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Background: Understanding the intricate relationship between consciousness and the midbrain's structures remains a significant challenge in neuroscience. Transient lesions are perfect examples of the physiological functioning mechanism of these structures., Observations: The authors present the case of a 49-year-old female who experienced a transient disorder of consciousness due to a midbrain hematoma following surgical interventions to remove a cavernous malformation in the midbrain. This case explores the interplay between the ascending reticular activating system (ARAS) and the thalamic centers, highlighting the role of structural disruptions in influencing consciousness levels. Notably, the patient's recovery correlated with the resolution of midbrain edema, reinstating normal ARAS function and consciousness., Lessons: In patients affected by midbrain lesions, edema can lead to a fluctuating neurological status, which can be difficult to diagnose. This case highlights the midbrain's crucial role in the consciousness network and the need to comprehend the intricate connections between subcortical and cortical structures for a comprehensive understanding of human consciousness. https://thejns.org/doi/10.3171/CASE2411.

Background: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD., Objective: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD., Methods: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy. Both patients had medically refractory SD and severe comorbidities contraindicating open surgery., Results: SD resolved at 4 and 12 days after MRgFUS, respectively. Adverse events (intraoperative hypothermia and postoperative facial paralysis) were mild and transient., Conclusion: Bilateral simultaneous MRgFUS pallidotomy under general anesthesia is safe and may be a valid alternative therapeutic option for fragile patients. Further studies are needed to assess long-term efficacy of the procedure., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: We assessed the Transcranial Electrical Stimulation (TES)-induced Corticobulbar-Motor Evoked Potentials (Cb-MEPs) evoked from Orbicularis Oculi (Oc) and Orbicularis Oris (Or) muscles with FCC5h/FCC6h-Mz, C3/C4-Cz and C5/C6/-Cz stimulation, during IntraOperative NeuroMonitoring (IONM) in 30 patients who underwent skull-base surgery., Methods: before (T0) and after (T1) the surgery, we compared the peak-to-peak amplitudes of Cb-MEPs obtained from TES with C3/C4-Cz, C5/C6-Cz and FCC5h/FCC6h-Mz. Then, we compared the response category (present, absent and peripheral) related to different montages. Finally, we classified the Cb-MEPs data from each patient for concordance with clinical outcome and we assessed the diagnostic measures for Cb-MEPs data obtained from FCC5h/FCC6h-Mz, C3/C4-Cz and C5/C6-Cz TES stimulation., Results: Both at T0 and T1, FCC5h/FCC6h-Mz stimulation evoked larger Cb-MEPs than C3/C4-Cz, less peripheral responses from direct activation of facial nerve than C5/C6-Cz. FCC5h/FCC6h-Mz stimulation showed the best accuracy and specificity of Cb-MEPs for clinical outcomes., Conclusions: FCC5h/FCC6h-Mz stimulation showed the best performances for monitoring the facial nerve functioning, maintaining excellent diagnostic measures even at low stimulus voltages., Significance: We demonstrated that FCC5h/FCC6h-Mz TES montage for Cb-MEPs in IONM has good accuracy in predicting the post-surgery outcome of facial nerve functioning., Competing Interests: Conflict of interests None., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The potential use of TEG/ROTEM® in evaluating the bleeding risk for rare coagulation disorders needs to be assessed, considering the common mismatch among laboratory tests and the clinical manifestations. As a result, there is currently no published data on the use of viscoelastic tests to assess coagulation in FVII deficient patients undergoing elective neurosurgery. We describe the case of a patient affected by severe FVII deficiency who underwent microvascular decompression (MVD) craniotomy for hemifacial spasm (HFS). The ROTEM® did not show a significant coagulopathy according to the normal ranges, before and after the preoperative administration of the recombinant activated FVII, but a substantial reduction in EXTEM and FIBTEM Clotting Times was noted. The values of coagulation in standard tests, on the contrary, were indicative of a coagulopathy, which was corrected by the administration of replacement therapy. Whether this difference between ROTEM® and standard tests is due to the inadequacy of thromboelastographic normal ranges in this setting, or to the absence of clinically significant coagulopathy, has yet to be clarified. Neurosurgery is a typical high bleeding risk surgery; additional data is required to clarify the potential role for thromboelastographic tests in the perioperative evaluation of the FVII deficient neurosurgical patients., (© 2024. The Author(s).)

Background:  Burnout in doctors is an important issue with far-reaching consequences. Community service doctors may be particularly vulnerable because of their specific roles (rural settings, junior positions and reduced supervision)., Aim:  This study aimed to determine the prevalence of burnout among community service doctors in South Africa (SA), the potential contributory and protective factors and the consequences thereof., Setting:  This was a national study of community service doctors in SA., Methods:  A quantitative, descriptive cross-sectional study was performed. The Maslach Burnout Inventory was used to measure burnout. The online questionnaire also included demographic data, workplace and individual characteristics., Results:  Of the 208 community service doctors analysed, 89% and 94% had high emotional exhaustion and depersonalisation, respectively, while 97% had a low personal accomplishment. Mental illness, financial difficulties, unmanageable volume of patients and female gender were found to be potential contributory factors. Having manageable patient volumes, satisfaction with their decision to study medicine, talking to colleagues and feeling supported by healthcare facility management were among the significant potential protective factors. Significant potential consequences of burnout included: leaving the government sector, ever being diagnosed with a mental illness, using alcohol as a coping mechanism and possible current major depression., Conclusion:  Burnout among community service doctors in SA is highly prevalent with significant potential consequences. There are a number of modifiable possible contributory and protective factors identified that may be targets for mental health interventions.Contribution: Healthcare burnout research is lacking in the African and specifically SA context. This void includes community service doctors.

Objectives: Airway reconstruction for laryngo tracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery., Design: Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery., Setting: Tertiary referral centre., Participants: With ethical approval, twenty consecutive adult (≥18 years) LTS patients undergoing airway reconstruction were prospectively recruited., Main Outcome Measures: These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index)., Results: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each time point: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6., Conclusions: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients' voice and swallowing., (© 2024 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objective: To critically assess the methodological characteristics and quality of interventional clinical trials investigating the effects of heated tobacco products (HTPs)., Data Sources: Web of Science (Core collection and MEDLINE), Scopus, MedRxiv, ClinicalTrials.gov and ICTRP trial databases and transnational HTP manufacturer online publication libraries were searched for clinical trials on HTPs published between January 2010 and April 2022., Study Selection: Interventional clinical trials of any design, in which at least one group of adult participants used a currently marketed HTP, were selected by two reviewers with good or very good agreement., Data Extraction: Data relating to trial characteristics and effects of intervention on primary outcomes were extracted using a predesigned form. Risk of bias was assessed using Cochrane's Risk of Bias tool v1., Data Synthesis: 40 trials were included, 29 of which were tobacco industry affiliated. Methodological characteristics, such as registration, design, setting, comparator interventions, participants, outcomes and analyses, varied between trials, though there were few significant differences between industry-affiliated and independent trials. Of the 40 trials, 33 were judged to be at high risk of bias and 6 at unclear risk of bias. Trial findings were not significantly associated with either affiliation or risk of bias., Conclusions: The conduct and reporting of HTP interventional clinical trials were poor in many respects and limited to investigating effects of short-term exposure. These trials fall short of what is needed to determine whether HTPs are beneficial to public health, meaning they may not be a sound basis for tobacco control policy decisions., Competing Interests: Competing interests: GMJT has previously received funding from Pfizer, who manufacture smoking cessation products. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Short peripheral catheters (SPCs) are used to provide intravenous therapies in hospitalized patients. Recently, the category of SPC has become more complex, with the introduction in clinical practice of "integrated" SPCs (ISPCs), renewed regarding the material (polyurethane rather than polytetrafluoroethylene) and design (large wing; pre-assembled extension; preassembled needle-free connector (NFC))., Methods: This systematic review and meta-analysis aimed to analyze randomized controlled trials (RCTs) and quasi-randomized studies in hospitalized patients, analyzing the risk of overall catheter failure as well as the risk of each type of complication (occlusion, infiltration, thrombophlebitis, and dislodgement) for ISPCs compared to non-integrated SPCs. These systematic review and meta-analysis were registered on PROSPERO (CRD42022322970)., Data Sources: We searched PUBMED ® , EMBASE ® , and the Cochrane Controlled Clinical Trials register from April to November 2022., Results: Included Studies: The research identified 1260 articles. After the abstract review, 13 studies were included for full manuscript review and, after that, six papers (4727 patients) were included in the meta-analysis., Description of the Effect: We found a significantly reduced risk of catheter failure (pooling all complications) for ISPCs compared to SPCs ( p  = 0.002 RR 0.65; 95% CI 0.63-0.9). A significant reduction in the risks of occlusion ( p  = 0.007 RR 0.72; 95% CI 0.56-0.92) was observed. As regards the risk of infiltration, thrombophlebitis, and dislodgement, the analysis showed a trend in favor of ISPCs, though not statistically significant (respectively p  = 0.2 RR 0.84; 95% CI 0.64-1.1; p  = 0.25 RR 0.91; 95% CI 0.78-1.07; p  = 0.06 RR 0.72; 95% CI 0.52-1.01)., Conclusions: ISPCs significantly reduce the risks of catheter failure (overall complications) and occlusion. More RCTs are needed to understand if the preassembled ISPC is better than the composted closed system (non-integrated SPC + extension line + NFC)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: In pediatric patients, PICC insertion is often performed under sedation to reduce pain and anxiety, which is associated with risks such as laryngospasm, apnea, and hypoxia. Furthermore, it requires a pediatric anesthesiologist. The aim of our study was to evaluate the VR as an alternative to pharmacological sedation to reduce those risks and the overall cost., Methods: We tested a VR immersive experience for ten children requiring a PICC. To achieve this, we ran a software, specifically designed for the pediatric healthcare setting, on a commercially available VR headset.In order to evaluate this new practice, we recorded the following data:Patient's anxiety before and after the procedure, recorded through a modified numeric rating scale from 0 (no anxiety) to 10 (worst anxiety imaginable).Patient's pain before (e.g., because of preexisting medical conditions) and after the procedure through a Wong-Baker scale.Caregiver's satisfaction.No active or passive restraint was enforced during the whole procedure, patients had to keep their arms still all by themselves., Result: Out of the 10 patients only in a single case, we had to interrupt the attempt with the VR technique and let the anesthesiologist perform a sedation. From the immediate beginning said patient had trouble adapting to the virtual environment and tried to remove the headset.In all other cases, we noticed a drop in the anxiety level of the patient and the pain never increased. Globally, caregivers were pleased with the experience and reported an average satisfaction rate of 9.3 out of 10., Conclusion: Virtual reality seems a valid alternative to traditional sedation in pediatric patients undergoing a PICC placement procedure. Additional studies, with adequate sample size, of patients are necessary to assess the benefit from this new approach, as well as its impact on the overall procedure length., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Torri is currently employed by Becton Dickinson Italia Spa.

This article presents findings from an interdisciplinary project which invited readers to experience the impact of dementia via fictional characters' narratives. Combining methods from critical gerontology and literary linguistics-a field that examines the language of literature-we undertook an empirical reader response study of dementia fiction. We constructed a large corpus of dementia fiction; selecting 12 extracts, each containing first-hand, focalized accounts of fictional characters' experiences of living with dementia. Readers (31) were purposively sampled for 4 separate reading groups-student social workers (9); general public (9); family carers (6); and people with dementia (7). Over 6 weeks they engaged in separate, facilitated, on-line group discussions of extracts. Discussions were independently coded using ATLAS.ti. Although readers from all 4 groups reported that fictional characters drew them into the internal life of someone with dementia, some carers questioned whether fictional characters' experiences were plausible. Readers with dementia recognized themselves in the extracts; viewing fictional characters as eloquent envoys of their lived experiences of diagnosis, social isolation, loss of language, and use of humor. Fictional characters offer an entry point for understanding contrasts in caregiver and care-receiver experiences of dementia. Fictional characters are potentially useful for moving dementia narratives beyond monstrous cultural metaphors and onto a disability-based rights agenda., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Mindfulness-based programs can help lower psychological distress among parents of children with developmental disabilities. However, less is known about the functions of mindfulness in relation to parental outcomes. In a cross-sectional survey, mothers of children with developmental disabilities (N = 313) reported on their child's behavior problems, trait mindfulness, mindful parenting, and a range of outcomes (anxiety and depression symptoms, parenting stress, family satisfaction, and positive gain). Neither trait mindfulness or mindful parenting acted as moderators between child behavior problems and outcome variables, although both had main effect (compensatory) associations with parent outcomes. Benefits of mindfulness-based programs may be general rather than specifically in the context of high child behavior problems, given the lack of evidence for the moderating function of mindfulness., (©AAIDD.)

Competing Interests: No relevant disclosures.

Background and Objectives: Pulmonary complications are a leading cause of morbidity after cardiac surgery. The aim of this study was to develop models to predict postoperative lung dysfunction and mortality. Materials and Methods: This was a single-center, observational, retrospective study. We retrospectively analyzed the data of 11,285 adult patients who underwent all types of cardiac surgery from 2003 to 2015. We developed logistic predictive models for in-hospital mortality, postoperative pulmonary complications occurring in the intensive care unit, and postoperative non-invasive mechanical ventilation when clinically indicated. Results: In the "preoperative model" predictors for mortality were advanced age ( p < 0.001), New York Heart Association (NYHA) class ( p < 0.001) and emergent surgery ( p = 0.036); predictors for non-invasive mechanical ventilation were advanced age ( p < 0.001), low ejection fraction ( p = 0.023), higher body mass index ( p < 0.001) and preoperative renal failure ( p = 0.043); predictors for postoperative pulmonary complications were preoperative chronic obstructive pulmonary disease ( p = 0.007), preoperative kidney injury ( p < 0.001) and NYHA class ( p = 0.033). In the "surgery model" predictors for mortality were intraoperative inotropes ( p = 0.003) and intraoperative intra-aortic balloon pump ( p < 0.001), which also predicted the incidence of postoperative pulmonary complications. There were no specific variables in the surgery model predicting the use of non-invasive mechanical ventilation. In the "intensive care unit model", predictors for mortality were postoperative kidney injury ( p < 0.001), tracheostomy ( p < 0.001), inotropes ( p = 0.029) and PaO 2 /FiO 2 ratio at discharge ( p = 0.028); predictors for non-invasive mechanical ventilation were kidney injury ( p < 0.001), inotropes ( p < 0.001), blood transfusions ( p < 0.001) and PaO 2 /FiO 2 ratio at the discharge ( p < 0.001). Conclusions: In this retrospective study, we identified the preoperative, intraoperative and postoperative characteristics associated with mortality and complications following cardiac surgery.

The quest for simple systems achieving the photoreductive splitting of four-membered ring compounds is a matter of interest not only in organic chemistry but also in biochemistry to mimic the activity of DNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidatively generated lesion of guanine, has been shown to act as an intrinsic photoreductant by transferring an electron to bipyrimidine lesions and provoking their cycloreversion. But, in spite of appropriate photoredox properties, the capacity of guanine to repair cyclobutane pyrimidine dimer is not clearly established. Here, dyads containing the cyclobutane thymine dimer and guanine or 8-oxoguanine are synthesized, and their photoreactivities are compared. In both cases, the splitting of the ring takes place, leading to the formation of thymine, with a quantum yield 3.5 times lower than that for the guanine derivative. This result is in agreement with the more favored thermodynamics determined for the oxidized lesion. In addition, quantum chemistry calculations and molecular dynamics simulations are carried out to rationalize the crucial aspects of the overall cyclobutane thymine dimer photoreductive repair triggered by the nucleobase and its main lesion.

Charged residues on the surface of proteins are critical for both protein stability and interactions. However, many proteins contain binding regions with a high net charge that may destabilize the protein but are useful for binding to oppositely charged targets. We hypothesized that these domains would be marginally stable, as electrostatic repulsion would compete with favorable hydrophobic collapse during folding. Furthermore, by increasing the salt concentration, we predict that these protein folds would be stabilized by mimicking some of the favorable electrostatic interactions that take place during target binding. We varied the salt and urea concentrations to probe the contributions of electrostatic and hydrophobic interactions for the folding of the yeast SH3 domain found in Abp1p. The SH3 domain was significantly stabilized with increased salt concentrations due to Debye-Huckel screening and a nonspecific territorial ion-binding effect. Molecular dynamics and NMR show that sodium ions interact with all 15 acidic residues but do little to change backbone dynamics or overall structure. Folding kinetics experiments show that the addition of urea or salt primarily affects the folding rate, indicating that almost all the hydrophobic collapse and electrostatic repulsion occur in the transition state. After the transition state formation, modest yet favorable short-range salt bridges are formed along with hydrogen bonds, as the native state fully folds. Thus, hydrophobic collapse offsets electrostatic repulsion to ensure this highly charged binding domain can still fold and be ready to bind to its charged peptide targets, a property that is likely evolutionarily conserved over 1 billion years., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Introduction: Mindfulness-based programmes (MBPs) have an established, growing evidence base as interventions to optimise health, well-being and performance of individual participants. Emerging evidence suggests that MBPs also enhance prosociality, encouraging individuals to contribute to positive social change. This study focuses on the potential of MBPs to facilitate development of participants' inner resources that support prosocial shifts. The review seeks to detect shifts in MBP benefit from individual toward 'bigger than self', informing and empowering individual and collective responses to complex societal and global issues. The review aims to map current literature on MBPs and social change, into a descriptive overview with commentary on quality, trends, theoretical models and gaps, and on how training in MBPs potentially enables individual and collective responses to societal and global issues. Recommendations for future directions for researchers seeking to advance this evidence base, and practitioners developing innovative MBPs for this purpose will be provided., Methods and Analysis: A scoping review of peer-reviewed literature will be undertaken and reported on according to the Joanna Briggs Institute (JBI) Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance. Systematic searches of four scientific databases will be undertaken to identify potentially eligible articles published from all time to current date. Data will be extracted using an extraction template and analysed descriptively using narrative synthesis., Ethics and Dissemination: This scoping review involves no human participants, so ethics is not required. Findings will be shared through professional networks, conference presentations and journal publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The low affinity metabotropic glutamate receptor mGluR 7 has been implicated in numerous CNS disorders; however, a paucity of potent and selective activators has hampered full delineation of the functional role and therapeutic potential of this receptor. In this work, we present the identification, optimization, and characterization of highly potent, novel mGluR 7 agonists. Of particular interest is the chromane CVN636 , a potent (EC 50 7 nM) allosteric agonist which demonstrates exquisite selectivity for mGluR 7 compared to not only other mGluRs, but also a broad range of targets. CVN636 demonstrated CNS penetrance and efficacy in an in vivo rodent model of alcohol use disorder. CVN636 thus has potential to progress as a drug candidate in CNS disorders involving mGluR 7 and glutamatergic dysfunction., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Background: Acquired laryngotracheal stenosis (LTS) is a rare condition that causes breathlessness and dyspnoea. Patients have reconstructive airway surgery to improve their breathing difficulties, but both LTS and the surgery can cause voice difficulties. The existing evidence base for management of voice difficulties for adults with LTS focuses on symptoms. There is limited information to provide clinical guidance for speech and language therapists (SLTs) and a limited understanding of the impact of voice changes on adults with LTS., Aim: To investigate the lived experience of adults with laryngotracheal stenosis (LTS), who have had reconstructive surgery; here focussing on voice concerns with the aim of guiding clinical care for SLTs., Methods and Procedures: A phenomenological, qualitative study design was used. Focus groups and semi-structured interviews were completed with adults living with LTS who had had reconstructive surgery. Audio recordings were transcribed and inductive thematic analysis was used by the research team to identify themes and sub-themes., Outcomes and Results: A total of 24 participants (five focus groups and two interviews) took part in the study before thematic saturation was identified in analysis. Three main themes were identified specific to the experience of living with LTS: the Medical, Physical and Emotional journey. All participants referenced voice difficulties as they related to each of these overall themes. Sub-themes directly related to voice included experience of surgery, information provision, staff expertise/complacency, symptoms, symptom management, identity, support networks, impact on life and living with a chronic condition., Conclusions and Implications: In this qualitative study participants have described the integral part voice difficulties play in their lived experience of LTS and reconstructive surgery. This is considered in the context of their clinical care and the need for individualised management and information provision throughout the course of their condition. The broader research literature relating to voice difficulties is explored with links made to people with LTS and recommendations made for future research into people living with LTS and dysphonia., What This Paper Adds: What is already known on this subject Adults with laryngotracheal stenosis (LTS) experience voice changes as a result of their condition, and the surgeries necessary as a treatment. These changes can lead to altered pitch, vocal fatigue, loss of pitch range and loss of volume control. Although there are known psychosocial implications both to living with a chronic condition and voice difficulties there has been no research exploring this in adults with LTS, and there is minimal clinical guidance for speech and language therapists (SLTs) working with these patients. What this paper adds to existing knowledge This research is the first study to explore the lived experience of adults with LTS who undergo reconstructive surgery, focusing on their voice concerns. This study demonstrates the multifactorial impacts of voice changes on all aspects of the lives of adults with LTS and the need for individualised information provision and clinical care to help support them. What are the potential or actual clinical implications of this work? Adults with LTS want expert SLTs to facilitate their care and support them throughout their LTS journey alongside other support networks. They want to be carefully prepared for reconstructive surgery and given clear information about symptoms and management of their voice difficulties. This has led to the reorganisation of the care pathway at our centre, and the introduction of a patient-led pretreatment session., (© 2022 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Introduction: Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM-B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well-being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment., Methods: This was a qualitative study embedded within a feasibility randomized-controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty-six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi-structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM-B as a theoretical frame., Results: Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms., Motivation: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention., Conclusion: People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation., Patient or Public Contribution: Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Chronic nonspecific low back pain (LBP) is a complex and multifaceted problem. The following Perspective piece tries to help make sense of this complexity by describing a model for the development and maintenance of persistent LBP that integrates modifiable factors across the biopsychosocial spectrum. The Fit-for-Purpose model posits the view that chronic nonspecific LBP represents a state in which the person in pain holds strong and relatively intransient internal models of an immutably damaged, fragile, and unhealthy back, and information that supports these models is more available and trustworthy than information that counters them. This Perspective proposes a corresponding treatment framework for persistent pain that aims to shift internal models of a fragile, damaged, unhealthy, and unchangeable self toward the formulation of the back as healthy, strong, adaptable, and fit for purpose and to provide the system with precise and trustworthy evidence that supports this supposition while minimizing information that works against it., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Takotsubo syndrome (TS) represents a form of nonischemic cardiomyopathy characterized by sudden and temporary weakening of the myocardium. Many data suggest a primary role for sympathetic overstimulation in its pathogenesis. Nevertheless, these correlates are less easily identified during anesthesia., Observations: A 50-year-old female patient with a 4-year history of drug-resistant left trigeminal neuralgia. She was scheduled for surgical microvascular decompression. In the operating room, after induction of general anesthesia and oral intubation, the electrocardiogram revealed a significant ST segment elevation along with a sudden decrease in systolic blood pressure and heart rate. Administration of atropine caused a conversion into ventricular tachycardia. The advanced cardiac life support protocols were applied with prompt defibrillation and rapid recovery at sinus rhythm. A transthoracic echocardiogram revealed apical akinesia with ballooning of the left ventricle with a reduction of systolic function. An emergency coronary arteriography was performed, showing normal epicardial coronary vessels. After 4 days, echocardiography revealed normalization of the left ventricular function with improvement of the ejection fraction., Lessons: In patients affected by trigeminal neuralgia, chronic pain can lead to a state of adrenergic hyperactivation, which can promote TS during the induction of general anesthesia, probably through the trigeminocardiac reflex.

Background: Worldwide, approximately 24% of all adults smoke, but smoking is up to twice as prevalent in people with mental ill-health. There is growing evidence that smoking may be a causal risk factor in the development of mental illness, and that smoking cessation leads to improved mental health., Methods: In this scholarly review we have: (1) used a modern adaptation of the Bradford-Hill criteria to bolster the argument that smoking could cause mental ill-health and that smoking cessation could reverse these effects, and (2) by considering psychological, biological, and environmental factors, we have structured the evidence to-date into a stress-diathesis model., Results: Our model suggests that smoking is a psychobiological stressor, but that the magnitude of this effect is mediated and modulated by the individual's diathesis to develop mental ill-health and other vulnerability and protective factors. We explore biological mechanisms that underpin the model, such as tobacco induced damage to neurological systems and oxidative stress pathways. Furthermore, we discuss evidence indicating that it is likely that these systems repair after smoking cessation, leading to better mental health., Conclusion: Based on a large body of literature including experimental, observational, and novel causal inference studies, there is consistent evidence showing that smoking can negatively affect the brain and mental health, and that smoking cessation could reverse the mental ill-health caused by smoking. Our model suggests that smoking prevention and treatment strategies have a role in preventing and treating mental illness as well as physical illness., (© 2022 The Authors.)

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood-brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016-2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3-78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma.

Seven siphoviruses were isolated from soil using Streptomyces hosts. Their genome sequences ranged from 42,730 to 57,624 bp long and had a GC content of approximately 60%. Based on their gene content similarity to actinobacteriophages, all seven phages were assigned to cluster BI. For several of these phages, multiple ribosomal frameshifts were identified.

Despite the increasing popularity of flow diverters (FDs) as an endovascular option for intracranial aneurysms, the treatment of complex aneurysms still represents a challenge. Combined strategies using a flow-preservation bypass could be considered in selected cases. In this study, we retrospectively reviewed our series of patients with complex intracranial aneurysms submitted to bypass. From January 2015 to May 2022, 23 patients were selected. We identified 11 cases (47.8%) of MCA, 6 cases (26.1%) of ACA and 6 cases (26.1%) of ICA aneurysms. The mean maximal diameter was 22.73 ± 12.16 mm, 8 were considered as giant, 9 were fusiform, 8 presented intraluminal thrombosis, 10 presented wall calcification, and 18 involved major branches or perforating arteries. Twenty-five bypass procedures were performed in 23 patients (two EC-IC bypasses with radial artery graft, seventeen single- or double-barrel STA-MCA bypasses and six IC-IC bypasses in anterior cerebral arteries). The long-term bypass patency rate was 94.5%, and the total aneurysm exclusion was 95.6%, with a mean follow-up of 28 months. Median KPS values at last follow-up was 90, and a favorable outcome (KPS ≥ 70 and mRS ≤ 2) was obtained in 87% of the cases. The use of bypass techniques represents, in selected cases, a valid therapeutic option in the management of complex anterior circulation aneurysms when a simpler direct approach, including the use of FD, is considered not feasible.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce., Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU., Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021., Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine)., Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders., Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients., Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Photosensitized thymine<>thymine (Thy<>Thy) formation and repair can be mediated by carbazole (Cbz). The former occurs from the Cbz triplet excited state via energy transfer, while the latter takes place from the singlet excited state via electron transfer. Here, fundamental insight is provided into the role of the topology and excited state multiplicity, as factors governing the balance between both processes. This has been achieved upon designing and synthesizing different isomers of trifunctional systems containing one Cbz and two Thy units covalently linked to the rigid skeleton of the natural deoxycholic acid. The results shown here prove that the Cbz photosensitized dimerization is not counterbalanced by repair when the latter, instead of operating through-space, has to proceed through-bond.

Objectives: To investigate how the symptoms of mucus and cough impact adults living with laryngotracheal stenosis, and to use this information to guide future research and treatment plans., Methods: A survey was developed with the support of patient advisors and distributed to people suffering with laryngotracheal stenosis. The survey comprised 15 closed and open questions relating to mucus and cough and included the Leicester Cough Questionnaire (LCQ). Descriptive statistics, X 2 and thematic analyses were completed., Results: In total, 641 participants completed the survey, with 83.62% (n = 536) reporting problems with mucus; 79% having daily issues of varying severity that led to difficulties with cough (46.18%) and breathing (20.90%). Mucus affected voice and swallowing to a lesser degree. Respondents described a range of triggers; they identified smoky air as the worst environmental trigger. Strategies to manage mucus varied widely with drinking water (72.26%), increasing liquid intake in general (49.35%) and avoiding or reducing dairy (45.32%) the most common approaches to control symptoms. The LCQ showed a median total score of 14 (interquartile range 11-17) indicative of cough negatively affecting quality of life. Thematic analysis of free text responses identified 4 key themes-the Mucus Cycle, Social impact, Psychological impact, and Physical impact., Conclusion: This study shows the relevance of research focusing on mucus and cough and its negative impact on quality of life, among adults with laryngotracheal stenosis. It demonstrates the inconsistent advice and management strategies provided by clinicians for this issue. Further research is required to identify clearer treatment options and pathways.

Polycyclic aromatic hydrocarbons (PAHs) are the most widespread xenobiotic pollutants in water and their abatement usually involves expensive and energy-consuming treatments. In this work, anthracene (AN) was selected as the recalcitrant model of PAHs and its solar light-stimulated heterogeneous photocatalytic abatement in aerated aqueous media was investigated using a new TiO 2 derived thermoplastic nanocomposite in thin film form. The results were also compared with the benchmark TiO 2 photocatalyst in slurry form. Finally, the possible contribution of reactive intermediates such as hydroxyl radical, AN radical cation and singlet oxygen, was investigated by using a hydroxyl radical trap and laser flash photolysis. Based on the obtained results, a feasible mechanism for AN photodegradation, which involves hydroxyl radical as the key oxidizing species is proposed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To assess the effectiveness and safety of intravenous (IV) dexmedetomidine for sedation in ophthalmic surgery., Methods: Prospective, observational, uncontrolled, single-center study. Patients were sedated with a continuous dexmedetomidine IV infusion started 15 min before regional anesthesia administration and maintained up to the end of surgery. Effectiveness of dexmedetomidine was assessed by the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) targeted at 5. Safety was assessed by the incidence of patients' movements/snoring and by the incidence of respiratory and haemodynamic complications. An eleven-point numerical rating scale (NRS) was used to assess the level of satisfaction of both the surgeon and the patient., Results: 123 patients (73 males, mean age: 63 ± 13) were included; 81 (81/123; 65.8%) patients reached the requested MOAA/S score of 5. Any intraoperative movement - mostly voluntary - occurred in 34 (34/123; 27.6%) cases with no need for a switch to general anaesthesia; no ocular complications related to the intraoperative movements occurred. Intraoperative snoring occurred in 30 (30/123; 24.4%) patients and it did not affect the surgical manoeuvres. Respiratory drive depression requiring manual or mechanical ventilation never occurred. Bradycardia occurred in 14 (14/123; 11.3%), cases but only 4 (4/123; 3.2%) patients required atropine administration, which was always effective. Intraoperative analgesia was consistently obtained and both the surgeons and the patients reported a high NRS satisfaction score., Conclusion: Dexmedetomidine provided adequate sedation in patients undergoing ocular surgery under local anaesthesia and showed a good effectiveness and safety profile. Upper airway obstruction, apnoea and snoring can occur.

Background/purpose: Whilst much is known about the survival outcomes of patients that suffer an in-hospital cardiac arrest (IHCA) in Australia very little is known about the functional outcomes of survivors. This study aimed to describe the functional outcomes of a cohort of patients that suffered an in-hospital cardiac arrest (IHCA) and survived to hospital discharge in a regional Australian hospital., Methods: This is a single-centre retrospective observational cohort study conducted in a regional Australian hospital. All adult patients that had an IHCA in the study hospital between 1 Jan 2017 and 31 Dec 2019 and survived to hospital discharge were included in the study. Functional outcomes were reported using the Modified Rankin Scale (mRS), a six-point scale for which increasing scores represent increasing disability. Scores were assigned through a retrospective review of medical notes., Results: Overall, 102 adult patients had an IHCA during the study period, of whom 50 survived to hospital discharge. The median age of survivors was 68 years, and a third had a shockable initial arrest rhythm. Of survivors, 47 were able to be assigned both mRS scores. At discharge, 81% of patients achieved a favourable functional outcome (mRS 0-3 or equivalent function at discharge equal to admission)., Conclusions: Most survivors to hospital discharge following an IHCA have a favourable functional outcome and are discharged home. Although these results are promising, larger studies across multiple hospitals are required to further inform what is known about functional outcomes in Australian IHCA survivors., Competing Interests: Conflict of Interest None., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Venous Access Devices (VADs) are the most used devices in COVID-19 patients., Objective: Identify VADs implanted, catheter related thrombosis (CRT), catheter-related bloodstream infection (CRBSI), and accidental remove of VADs in both COVID-19 positive and COVID-19 free patients. Successive analysis was conducted comparing COVID-19 positive patients with COVID-19 free with inverse probability propensity score weights using simple regression to account for these two confounders (peripheral tip as central/peripheral and hospitalization as no/yes)., Methods: This multicenter, retrospective cohort study collected data from seven hospitals in Lombardy during the pandemic period from February 21st to May 31st 2020., Results: A total of 2206 VADs were evaluated, 1107 (50.2%) of which were inserted in COVID-19 patients. In COVID-19 cohort the first choice was Long Peripheral Cannula in 388 patients (35.1%) followed by Midline Catheter in 385 (34.8%). The number of "central tip" VADs inserted in COVID-free inpatients and COVID-19 positive were similar (307 vs 334). We recorded 42 (1.9%) CRT; 32 (79.2%) were observed in COVID-19 patients. A total of 19 CRBSI were diagnosed; 15 (78.95%) were observed in COVID-19. Accidental removals were the more represented complication with 123 cases, 85 (69.1%) of them were in COVID-19. COVID-19 significantly predicted occurrence of CRT (OR = 2.00(1.85-5.03); p  < 0.001), CRSB (OR = 3.82(1.82-8.97); p  < 0.001), and Accidental Removal (OR = 2.39(1.80-3.20); p  < 0.001) in our propensity score weighted models., Conclusions: CRT, CRBSI, and accidental removal are significantly more frequent in COVID-19 patients. Accidental removals are the principal complication, for this reason, the use of subcutaneously anchored securement is recommended for a shorter period than usual.

Background : Good sleep quantity and quality are essential for patient recovery while in the intensive care unit (ICU). Patients commonly report poor sleep while in the ICU, and therefore, identifying the modifiable factors that patients perceive as impacting their sleep is important to improve sleep and recovery. This study also assessed night-time light and sound levels in an ICU in an effort to find modifiable factors. Methods : A total of 137 patients (51F) aged 58.1 ± 16.8 years completed a survey including questions about their sleep before and during their ICU stay, factors contributing to poor sleep in the ICU, and perceived factors that may have improved their sleep in the ICU. Night-time light and sound levels were measured in patient rooms and nurses' stations. Results : Patients reported poorer sleep quantity and quality while in the ICU compared to home. Among the most common reasons for poor sleep, easily modifiable factors included noise (50.4%) and lights (45.3%), potentially modifiable factors included pain (46.7%), and non-modifiable factors included IV lines (42.3%). Patients felt their sleep would have been improved with interventions such as dimming lights (58.4%) and closing doors/blinds at night (42.3%), as well as potentially implementable interventions such as a sleeping pill (51.8%). Overnight sound levels in bedrooms were above the recommended levels (40 dB) and light levels averaged over 100 lux. Conclusions : Sleep quality and quantity were both worse in ICU than at home. Modifiable factors such as sound and light are common factors that patients perceive impact their sleep in the ICU. Readily implementable sleep management strategies aimed at minimizing the impacts of sound and light levels in the ICU are ways to improve patients' sleep in the ICU.

Objective and design: Following COVID-19 infection, children can develop an hyperinflammatory state termed Multisystem Inflammatory Syndrome in Children (MIS-C). Lung Ultrasound (LUS) features of COVID-19 in children have been described, but data describing the LUS findings of MIS-C are limited. The aim of this retrospective observational study conducted between 1 March and 31 December 2020, at a tertiary pediatric hospital in Milano, is to describe LUS patterns in patients with MIS-C and to verify correlation with illness severity. The secondary objective is to evaluate concordance of LUS with Chest X-ray (CXR). Methodology: Clinical and laboratory data were collected for all patients (age 0−18 years) admitted with MIS-C, as well as LUS and CXR patterns at admission. PICU admission, needed for respiratory support and inotrope administration, hospital, and PICU length of stay, were considered as outcomes and evaluated in the different LUS patterns. An agreement between LUS and CXR evaluation was assessed with Cohen’ k. Results: 24 children, who had a LUS examination upon admission, were enrolled. LUS pattern of subpleural consolidations < or > 1 cm with or without pleural effusion were associated with worse Left Ventricular Ejection Fraction at admission and need for inotropes. Subpleural consolidations < 1 cm were also associated with PICU length of stay. Agreement of CXR with LUS for consolidations and effusion was slight. Conclusion: LUS pattern of subpleural consolidations and consolidations with or without pleural effusion are predictors of disease severity; under this aspect, LUS can be used at admission to stratify risk of severe disease.

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology and laryngeal involvement is seen in a small percentage of cases. Dysphagia is a common but under-reported symptom. Little is known about how dysphagia typically presents or is managed in the context of this fluctuating disease. We present our case series using an SLT-led model of assessment and management., Methods: A literature search was conducted for any articles that reported both laryngeal sarcoidosis and dysphagia. We then analysed a case series of laryngeal sarcoidosis patients treated at Charing Cross Hospital. We report on multidimensional swallowing evaluation and rehabilitative interventions., Results: Seventeen papers report both laryngeal sarcoidosis and dysphagia, with only one paper giving details on the nature of the dysphagia and the treatment provided. In our case series (n = 7), patients presented with FOIS Scores ranging from 5 to 7 pre-operatively (median = 6). Aspiration (median PAS Score = 6 and Range = 3-8) and pharyngeal residue were common. Sensory issues were also prevalent with most unaware of the extent of their difficulties. Management interventions included safe swallowing advice, compensatory strategies, exercises and close surveillance given their potential for repeated surgical interventions., Conclusion: Laryngeal sarcoidosis is a rare condition. Dysphagia is under-reported and our experience highlights the need for specialist dysphagia intervention. Further research is required to understand dysphagia management requirements in the context of this fluctuating disease process., (© 2021. The Author(s).)

Objective: To examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care., Design: Systematic review and meta-analysis of randomised controlled trials., Eligibility Criteria for Selection of Studies: Randomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up., Data Sources: Trials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021., Data Extraction and Synthesis: Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated., Main Outcome Measures: Primary outcome was weight change from baseline to 12 months. Secondary outcome was weight change from baseline to ≥24 months. Change in waist circumference was assessed at 12 months., Results: 34 trials were included: 14 were additional, from a previous review. 27 trials (n=8000) were included in the primary outcome of weight change at 12 month follow-up. The mean difference between the intervention and comparator groups at 12 months was -2.3 kg (95% confidence interval -3.0 to -1.6 kg, I 2 =88%, P<0.001), favouring the intervention group. At ≥24 months (13 trials, n=5011) the mean difference in weight change was -1.8 kg (-2.8 to -0.8 kg, I 2 =88%, P<0.001) favouring the intervention. The mean difference in waist circumference (18 trials, n=5288) was -2.5 cm (-3.2 to -1.8 cm, I 2 =69%, P<0.001) in favour of the intervention at 12 months., Conclusions: Behavioural weight management interventions for adults with obesity delivered in primary care are effective for weight loss and could be offered to members of the public., Systematic Review Registration: PROSPERO CRD42021275529., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: This research was supported by the National Institute for Health and Care Research Leicester Biomedical Research Centre; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Infantile hypertrophic pyloric stenosis (IHPS), which causes gastric outlet obstruction and hypochloremic hypokalemic metabolic alkalosis, could pose a risk of postoperative apnea in patients. The aim of this study is to evaluate the incidence of postoperative apnea in babies admitted to a tertiary-level pediatric surgical center in Milano, Italy with diagnosis of IHPS in 2010-2019. The secondary objective is to evaluate the risk factors for postoperative apnea., Methods: This is a single-center, retrospective, observational cohort study. All patients admitted to our institution with diagnosis of IHPS during the study period were enrolled. Demographic and surgical variables, along with blood gas parameters, were obtained from the population. Postoperative apnea was defined as a respiratory pause longer than 15 s or a respiratory pause lasting less than 15 s, but associated with either bradycardia (heart rate <120 per minute), desaturation (SatO 2 <90%), cyanosis, or hypotonia. Occurrence was obtained from nursing charts and was recorded as a no/yes dichotomous variable., Results: Of 122 patients, 12 (9.84%) experienced apnea and 110 (90.16%) did not. Using univariate analysis, we found that only postoperative hemoglobin was significantly different between the groups (p=0.03). No significant multivariable model was better than this univariate model for prediction of apnea., Conclusions: Postoperative anemia, possibly due to hemodilution, increased the risk of postoperative apnea. It could be hypothesized that anemia can be added as another apnea-contributing factor in a population at risk due to metabolic changes., 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.)

Photorepair mechanism of (6-4) photoproducts (6-4PP) by photolyase has been the subject of active debate over the years. The initial rationalization based on electron transfer to an oxetane or azetidine intermediate formed upon binding to the enzyme has been questioned, and there is now a more general consensus that the lesion is directly reduced from the excited flavin cofactor. However, the accepting moiety, i.e. the 5-methyl-2-pyrimidone or 5-hydroxy-5,6-dihydrothymine, has not been fully identified yet. In this work, spectroscopic experiments have been run to determine which of the 5'- or 3'-base of 6-4PP is more prone to be reduced. For this aim, the two building blocks of 6-4PP were synthesized and used as electron acceptors. Instead of the short-lived photolyase cofactor, which does not provide a time window compatible with diffusion-controlled intermolecular processes, carbazole, 2-methoxynaphthalene and phenanthrene have been selected as electron donors due to their appropriate singlet lifetimes and reduction potentials. Steady-state and time-resolved fluorescence revealed that, in solution, the pyrimidone chromophore is the most easily reduced moiety. This was confirmed by transient absorption experiments consisting of quenching of the solvated electron by the two moieties of 6-4PP., (© 2022 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)

CX5461, a compound initially identified as an RNA polymerase inhibitor and more recently as a G-quadruplex binder, binds copper to form a complex. Our previous publication showed that the complexation reaction can be leveraged to formulate copper-CX5461 inside liposomes, improving the apparent solubility of CX5461 by over 500-fold and reducing the elimination of CX5461 from the plasma compartment following intravenous administration. In mouse models of acute myeloid leukemia, the resulting formulation was more effective than the free drug solution of CX5461 (pH 3.5) currently used in clinical trials. However, the gains observed with the liposomal formulation were minimal, despite significant increases in circulation half-life. Since the formulation technology used relied on liposomes and the fate of most compounds associated with liposomes is dependent on liposomal lipid composition, the studies described here were designed to evaluate how simple changes in lipid composition could affect therapeutic activity. The previously reported formulation method was simplified to ensure an easy scale-up process. In the modified method, pre-measured solid CX5461 was added to copper-containing liposomes prior to an incubation at 60 °C, which enabled copper-CX5461 complexation inside DSPC/Chol or DMPC/Chol liposomes. Efficacy was determined in BRCA-normal (BxPC3) and BRCA-deficient (Capan-1) models of pancreatic cancer. Both liposomal formulations enhanced the circulation lifetime of CX5461 compared to the free drug solution (pH 3.5). Unlike most compounds that are loaded using a transmembrane pH-gradient, the dissociation of CX5461 from liposomes prepared using the copper complexation method were comparable for DSPC/Chol and DMPC/Chol liposomes, in vitro and in vivo. Nonetheless, copper CX5461 prepared using DMPC/Chol liposomes exhibited superior efficacy. The reason for the improved activity of DMPC/Chol copper-CX5461 was not readily explained by the release data and may be due to the fact that DMPC/Chol liposomes are less stable following localization in the tumor. The results indicate that the therapeutic effects of copper-CX5461 will be dependent on liposomal lipid composition and that liposomal CX5461 should exhibit superior benefits when used to treat BRCA-deficient cancers., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)