Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

A stochastic model for topographically influenced cell migration.

Migrating cells traverse a range of topographic configurations presented by the native extracellular environment to conduct their physiologic functions. It is well documented cells can modulate their behaviour in response to different topographic features, finding promising applications in biomaterial and bioimplant design. It is useful, in these areas of research, to be able to predict which topographic arrangements could be used to promote certain patterns of migration prior to laboratory experimentation. Despite a profusion of study and interest shown in these fields by experimentalists, the related modelling literature is as yet relatively sparse and tend to focus more on either cell-matrix interaction or morphological responses of cells. We propose a mathematical model for individual cell migration based on an Ornstein-Uhlenbeck process, and set out to see if the model can be used to predict migration patterns on 2-d isotropic and anisotropic topographies, whose characteristics can be broadly described as either uniform flat, uniform linear with variable ridge density or non-uniform disordered with variable feature density. Results suggest the model is capable of producing realistic patterns of migration for flat and linear topographic patterns, with calibrated output closely approximating NIH3T3 fibroblast migration behaviour derived from an experimental dataset, in which migration linearity increased with ridge density and average speed was highest at intermediate ridge densities. Exploratory results for non-uniform disordered topographies suggest cell migration patterns may adopt disorderedness present in the topography and that 'distortion' introduced to linear topographic patterns may not impede linear guidance of migration, given its magnitude is bounded within certain limits. We conclude that an Ornstein-Uhlenbeck based model for topographically influenced migration may be useful to predict patterns of migration behaviour for certain isotropic (flat) and anisotropic (linear) topographies in the NIH3T3 fibroblast cell line, but additional investigation is required to predict with confidence migration patterns for non-uniform disordered topographic arrangements.

Adaptive behaviour deficits in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes. METHODS: Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes. RESULTS: Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders. CONCLUSIONS: Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.

The prevalence of anxiety disorders in dermatology outpatients: A systematic review and meta-analysis.

Anxiety is common in those with medical conditions and has significant impacts on mental well-being as well as physical health outcomes. While several systematic reviews have examined the prevalence of anxiety in specific dermatological conditions, no reviews have examined the prevalence across the entire dermatology outpatient setting. This systematic review aims to provide an overview to dermatologists of the prevalence of, and trends in, anxiety in their outpatient clinics. As such, prevalence of anxiety in dermatology outpatient clinics was examined, and variations across type of anxiety and dermatological conditions were assessed. A search of PubMed, Embase, Cochrane and PsycINFO was conducted for studies that assessed anxiety prevalence in dermatology outpatients, with the last search conducted on 7 September 2022. Results underwent title/abstract and full-text screening, followed by data extraction. Studies of patients 16 years and older and representative of dermatology clinics were included. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis was conducted using CMA software, and subgroup analysis was conducted on relevant variables. 5423 studies were identified, and 32 included, with a total n = 12,812 participants. Under the random effects model, prevalence was estimated at 26.7% (95%CI 22.4-31.4; 95%PI 9.7-55.4). Subgroup analysis revealed a higher prevalence among studies of psoriasis patients than general dermatology studies. Estimates of prevalence were higher when assessed via self-report screening than diagnostic interview. Anxiety occurred frequently among dermatology outpatients, especially psoriasis outpatients, at a higher rate than common estimates of prevalence in the general population. Given the effect of anxiety on patient outcomes and well-being, dermatologists are encouraged to consider how anxiety may impact patients in their clinic, and how they can best identify patients with anxiety and subsequently support them.

Assessment of the current performance of grazing infrastructure across Irish dairy farms.

The increased average Irish dairy herd size in a post-quota environment has put heightened pressure on grazing infrastructure. In a rotational grazing system, grazing infrastructure consists of the paddock system, which delineates the grazing areas into appropriately sized grazing parcels, and the roadway network, which connects these paddocks to the milking parlor. Where herd size has increased without corresponding adaptations to the infrastructure, farm management and roadway network performance has been affected. The links between suboptimal grazing infrastructure and roadway network efficiency are poorly understood and not widely documented. The aims of this study were to (1) analyze the effect of herd expansion and paddock size on pasture allocations per paddock, (2) identify the factors that affect the total distance walked per year, and (3) create a metric to compare the efficiency of roadway networks across farms of varying grazing platforms. A sample population of 135 Irish dairy farms with a median herd size of 150 cows was used for this analysis. Herds were split into the following 5 categories: <100 cows, 100 to 149 cows, 150 to 199 cows, 200 to 249 cows, and ≥250 cows. Herds with ≥250 cows had a greater number of paddocks per farm and rotated around the grazing paddocks more frequently, with 46% of paddocks only suitable for 12 h allocations relative to herd size, compared with just 10% to 27% of paddocks for herds with <100 cows to herds with 200-249 cows. When predicting the total distance walked per year on each study farm, the mean distance from a paddock to the milking parlor was the strongest indicator (R2 = 0.8247). Other metrics, such as herd size, have failed to account for the location of the milking parlor relative to the grazing platform. The creation of the relative mean distance from a paddock to milking parlor (RMDMP) metric allowed the calculation of a farm's roadway network efficiency for moving the herd between paddocks and the milking parlor. The analyzed farms increased their efficiency in terms of RMDMP (0.34-40.74%) as they increased herd size post quota. However, the position of new additional paddocks relative to the milking parlor substantially affected their RMDMP.

A distinct cognitive profile in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is associated with mild to moderate intellectual disability as well as comorbid psychopathology such as ADHD, anxiety, ASD and schizophrenia. A greater understanding of specific profiles that could increase risk for psychopathology is necessary in order to best understand and support individuals with 3q29 deletion syndrome. The goal of this study was to thus carefully outline the strengths and weaknesses of these individuals. A second goal was to ask whether the cognitive impact of the deletion predicted psychopathology in other domains. METHODS: We systematically evaluated cognitive ability, adaptive behaviour and psychopathology in 32 individuals with the canonical 3q29 deletion using gold-standard instruments and a standardised phenotyping protocol. RESULTS: Mean full scale IQ was 73 (range 40-99). Verbal subtest score (mean 80, range 31-106) was slightly higher and had a greater range than non-verbal subtest score (mean 75, range 53-98). Spatial ability was evaluated in a subset (n = 24) and was lower than verbal and non-verbal ability (mean 71, range 34-108). There was an average 14-point difference between verbal and non-verbal subset scores; 60% of the time the verbal subset score was higher than the non-verbal subset score. Study subjects with a verbal ability subtest score lower than the non-verbal subtest score were four times more likely to have a diagnosis of intellectual disability (suggestive, P value 0.07). The age at which a child first spoke two-word phrases was strongly associated with measures of verbal ability (P value 2.56e-07). Cognitive ability was correlated with adaptive behaviour measures (correlation 0.42, P value 0.02). However, although group means found equivalent scores, there was, on average, a 10-point gap between these skills (range -33 to 33), in either direction, in about 50% of the sample, suggesting that cognitive measures only partially inform adaptive ability. Cognitive ability scores did not have any significant relationship to cumulative burden of psychopathology nor to individual neurodevelopmental or psychiatric diagnoses. CONCLUSIONS: Individuals with 3q29 deletion syndrome have a complex pattern of cognitive disability. Two-thirds of individuals with the deletion will exhibit significant strength in verbal ability; this may mask deficits in non-verbal reasoning, leading to an overestimation of overall ability. Deficits in verbal ability may be the driver of intellectual disability diagnosis. Cognitive ability is not a strong indicator of other neurodevelopmental or psychiatric impairment; thus, individuals with 3q29 deletion syndrome who exhibit IQ scores within the normal range should receive all recommended behavioural evaluations.

Outcomes of Total Knee Arthroplasty Revisions in Obese and Morbidly Obese Patient Populations.

BACKGROUND: The obese population is at higher risk for complications following primary total knee arthroplasty (TKA), but little data is available regarding revision outcomes. This study aimed to investigate the role of body mass index (BMI) in the cause for revision TKA and whether BMI classification is predictive of outcomes. METHODS: A multi-institutional database was generated, including revision TKAs from 2012 to 2019. Data collection included demographics, comorbidities, surgery types (primary revision, repeat revision), reasons for revision, lengths of hospital stay, and surgical times. Patients were compared using 3 BMI categories: nonobese (18.5 to 29.9), obese (30 to 39.9), and morbidly obese (≥40). Categorical and continuous variables were analyzed using chi-square and 1-way analysis of variance tests, respectively. Regression analyses were used to compare reasons for revision among weight classes. RESULTS: Obese and morbidly obese patients showed significant risk for repeat revision surgery in comparison to normal weight patients. Obese patients were at higher risk for primary revision due to stiffness/fibrosis and repeat revision due to malposition. In comparison to the obese population, morbidly obese patients were more likely to require primary revision for dislocation and implant loosening. CONCLUSION: Significant differences in primary and repeat revision etiologies exist among weight classes. Furthermore, obese and morbidly obese patients have a greater risk of requiring repeat revision surgery. These patients should be informed of their risk for multiple operations, and surgeons should be aware of the differences in revision etiologies when anticipating complications following primary TKA.

Electrochemical treatment of textile wastewater using copper electrodes.

The conventional electrode aluminum used in electrocoagulation (EC) for the textile wastewater undergoes pitting type of corrosion, so dissolution of the same is very high during electrolysis. This research focuses on the treatment of real-time textile effluent with copper electrodes that corrode uniformly during electrolysis, with optimizing operating parameters for high color removal efficiency (CRE%). The sludge acquired was analyzed by XPS and XRD to study the mechanism of dye removal. The treated effluent was subjected to phytotoxicity analysis using Vigna radiata to study the toxicity effect of the intermediary products. 98.6% of CRE was attained in treating the effluent with copper electrodes. XPS and XRD results showed that both Cu(OH)2 and CuO served as coagulants in the dye removal. The phytotoxicity results showed that the percentage of germination, shoot and root lengths of Vigna radiata in the treated effluent were similar to the results obtained for the control.

Association between hamstring coactivation during isokinetic quadriceps strength testing and knee cartilage worsening over 24 months.

OBJECTIVE: This study aimed to determine longitudinal associations, including sex-specific differences, between greater knee flexor antagonist coactivation and worsening cartilage morphology in knees with or at risk for osteoarthritis (OA). DESIGN: Baseline measurements were collected at the 60-month visit of a longitudinal osteoarthritis study following community-dwelling participants (MOST). Knee flexor and extensor muscle activity were measured with surface electromyography during a maximal isokinetic knee extension task. MRI analyzed knee cartilage morphology at baseline and 24-month follow-up. Multivariable adjusted logistic regression models were used to assess associations between coactivation level and cartilage morphology worsening. RESULTS: Analysis of 373 women (mean ± SD age 67.4 ± 7.3 years and BMI 29.7 ± 5.0 kg/m2) and 240 men (66.5 ± 7.8 years and 29.9 ± 4.5 kg/m2) revealed that women had greater medial (P < 0.001), lateral (P < 0.001), and combined (P < 0.001) hamstring coactivation than men. In both sexes, combined hamstring coactivation was associated with patellofemoral cartilage morphology worsening [1.23 (1.02, 1.49)] and to a less significant degree with whole knee cartilage morphology worsening [1.21 (0.98, 1.49)]. In men, greater combined hamstring coactivation was associated with increased risk for whole knee [1.59 (1.06, 2.39)] and patellofemoral [1.38 (1.01, 1.88)] cartilage morphology worsening and point estimates suggested association between medial hamstring coactivation and medial tibiofemoral cartilage morphology worsening. No significant associations were detected between greater hamstring coactivation and cartilage morphology worsening in women. CONCLUSIONS: These findings suggest a longitudinal relationship between antagonist hamstring coactivation during isokinetic knee extensor testing and worsening of cartilage morphology over 24 months in men with or at risk for knee OA.

Placenta accreta spectrum: a non-oncologic challenge for gynecologic oncologists.

Placenta accreta spectrum disorders are a major risk factor for severe postpartum hemorrhage and maternal death worldwide, with a rapidly growing incidence in recent decades due to increasing rates of cesarean section. Placenta accreta spectrum disorders represent a complex surgical challenge, with the primary concern of massive obstetrical hemorrhagic sequelae and organ damage, occurring in the context of potentially significant anatomical and physiological changes of pregnancy. Most international obstetrical organizations have published guidelines on placenta accreta spectrum, embracing the creation of regionalized 'Centers of Excellence' in the diagnosis and management of placenta accreta spectrum, which includes a dedicated multidisciplinary surgical team. One mandatory criterion for these Centers of Excellence is the presence of a surgeon experienced in complex pelvic surgeries. Indeed, many institutions in the United States and worldwide rely on gynecologic oncologists in the surgical management of placenta accreta spectrum due to their experience and skills in complex pelvic surgery. Surgical management of placenta accreta spectrum frequently includes challenging pelvic dissection in regions with distortion of anatomy alongside large aberrant neovascularization. With a goal of definitive management through cesarean hysterectomy, surgeons require a systematic and thoughtful approach to promote prevention of urologic injuries, embrace measures to secure challenging hemostasis and, in selected cases, employ conservative management where indicated or desired. In this review recommendations are made for gynecologic oncologists regarding the management and important considerations in the successful care of placenta accreta spectrum disorders. Where required, gynecologic oncologists are encouraged to be proactively involved in the management of placenta accreta spectrum, not only intra-operatively, but also in the development of clinical protocols, guidelines, and pre-operative counseling of patients, as a 'call if needed' approach is suboptimal for this potentially major and life-threatening condition.

A qualitative analysis of online misinformation and conspiracy theories in psoriasis.

Psoriasis is a chronic, hereditary disease with a complex immunopathogenesis, rendering it susceptible to misinformation. Misinformation related to psoriasis can have negative effects both on the public perception of psoriasis and on patients' knowledge of psoriasis. To characterize misinformation related to psoriasis available online, we performed a formal literature review via PubMed and a thematic review via Google. Key themes of misinformation included 'victim-blaming' (hygiene), 'vector' (contagion), 'vaccination', 'vilification' of conventional therapy, 'validation' of natural treatment and diet, 'veneration' of cures and 'vocalization' from celebrities. Misinformation related to psoriasis is pervasive on social media and other websites. Dermatologists, as patient advocates, should be aware of the content of misinformation available online and combat misleading health information to optimize health outcomes for patients with psoriasis.

Confidence of Irish dermatologists in caring for patients with skin of colour.

To assess Irish dermatologists' confidence with dermatology in patients with skin of colour (SOC), an online survey was distributed to all members of the Irish Association of Dermatology (IAD) by email. Half (50%) of respondents were 'not confident' or 'not at all confident' in diagnosing skin conditions and one-third (33.9%) were 'not confident' or 'not at all confident' in managing skin conditions in patients with SOC. Irish dermatologists have low confidence with skin pathology in SOC, and specific training could reduce this disparity.

Small Fiber Neuropathy.

PURPOSE OF REVIEW: This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the distinctive features of SFN. RECENT FINDINGS: While the management of SFNs is ideally aimed at treating the underlying cause, most patients will require pain control via multiple, concurrent therapies. Herein, we highlight the most up-to-date information for diagnosis, medication management, interventional management, and novel therapies on the horizon. Despite the prevalence of small fiber neuropathies, there is no clear consensus on guidelines specific for the treatment of SFN. Despite the lack of specific guidelines for SFN treatment, the most recent general neuropathic pain guidelines are based on Cochrane studies and randomized controlled trials (RCTs) which have individually examined therapies used for the more commonly studied SFNs, such as painful diabetic neuropathy and HIV neuropathy. The recommendations from current guidelines are based on variables such as number needed to treat (NNT), safety, ease of use, and effect on quality of life.

Ultra-low-dose cone-beam CT compared to standard dose in the assessment for acute fractures.

PURPOSE: Multi-detector computed tomography (MDCT) is superior in fracture detection than conventional radiography; however, dose is increased. Cone-beam computed tomography (CBCT) offers higher spatial resolution and lower dose than MDCT. Manufacturers offer an ultra-low-dose algorithm. This study compares the diagnostic accuracy of the ultra-low-dose CBCT (ULDCBCT) with that of the standard-dose CBCT (SDCBCT). MATERIALS AND METHODS: In total, 64 patients were scanned with both the SDCBCT and the ULDCBCT protocols. Both studies were reported by two consultant radiologists with fellowship training in emergency radiology separated in time. The reporter recorded a diagnosis of fracture or normal and diagnostic confidence using a 5-point Likert scale. The gold standard was taken as the SDCBCT. Reporters were blinded to the indication and the SDCBCT report. Cases of discrepancy were resolved by consensus. RESULTS: There were 34 fractures and 30 cases had no fracture. Several fractures were missed using the UDCBCT, and there were also several cases of overdiagnosis. ULD was inferior to SD for fracture diagnosis (p < 0.00001). The diagnostic accuracy of ULDCBCT was 82.8% (75.1-88.9 CI). The diagnostic accuracy of plain radiograph was 64% (55.1-75.7% CI). Diagnostic confidence was reduced; the mean confidence for SDCBCT was 4.68 vs 4.12 for ULDCBCT (p < 0.001). The Kappa for interobserver agreement was 0.6. CONCLUSION: ULDCBCT is inferior to SDCBCT in fracture detection and confidence is reduced. For diagnostic studies, the standard dose should be used.

PE MIMICS: a structured approach for the emergency radiologist in the evaluation of chest pain.

Chest pain is a common reason for presentation to the emergency department. In many cases, a CTPA or CT thoracic aorta is performed during work up to assess for pulmonary embolism and aortic pathology, critical diagnoses that can be difficult to out rule clinically. However, the causes of chest pain are myriad. It is therefore crucial for the interpreting radiologist to be cognizant of other potential etiologies when interpreting these studies. The purpose of this pictorial essay is to highlight the causes of non-PE or aortic-related chest pain and provide radiologists with a structured approach to interpreting these studies, ensuring a comprehensive search strategy so that important pathologies are not missed.

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Clinical value of weight-bearing CT and radiographs for detecting patellofemoral cartilage visualized by MRI in the MOST study.

OBJECTIVE: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI. DESIGN: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared. RESULTS: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good. CONCLUSION: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint.

Mitochondria-targeted antioxidant MitoQ ameliorates ischaemia-reperfusion injury in kidney transplantation models.

BACKGROUND: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. METHODS: MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood. RESULTS: Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054). CONCLUSION: Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.

Scratching the surface: a review of online misinformation and conspiracy theories in atopic dermatitis.

Misinformation is one of the greatest threats to global health. Atopic dermatitis (AD) is a common skin disorder with a complex multifactorial aetiology, rendering it susceptible to misinformation. Little is known about the content of misinformation regarding AD online. We performed a review of AD-related misinformation available online, via PubMed for scientific papers and Google for nonscientific websites. Key areas of misinformation were identified, including 'simple cures' for AD, diet, chemicals, dust, vaccines, red skin syndrome and alternative therapies. Patients with AD and their families are vulnerable to misinformation given the severe impact of AD on quality of life. Dermatologists must be aware of the false AD-related content being shared online, and be prepared to refute and rebut misinformation by providing appropriate evidence.