verbatim, condensed into agreed outcome terms and coded into domains using standard COMET taxonomy. Outcome reporting consistency, where outcomes were fully reported throughout the methods and results of their respective articles was also assessed., Results: Some 103 studies were eligible. There were 1183 verbatim outcomes extracted, spanning 22 domains. No outcome was reported unanimously, with the most widely reported outcome of primary patency featuring in 51 articles (<50%). There was a predominant focus on reporting clinical outcomes (n = 963 [81%]), with treatment durability (n = 278 [23%]) and clinical severity (n = 108 [9%]) reported frequently. Life impact outcomes were relatively under-reported (n = 60 [5%]). Outcome reporting consistency was poor, with just 50% of outcomes reported fully., Conclusions: Outcome reporting in studies of people with CVI of the deep veins is currently heterogeneous. Life impact outcomes, which likely reflect patients' priorities are under-reported. This study provides the first step in the development of a COS for people with lower limb CVI of the deep veins., (Copyright © 2022 Society for Vascular Surgery. All rights reserved.)

Lumbosacral nerve bowstring disease (LNBD) is a syndrome of neurological symptoms caused by differences in the development speed of lumbosacral bone tissue and nerve tissue, which result in a longitudinal stretch of the slow-growing nerve tissue. LNBD is usually caused by congenital factors and accompanied by other lumbosacral diseases, such as lumbar spinal stenosis, lumbar spondylolisthesis, and iatrogenic factors. The main symptoms of LNBD are lower extremity neurological symptoms and fecal dysfunction. The conservative treatment of LNBD includes rest, functional exercise, and drug therapy, but it usually fails to achieve satisfactory clinical results. Few studies have reported on the surgical treatment of LNBD. In this study, we used posterior lumbar interbody fusion (PLIF) to shorten the spine (0.6-0.8mm/segment). This reduced the axial tension of the lumbosacral nerves and relieved the patient's neurological symptoms. We report on the case of a 45 year old male patient whose main symptoms were left lower extremity pain, decreased muscle strength, and hypoesthesia. The above symptoms were significantly relieved 6 months after surgery.

Purpose: The purpose of this study is to investigate the clinical effect of posterior lumbar fusion surgery on patients who suffer from lumbar disc herniation concurrent with peroneal nerve paralysis., Methods: The patients suffering from peroneal nerve paralysis and undergoing posterior lumbar fusion surgery between January 2012 and December 2019 were retrospectively reviewed. The data of the identified patients were then collected and processed. All patients were followed up post-operatively after discharge from the hospital. The data was analyzed in terms of Oswestry disability index (ODI), visual analogue scale (VAS) score, and relative lower-limb muscle strength., Results: A total of 87 patients (52 males and 35 females) aged 54 ± 11 years met the inclusion criteria for this study. These patients stayed in hospital for 16 ± 6 days and were followed up for 81 ± 24 months. Data analysis showed that muscle strength of the tibialis anterior and extensor digitorum significantly recovered at the last follow-up with a grade of 3 (median), compared to grade 0 at admission ( p  < 0.001). Furthermore, the median VAS score decreased to 1 at the last follow-up from 6 at admission ( p  < 0.001), and the ODI greatly improved with 10% (median) at the last follow-up, while it was 58% at admission ( p  < 0.001). The ODI improvement rate was 60% on average at the last follow-up. Multivariate regression analysis regarding the ODI and muscle strength improvement rates showed that advanced age was a risk factor for postoperative recovery., Conclusions: Most of the patients suffering from lumbar disc herniation concurrent with peroneal nerve paralysis can improve after undergoing posterior lumbar fusion surgery, but few can reach full recovery. Advanced age might be a risk factor that affects the prognosis of these patients after surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gao, Li, Li, Rudd, Wang, Gao, Ding and Yang.)

Purpose: To investigate the incidence and risk factors of lumbar plexus injury (LPI) after oblique lumbar interbody fusion (OLIF) surgery., Methods: A total of 110 patients who underwent OLIF surgery between January 2017 and January 2021 were retrospectively reviewed. Patients were divided into two groups: the group with LPI (LPI group) and the group without LPI (non-LPI group). The baseline demographic data, surgical variables and radiographic parameters were compared and analyzed between these two groups., Results: Among all participants, 13 (8.5%) had LPI-related symptoms postoperatively (short-term), and 6 (5.5%) did not fully recover after one year (long-term). Statistically, there were no significant differences in the baseline demographic data, surgery duration, intraoperative blood loss, preoperative diagnosis, surgical procedures used and incision length. Compared with the non-LPI group, patients in the LPI group had a narrower OLIF channel space. In LPI group, the anterior edge of left psoas major muscle overpasses the anterior edge of surgical intervertebral disk (IVD) on axial MRI. Logistic regression analysis revealed that narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD on axial MRI were independently associated with both short-term and long-term LPI., Conclusion: Narrow OLIF channel space and the anterior edge of left psoas major muscle overpassing the anterior edge of surgical IVD are significant risk factors of OLIF surgery-related LPI. Surgeons should use preoperative imaging to adequately assess these risk factors to reduce the occurrence of LPI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Changes in sleep during mid-to-late life are associated with risk for Alzheimer's disease (AD). Mechanistic understanding of this association necessitates measurement tools able to quantify these sleep changes longitudinally and accurately. We conducted a systematic review with meta-analysis of validity studies of non-invasive sleep-measuring devices published since 2015 that record sleep metrics associated with AD in adults over 40 (mean 52.9, SD 6.1 years). We reviewed 52 studies, including 32 wearable and ten non-wearable single or multi-sensor devices validated against polysomnography (minimum one night). The apnoea hypopnoea index and oxygen desaturation index were accurately measured across devices. Total sleep time and sleep efficiency were significantly overestimated (p < 0.001) by mean 33.2 minutes and 7.6%, respectively. Slow wave sleep duration was inaccurately measured except by a headband device with electroencephalography. There was no significant difference in accuracy between participants with and without sleep disorders. Studies were undermined by high risk of bias from closed-access algorithms and classification thresholds, and incomplete reporting of accuracy data. Only one study investigated slow wave activity, and none investigated sleep spindles. Nonetheless, we have identified devices that could be used in future studies of sleep and AD risk and discuss some of the limitations of available research., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aims to compare the outcomes between two anterior decompression and fusion techniques to treat multilevel cervical spondylotic myelopathy (MCSM)., Methods: After the screening for eligibility, a total of 66 patients were admitted to this study. These participants underwent anterior surgeries due to MCSM in our hospital between June 2016 and July 2018. All participants underwent either the anterior cervical discectomy and fusion (ACDF) surgery (ACDF group) or the combination of ACDF and anterior cervical corpectomy and fusion (ACCF), which was the anterior cervical hybrid decompression and fusion (ACHDF) surgery group. All the patients were followed up ≥18 months, the average latest followed up time was 23.64 (±2.69) months. The length of hospitalization, operation time, blood loss, visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, improvement rate, Hounsfield units (HU) of C3-C7, cobb angle, and anterior column height of fusion levels pre and post operation were analyzed., Results: There were no statistical differences between the ACDF and ACHDF groups regarding the length of hospitalization, operation time, blood loss, HU of C3-C7, VAS, JOA score, improvement rate, cobb angle, and anterior column height in fusion levels in pre-operation and 3 months after operation (all P  > 0.05). However, compared with the ACHDF group, the ACDF group achieved significantly better improvement in the anterior column height of fusion levels in the final 18-29 months post-operatively ( P  < 0.05)., Conclusions: Both approaches of ACDF alone and a combination of ACDF and ACCF can achieve satisfactory outcomes in the treatment of MCSM, but ACDF has better outcomes in maintaining anterior column height of fusion levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Tian, Zhao, Han, Rudd, Li, Ding and Yang.)

Functional dyspepsia (FD) is a common disorder of gut-brain interaction, affecting approximately 7% of individuals in the community, with most patients managed in primary care. The last British Society of Gastroenterology (BSG) guideline for the management of dyspepsia was published in 1996. In the interim, substantial advances have been made in understanding the complex pathophysiology of FD, and there has been a considerable amount of new evidence published concerning its diagnosis and classification, with the advent of the Rome IV criteria, and management. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based diagnosis and treatment of patients. The approach to investigating the patient presenting with dyspepsia is discussed, and efficacy of drugs in FD summarised based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of pairwise and network meta-analyses. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system. These provide both the strength of the recommendations and the overall quality of evidence. Finally, in this guideline, we consider novel treatments that are in development, as well as highlighting areas of unmet need and priorities for future research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objectives: Sleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment., Methods: This review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception-March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure., Results: Nineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). "Unspecified MCI" was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters., Conclusions: Alongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Objective: To identify implantable devices currently used for vascular and endovascular procedures, to ascertain how many have randomised controlled trial (RCT) evidence available, and to assess the quality of that evidence., Data Sources: MEDLINE, Embase, DARE, PROSPERO, clinical trial registries, and Cochrane databases., Review Methods: A list of current devices used in both vascular and endovascular procedures was generated by searching conference proceedings, manufacturer catalogues, and websites. MEDLINE, Embase, DARE, PROSPERO, clinical trial registries, and Cochrane databases were searched from inception up to June 2020. The primary outcome was the availability of RCTs to support the use of a vascular implantable device. RCTs were then quality assessed using the Cochrane risk of bias tool., Results: A total of 116 current vascular implantable devices were identified. The systematic literature review identified 165 RCTs. Eighty-three of the RCTs (50.3%) applied to 33 of the 116 (28.4%) current implantable devices. When grouped by device type, eight of the 13 types (62%) had at least one RCT performed. There was a high risk of bias across the majority of the RCTs, with only nine (5.4%) deemed to be at low risk of bias. Only 22 (13.3%) RCTs had a clear safety outcome., Conclusion: Sixty-two per cent of implantable device types for use in vascular and endovascular interventions had at least one RCT available to show equivalence to previous devices or safety. RCTs were generally of low quality and are decreasing in frequency with time. With medical implantable device failure being increasingly recognised as causing significant harm to patients worldwide, there is a clear need for a more robust implantable device regulation and approval systems., (Copyright © 2022 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the correlation between tamoxifen (TAM) and lumbar intervertebral disc (IVD) degeneration (IVDD)., Methods: The patients who visited the department of spine surgery from January 2015 to December 2020 were retrospectively reviewed. Those with a history of breast cancer surgery were identified and their data were collected. These data included patients' age, body mass index (BMI), menstrual history, postoperative history, drug treatment plan, and imaging data. The participants were divided into the TAM group and the non-TAM group. Lumbar IVDD was assessed by lumbar lordosis (LL), vertebral CT density, lumbar disc height index (DHI), Modic changes, and modified Pfirrmann grading score. SPSS 20 was used for statistical analysis., Results: A total of 75 patients were included in this study, 46 patients in the TAM group and 29 patients in the non-TAM group. No significant differences were present in age, BMI, postoperative history, LL, and vertebral CT density between the two groups. The DHI of L1/2 and L2/3 in the TAM group was lower compared to the non-TAM group ( P =0.038 and P =0.034, respectively), while comparisons regarding the DHI of L3/4, L4/5, and L5/S1, and the average DHI between TAM and non-TAM groups were not significant. The modified Pfirrmann grading scores of the L1/2 and L2/3 IVDs in the TAM group were higher than those in the non-TAM group ( P =0.004 and P =0.025, respectively). Comparisons of L3/4, L4/5, and L5/S1 between the two groups were not significant. The comparisons regarding the occurrence of Modic changes did not show a significant difference between the TAM and non-TAM groups., Conclusions: This study indicates that there might be some positive correlation between TAM use and lumbar IVDD. In particular, the degeneration of L1/2 and L2/3 has shown a correlation with TAM use., Competing Interests: The authors declare no conflicts of interest regarding this study., (Copyright © 2022 Xiangyu Li et al.)

Background: There are increasing numbers of reports of cognitive activity, consciousness, awareness and recall related to cardiopulmonary resuscitation (CPR) and interventions such as the use of sedative and analgesic drugs during CPR., Objectives: This scoping review aims to describe the available evidence concerning CPR-related cognitive activity, consciousness, awareness and recall and interventions such as the use of sedative and analgesic drugs during CPR., Methods: A literature search was conducted of Medline, Embase and CINAHL from inception to 21 October 2021. We included case studies, observational studies, review studies and grey literature., Results: We identified 8 observational studies including 40,317 patients and 464 rescuers, and 26 case reports including 33 patients. The reported prevalence of CPR-induced consciousness was between 0.23% to 0.9% of resuscitation attempts, with 48-59% of experienced professional rescuers surveyed estimated to have observed CPR-induced consciousness. CPR-induced consciousness is associated with professional rescuer CPR, witnessed arrest, a shockable rhythm, increased return of spontaneous circulation (ROSC), and survival to hospital discharge when compared to patients without CPR-induced consciousness. Few studies of sedation for CPR-induced consciousness were identified. Although local protocols for treating CPR-induced consciousness exist, there is no widely accepted guidance., Conclusions: CPR-related cognitive activity, consciousness, awareness and recall is uncommon but increasingly reported by professional rescuers. The data available was heterogeneous in nature and not suitable for progression to a systematic review process. Although local treatment protocols exist for management of CPR-induced consciousness, there are no widely accepted treatment guidelines. More studies are required to investigate the management of CPR-induced consciousness., Competing Interests: RLW, QO, IRD, SR, BWB declare no conflicts of interest. SP has received grants in the past for studies of awareness during CPR. JS is an Editor of Resuscitation and received payment from the publisher Elsevier., (© 2022 The Author(s).)

Immune checkpoint inhibitors and related molecules can achieve tumour regression, and even prolonged survival, for a subset of cancer patients with an otherwise dire prognosis. However, it remains unclear why some patients respond to immunotherapy and others do not. PET imaging has the potential to characterise the spatial and temporal heterogeneity of both immunotherapy target molecules and the tumor immune microenvironment, suggesting a tantalising vision of personally-adapted immunomodulatory treatment regimens. Personalised combinations of immunotherapy with local therapies and other systemic therapies, would be informed by immune imaging and subsequently modified in accordance with therapeutically induced immune environmental changes. An ideal PET imaging biomarker would facilitate the choice of initial therapy and would permit sequential imaging in time-frames that could provide actionable information to guide subsequent therapy. Such imaging should provide either prognostic or predictive measures of responsiveness relevant to key immunotherapy types but, most importantly, guide key decisions on initiation, continuation, change or cessation of treatment to reduce the cost and morbidity of treatment while enhancing survival outcomes. We survey the current literature, focusing on clinically relevant immune checkpoint immunotherapies, for which novel PET tracers are being developed, and discuss what steps are needed to make this vision a reality., (© 2022. The Author(s).)

Introduction: Indications on the development of the health library and knowledge workforce (LKS) in England suggest that more staff may need to shift into clinical librarian (CL) roles. Anecdotal evidence suggested that CL roles have changed recently., Objectives: To examine perceptions of CL tasks and required personal characteristics of CLs, amongst both practising CLs and other LKS staff in England., Methods: An online survey was followed by descriptive statistical and content analysis to identify any differences in perceptions between the CL and non-CL staff groups., Results: Response rate: 10% (123/1181). Both staff groups identified literature searching as the top core task and agreed on the main CL roles. Perceptions on the necessary personal characteristics were also similar. Ranking differed for a few tasks: non-CL staff may ascribe more importance to some tasks (evidence synthesis, critical appraisal training and attending ward rounds/team meetings) than the CL staff state. CLs spent more time on staff management, and less time on study skills training than non-CL staff perceived., Discussion: Results indicated that CL roles are continuing to develop, but that CLs are more integrated into library administration than some non-CL staff believe., Conclusion: Shared perceptions around CL roles should help workforce development., (© 2021 Health Libraries Group.)

Water is ubiquitous in life - from making up the majority of the Earth's surface (by area) to over half of the human body (by weight). It stands to reason that materials are likely to contact water at some point during their lifetime. In the specific case of sensors however, there is a need to consider materials that display stable function while immersed in aqueous applications. This mini-review will discuss the most recent advances (2018 to 2021) in the application of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) in aqueous environments. At its heart, the use of PEDOT in aqueous applications relies on nanoscale understanding and/or nanoengineered structures and properties. This enables their use in water-based settings such as within the human body or buried in agricultural soils., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Most major lower limb amputations are related to peripheral artery disease (PAD) or diabetes. Just 40% of patients who undergo major lower limb amputation will use a prosthesis yet measures of surgical success commonly focus on prosthesis use. Patient reported outcome measures (PROMs) are valuable to comprehensively evaluate health related quality of life (HRQL) after surgery. This systematic review aimed to identify and describe PROMs available to assess HRQL in patients after amputation for PAD or diabetes., Methods: A search was conducted based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) for systematic reviews of PROMs. Ovid MEDLINE, Ovid EMBASE, PsycINFO, CINAHL, and Cochrane CENTRAL were also searched from inception until August 2019. Included were articles describing the development, measurement properties, or evaluation of HRQL via a PROM in adult patients after amputation for PAD or diabetes. Studies of amputation exclusively for trauma or malignancy were excluded. Data were collected on study characteristics, PROM characteristics (generic/disease specific), and properties of amputation specific PROMs., Results: Of 3 317 abstracts screened, 111 full text articles were assessed for eligibility and 64 included. Fifty-six studies evaluated HRQL, with 23 (46%) of these using an amputation specific PROM to do so. Eleven different amputation specific PROMs were identified, 10 (91%) of which were developed only for prosthesis users. One measure was suitable for use in all patients after amputation. This "Amputee single item mobility measure" includes a single item evaluating mobility. Nine studies reported some psychometric testing of an amputation specific PROM., Conclusion: A well tested, multidimensional PROM applicable to wheelchair and prosthetic users after amputation is lacking and urgently needed for studies in this field. Future work to develop an appropriate measure is required., Competing Interests: Conflict of interest None., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Adults aged ≥60 years now represent the majority of patients presenting with major trauma. Falls are the most common cause of injury, accounting for nearly three-quarters of all traumas in this population. Trauma to the thorax represents the second most common site of injury in this population, and is often associated with other serious injuries. Mortality rates are 2-5 times higher in older adults compared to their younger counterparts, often despite equivalent injury severity scores. Risk scoring systems have been developed to identify rib fracture patients at high risk of deterioration. Overall mortality from rib fractures is high, at approximately 10% for all ages. Mortality and morbidity from rib fractures primarily derive from pain-induced hypoventilation, pneumonia and respiratory failure. The main goal of care is therefore to provide sufficient analgesia to allow respiratory rehabilitation and prevent pulmonary complications. The provision of analgesia has evolved to incorporate novel regional anaesthesia techniques into conventional multimodal analgesia. Analgesia algorithms may aid early aggressive management and escalation of pain control. The current role for surgical fixation of rib fractures remains unclear for older adults who have been underrepresented in the research literature. Older adults with rib fractures often have multi-morbidity and frailty which complicate their injuries. Trauma services are evolving, and increasingly geriatricians will be embedded into trauma services to deliver comprehensive geriatric assessment. This review aims to provide an evidence-based overview of the management of rib fractures for the physician treating older patients who have sustained trauma., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Emergency surgery encompasses more than 50 per cent of the surgical workload; however, research efforts are disproportionally low. The mode of anaesthesia used during emergency surgery may affect outcomes, but the extent of research and the impact of the different modes of anaesthesia used are unclear., Methods: MEDLINE and Embase were searched using scoping review methodology with a rapid systematic search strategy, identifying any study comparing locoregional (local, nerve block, subarachnoid, epidural) anaesthesia with general anaesthesia. All studies describing outcomes of emergency surgery with differing modes of anaesthesia were identified. Excluded were: studies published before 2003, studies enrolling patients aged less than 18 years and studies using sedation only., Results: Forty-two studies were identified, describing 11 surgical procedures. Most publications were retrospective cohort studies (32). A very broad range of clinical and patient-reported outcomes were described, with wide variation in the outcomes reported in different studies., Conclusion: Reporting of mode of anaesthesia is inconsistent across different procedures and is often absent. There is a need for directed research efforts to improve the reporting standards of anaesthesia interventions, to understand the role of different modes of anaesthesia in specific emergency surgical procedures, and to standardize outcome reporting using core outcome sets., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Sequencing highly-variable 16S regions is a common and often effective approach to the study of microbial communities, and next-generation sequencing (NGS) technologies provide abundant quantities of data for analysis. However, the speed of existing analysis pipelines may limit our ability to work with these quantities of data. Furthermore, the limited coverage of existing 16S databases may hamper our ability to characterise these communities, particularly in the context of complex or poorly studied environments., Results: In this article we present the SigClust algorithm, a novel clustering method involving the transformation of sequence reads into binary signatures. When compared to other published methods, SigClust yields superior cluster coherence and separation of metagenomic read data, while operating within substantially reduced timeframes. We demonstrate its utility on published Illumina datasets and on a large collection of labelled wound reads sourced from patients in a wound clinic. The temporal analysis is based on tracking the dominant clusters of wound samples over time. The analysis can identify markers of both healing and non-healing wounds in response to treatment. Prominent clusters are found, corresponding to bacterial species known to be associated with unfavourable healing outcomes, including a number of strains of Staphylococcus aureus., Conclusions: SigClust identifies clusters rapidly and supports an improved understanding of the wound microbiome without reliance on a reference database. The results indicate a promising use for a SigClust-based pipeline in wound analysis and prediction, and a possible novel method for wound management and treatment.

Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses. From this list, 33 genes are common to syndromic intellectual disability (S-ID) and 58 genes are common to certain neurological and neuropsychiatric disorders that often include intellectual disability as a clinical feature. We examined the evolutionary constraint and brain expression of these gene sets, and we performed gene network and protein-protein interaction analyses using GeneGO MetaCore TM and DAPPLE, respectively. The 245 NS-ID candidate genes were over-represented in axon guidance, synaptogenesis, cell adhesion and neurotransmission pathways, all of which are key neurodevelopmental processes for the establishment of mature neuronal circuitry in the brain. These 245 genes exhibit significantly elevated expression in human brain and are evolutionarily constrained, consistent with expectations for a brain disorder such as NS-ID that is associated with reduced fecundity. In addition, we report enrichment of dopaminergic and glutamatergic pathways for those candidate NS-ID genes that are common to S-ID and/or neurological and neuropsychiatric disorders that exhibit intellectual disability. Collectively, this study provides an overview and analysis of gene networks associated with NS-ID and suggests modulation of neurotransmission, particularly dopaminergic and glutamatergic systems as key contributors to synaptic dysfunction in NS-ID.

Owing to changes in their chemistry and structure, polymers can be fabricated to demonstrate vastly different electrical conductivities over many orders of magnitude. At the high end of conductivity is the class of conducting polymers, which are ideal candidates for many applications in low-cost electronics. Here, we report the influence of the nature of the doping anion at high doping levels within the semi-metallic conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) on its electronic transport properties. Hall effect measurements on a variety of PEDOT samples show that the choice of doping anion can lead to an order of magnitude enhancement in the charge carrier mobility > 3 cm 2 /Vs at conductivities approaching 3000 S/cm under ambient conditions. Grazing Incidence Wide Angle X-ray Scattering, Density Functional Theory calculations, and Molecular Dynamics simulations indicate that the chosen doping anion modifies the way PEDOT chains stack together. This link between structure and specific anion doping at high doping levels has ramifications for the fabrication of conducting polymer-based devices. © 2017 The Authors. Journal of Polymer Science Part B: Polymer Physics Published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56 , 97-104.

Nitrogen (N) as a nutrient, in the form of nitrate (NO 3 - ), is essential for plant growth. Chemical fertilizers are used to increase crop yields, but overuse can lead to forms of environmental pollution necessitating methods to detect and monitor the level of NO 3 - in-situ in agricultural soils. Herein we report for the first time the NO 3 - selectivity of the inherently conducting polymer poly (3,4-ethylenedioxythiophene) (PEDOT). This selectivity occurs when PEDOT thin films are exposed to an aqueous environment containing not only NO 3 - , but a mixture of other ions present in concentrations (ppm) typical of real agricultural soil. The PEDOT sensitivity to absorb NO 3 - from solution is determined to be <1 ppm.

Plant genetic resources are a substantial opportunity for plant breeding, preservation and maintenance of biological diversity. As part of the German Network for Bioinformatics Infrastructure (de.NBI) the German Crop BioGreenformatics Network (GCBN) focuses mainly on crop plants and provides both data and software infrastructure which are tailored to the needs of the plant research community. Our mission and key objectives include: (1) provision of transparent access to germplasm seeds, (2) the delivery of improved workflows for plant gene annotation, and (3) implementation of bioinformatics services that link genotypes and phenotypes. This review introduces the GCBN's spectrum of web-services and integrated data resources that address common research problems in the plant genomics community., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Conducting polymers represent a field of materials innovation that bridges the properties of metals (electrical conduction) with those of traditional polymers (mechanical flexibility). Although electronic properties have been studied, minimal attention is given to their mechanical properties such as tensile strength. This study presents macroscopic wires made from the vapor phase polymerization of poly(3,4-ethylenedioxythiophene) using triblock copolymers as a molecular template. These macroscopic wires are conductive (up to 5 × 10 4 S/m), and possess tensile properties (Young's modulus ∼1.1 GPa; tensile strength ∼90 MPa) comparable to commercially available polymers (Nylon-6 and poly(methyl methacrylate)), without need for nonconductive mechanical fillers.

Aim: Macrophage infiltration contributes to the pathogenesis of Type 2 diabetes. Mesenchymal stem cells (MSCs) possess immunomodulatory properties, making them an ideal candidate for therapeutic intervention. This study investigated whether MSCs can modulate the phenotype of monocytes isolated from Type 2 diabetic patients with end-stage renal disease., Materials & Methods: Monocytes from control (n = 4) and Type 2 diabetic patients with end-stage renal disease (n = 5) were assessed using flow cytometry and microarray profiling, following 48 h of co-culture with MSCs., Results: Control subjects had a greater proportion of CD14(++)CD16(-) monocytes while diabetic patients had a higher proportion of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes. MSCs promoted the proliferation of monocytes isolated from diabetic patients, reduced HLA-DR expression in both groups and promoted the expression of anti-inflammatory genes., Conclusion: MSC-derived factors alter the polarization of monocytes isolated from healthy and diabetic subjects toward an M2 phenotype.

Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM., (©2015 American Association for Cancer Research.)

Background: In August 2012, the Centers for Disease Control and Prevention released recommendations to screen persons born from 1945 to 1965 for hepatitis C virus (HCV). In September 2012, Warm Springs Health and Wellness Center (WSHWC) initiated a quality improvement (QI) project to conduct HCV screening among all patients in this birth cohort., Methods: Screening rates were tracked using a nationally standardized HCV screening measure in the Indian Health Service. At the end of the project period, WSHWC staff took a brief survey to review the impact of the HCV QI Project., Results: Screening for HCV among eligible patients at WSHWC increased from 5% (47/938) in September 2012 to 76% (593/785) in September 2014. Survey data indicated that clinicians felt increased screening for HCV had a positive impact on patient communication and care., Conclusions: Primary care clinics can successfully increase HCV screening in a relatively short time period. Age based screening recommendation may provide opportunities to increase communication with others at risk for HCV. As more patients are screened, it will be important to ensure appropriate linkage to care for HCV patients., (© The Author(s) 2015.)

West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed -1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1'. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.

Background: Lichens are symbiotic organisms with a fungal and an algal or a cyanobacterial partner. Lichens inhabit some of the harshest climates on earth and most lichen species are desiccation-tolerant. Lichen desiccation-tolerance has been studied at the biochemical level and through proteomics, but the underlying molecular genetic mechanisms remain largely unexplored. The objective of our study was to examine the effects of dehydration and rehydration on the gene expression of Cladonia rangiferina., Results: Samples of C. rangiferina were collected at several time points during both the dehydration and rehydration process and the gene expression intensities were measured using a custom DNA microarray. Several genes, which were differentially expressed in one or more time points, were identified. The microarray results were validated using qRT-PCR analysis. Enrichment analysis of differentially expressed transcripts was also performed to identify the Gene Ontology terms most associated with the rehydration and dehydration process., Conclusions: Our data identify differential expression patterns for hundreds of genes that are modulated during dehydration and rehydration in Cladonia rangiferina. These dehydration and rehydration events clearly differ from each other at the molecular level and the largest changes to gene expression are observed within minutes following rehydration. Distinct changes are observed during the earliest stage of rehydration and the mechanisms not appear to be shared with the later stages of wetting or with drying. Several of the most differentially expressed genes are similar to genes identified in previous studies that have investigated the molecular mechanisms of other desiccation-tolerant organisms. We present here the first microarray experiment for any lichen species and have for the first time studied the genetic mechanisms behind lichen desiccation-tolerance at the whole transcriptome level.

A novel bacterium was isolated from a freshwater hot spring, the Hale House Spring, located at Hot Springs National Park, Hot Springs, AR, USA. Cells of strain MP-01(T) stained Gram-negative, were rod-shaped, non-motile, strictly anaerobic and chemo-organotrophic and did not form spores. Growth occurred at 50-65 °C, with an optimum at 60 °C, at pH 6.0-8.0, with an optimum at pH 6.5-7.0, and at NaCl concentrations up to 0.5 % (w/v), with optimum growth in the absence of NaCl. Strain MP-01(T) was capable of fermentative growth on pyruvate or proteinaceous substrates as well as reducing Fe(III) and Mn(IV). Major fatty acids were iso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0 and iso-C17 : 0. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine and the major isoprenoid quinone was MK-10. In the polyamine pattern, sym-homospermidine was the predominant compound. The DNA G+C content was 62.7 mol%. Analysis of the 16S rRNA gene sequence of the isolate indicated that strain MP-01(T) represents the first reported cultivated member of subdivision 23 of the Acidobacteria. It is proposed that strain MP-01(T) represents a novel genus and species, for which the name Thermoanaerobaculum aquaticum gen. nov., sp. nov. is proposed. The type strain of Thermoanaerobaculum aquaticum is MP-01(T) ( = DSM 24856(T) = JCM 18256(T)).

A novel bacterial strain designated HA-01(T) was isolated from a freshwater terrestrial hot spring located at Hot Springs National Park, Arkansas, USA. Cells were Gram-negative-staining, rod-shaped, aerobic, chemo-organotrophic, oxidase- and catalase-positive, non-spore-forming and motile by means of a single polar flagellum. Growth occurred at 37-60 °C, with an optimum between 45 and 50 °C, and at pH 6.5-8.5, with an optimum between pH 6.5 and 7.0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the closest relatives of strain HA-01(T) were Solimonas aquatica NAA-16(T) (93.8 %), Solimonas flava CW-KD 4(T) (94.1 %), Solimonas soli DCY12(T) (93.1 %), Solimonas variicoloris MN28(T) (94.0 %), Nevskia ramosa Soe1(T) (91.2 %) and Hydrocarboniphaga effusa AP103(T) (91.1 %). Major fatty acids consisted of C(16 : 0), iso-C(16 : 0), C(16 : 1)ω5c and summed feature 8 (C(18 : 1)ω9c, C(18 : 1)ω7c and C(18 : 1)ω6c). Polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and the major isoprenoid quinone was Q-8. The DNA G+C content was 64.4 mol%. Based on phylogenetic, phenotypic and chemotaxonomic evidence, it is proposed that strain HA-01(T) represents a novel species in a new genus for which the name Fontimonas thermophila gen. nov., sp. nov. is proposed. The type strain of the type species is HA-01(T) (= DSM 23609(T) = CCUG 59713(T)). A new family, Solimonadaceae fam. nov., is also proposed to replace Sinobacteriaceae Zhou et al. 2008.

Background: Lichens are symbiotic organisms that have a remarkable ability to survive in some of the most extreme terrestrial climates on earth. Lichens can endure frequent desiccation and wetting cycles and are able to survive in a dehydrated molecular dormant state for decades at a time. Genetic resources have been established in lichen species for the study of molecular systematics and their taxonomic classification. No lichen species have been characterised yet using genomics and the molecular mechanisms underlying the lichen symbiosis and the fundamentals of desiccation tolerance remain undescribed. We report the characterisation of a transcriptome of the grey reindeer lichen, Cladonia rangiferina, using high-throughput next-generation transcriptome sequencing and traditional Sanger EST sequencing data., Results: Altogether 243,729 high quality sequence reads were de novo assembled into 16,204 contigs and 49,587 singletons. The genome of origin for the sequences produced was predicted using Eclat with sequences derived from the axenically grown symbiotic partners used as training sequences for the classification model. 62.8% of the sequences were classified as being of fungal origin while the remaining 37.2% were predicted as being of algal origin. The assembled sequences were annotated by BLASTX comparison against a non-redundant protein sequence database with 34.4% of the sequences having a BLAST match. 29.3% of the sequences had a Gene Ontology term match and 27.9% of the sequences had a domain or structural match following an InterPro search. 60 KEGG pathways with more than 10 associated sequences were identified., Conclusions: Our results present a first transcriptome sequencing and de novo assembly for a lichen species and describe the ongoing molecular processes and the most active pathways in C. rangiferina. This brings a meaningful contribution to publicly available lichen sequence information. These data provide a first glimpse into the molecular nature of the lichen symbiosis and characterise the transcriptional space of this remarkable organism. These data will also enable further studies aimed at deciphering the genetic mechanisms behind lichen desiccation tolerance.

Helicobacter pylori is the main bacterial causative agent of gastroduodenal disorders and a risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The draft genomes of 10 closely related H. pylori isolates from the multiracial Malaysian population will provide an insight into the genetic diversity of isolates in Southeast Asia. These isolates were cultured from gastric biopsy samples from patients with functional dyspepsia and gastric cancer. The availability of this genomic information will provide an opportunity for examining the evolution and population structure of H. pylori isolates from Southeast Asia, where the East meets the West.

Water chemistry, energetic modeling, and molecular analyses were combined to investigate the microbial ecology of a biofilm growing in a thermal artesian spring within Hot Springs National Park, AR. This unique fresh water spring has a low dissolved chemical load and is isolated from both light and direct terrestrial carbon input - resulting in an oligotrophic ecosystem limited for fixed carbon and electron donors. Evaluation of energy yields of lithotrophic reactions putatively linked to autotrophy identified the aerobic oxidation of methane, hydrogen, sulfide, ammonia, and nitrite as the most exergonic. Small subunit (SSU) rRNA gene libraries from biofilm revealed a low-diversity microbial assemblage populated by bacteria and archaea at a gene copy ratio of 45:1. Members of the bacterial family 'Nitrospiraceae', known for their autotrophic nitrite oxidation, dominated the bacterial SSU rRNA gene library (approximately 45%). Members of the Thaumarchaeota ThAOA/HWCGIII (>96%) and Thaumarchaeota Group I.1b (2.5%), which both contain confirmed autotrophic ammonia oxidizers, dominated the archaeal SSU rRNA library. Archaea appear to dominate among the ammonia oxidizers, as only ammonia monooxygenase subunit A (amoA) genes belonging to members of the Thaumarchaeota were detected. The geochemical, phylogenetic, and genetic data support a model that describes a novel thermophilic biofilm built largely by an autotrophic nitrifying microbial assemblage. This is also the first observation of 'Nitrospiraceae' as the dominant organisms within a geothermal environment., (© 2012 Blackwell Publishing Ltd.)

DNA extraction from formalin-fixed paraffin-embedded (FFPE) tissues is difficult and requires special protocols in order to extract small amounts of DNA suitable for amplification. Most described methods report an amplification success rate between 60 and 80%; therefore, there is a need to improve molecular detection and identification of fungi in FFPE tissue. Eighty-one archived FFPE tissues with a positive Gomori methenamine silver (GMS) stain were evaluated using five different commercial DNA extraction kits with some modifications. Three different panfungal PCR assays were used to detect fungal DNA, and two housekeeping genes were used to assess the presence of amplifiable DNA and to detect PCR inhibitors. The sensitivities of the five extraction protocols were compared, and the quality of DNA detection (calculated for each kit as the number of housekeeping gene PCR-positive samples divided by the total number of samples) was 60 to 91% among the five protocols. The efficiencies of the three different panfungals used (calculated as the number of panfungal-PCR-positive samples divided by the number of housekeeping gene PCR-positive samples) were 58 to 93%. The panfungal PCR using internal transcribed spacer 3 (ITS3) and ITS4 primers yielded a product in most FFPE tissues. Two of the five DNA extraction kits (from TaKaRa and Qiagen) showed similar and promising results. However, one method (TaKaRa) could extract fungal DNA from 69 of the 74 FFPE tissues from which a housekeeping gene could be amplified and was also cost-effective, with a nonlaborious protocol. Factors such as sensitivity, cost, and labor will help guide the selection of the most appropriate method for the needs of each laboratory.