Exercise-induced modulation of neuroinflammation in ageing.

Optimal performance of the central nervous system (CNS) depends on dynamic, multidirectional communication between different cell types both within and without the CNS to maintain the homeostatic environment. Ageing, in turn, is associated with CNS disequilibrium resulting in suboptimal functioning of its cells and potential cognitive impairment. Emerging evidence indicates that inter-organ communication influences the functioning of CNS cell types, which are subject to age- and environment-dependent alterations. Endurance exercise has specifically been demonstrated to have a marked impact on neuroimmune communications, particularly those involving microglia, the resident macrophages of the CNS parenchyma, as well as microglia-astrocyte interactions in rodents. Via its action on CNS glial cells, regular aerobic exercise has been shown to provide an adaptive advantage against perturbations to homeostasis, such as immunological challenge or ageing. In light of the accumulating evidence and evolutionary reasoning it may be argued that recurrent exercise-associated inter-organ signalling is necessary for the optimisation of glial function and hence CNS equilibrium. This, in turn, would imply that the absence of exercise-derived mediators and dysregulated inter-organ communication associated with a sedentary lifestyle may contribute to CNS dyshomeostasis, which is accelerated during ageing. As well as exploring the evidence of the impact of exercise on glial function, here we suggest potential next steps in identifying the mechanistic underpinnings of these effects and the potential importance of sex differences.

Mohs micrographic surgery for the treatment of primary cutaneous mucinous carcinoma.

Primary cutaneous mucinous carcinoma (PCMC) is a rare adnexal tumour of the skin. Clinically, it appears as a benign cyst, but it has characteristic histopathology. It is a slow-growing tumour that rarely metastasizes but is associated with significant morbidity due to its high recurrence rate. Standard practice has been to surgically remove it with a wide local excision of 1-2-cm margin. In the last decade, increasing reports of Mohs micrographic surgery (MMS) for the treatment of PCMC have been described. MMS appears to reduce recurrence rates while allowing for more conservative margins. Given the rarity of PCMC, there are no prospective randomized control trials on treatment. This is the largest case series of PCMC treated by MMS to date.

The pits.

A 71-year-old woman presented with a rash in the bilateral axillae. Histopathology showed hyperkeratosis and parakeratosis with retention of basophilic keratohyalin granules.

Painful flexural plaques.

A 30-year-old man presented with a 6-year history of eroded, orange-red plaques with a subtle nodular edge in the bilateral axilla, groin and perianal skin leading to pain, scarring and limited shoulder extension. Click https://www.wileyhealthlearning.com/#/online-courses/9b96cb7b-9903-4244-b741-3690a7e5b398 for the corresponding questions to this CME article.

Radiation-induced subacute cutaneous lupus erythematosus.

We present an unusual case of radiation-induced subacute cutaneous lupus erythematosus (SCLE) occurring in a patient with non-Hodgkin lymphoma. Dermatologists should be aware of the ability of low-dose radiation treatment to induce a first presentation or flare of SCLE, with the possibility of extension of disease outside of the radiation field.

A qualitative study exploring personal recovery meaning and the potential influence of clinical recovery status on this meaning 20 years after a first-episode psychosis.

PURPOSE: Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.e. personal recovery). METHODS: Twenty participants were purposefully sampled from an epidemiologically representative FEP incidence cohort. At 20-year follow-up, semi-structured interviews were conducted with 10 cohort members who met full 'functional recovery criteria' (Clinically Recovered Group) and 10 who did not (Not Clinically Recovered Group). A thematic analysis was performed to develop shared themes and group-specific sub-themes to capture agreement and divergence between groups. RESULTS: Five shared themes were produced: pursuing balance in conflict, generating meaning in life, experiencing a dynamic personal relationship with time, redressing inequality while managing added challenges/vulnerability, and directing life from resilience to flourishing. The five group-specific sub-themes developed illuminate differences in the meaning ascribed to personal recovery by each group. CONCLUSION: Findings emphasise the role of time in how personal recovery is conceptualised by service users and identify ways clinical recovery may influence personal recovery meaning in FEP at mid-later life. Mental health services failing to consider temporal changes in meaning-making and discounting clinical recovery risk ignoring key factors affecting personal recovery.

Multisensory perception is not influenced by previous concussion history in retired rugby union players.

BACKGROUND: To assess whether concussion history adversely affects multisensory integration, we compared susceptibility to the Sound-Induced Flash Illusion (SIFI) in retired professional rugby players compared to controls. METHODS: Retired professional rugby players ((N = 58) and retired international rowers (N = 26) completed a self-report concussion history questionnaire and the SIFI task. Susceptibility to the SIFI (i.e., perceiving two flashes in response to one flash paired with two beeps) was assessed at three stimulus onset asynchronies (70 ms, 150 ms or 230 ms).Logistic mixed-effects regression modeling was implemented to evaluate how athlete grouping, previous concussion history and total number of years playing sport, impacted the susceptibility to the SIFI task. The statistical significance of a fixed effect of interest was determined by a likelihood ratio test. RESULTS: Former rugby players had significantly more self-reported concussions than the rower group (p < 0.001). There was no impact of athlete grouping (i.e., retired professional rugby players and retired international rowers), years participation in elite sport or concussion history on performance in the SIFI. CONCLUSION: A career in professional rugby, concussion history or number of years participating in professional rugby was not found to be predictive of performance on the SIFI task.

Exercise-induced re-programming of age-related metabolic changes in microglia is accompanied by a reduction in senescent cells.

Microglial activation and neuroinflammatory changes are characteristic of the aged brain and contribute to age-related cognitive impairment. Exercise improves cognitive function in aged animals, perhaps because of a modulatory effect on microglial activation. Recent evidence indicates that inflammatory microglia are glycolytic, driven by an increase in 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that is described as the master regulator of glycolysis. Here we investigated whether microglia from aged animals exhibited a glycolytic signature and whether exercise exerted a modulatory effect on this metabolic profile. Young (4 month-old) and aged (18 month-old) mice were trained for 10 days on a treadmill. One day before sacrifice, animals were assessed in the novel object recognition and the object displacement tests. Animals were sacrificed after the last bout of exercise, microglial cells were isolated, cultured for 5 days and assessed for metabolic profile. Performance in both behavioural tests was impaired in sedentary aged animals and exercise attenuated this age-related effect. A significant increase in glycolysis, glycolytic capacity and PFKFB3 was observed in microglia from aged animals and exercise ameliorated these effects, while it also increased the phagocytic capacity of cells. The senescent markers, ß-galactosidase and p16INK4A, were increased in microglia from sedentary aged mice, and expression of these markers was significantly decreased by exercise. The data demonstrate that the exercise-related improved cognition is orchestrated by a normalization of the metabolic profile and functionality of microglia.

The iHOPE-20 study: Relationships between and prospective predictors of remission, clinical recovery, personal recovery and resilience 20 years on from a first episode psychosis.

OBJECTIVE: Knowledge of outcome in psychotic illness is limited by the paucity of very long-term epidemiologically representative studies of incidence first episode psychosis (FEP) cohorts that measure and compare outcomes reflecting modern clinical practice, mental health policy and research agendas. Our study aimed to address this gap. METHOD: iHOPE-20 is a prospective 20-year follow-up study of a FEP incidence cohort (N = 171) conducted between 2014 and 2017 in Ireland. Data from previous studies and medical records were used to recruit cohort members. We assessed remission, clinical recovery, personal recovery and resilience at 20 years; explored the relationships between these outcomes and examined the predictive value of baseline characteristics in determining them. RESULTS: At follow-up, 20 out of 171 cohort members (11.70%) were deceased. We assessed 80 out of 151 alive cohort members (53% recruitment rate); 65% were in remission; 35.2% were in Full Functional Recovery and 53.7% confirmed they were fully recovered according to their personal definition of recovery. A complex array of relationships between outcomes was found. Outcomes were better for people who had a short duration of untreated psychosis, displayed higher premorbid social adjustment (between the ages of 5-11) and at baseline, were older, not living alone, in full-time employment, given a non-affective diagnosis, and had lower Global Assessment of Functioning scores. CONCLUSION: Among participants, full remission of psychotic symptoms and personally defined recovery was not just possible but likely in the very long term. However, attaining positive functional outcomes and building resilience in FEP remain key challenges for mental health services.

The iHOPE-20 study: mortality in first episode psychosis-a 20-year follow-up of the Dublin first episode cohort.

PURPOSE: Increased mortality rates have been found in those with a diagnosis of psychosis; studies suggest a shortened life expectancy of up to 20 years less than that of the general population. This study aimed to investigate the mortality of a first episode psychosis cohort at 20-year follow-up, compare it to that of the general Irish population, and explore whether the mortality gap has changed over time. METHODS: 171 individuals diagnosed with a first episode psychosis identified between 1995 and 1999 in a community mental health service were traced. Mortality was established by matching death certificates to deceased cohort members (using name, age at date of death, and address at date of death). Date of first presentation to service was used as date of entry point and date of death or end of follow-up as the end point. RESULTS: Of the 171 cases there were 20 deaths during follow-up. Nine deaths were attributed to natural causes; 7 to unnatural causes; and 4 were unknown. Comparing standardised mortality rates at 20-year follow-up to those at 12 year showed a reduction in rates over time. CONCLUSION: Findings suggest that the mortality gap in people with schizophrenia and other psychoses remains high, especially in young males.

Interrater Agreement and Diagnostic Accuracy of a Novel Computer-Aided Detection Process for the Detection and Prevention of Retained Surgical Instruments.

OBJECTIVE: The purpose of this study is to evaluate the diagnostic accuracy of a process incorporating computer-aided detection (CAD) for the detection and prevention of retained surgical instruments using a novel nondeformable radiopaque µTag. MATERIALS AND METHODS: A high-specificity CAD system was developed iteratively from a training set (n = 540 radiographs) and a validation set (n = 560 radiographs). A novel test set composed of 700 thoracoabdominal radiographs (410 with a randomly placed µTag and 290 without a µTag) was obtained from 10 cadavers embedded with confounding iatrogenic objects. Data were analyzed first by the blinded CAD system; radiographs coded as negative (n = 373) were then independently reviewed by five blinded radiologists. The reference standard was the presence of a µTag. Sensitivity and specificity were calculated. Interrater agreement was assessed with Cohen kappa values. Mean (± SD) image analysis times were calculated. RESULTS: The high-specificity CAD system had one false-positive (sensitivity, 79.5% [326/410]; specificity, 99.7% [289/290]). A combination of the CAD system and one failsafe radiologist had superior sensitivity (98.5% [404/410] to 100% [410/410]) and specificity (99.0% [287/290] to 99.7% [289/290]), with 327 (47%) radiographs not requiring immediate radiologist review. Interrater agreement was almost perfect for all radiologist pairwise comparisons (κ = 0.921-0.992). Cumulative mean image analysis time was less than one minute (CAD, 29 ± 2 seconds; radiologists, 26 ± 16 seconds). CONCLUSION: The combination of a high-specificity CAD system with a failsafe radiologist had excellent diagnostic accuracy in the rapid detection of a nondeformable radiopaque µTag.

Effects of match play and training on circulating S100B concentration in professional rugby players.

OBJECTIVES: Examine the effects of match play and a season of training on serum S100B concentration in male professional rugby players. To assess the influence of contact play, values were compared with age- and fitness-matched athletes not involved in a contact sport. METHODS: Over a 2-year period, blood samples were collected from 38 players in pre-season, end of season, and post-matches (within 2 h). A control group of rowers (n = 15) was assessed pre- and post-training. RESULTS: S100B concentration changed significantly over a season (χ2(2) = 17.636, p < 0.0005); post-match values were significantly increased from baseline (early season: Z = -3.670, p < 0.0005; late season: Z = -3.408, p = 0.001). There were no significant differences in S100B concentrations between pre-seasons (Z = -1.601, p = 0.109), or between end of season and subsequent pre-season (Z = -0.330, p = 0.741). While comparable at baseline, samples taken from rugby players post-match were significantly increased compared with samples taken from rowers post-exercise (U = 47.0, p < 0.0005). CONCLUSION: Exercise has a significant effect on circulating S100B in elite male athletes, with levels following rugby matches significantly higher than following non-contact sport. This elevation in S100B is temporary, with a return to baseline values after periods without play.

Use of Blood Biomarkers in the Assessment of Sports-Related Concussion-A Systematic Review in the Context of Their Biological Significance.

OBJECTIVES: To critically review current knowledge on the positive and negative predictive value of blood biomarkers for concussion; to illustrate the clinical and biological contexts that help evaluate the use of these markers in sport-related traumatic brain injuries (TBIs). METHODS: This systematic review was performed in accordance with PRISMA guidelines. We reviewed the measurement, clinical utility, endpoint, and biological significance of blood biomarkers in concussion. RESULTS: A total of 4352 publications were identified. Twenty-six articles relating to blood biomarkers were included in the review. Four common blood biomarkers, namely S100B, tau, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), were examined. Overall, the studies showed S100B measurement and use, either acutely or at several time points, can distinguish injured from noninjured patients with an uncertain degree of utility in predicting mortality. At present, S100B has largely become an acceptable biomarker of TBI; however, studies have begun to highlight the need to incorporate clinical symptoms instead of S100B concentration in isolation on the basis of inconsistent results and lack of specificity across published studies. Further research is needed to evaluate and validate the use of tau, NSE, and GFAP as a diagnostic aid in the management of concussion and TBI. CONCLUSIONS: At present, blood biomarkers have only a limited role in the evaluation and management of concussion. Although several biomarkers of brain injury have been identified, continued research is required. S100B holds promise as the most clinically useful diagnostic biomarker. Blood biomarkers, in combination with other clinical data, such as head computed tomography, would maximize the diagnostic accuracy. The methodological limitations evident in blood biomarker research results in the need for the clinical utility of blood biomarker use in concussion to be further explored.

'Recovery' in the Real World: Service User Experiences of Mental Health Service Use and Recommendations for Change 20 Years on from a First Episode Psychosis.

Little is known about how recovery oriented policy and legislative changes influence service users' perceptions of mental health care over time. Although the recovery approach is endorsed in many countries, qualitative research examining its impact on service use experiences has been lacking. This study aimed to explore this impact as well as experiences of service utilisation and suggestions for change with people diagnosed with a First Episode Psychosis between 1995 and 1999. Participants had used services during the 10 year period prior to, and 10 years post, policy and legislative shifts to the recovery approach. Semi-structured interviews were conducted with 10 participants who met criteria for 'full functional recovery' and 10 who did not. Data were analysed using Thematic Networks Analysis to develop Basic, Organising, and Global Themes. Over time, recovered participants perceived an improvement in service quality through the 'humanising' of treatment and non-recovered participants experienced their responsibility in recovery being recognised, but felt abandoned to the recovery approach. Findings suggest the importance of viewing service users as demonstrating personhood and having societal value; examining the personal meaning of psychotic experiences; and matching expectations with what services can feasibly provide. The implementation and the principal tenets of the recovery approach warrant further investigation.

Clozapine Use in a Cohort of First-Episode Psychosis.

PURPOSE/BACKGROUND: For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducing psychotic symptoms. METHODS/PROCEDURES: Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 (N = 171). Data were obtained from first presentation up to December 31, 2013 or until the patient was discharged or transferred. Information on service use and physical health was gathered using a data collection template designed specifically for this audit. FINDINGS/RESULTS: Twenty-eight (16.3%) of the cohort were prescribed clozapine. Data were available for 24 individuals. Of this clozapine subsample, the mean age at baseline was 23.11 (SD = 4.58); 82.14% (n = 23) were male; and 82.14% (n = 23) had a baseline diagnosis of schizophrenia. The mean time to first trial of clozapine was 6.7 years. The mean number of antipsychotics prescribed before clozapine trial was 4.85. After the initiation of clozapine, the mean number of hospital admissions reduced from 6.04 per year to 0.88 per year. IMPLICATIONS/CONCLUSIONS: Nearly 1 in 5 of the original cohort was considered to have a suboptimal response to trials of antipsychotic medication. The use of clozapine for treatment-resistant schizophrenia is underutilized, and better understanding of the barriers to prescribing clozapine is necessary given the implications for patient's quality of life and hospital admission rates. Physical health data further emphasizes the importance of physical health monitoring in this vulnerable population.

Practical Approaches to Quality Improvement for Radiologists.

Continuous quality improvement is a fundamental attribute of high-performing health care systems. Quality improvement is an essential component of health care, with the current emphasis on adding value. It is also a regulatory requirement, with reimbursements increasingly being linked to practice performance metrics. Practice quality improvement efforts must be demonstrated for credentialing purposes and for certification of radiologists in practice. Continuous quality improvement must occur for radiologists to remain competitive in an increasingly diverse health care market. This review provides an introduction to the main approaches available to undertake practice quality improvement, which will be useful for busy radiologists. Quality improvement plays multiple roles in radiology services, including ensuring and improving patient safety, providing a framework for implementing and improving processes to increase efficiency and reduce waste, analyzing and depicting performance data, monitoring performance and implementing change, enabling personnel assessment and development through continued education, and optimizing customer service and patient outcomes. The quality improvement approaches and underlying principles overlap, which is not surprising given that they all align with good patient care. The application of these principles to radiology practices not only benefits patients but also enhances practice performance through promotion of teamwork and achievement of goals.

Non-pharmacological Approaches to Cognitive Enhancement.

Pharmaceuticals and medical devices hold the promise of enhancing brain function, not only of those suffering from neurodevelopmental, neuropsychiatric or neurodegenerative illnesses, but also of healthy individuals. However, a number of lifestyle interventions are proven cognitive enhancers, improving attention, problem solving, reasoning, learning and memory or even mood. Several of these interventions, such as physical exercise, cognitive, mental and social stimulation, may be described as environmental enrichments of varying types. Use of these non-pharmacological cognitive enhancers circumvents some of the ethical considerations associated with pharmaceutical or technological cognitive enhancement, being low in cost, available to the general population and presenting low risk to health and well-being. In this chapter, there will be particular focus on the effects of exercise and enrichment on learning and memory and the evidence supporting their efficacy in humans and in animal models will be described.

How to perform a critical appraisal of diagnostic tests: 7 steps.

The critically appraised topic (CAT) is a format in evidence-based practice for sharing information. A CAT is a standardized way of summarizing the most current research evidence focused on a pertinent clinical question. Its aim is to provide both a critique of the most up-to-date retrieved research and an indication of the clinical relevance of results. A clinical question is initially generated following a patient encounter, which leads to and directs a literature search to answer the clinical question. Studies obtained from the literature search are assigned a level of evidence. This allows the most valid and relevant articles to be selected and to be critically appraised. The results are summarized, and this information is translated into clinically useful procedures and processes.

Midlife hypertension is a risk factor for some, but not all, domains of cognitive decline in later life: a systematic review and meta-analysis.

INTRODUCTION: Management of midlife blood pressure and hypertension status may provide a window of intervention to mitigate cognitive decline with advancing age. The aim of this review was to investigate the relationship between midlife hypertension and cognition in midlife and later life. METHODS: Online electronic databases were searched from their inception to May 2022. Studies assessing midlife (40-65 years) hypertension and cognition at mid and/or later-life were included. A random effects meta-analysis was deemed appropriate. RESULTS: One hundred forty-nine studies across 26 countries were included. Qualitative synthesis found negative relationships between midlife hypertension and later life cognition in the domains of memory, executive function, and global cognition. Metanalytical evidence revealed midlife hypertension negatively impacts memory, executive function, and global cognition but had no observed effect on attention at midlife. DISCUSSION: Hypertension at midlife has a significant negative impact on cognition in mid-life and later life, namely memory, executive function, and global cognition.

ACR Appropriateness Criteria® Workup of Pleural Effusion or Pleural Disease.

Pleural effusions are categorized as transudative or exudative, with transudative effusions usually reflecting the sequala of a systemic etiology and exudative effusions usually resulting from a process localized to the pleura. Common causes of transudative pleural effusions include congestive heart failure, cirrhosis, and renal failure, whereas exudative effusions are typically due to infection, malignancy, or autoimmune disorders. This document summarizes appropriateness guidelines for imaging in four common clinical scenarios in patients with known or suspected pleural effusion or pleural disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.