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Objective: To analyse the risk factors of hypoparathyroidism and hypocalcaemia after total thyroidectomy. Methods: Clinical data of patients who underwent total thyroidectomy at a tertiary care hospital in southern part of India were collected retrospectively from January 2021 to May 2023. Multivariate logistic regression was used to analyse the risk factors associated with transient hypoparathyroidism and hypocalcaemia separately. Results: A total of 300 patients who underwent total thyroidectomy were enroled. The median age of the study population was 41 years, and 70% were females. Histopathological examination showed that 80.3% had thyroid cancer. The incidence of postoperative transient hypoparathyroidism was 26.7%, while postoperative transient hypocalcaemia was 12.3%. Multivariate analysis showed that the presence of hypothyroidism before surgery (OR = 3.230, 95% CI: 1.368–7.624, P = 0.007), performing central compartment neck dissection (CCND) (OR = 2.196, 95% CI: 1.133–4.257, P = 0.02) and parathyroid gland in the surgical specimen (OR = 5.547, 95% CI: 3.065–10.036, P < 0.0001) were independent predictors of postoperative transient hypoparathyroidism. Female gender (OR = 2.689, 95% CI: 1.049–6.895, P = 0.039), presence of parathyroid in the surgical specimen (OR = 1.067, 95% CI: 0.367–8.438, P = 0.004) and performing CCND (OR = 2.192, 95% CI: 0.990–4.850, P = 0.05) were independent predictors of postoperative transient hypocalcaemia. Conclusion: Hypoparathyroidism and hypocalcaemia after thyroid surgery are common, and most of them are transient. The independent predictors of hypoparathyroidism and hypocalcaemia differ. Hypoparathyroidism appears to be a better predictor for patients who will develop postoperative hypocalcaemia.

A variety of tumors involve the anal canal because the anal canal forms the transition between the digestive system and the skin, and this anatomical region is made of a variety of different cells and tissues. Magnetic resonance imaging (MRI) is the modality of choice for diagnosis and local staging of the anal canal and perianal neoplasms. In this pictorial review, we demonstrate the MRI anatomy of the anal canal and perianal region and display the imaging spectrum of tumors in the region along with an overview of its management. Imaging appearances of many tumorlike lesions that can cause diagnostic dilemmas are also demonstrated with pointers to differentiate between them.

Timothy Deer,1,&ast; Robert Heros,2,&ast; Edward Tavel,3 Sayed Wahezi,4 Robert Funk,5 Patrick Buchanan,6 Anne Christopher,7 Jacqueline Weisbein,8 Christopher Gilligan,9 Denis Patterson,10 Ajay Antony,11 Mohab Ibrahim,12 Nathan Miller,13 Keith Scarfo,14 Gayle Johnson,15 Thadchaigeni Panchalingam,15 Udoka Okaro,15 James Yue16 1Pain Management, The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 2Pain Management, Spinal Diagnostics, Tualatin, OR, USA; 3Pain Management, Clinical Trials of South Carolina, Charleston, SC, USA; 4Pain Management, Montefiore Medical Center, Bronx, NY, USA; 5Pain Management, Indiana Spine Group, Indianapolis, IN, USA; 6Pain Management, Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 7Pain Management, Saint Louis Pain Consultants, Chesterfield, MO, USA; 8Pain Management, Napa Valley Orthopedic Medical Group, Napa, CA, USA; 9Pain Management, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA; 10Pain Management, Nevada Advanced Pain Specialists, Reno, NV, USA; 11Pain Management, the Orthopedic Institute, Gainesville, FL, USA; 12Pain Management, Coastal Pain & Spinal Diagnostics Medical Group, Carlsbad, CA, USA; 13Pain Management, Banner University Medical Center, Tucson, AZ, USA; 14Pain Management, Rhode Island Hospital, Providence, RI, USA; 15Neuromodulation, Abbott Labs, Austin, TX, USA; 16Orthopaedic spine Surgery, Connecticut Orthopedics, Hamden, CT, USA&ast;These authors contributed equally to this workCorrespondence: Timothy Deer, Pain Management, The Spine and Nerve Center of the Virginias, 400 Court Street, Suite 100, Charleston, WV, 25301, USA, Tel +1 304 347 – 6120, Fax +1 304 347 – 6126, Email doctdeer@aol.comAim: Low Back Pain (LBP) is a prevalent condition. Spinal cord stimulation (SCS) has emerged as a more effective, long-term treatment compared to conventional medical management (CMM). The DISTINCT study enrolled and randomized chronic LBP patients with no indication of traditional spine surgery. This analysis focuses comparing study outcomes on patients initially randomized to receive CMM treatment and subsequently crossed over to SCS after 6 months.Purpose: To compare the therapeutic effectiveness and cost-efficiency of passive recharge burst SCS to CMM.Patients and Methods: A total of 269 patients were enrolled with 162 randomly assigned to SCS and 107 to CMM. The DISTINCT study design allowed a crossover to the alternative treatment arm after 6 months. Patients underwent a trial and received a permanent implant if they reported ≥ 50% pain reduction. Outcome analysis included pain (NRS), disability (ODI), catastrophizing (PCS), quality of life (PROMIS-29) and health care utilization.Results: Seventy out of eighty-one patients opted to cross over to trial SCS at 6M with 94% (66/70) undergoing a trial. Among those, 88% (58/66) reported a ≥ 50% or more pain relief and 55 received a permanent implant. At 12M visit, 71.4% reported a ≥ 50% pain improvement sustained at the 18M visit, with 24.5% (12/49) indicating a ≥ 80% improvement. Disability reductions (79% meeting the minimally important difference of a 13-point decrease), decreased catastrophizing, and significant improvements in all PROMIS-29 domains were noted. Furthermore, 42% of the patients reported decreased or discontinued opioid usage. Clinical benefits at the 12M visit were sustained through the 18M visit accompanied by a significant reduction in healthcare utilization and a &dollar;1214 cost savings.Conclusion: SCS demonstrates superior, long-term performance and safety outcomes compared to CMM therapy in LBP patients who received both CMM and SCS therapy. Additionally, SCS patients experienced reduced healthcare resource utilization and lower costs compared to those receiving CMM.Keywords: DISTINCT, low back pain, BurstDR, spinal cord stimulation, healthcare utilization, persistent spinal pain syndrome, neuromodulation

Abstract Interleukin-1α is a suggested dual-function cytokine that diverged from interleukin-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of interleukin-1α, including a nuclear localisation sequence and histone acetyltransferase-binding domains. Why evolution modified pro-interleukin-1α’s subcellular location and protein interactome, and how this shaped interleukin-1α’s intracellular role, is unknown. Here we show that TurboID proximity labelling with pro-interleukin-1α suggests a nuclear role for pro-interleukin-1α that involves interaction with histone acetyltransferases, including EP300. We also identify and validate inactivating mutations in the pro-interleukin-1α nuclear localisation sequence of multiple mammalian species, including toothed whales, castorimorpha and marsupials. However, histone acetyltransferase-binding domains are conserved in those species that have lost pro-interleukin-1α nuclear localisation. Together, these data suggest that histone acetyltransferase binding and nuclear localisation occurred together, and that while some species lost the nuclear localisation sequence in their pro-interleukin-1α, histone acetyltransferase binding ability was maintained. The nuclear localisation sequence was lost from several distinct species at different evolutionary times, suggesting convergent evolution, and that the loss of the nuclear localisation sequence confers some important biological outcome.

Abstract Background Diabetes inpatient specialist services vary across the country, with limited evidence to guide service delivery. Currently, referrals to diabetes inpatient specialists are usually ‘reactive’ after diabetes-related events have taken place, which are associated with an increased risk of morbidity/mortality and increased length of hospital stay. We propose that a proactive diabetes review model of care, delivered by diabetes inpatient specialist nurses, may contribute to the prevention of such diabetes-related events and result in a reduction in the risk of harm. Method We will conduct a cluster randomised feasibility study with process evaluation. The proactive diabetes review model (PDRM) is a complex intervention that focuses on the prevention of potentially modifiable diabetes-related harms. All eligible patients will receive a comprehensive, structured diabetes review that aims to identify and prevent potentially modifiable diabetes-related harms through utilising a standardised review structure. Reviews are undertaken by a diabetes inpatient specialist nurse within one working day of admission. This differs from usual care where patients are often only seen after diabetes-related harms have taken place. The trial duration will be approximately 32 weeks, with intervention delivery throughout. There will be an initial 8-week run-in phase, followed by a 24-week data collection phase. Eight wards will be equally randomised to either PDRM or usual care. Adult patients with a known diagnosis of diabetes admitted to an included ward will be eligible. Data collection will be limited to that typically collected as part of usual care. Data collected will include descriptive data at both the ward and patient level and glucose measures, such as frequency and results of capillary glucose testing, ketonaemia and hypoglycaemic events. The analysis aims to determine the fidelity and acceptability of the intervention and the feasibility of a future definitive trial. Whilst this study is primarily about trial feasibility, the findings of the process evaluation may lead to changes to both trial processes and modifications to the intervention. A qualitative process evaluation will be conducted in parallel to the trial. A minimum of 22 patients, nurses, doctors, and managers will be recruited with methods including direct non-participant observation and semi-structured interviews. The feasibility of a future definitive trial will be assessed by evaluating recruitment and randomisation processes, staffing resources and quality of available data. Discussion The aim of this cluster randomised feasibility trial with a process evaluation is to explore the feasibility of a definitive trial and identify appropriate outcome measures. If a trial is feasible and the effectiveness of PDRM can be evaluated, this could inform the future development of inpatient diabetes services nationally. Trial registration UK Clinical Research Network, 51,167. ISRCTN, ISRCTN70402110. Registered on 21 February 2022.

Non-malignant conditions of the prostate and seminal vesicles are much more common in imaging practice than prostate cancer. They include benign prostatic hyperplasia, infective and inflammatory prostatitis, prostatic and periprostatic cysts, and benign tumors. The advances in magnetic resonance imaging (MRI) of the prostate gland have dramatically improved the ability to identify these entities, many of them being identified incidentally in patients evaluated for other indications. Good knowledge of these conditions can aid in precise diagnosis and avoid interpretation pitfalls. In this article, we present non-malignant conditions of the prostate gland using several imaging modalities, including transrectal ultrasound, MRI, and computed tomography. We also present the pathological correlation for benign tumors.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Aaron Calodney,1 Nomen Azeem,2 Patrick Buchanan,3 Ioannis Skaribas,4 Ajay Antony,5 Christopher Kim,6 George Girardi,7 Chau Vu,8 Christopher Bovinet,9 Rainer Vogel,10 Sean Li,11 Navdeep Jassal,12 Youssef Josephson,13 Timothy Lubenow,14 Christopher M Lam,15 Timothy R Deer6 1Precision Spine Care, Tyler, TX, USA; 2Florida Spine and Pain Specialists, Tampa, FL, USA; 3Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 4Expert Pain P.A, Houston, TX, USA; 5The Orthopaedic Institute, Gainesville, FL, USA; 6The Spine and Nerve Center, Charleston, WV, USA; 7Front Range Pain Medicine, Fort Collins, CO, USA; 8Evolve Restoration Center, Santa Rosa, CA, USA; 9The Spine Center of Southeast Georgia, Brunswick, GA, USA; 10Comprehensive and Interventional Pain Management, Henderson, NV, USA; 11Premier Pain Centers, Shrewsbury, NJ, USA; 12Excel Pain and Spine, Lakeland, FL, USA; 13The Pain Management Center, Voorhees Township, NJ, USA; 14Rush University Medical Center, Chicago, IL, USA; 15University of Kansas Medical Center, Kansas City, KS, USACorrespondence: Aaron Calodney, Precision Spine Care, Tyler, TX, USA, Email aaroncalodney@me.comIntroduction: Research suggests that sacroiliac joint (SIJ) dysfunction is responsible for 15% to 30% of reported low back pain cases. Recently, there has been an increasing interest in SIJ fusion using minimally invasive surgery (MIS) due to safety. Initially, devices designed for MIS were intended for lateral approaches. A minimally invasive sacroiliac fusion implant for use with a posterior approach has been developed and is regulated for clinical use under the regulatory framework required for human cells, tissues, or cellular or tissue-based products (HCT/Ps).Methods: A multi-center, prospective, single-arm study was launched after initial studies provided preliminary data to support safety, efficacy, and durability of this minimally invasive sacroiliac posterior fusion LinQ allograft implant (NCT04423120). Preliminary results were reported previously. Final results for the full participant cohort are presented here.Results: One-hundred and fifty-nine (159) participants were enrolled across 16 investigational sites in the US between January 2020 and March 2022. One-hundred and twenty-two (122) participants were implanted. At the 1-month follow-up, 82 participants satisfied all criteria for the composite responder endpoint, representing 73.2% of the study cohort. These results stayed consistent across the remaining study timepoints with 66.0%, 74.4%, and 73.5% of participants classified as responders at the 3-, 6- and 12-month follow-up visits, respectively. VAS scores were significantly reduced (p < 0.0001) and ODI scores were significantly improved (p < 0.0001). All domains of the PROMIS-29 were also significantly improved (all p’s < 0.0001). Only one procedure-related serious AE was reported in the study.Conclusion: These results suggest that the posterior approach LinQ Implant System is a safe and effective treatment for sacroiliac joint dysfunction at 12 months, with results that are favorable compared to outcomes reported for an FDA-cleared lateral approach.Keywords: sacroiliac joint disease, sacroiliac fusion, single point posterior fusion, back pain, minimally invasive spine surgery, sacroiliitis

Abstract Genome wide association studies (GWAS) have identified a number of genomic loci that are associated with Parkinson’s disease (PD) risk. However, the majority of these variants lie in non-coding regions, and thus the mechanisms by which they influence disease development, and/or potential subtypes, remain largely elusive. To address this, we used a massively parallel reporter assay (MPRA) to screen the regulatory function of 5254 variants that have a known or putative connection to PD. We identified 138 loci with enhancer activity, of which 27 exhibited allele-specific regulatory activity in HEK293 cells. The identified regulatory variant(s) typically did not match the original tag variant within the PD associated locus, supporting the need for deeper exploration of these loci. The existence of allele specific transcriptional impacts within HEK293 cells, confirms that at least a subset of the PD associated regions mark functional gene regulatory elements. Future functional studies that confirm the putative targets of the empirically verified regulatory variants will be crucial for gaining a greater understanding of how gene regulatory network(s) modulate PD risk.

Objective The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT).

From the past decades, rodent models have played role in evaluating the use of several drugs for the treatment of brain diseases. Generally, these tests are performed by recoding a video and examine to carry out various annotation about the behavior and activities of the rodents. However, the video must be executed continuously to ensure proper annotation that causes time complexity and increases the human observation error. Conventional techniques for rodent behavioral analysis process are not affordable for the research purpose due to increase cost and poor interpretability. To tackle this issue, a new and effective deep learning (DL) technique is introduced to analyze the multiclass behaviors in rodents under real-time scenario. At first, the video captured from camera is preprocessed by performing frame conversion and noise removal process. For removing the noise, the Butterworth-amended unsharp mask filtering (B_UMF) technique is emphasized thereby improving the image quality. Finally, the Evolutionary Gravity Neocognitron Neural Network (EGravity-NCNN) model is proposed to classify multiple rodent behaviours using adaptive feature learning. The simulation process for the developed method is carried out via the Python platform and various performance like accuracy, precision and recall are scrutinized and compared with conventional schemes. The developed method achieved the overall accuracy of 97.33 %, precision of 96.29 %, and recall of 97.02 % for the classification of rodent behaviours accurately.

Background Quality of life and care varies between and within the care homes in which almost half a million older people live and over half a million direct care staff (registered nurses and care assistants) work. The reasons are complex, understudied and sometimes oversimplified, but staff and their work are a significant influence. Objective(s) To explore variations in the care home nursing and support workforce; how resident and relatives’ needs in care homes are linked to care home staffing; how different staffing models impact on care quality, outcomes and costs; how workforce numbers, skill mix and stability meet residents’ needs; the contributions of the care home workforce to enhancing quality of care; staff relationships as a platform for implementation by providers. Design Mixed-method (QUAL-QUANT) parallel design with five work packages. WP1 – two evidence syntheses (one realist); WP2 – cross-sectional survey of routine staffing and rated quality from care home regulator; WP3 – analysis of longitudinal data from a corporate provider of staffing characteristics and quality indicators, including safety; WP4 – secondary analysis of care home regulator reports; WP5 – social network analysis of networks likely to influence quality innovation. We expressed our synthesised findings as a logic model. Setting English care homes, with and without nursing, with various ownership structures, size and location, with varying quality ratings. Participants Managers, residents, families and care home staff. Findings Staffing’s contribution to quality and personalised care requires: managerial and staff stability and consistency; sufficient staff to develop ‘familial’ relationships between staff and residents, and staff–staff reciprocity, ‘knowing’ residents, and skills and competence training beyond induction; supported, well-led staff seeing modelled behaviours from supervisors; autonomy to act. Outcome measures that capture the relationship between staffing and quality include: the extent to which resident needs and preferences are met and culturally appropriate; resident and family satisfaction; extent of residents living with purpose; safe care (including clinical outcomes); staff well-being and job satisfaction were important, but underacknowledged. Limitations Many of our findings stem from self-reported and routine data with known biases – such as under reporting of adverse incidents; our analysis may reflect these biases. COVID-19 required adapting our original protocol to make it feasible. Consequently, the effects of the pandemic are reflected in our research methods and findings. Our findings are based on data from a single care home operator and so may not be generalised to the wider population of care homes. Conclusions Innovative and multiple methods and theory can successfully highlight the nuanced relationship between staffing and quality in care homes. Modifiable characteristics such as visible philosophies of care and high-quality training, reinforced by behavioural and relational role modelling by leaders can make the difference when sufficient amounts of consistent staff are employed. Greater staffing capacity alone is unlikely to enhance quality in a cost-effective manner. Social network analysis can help identify the right people to aid adoption and spread of quality and innovation. Future research should focus on richer, iterative, evaluative testing and development of our logic model using theoretically and empirically defensible – rather than available – inputs and outcomes. Study registration This study is registered as PROSPERO CRD42021241066 and Research Registry registration: 1062. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/144/29) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 8. See the NIHR Funding and Awards website for further award information. Plain language summary This study was about the relationship between staffing and quality in care homes. Almost half a million older people live in care homes in England. Why quality of care and quality of life for residents vary so much between and within homes is unknown, but staff and the ways they work are likely to be important. Researching staffing and quality is difficult: quality means different things to different people and a lot of things shape how quality feels to residents, families and staff. In the past, researchers have oversimplified the problem to study it and may have missed important influences. We took a more complex view. In five interlinked work packages, we collected and analysed: (1) research journal articles; (2) national data from different care homes; (3) data from a large care organisation to look at what it is about staffing that influences quality; (4) reports and ratings of homes from the Care Quality Commission; and (5) we looked at the networks between staff in homes that shape how quality improvement techniques might spread. We used theories about how our findings might be linked to plan for this data collection and analysis. The results were combined into something called a ‘logic model’ – a diagram and explanation that make it easier for managers, researchers and people interested in care homes to see how staffing influences quality. Staffing considerations that might improve quality include: not swapping managers too much; having sufficient and consistent staff for family-like relationships in homes and putting residents’ needs first; supporting staff and giving them freedom to act; and key staff leading by example. Research examining care home quality should capture those aspects that mean the most to residents, their families and staff. Scientific summary Background An estimated 425,000 older people in England live in 18,000 care homes: with nursing, without nursing, or dual registered homes. They are some of the oldest and the most vulnerable people in society. Resident dependency levels and care needs are often similar in homes with and without nursing – but their workforces differ significantly. In homes with nursing care, registered nurses (RNs) are employed to provide clinical care and supervise care delivery, mainly from a large workforce of non-registered care assistants. Care homes without nursing comprise only social care staff or care assistants. The NHS provides health care – including nursing care – as required; for example, supporting specialist care for residents at the end of life. Staffing profiles and establishments vary between providers and so studying care homes and their workforce is complex. Conceptually, quality is similarly complex; it is contested, contingent, contextualised, dynamic and often deeply personal. Two dimensions of quality require consideration in care homes: quality of care and quality of life. While care home staff and their work are likely determinants of quality, research into the staffing–quality relationship is comparatively scant. Measuring quality often focuses on clinical outcomes, such as pressure ulcer prevalence, falls or medication errors. Many studies are in North American long-term care and the few English studies’ primary focus has been on staff turnover and quality and working conditions and quality. Our mixed-methods study addresses some of the theoretical gaps and methodological challenges associated with understanding staffing’s relationship to quality. Using established theory we focused on the structures, processes and outcomes of quality. Our aim of investigating workforce models of nursing and care support in care homes that effectively benefit residents, relatives and staff was addressed through six objectives, which were the focus of five linked work packages (WP). Objectives Describe variations in the characteristics of the care home nursing and support workforce (WP1). Identify the dependency and needs of residents and relatives in care homes and their association with care home staffing (WP2, WP3). Examine how different care home staffing models (including new roles) impact on quality of care, resident outcomes and NHS resources (WP1, WP2, WP3). Explain how care home workforce (numbers, skill mix and stability) might meet the dependency and needs of residents (WP1, WP2, WP3, WP4). Explore and understand the contributions of the nursing and support workforce (including innovations in nursing and support roles) in care homes to enhance quality of care (WP1, WP4). Translate methods used for modelling the relationships between staffing and quality to provide a platform for sector-wide implementation (WP5). Methods A mixed-method (QUAL-QUANT) parallel design built around Donabedian’s theoretical framework of structures, processes and outcomes was the basis for our exploration of the relationship between care home staffing and quality. The coronavirus disease 2019 (COVID-19) pandemic meant some deviation from our original protocol was necessary. Work package 1 (WP1) was two evidence reviews: a systematic review synthesising 36 studies of care home staff perceptions of their roles and responsibilities in promoting quality; a realist review (n = 66 studies) then developed evidence and theory-based explanations of how care home staff behaviours promote quality of care and quality of life, why and in what circumstances. Work packages 2 and 3 used routinely collected measures of staffing and examined their relationship to quality. WP2 was a cross-sectional observational study, modelling the relationship between care quality – as measured in Care Quality Commission (CQC) inspection reports – and care home workforce characteristics from the National Minimum Data Set for Social Care (NMDS-SC). WP3 analysed routinely collected longitudinal data measures of workforce, nurse-sensitive indicators of care quality, resident characteristics and home characteristics from a large corporate care home provider over 42 months. A cost analysis from a provider perspective was also undertaken. Work package 4 used documentary analysis of 30 purposively sampled, publicly available, inspection reports from the English national quality regulator (CQC) from homes rated as outstanding or inadequate to examine (1) how staffing structures influenced quality and (2) the care processes that explain the relationship between staffing and quality. In WP5, care homes (n = 11) were purposively sampled and social network analysis (SNA) using questionnaires and roster name generation was used to map the self-reported advice and influence relationships present in care homes. To assess homes’ readiness for innovation and work-related barriers to adoption of our (translated) findings, eight managers completed an adapted version of the Normalisation MeAsure Development questionnaire (NoMAD) questionnaire – an operationalised instrument of Normalisation Process Theory. Public and stakeholder involvement and engagement We worked closely with the public and stakeholders throughout, from question formulation through to synthesis. Two advisory groups were formed: (1) a resident and relative group and (2) a care home manager group. The study steering committee (SSC) contained key stakeholders – including relatives – to provide oversight and guidance. These mechanisms ensured perspectives other than the research team informed and improved research design and implementation and prompted wider conversations and learnRNing that benefited the research. Ethics approval Work package 2 and WP3 were approved (2 August 2017) by the Social Care Research Ethics Committee (17/WM/0232). WP5 was approved (21 June 2019) by the University of Leeds, Faculty of Medicine and Health, Ethics and Governance Committee (HREC 18-028). Findings The five linked WP findings were synthesised using a logic model to explain what is likely to work, why and how, and the interactions between structures, processes and outcomes important for the staffing–quality relationship. Managerial stability was important: care homes with a manager in-post in the 12 months prior to a CQC inspection were more likely to be rated as good or outstanding (WP2). Managers made those workforce decisions necessary for meeting residents’ care and safety needs (WP4). Managers of care homes rated good or outstanding had authority and flexibility to secure the workforce they judged necessary (WP4). Cohesive working relationships between managers and their corporate senior management team or owner helped managers enact their decisions (WP4). Higher staff-to-bed ratios were associated with a greater chance of a good or outstanding CQC inspection score (WP2). More care from RNs was associated with fewer falls with fractures, urinary tract infections (UTIs) and medication errors (WP3). Use of agency nurses to cover for staff sickness or unfilled vacancies was not associated with more falls, infections or pressure ulcers, but was associated with more medication errors (WP3). Simply increasing nursing input is unlikely to be a cost-effective way of reducing adverse incidents in care homes (WP3). WP4 (and WP1ii) identified the importance of having ‘sufficient’ staff to meet residents’ needs and preferences and improve outcomes. But detail of how staffing levels were determined by managers and consistent use of tools to support professional judgement about staffing (WP4) was lacking. Staff stability and minimising agency staff use were perceived as necessary conditions for quality (WP4). Having experienced care staff, that is, staff in post for 5 years, was likely to improve quality, as measured by ratings (WP2). A stable workforce was also associated with skills and competence (WP1i, WP1ii, WP4). Opportunities for staff induction, training and continuing professional development, alongside staff supervision, were extensive in care homes rated as outstanding (WP4). High staff turnover reduced opportunities for developing broader staff skills and competence, narrowing it to staff induction and mandatory training (WP4). Staffing consistency was important for organising care and work (WP1i, WP1ii, WP4). Larger homes were less likely to be rated positively (WP2). Other WPs highlighted the importance of team size (not home size) as a lever for promoting quality (WP1i, WP1ii, WP4). Small groups of linked residents and staff (5–15 residents per staff member based on level of resident dependency) promoted familiarity, communication and a family-like environment for cultivating relationships (WP1ii). Establishing these family-like relationships and ‘knowing’ residents promoted personalisation of resident care (WP1i), encouraging staff to go beyond purely assisting residents with physical tasks, towards addressing wider social and emotional needs (WP1ii). The reviews (WP1i, WP1ii) highlight where the requisite roles and responsibilities of the workforce might help achieve this. Developing relationships based on consultation – with families, professionals outside the home and residents – to support residents was a feature of homes rated as outstanding (WP1i, WP1ii, WP4). These relationships informed care planning and personalisation of care (WP1i). Relationships between staff and families also legitimised family involvement in care to support quality (WP1ii). Unit-level supervisors that role modelled relationship building were important levers for realising team ambitions of relationship-based quality (WP1ii, WP4). Staffing consistency was important for teamworking. In care homes rated outstanding, staff reported working together and supporting each other towards a collective vision of care and support (WP4). Staff that felt supported, valued and – with (managerial) ‘permission’ – able to prioritise residents’ needs, adapted and adopted behaviours promoting residents’ expressing preferences for care (WP1ii, WP4). More autonomy in day-to-day work, with associated accountability, led to greater staff engagement and satisfaction (WP1ii, WP4). Team reciprocity was linked to open communication, information exchange, advice and influence (WP1ii, WP5). Reciprocity encouraged teams to draw on each other’s knowledge and skills to promote individualised care and enhance quality (WP1i, WP1ii, WP4). Combining written and verbal staff communication was a feature in homes rated as outstanding and linked to better resident care (WP4). Visible unit-level supervisors – not always managers – fostered teamworking. They also minimised conflicts, enabling team reciprocity and relationships (WP1ii). Social networks can promote or hinder the behavioural mechanisms influencing quality (WP5). Networks that were interconnected, dense or cohesive, built around strong advice and influence relationships, had higher chances of implementing change associated with innovation around quality (WP5). The care home manager – as opinion leader (i.e. providing most advice and influence and receiving most advice and influence) – was pivotal in implementing innovation-related change (WP5). Leadership and management behaviours promoted resident-centred approaches; ensured effective communication; promoted staff confidence; offered practical and emotional support and recognition to staff; and encouraged diversity (WP1ii). Staff feeling valued was linked to greater staff commitment and contribution to quality (WP4). A managerially endorsed philosophy of care (valuing residents and staff) encouraged the staff behaviours needed for individualised resident care (WP1ii, WP4). Based on our analysis, measuring the following resident outcomes would provide a more meaningful picture of the relationship between staffing and quality: the extent to which resident needs and preferences are met (and culturally appropriate) (WP1i, WP1ii, WP4); resident and family satisfaction (WP1i, WP1ii, WP4); residents living with purpose to promote their quality of life and well-being (WP1i, WP1ii, WP4); and safe care for residents (including clinical outcomes) (WP1i, WP1ii, WP2, WP3, WP4). Staff well-being and job satisfaction were important outcomes which influenced quality as experienced by residents. Conclusions Our study makes a novel and important contribution to understanding the importance of the relationship between staff, their work and behaviours and quality in care homes. We have attempted to shift the debate away from a reductionist picture of numbers of staff and their relationship to clinical indicators, towards a more nuanced recognition of the ways in which staff in the right amounts and with the right behaviours can meet resident’s needs and preferences. Staffing needs to be stable, skilled and competent to realise the benefits of person-focused organisation of care, and enhanced teamworking. Leadership, reward and recognition of staff and a shared philosophy of care provide needed context for the relationships required to improve quality as experienced by residents. Our findings will be useful for people and organisations making policy and delivering services that want to work towards the best ways to deploy and support quality in care homes using their most valuable resource: their staff. Implications for social care Understanding that numbers of staff alone are a necessary but not sufficient condition for care home quality. Quality improves in homes when more care is provided by RNs. Simply introducing ‘more’ staff (particularly RNs) is unlikely to be a cost-effective way of reducing adverse incidents in care homes. Quality relies on the who, what and how of staffing arrangements and organisation of work. Leadership is key, influencing how organisational resources are used to promote the environments and cultures needed for quality-promoting relationships to flourish. Realising and supporting the potential of the staffing resource (clinical, care, social and cultural skills and competence) are essential for quality. Opportunities for learning and development demonstrate an organisation values staff and may support staff retention. A focus on the structures that support staffing consistency (stability, skill and competence) is important for influencing processes (the organisation of care and teamworking) and outcomes for residents and staff. Developing transparent approaches that enable care home managers to effectively judge and make decisions about staffing levels is crucial for safe and appropriate care for residents. Reciprocal relationships, beyond the immediate care team and including residents, their families and health and social care professionals promote quality. Leadership and management behaviours influence staff commitment and thus their contribution to quality. A ‘visible’ unit supervisor and staff who ‘connect’ and influence the team are essential for quality and innovation in care homes. Implications for research Future research should: Unpack the contribution of direct care support workforce (including care assistants, senior care assistants and nursing associates) working at different levels of skills and competence to care home quality. Explore how training for care assistants, senior care assistants and nursing associates contributes to improving quality. Consider differences for temporary (i.e. step-up or step-down care) versus permanent (i.e. long-term placement) care home residents. Explore how resident population levels of dependency are related to quality. Use innovative methods to capture quality in ways that recognise individual stakeholder views, values, expectations and preferences and address both quality of care and quality of life. Develop robust social network interventions to change network structures to enhance reciprocity and advice and influence relationships to embed innovations for enhancing quality. Consider machine learning methods for analysis of routine data because these methods are better able to identify non-linear relationships between staffing and care quality indicators than traditional regression analysis in order to better identify minimum adequate staffing levels. Use methods to promote more accurate modelling of the staffing–quality relationship through data linkage. Further test and develop our logic model. Study registration This study is registered as PROSPERO CRD42021241066 and Research Registry registration: 1062. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/144/29) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 8. See the NIHR Funding and Awards website for further award information.

ABSTRACTBackground Physiological and pharmacological variances from younger patients make geriatric patients anesthetically challenging. Opioids though effectively controlling pain may cause serious complications in elderly. Non-opioid analgesics are being considered for adequate analgesia with fewer complications.Methods Reaching OR, MAP and HR were recorded (T0), thirty patients were assigned into: OFA group received dexmedetomidine 1 µg/kg over 10 min loading dose, then infusing dexmedetomidine (0.3 µg/kg/h), lidocaine (2 mg/kg/h) and magnesium sulfate (1.5 g/h) during surgery and OA group received fentanyl 2 µg/kg loading dose then infusion (1 µg/kg/h) during surgery. MAP and HR were documented after starting infusions (T1), after intubation (T2), visualizing surgical field with arthroscope (T3) then every 10 min till end. Surgeon graded surgical field (T3) then every 10 min till end. Postoperatively OAA/S, MAP and HR were recorded. NRS was assessed in PACU, at 1 h, 2 h, 8 h, 16 h and 24 h. Patients scoring ≥ 4 received paracetamol 1 gm IV infusion (4 g/24 h maximum dose) documenting first 24 hours total dose and postoperative complications. AMT was assessed postoperatively for three days. Patients scoring

In this work, AgNPs were synthesized using an anthocyanin extract from Peruvian purple potato INIA 328—Kulli papa. The anthocyanin extract was obtained through a conventional extraction with acidified ethanolic aqueous solvent. This extract acted as both a reducing and stabilizing agent for the reduction of silver ions. Optimization of synthesis parameters, including pH, reaction time, and silver nitrate (AgNO3) concentration, led to the optimal formation of AgNPs at pH 10, with a reaction time of 30 min and an AgNO3 concentration of 5 mM. Characterization techniques such as X-ray diffraction (XRD) and dynamic light scattering (DLS) revealed that the AgNPs had a crystallite size of 9.42 nm and a hydrodynamic diameter of 21.6 nm, with a zeta potential of −42.03 mV, indicating favorable colloidal stability. Fourier Transform Infrared (FTIR) analysis confirmed the presence of anthocyanin functional groups on the surface of the AgNPs, contributing to their stability. Furthermore, the bacterial activity of the AgNPs was evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). For E. coli, the MIC was 0.5 mM (0.05 mg/mL) and the MBC was 4.5 mM (0.49 mg/mL). Similarly, for S. aureus, the MIC was 0.5 mM (0.05 mg/mL) and the MBC was 4.0 mM (0.43 mg/mL). These results highlight the potential benefits of AgNPs synthesized from Peruvian purple potato anthocyanin extract, both in biomedical and environmental contexts.

Aim Magnetic resonance imaging (MRI) of anorectal malignancy is often reported assuming low rectal adenocarcinoma (LRC). The biopsy may, however, reveal squamous cell carcinoma (SCC). Thus, the aim was to compare the imaging findings of SCC and LRC.

Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices.

In 2018, the da Vinci Single Port (SP) robotic system was approved by the US Food and Drug Administration for urologic procedures. Available studies for the application of SP to prostate cancer surgery are limited. The aim of our study is to summarize the current evidence on the techniques and outcomes of SP robot-assisted radical prostatectomy (SP-RARLP) procedures. A narrative review of the literature was performed in January 2023. Preliminary results suggest that SP-RALP is safe and feasible, and it can offer comparable outcomes to the standard multiport RALP. Extraperitoneal and transvesical SP-RALP appear to be the two most promising approaches, as they offer decreased invasiveness, potentially shorter length of stay, and better pain control. Long-term, high-quality data are missing and further validation with prospective studies across different sites is required.

The PIEZO1 channel and the PECAM1 cell adhesion molecule interact and PIEZO1 cooperates with PECAM1 and CDH5 cell junctions during mechanical stress.

Background Medicine prescribing, monitoring and administration in care homes can be significantly enhanced. Effective interventions to improve pharmaceutical care and resident outcomes are required. The enablement of pharmacists to prescribe provides an opportunity for pharmacist independent prescribers to assume responsibility for improving pharmaceutical care, medication-related outcomes and resident safety whilst reducing general practitioner workload. Objective(s) To determine the effectiveness and cost-effectiveness of pharmacist independent prescribing in care homes. Design Development work was undertaken through five work packages before the delivery of the definitive trial. Triads of pharmacist independent prescribers, care home and general practice with responsibility over 20 care home residents were recruited and cluster randomised to intervention or usual care for 6 months. Researchers were blinded at recruitment stage only. Recruitment of 880 residents was required to provide 80% statistical power, to show a 21% reduction in falls over 6 months, assuming 20% attrition. Randomisation was undertaken electronically at triad level, stratified by geographical area. Intention-to-treat analysis undertaken using a negative binomial model. Parameters were estimated using a generalised estimating equation approach. Costs were captured from an NHS perspective. Quality of life (EuroQol; five domain; five level) was collected by proxy to enable cost/quality-adjusted life-year estimation. A concurrent process evaluation was performed. Safety was monitored through a review of pharmacist independent prescriber activities, independent concerns reporting and review of adverse events. Participants Forty-nine triads of general practitioners, pharmacist independent prescribers and care homes were recruited with 454 residents allocated to the intervention arm and 428 to the control arm. Intervention Medication review and care planning, medication reconciliation, staff training, support with care home medication-related procedures, deprescribing and authorisation of monthly prescriptions. Main outcome measure Fall rate per person over 6 months. Results Data for 449 intervention and 427 control residents available for final analysis. The 6-month fall rate ratio in favour of intervention was 0.91 (95% confidence interval 0.66 to 1.26; p=0.58). No significant difference in secondary outcomes was identified except Drug Burden Index (rate ratio 0.83, 95% confidence interval 0.75 to 0.92; p

BackgroundUnder the pressure of Human Adenovirus (HAdV)-associated acute respiratory infection (ARI) outbreak in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) and examine the associated clinical features and risk factors of more severe cases.MethodsThis study evaluated pediatric patients with ARI which had tested positive for HAdV between October and November 2022 using a multiplex real-time PCR panel. Nasopharyngeal aspirates or nasal swab samples were used for sequencing to identify HAdV subtypes. Clinical data were collected retrospectively.ResultsAmong 97 successfully sequenced samples, the predominant subtypes were HAdV-B3 (83%), HAdV-B7 (16%) and HAdV-C2 (1%). Lower respiratory manifestations were found in 25% of the patients of which 5% were diagnosed with severe pneumonia. There was no significant association between HAdV subtype and clinical features except higher white blood cell and neutrophil counts in those detected with HAdV-B3 (pConclusionHAdV-B3 and HAdV-B7 were predominant in the outbreak. Co-detection of HAdV together with other respiratory viruses was a strong risk factor for lower respiratory tract illnesses and severe pneumonia. The findings advocate the advantages of multi-factor microbial panels for the diagnosis and prognosis of ARI in children.

The brain-expressed receptor GPR10 is involved in energy homeostasis in mice. Here the authors identify rare loss of function variants in GPR10 in people with severe obesity and showed that one of these variants causes obesity when modelled in mice, suggesting that future studies could explore GPR10 as a potential target for weight-loss therapy.

Abstract Background Canadians endured unprecedented mental health (MH) and support access challenges during the first COVID-19 wave. Identifying groups of individuals who remain at risk beyond the acute pandemic phase is key to guiding systemic intervention efforts and policy. We hypothesized that determinants of three complementary, clinically actionable psychiatric outcomes would differ across Canadian age groups. Methods The Personal Impacts of COVID-19 Survey (PICS) was iteratively developed with stakeholder feedback, incorporating validated, age-appropriate measures. Baseline, cross-sectional online data collected between November 2020-July 2021 was used in analyses. Age group-specific determinants were sought for three key baseline MH outcomes: (1) current probable depression, generalized anxiety disorder, obsessive–compulsive disorder and/or suicide attempt during COVID-19, (2) increased severity of any lifetime psychiatric diagnosis, and (3) inadequate MH support access during COVID-19. Multivariable logistic regression models were constructed for children, youth (self- and parent-report), young adults (19–29 years) and adults over 29 years, using survey type as a covariate. Statistical significance was defined by 95% confidence interval excluding an odds ratio of one. Results Data from 3140 baseline surveys were analyzed. Late adolescence and early adulthood were identified as life phases with the worst MH outcomes. Poverty, limited education, home maker/caregiver roles, female and non-binary gender, LGBTQ2S + status and special educational, psychiatric and medical conditions were differentially identified as determinants across age groups. Interpretation Negative psychiatric impacts of COVID-19 on Canadians that include poor access to MH support clearly persisted beyond the first wave, widening pre-existing inequity gaps. This should guide policy makers and clinicians in current and future prioritization efforts.

Background: In surgically high-risk patients with acute cholecystitis (AC), percutaneous cholecystostomy (PC) is an effective procedure. This study aimed to study the clinical outcomes of PC and to assess predictors for recurrence following PC placement. Methodology: A retrospective data review of all patients who underwent a PC for AC between 2010 and 2020 was performed. Results: Seventy-one patients underwent a PC with a mean age of 61.35 years (standard deviation: 14.11); 59 (83.1%) were male; 32 (45.1%) were the American Society of Anesthesiologists III and IV. Forty (56.3%) patients had multiple comorbid illnesses; 70 (98.6%) patients had Grade 2, 3 cholecystitis. All patients had ultrasound-guided drainage; 63 (88.7%) had transhepatic route. The mean duration till PC removal was 51.58 (1–313) days. Eleven (15.5%) patients developed recurrence after PC placement over a median of 40 (29–102) days; 6 (54.5%) were managed nonoperatively, 3 (27%) underwent laparoscopic cholecystectomy, and 2 (18%) developed cholangitis. After index admission with AC managed by PC, thirty-nine (54.9%) patients underwent cholecystectomy; 4(5.6%) at the index admission, 35 (49.3%) elective interval cholecystectomies. The rate of conversion to open at interval cholecystectomy among patients with no recurrence in the interval period was 31.88% (7/22), and 50% for patients with recurrent AC. Five (7.04%) patients had mortality at the index admission, and the overall 1-year mortality was 8.45% (6/71). Conclusion: A high clinical success rate and less procedure-related morbidity make PC a favorable procedure in surgically high-risk patients. Patients with a recurrent episode of AC were found to have higher rates of conversion at interval cholecystectomy. No specific predictor for recurrence was identified.

AIM: (1) To compare optical coherence tomography (OCT) parameters between amblyopic eyes and fellow eyes in patients presenting with anisometropic amblyopia. (2) To find OCT factors predicting the outcomes of occlusion therapy. MATERIALS AND METHODS: This prospective study was conducted in a tertiary eye care center for a period of 20 months. Fifty-four children diagnosed with anisometropic amblyopic were included in the study. After complete ophthalmic and OCT examination, patients were advised to undergo occlusion therapy with large spectacle patch. Patients were reviewed after 6 months to record improvement in visual acuity and analyze their OCT parameters. Statistical tests used were paired “t” test and independent “t” test. RESULTS: The mean age of 54 study patients was 9.24 ± 2.82 years. For comparison of OCT parameters, they were classified as myopic (22 patients), hypermetropic (24 patients), and astigmatic (8 patients) groups. In the anisomyopic amblyopia group, the mean inner macular thickness was significantly increased in fellow eyes (304.09 ± 11.06 μm) compared to amblyopic eyes (297.59 ± 14.16 μm). In the anisohyperopic amblyopia group, the outer macular thickness significantly increased in amblyopic eyes (286.43 ± 18.63 μm) when compared to fellow eyes (272.62 ± 14.90 μm). In the follow-up visit, 28 patients showed improvement and 6 patients did not show improvement in final best-corrected visual acuity, and the OCT parameters in amblyopic eyes of these two groups did not differ significantly. CONCLUSION: Abnormal experience in early life does not affect the maturation process of retinal layers as evident by OCT parameters, and these parameters cannot predict the outcomes of occlusion therapy.

Abstract Background In the UK, one third of people with dementia live in residential care homes, a sector where high staff turnover negatively affects continuity of care. To examine the effect of including personhood and citizenship principles in training, interventions need to be robustly tested, with outcomes relevant to residents with dementia. Methods Phase one intervention development: The training intervention (PERSONABLE) comprised five reflective exercises facilitated by a mental health nurse/researcher. PERSONABLE was informed by four focus groups, and one field exercise, consisting of care home staff and family members. Phase two feasibility testing: Participants were (i) care home residents with dementia and (ii) care home staff working in any role. After baseline measurements, care homes were randomly allocated to (i) staff receiving PERSONABLE training or (ii) training as usual. Feasibility outcomes were the recruitment and attrition of care homes, residents and staff members (measured ten weeks between randomisation and follow-up), the acceptability of the training intervention PERSONABLE, and acceptability of outcome measures. The care home environment was evaluated, at baseline, using the Therapeutic Environment Screening Survey for Residential Care Homes. Measurements conducted at baseline and follow-up were resident wellbeing (Dementia Care Mapping™), staff knowledge of and confidence with personhood and citizenship (Personhood in Dementia Questionnaire and a perceived ability to care visual analogue scale). Inter-rater agreement for Dementia Care Mapping™ was undertaken at follow-up in one intervention and one training as a usual care home. Results Phase one: The developed reflective approach to the PERSONABLE exercises appeared to give staff a holistic understanding of residents living with dementia, seeing them as autonomous people rather than reductively as persons with a condition. Phase two: Six care homes, 40 residents and 118 staff were recruited. Four residents were lost to follow-up. Twenty-nine staff in the PERSONABLE arm of the study received the training intervention. In the PERSONABLE arm, 26 staff completed both baseline and follow-up measurements compared to 21 in the training as the usual arm. The most common reason for the loss to follow-up of staff was leaving employment. For the outcome measure Dementia Care Mapping™, the proportion of overall agreement between the two observers was 18.6%. High attrition of staff occurred in those homes undergoing leadership changes. Conclusion With the right approach, it is possible to achieve good engagement during trial recruitment and intervention delivery of care home managers, staff and residents. Organisational changes are a less controllable aspect of trials but having a visible researcher presence during data collection helps to capitalise the engagement of those staff remaining in employment. Tailored, brief and flexible training interventions encourage staff participation. Simplification of study methods helps promote and retain sufficient staff in a definitive randomised controlled trial. This study found that some components of Dementia Care Mapping™ work effectively as an outcome measure. However, inter-rater reliability was poor, and the practical implementation of the measurement would need a great deal of further refinement to accurately capture the effect of a training intervention if delivered across a large number of clusters. The Dementia Care Mapping™ measurement fidelity issue would be further complicated if using multiple different unacquainted observers. Trial registration Registered with the ISRCTN under the title: Does a dementia workshop, delivered to residential care home staff, improve the wellbeing of residents with dementia? Trial identifier: ISRCTN13641553. Registered: 30/05/2017 http://www.isrctn.com/ISRCTN13641553 .

Purpose Usual interstitial pneumonia (UIP) pattern of interstitial lung disease (ILD) can have varied etiology, with connective tissue disease (CTD) being a common known cause. The anterior upper lobe (AUL) sign, exuberant honeycombing (EHC), and straight edge (SE) sign are recently described computed tomography (CT) signs in CTD-related UIP. We test the diagnostic value of these CT signs for CTD in patients with UIP and compare the incidence of these signs between CTD-related UIP and non–CTD-related UIP. We also evaluated the interobserver agreement in detection of these CT signs. Methods Retrospective study of all patients who had UIP pattern of ILD on CT thorax done from January 1, 2016 to January 31, 2019, was grouped into two: non–CTD-related UIP or CTD-related UIP. CT thorax was reviewed for the presence of these signs—AUL, SE, and EHC. The diagnostic values of these signs in diagnosing CTD-related UIP was assessed. For assessment of interobserver agreement, another radiologist reviewed a subset of 30 randomly selected cases and looked for the presence of these signs. Results Of the 156 patients included, 76 had CTD. The incidence of CT signs were significantly higher in CTD-related UIP. The specificities of AUL, EHC, and SE were 82.5, 75, and 85%, respectively. The EHC sign had highest sensitivity of 48.7%. Inclusion of more than one sign increased the specificity of diagnosis of CTD-related UIP; however, the sensitivity decreases. There was excellent interobserver agreement (0.81–0.87) for each of these signs. Conclusion The presence of SE, AUL, and EHC signs in cases with UIP pattern are specific imaging markers to diagnose underlying CTD; however, due to its low sensitivity, the absence of these signs cannot exclude the same. Because of its excellent interobserver agreement, these signs are reliable in the evaluation of CTD-related ILD.

Abstract Objectives The main aim of this study was to compare magnetic resonance imaging (MRI) findings of recurrent and treatment-naïve fistula-in-ano and to correlate imaging findings with anal sphincter morphology in recurrent fistula-in-ano. Methods This is a retrospective study of adult patients who underwent MRI for suspected fistula-in-ano in 2018. After excluding patients with alternative diagnosis, patients were stratified into recurrent (n = 103) and treatment-naïve (n = 106) fistula-in-ano groups. Two blinded radiologists reread MRI scans in consensus for fistula characteristics and anal sphincter morphology. We compared imaging features of recurrent and treatment-naïve fistula-in-ano, assessed the incidence of anal sphincter scarring among patients with recurrent fistula-in-ano, and studied its association with fistula features. Results Two-hundred nine patients (187 males) with mean age of 40.6 (standard deviation: 12.2) years were included. Trans-sphincteric, inter-sphincteric, extra-sphincteric, and supra-sphincteric fistula-in-ano were seen in 63.6, 33, 2.9, and 0.5%, respectively. There were secondary tracts, supralevator extension, and secondary cause for fistula in 49.3, 12.9, and 14.8%, respectively. There was no difference between the fistula features of recurrent and treatment-naïve fistula-in-ano, except for significantly fewer external openings among recurrent fistula-in-ano (p = 0.005). Among patients with recurrent fistula-in-ano, MRI detected anal sphincter defect/scarring was seen in 53.4% (n = 55) and was significantly associated with posterior fistula-in-ano (p = 0.031), collections and/or supralevator extension (p = 0.010), and secondary tracts (p = 0.015). Conclusion Fistula features of recurrent and treatment-naïve patients were mostly similar. There was high incidence (53.4%) of MRI-identified anal sphincter scarring/defect among recurrent fistula-in-ano, which was significantly associated with posterior fistula, collections, supra or translevator extension, and secondary tracts. Key Points MRI-identified anal sphincter scarring is very common among patients with recurrent fistula-in-ano and seen in more than half of them. There was significantly higher incidence of sphincter scarring among patients who had posterior fistula, collections, supralevator/translevator extension, and secondary tracts.

This paper aims to present aspects related to corporate governance, organisational resilience and sustainable practices developed by Brazilian companies during the COVID-19 pandemic. The methodological strategy included documentary research to identify sustainability reports published by companies listed on the Ibovespa index, which were examined through the content analysis technique. The results allowed light to be shed on opportunities for improvement concerning sustainability and corporate governance. Regarding organisational resilience, risk management is central for the development of sustainability practices by organisations. The support to society related to the COVID-19 pandemic was evidenced mainly through the donation of financial resources, equipment and hospital supplies. Practices related to reducing energy consumption and minimising waste generation were those most associated with environmental aspects. The actions identified were mapped according to their relations with the SDGs. Managers can benefit from the information presented in this study to enhance organisational sustainability and resilience, while researchers can use it as a starting point for future studies.

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1‐7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro‐X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR‐associated protein 9–mediated global prolylcarboxylpeptidase‐knockout and adeno‐associated virus serotype 9–mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg per day) for 4 weeks, aiming to investigate the cardioprotective effect of prolylcarboxylpeptidase against hypertensive cardiac hypertrophy. Prolylcarboxylpeptidase expression was upregulated after 2 weeks of angiotensin II infusion and then became downregulated afterward in wild‐type mouse myocardium, suggesting its compensatory function against angiotensin II stress. Moreover, angiotensin II–treated prolylcarboxylpeptidase‐knockout mice showed aggravated cardiac remodeling and dampened cardiac contractility independent of hypertension. We also found that prolylcarboxylpeptidase localizes in cardiomyocyte lysosomes, and loss of prolylcarboxylpeptidase led to excessive angiotensin II levels in myocardial tissue. Further screening demonstrated that hypertrophic prolylcarboxylpeptidase‐knockout hearts showed upregulated extracellular signal‐regulated kinases 1/2 and downregulated protein kinase B activities. Importantly, adeno‐associated virus serotype 9–mediated restoration of prolylcarboxylpeptidase expression in prolylcarboxylpeptidase‐knockout hearts alleviated angiotensin II–induced hypertrophy, fibrosis, and cell death. Interestingly, the combination of adeno‐associated virus serotype 9–mediated prolylcarboxylpeptidase overexpression and an antihypertensive drug, losartan, likely conferred more effective protection than a single treatment protocol to mitigate angiotensin II–induced cardiac dysfunction. Conclusions Our data demonstrate that prolylcarboxylpeptidase protects the heart from angiotensin II–induced hypertrophic remodeling by controlling myocardial angiotensin II levels.

Abstract Parkinson’s disease (PD) research has largely focused on the disease as a single entity centred on the development of neuronal pathology within the central nervous system. However, there is growing recognition that PD is not a single entity but instead reflects multiple diseases, in which different combinations of environmental, genetic and potential comorbid factors interact to direct individual disease trajectories. Moreover, an increasing body of recent research implicates peripheral tissues and non-neuronal cell types in the development of PD. These observations are consistent with the hypothesis that the initial causative changes for PD development need not occur in the central nervous system. Here, we discuss how the use of neuronal pathology as a shared, qualitative phenotype minimises insights into the possibility of multiple origins and aetiologies of PD. Furthermore, we discuss how considering PD as a single entity potentially impairs our understanding of the causative molecular mechanisms, approaches for patient stratification, identification of biomarkers, and the development of therapeutic approaches to PD. The clear consequence of there being distinct diseases that collectively form PD, is that there is no single biomarker or treatment for PD development or progression. We propose that diagnosis should shift away from the clinical definitions, towards biologically defined diseases that collectively form PD, to enable informative patient stratification. N-of-one type, clinical designs offer an unbiased, and agnostic approach to re-defining PD in terms of a group of many individual diseases.

Microalgae provide valuable bio-components with economic and environmental benefits. The monitoring of microalgal production is mostly performed using different sensors and analytical methods that, although very powerful, are limited to qualified users. This study proposes an automated Raman spectroscopy-based sensor for the online monitoring of microalgal production. For this purpose, an in situ system with a sampling station was made of a light-tight optical chamber connected to a Raman probe. Microalgal cultures were routed to this chamber by pipes connected to pumps and valves controlled and programmed by a computer. The developed approach was evaluated on Parachlorella kessleri under different culture conditions at a laboratory and an industrial algal platform. As a result, more than 4000 Raman spectra were generated and analysed by statistical methods. These spectra reflected the physiological state of the cells and demonstrate the ability of the developed sensor to monitor the physiology of microalgal cells and their intracellular molecules of interest in a complex production environment.

IntroductionAbnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation.AimAssess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin.MethodsCOVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested for the same period.Results33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p = 0.73) between patients admitted to a ward or escalated to ITU. Significant correlations were observed between FIBA5 (r = 0.62; pConclusionCOVID-19 patients were hypercoagulable on admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.

Abstract Preclinical rodent models suggest that psychosis involves alterations in the activity and glutamatergic function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (p peakFWE = 0.003, t = 4.4, z = 4.19) and a poor functional outcome (p peakFWE