Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischemia.

The bioactive lipid intermediate palmitoyl CoA (PCoA) can inhibit mitochondrial ADP/ATP transport, though the physiological relevance of this regulation remains unclear. We questioned whether myocardial ischemia provides a pathological setting in which PCoA regulation of ADP/ATP transport would be beneficial, and secondly, whether the chronically elevated lipid content within the diabetic heart could make mitochondria less sensitive to the effects of PCoA. PCoA acutely decreased ADP-stimulated state 3 respiration and increased the apparent Km for ADP twofold. The half maximal inhibitory concentration (IC50 ) of PCoA in control mitochondria was 22 µM. This inhibitory effect of PCoA on respiration was blunted in diabetic mitochondria, with no significant difference in the Km for ADP in the presence of PCoA, and an increase in the IC50 to 32 µM PCoA. The competitive inhibition by PCoA was localised to the phosphorylation apparatus, particularly the ADP/ATP carrier (AAC). During ischemia, the AAC imports ATP into the mitochondria, where it is hydrolysed by reversal of the ATP synthase, regenerating the membrane potential. Addition of PCoA dose-dependently prevented this wasteful ATP hydrolysis for membrane repolarisation during ischemia, however, this beneficial effect was blunted in diabetic mitochondria. Finally, using 31 P-magnetic resonance spectroscopy we demonstrated that diabetic hearts lose ATP more rapidly during ischemia, with a threefold higher ATP decay rate compared with control hearts. In conclusion, PCoA plays a role in protecting mitochondrial energetics during ischemia, by preventing wasteful ATP hydrolysis. However, this beneficial effect is blunted in diabetes, contributing to the impaired energy metabolism seen during myocardial ischemia in the diabetic heart.

Exploring rehabilitation potential in older people living with frailty: a qualitative focus group study.

BACKGROUND: Rehabilitation interventions are frequently cited as key in supporting frail older people's recovery following periods of decompensation and acute ill-health. Clinicians are required to make decisions about a patient's potential to respond to rehabilitation. 'Rehabilitation potential' decisions can determine access to services. In acute settings clinicians have limited time to assess and work with patients, families and carers. The complexities of ageing, recovery, rehabilitation and frailty may not be fully appreciated. This study aimed to explore multiple perspectives of the concept of rehabilitation potential and how it is assessed in older people living with frailty in the acute healthcare setting. METHODS: Five focus groups with a purposive sample of 28 participants which included clinicians and members of the public were conducted. Analysis comprised a thematic approach using the Framework method. RESULTS: Rehabilitation potential was found to encapsulate a complex decision-making process where clinicians judged an individual's ability to benefit from and participate in targeted rehabilitation. They asked, "Will it work?", "Is it wanted?" and "Is it available?" In order to predict who would benefit from rehabilitation interventions, clinicians assessed a range of holistic clinical and non-clinical factors. An iterative approach to assessment delivered by a multi-disciplinary team, centred around patient and carer needs and wants was needed to accommodate complexity. Participants believed that everyone had some form of potential but this was dependent on availability of rehabilitation resources and conceptualisations of frailty and rehabilitation. Tensions between iterative approaches to rehabilitation potential assessment and the realities of rapid decision making in the acute hospital setting were found. CONCLUSION: Rehabilitation potential decisions involve a complex process of multidisciplinary decision-making and prognostication on the likely outcome and benefit from rehabilitation programmes. These findings lay the foundation for developing structured approaches to rehabilitation potential decision making tools and guidance.

Optimal care for the management of older people non-weight bearing after lower limb fracture: a consensus study.

BACKGROUND: Older people who are non-weight-bearing after a lower limb fracture are at risk of poor outcomes but there are no clinical guidelines for this group of patients. Given the paucity of the research evidence base, we conducted a consensus exercise to ascertain expert opinion about the management of this group. METHODS: A three-round e-Delphi technique was planned to use the online JISC survey tool with a multidisciplinary panel of health professionals. Panellists were invited by email via professional organisations and UK NHS Trusts. The initial statements for this study were prepared by the authors based upon the findings of their scoping review. Consensus required >/= 70% agreement with statements. RESULTS: Only 2 survey rounds were required. Ninety panellists, representing seven clinical disciplines, reached consensus for 24 statements about general issues (osteoporosis detection and management, falls risk reduction and nutrition) and specific non-weight bearing issues (such as the need for activity to be promoted during this period). CONCLUSIONS: These findings can be used in the generation of a clinical guideline for this group of patients.

Understanding the Barriers and Facilitators to Employment for People with Bipolar Disorder.

People with Bipolar Disorder (BD) consistently report a desire for employment; however, this is not reflected in employment figures. Individuals' perceptions of barriers to employment, along with endorsement of facilitators to employment remain under-investigated. We aimed to address this limitation by: (i) first examining differences in employed versus unemployed individuals (demographic, clinical, functioning); then (ii) identifying barriers and/or facilitators to employment, perception of same, and subsequent impact on employment. We assessed demographics, functioning, and illness-related characteristics in 35 participants with BD (19 employed, 16 unemployed). Participants were asked to indicate perception of common barriers and facilitators to employment. Groups did not differ regarding demographic or clinical variables. High levels of absenteeism, termination of last role and commonly perceived barriers were attributed to mental ill-health. 93.3% of unemployed participants reportedly desired employment, and more perceived barriers were observed in the unemployed group. Identified facilitators included increased support and flexible work strategies. A comprehensive understanding of perceptions of limiting and helpful factors related to employment for people with BD was obtained. These findings have implications for service provision, encouraging targeted discussion, and tailored treatment approaches to individual's unique perceptions of factors related to employment.

The cost of diabetic foot ulcers and amputations to the National Health Service in England.

AIM: To estimate the healthcare costs of diabetic foot disease in England. METHODS: Patient-level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014-2015. RESULTS: The cost of health care for ulceration and amputation in diabetes in 2014-2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration. CONCLUSIONS: Diabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one-third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.

Adverse Childhood Experiences, Tobacco Use, and Obesity: A Crowdsourcing Study.

Background: Exposure to adverse childhood experiences (ACEs) increases health risk behavior in adulthood and is a risk for premature mortality. For example, ACEs are associated with both tobacco smoking and obesity, which remain significant health challenges for many adults, despite widespread knowledge about the risks. Objective: The present investigation used a novel online crowdsourcing platform (Amazon.com mechanical turk) to study the relationship between ACEs and later tobacco smoking and obesity. Methods: Participants were recruited based on smoking (n = 74 smokers; n = 75 nonsmokers) and stratified based on obesity (n = 52 BMI ≥ 30; n = 97 BMI < 30). Participants had no recent history of other substance use, except alcohol. The relationship between ACE score and smoking and obesity categories was analyzed using logistic regression. Results: The average age of the sample was 38.6-years old and was mostly female (66.4%), employed (82.6%) and college educated (63.1%). Those with 4+ ACEs had a significantly greater odds of cigarette use. Any ACEs exposure was associated with a significantly greater odds of obesity. Conclusions/Importance: Findings are concordant with previous studies and suggest crowdsourcing is a viable platform for studying ACEs and health behavior. Access to large samples and specific populations provided by crowdsourcing could help examine theoretical models about how exposure to ACEs could be connected to later adoption of high-risk behaviors such as tobacco cigarette smoking and obesity.

A novel mutation in LAMC3 associated with generalized polymicrogyria of the cortex and epilepsy.

Occipital cortical malformation is a rare neurodevelopmental disorder characterized by pachygyria and polymicrogyria of the occipital lobes as well as global developmental delays and seizures. This condition is due to biallelic, loss-of-function mutations in LAMC3 and has been reported in four unrelated families to date. We report an individual with global delays, seizures, and polymicrogyria that extends beyond the occipital lobes and includes the frontal, parietal, temporal, and occipital lobes. Next-generation sequencing identified a homozygous nonsense mutation in LAMC3: c.3190C>T (p.Gln1064*). This finding extends the cortical phenotype associated with LAMC3 mutations.

Managing anti-epileptic drug treatment in adult patients with intellectual disability: a serious conundrum.

BACKGROUND AND PURPOSE: About a quarter of people with epilepsy have intellectual disability (ID). This group has communication issues, premature mortality, more treatment resistance, difficulties in making informed choices and greater risks of physical and mental health comorbidities. There is no specific prescribing guidance for this large and vulnerable group. The literature on prescribing for epilepsy in this group was reviewed, in particular examining how antiepileptic drugs (AEDs) work regarding their side effect profiles, effects on specific epilepsy syndromes associated with ID and their individual strengths and weaknesses based on the nature and degree of ID. METHOD: This is a narrative review for which a comprehensive search was conducted to identify evidence for prescribing commonly used AEDs to people with ID including genetic syndromes specifically associated with epilepsy. RESULTS: A detailed analysis of the results has highlighted the urgent requirement for suitable and reliable evidence in AED prescribing amongst adults with epilepsy and ID as no studies taking account of the response to AEDs of the ID populations based on the WHO Diagnostic and Statistical Manual of Mental Disorders criteria of clinical severity of ID were identified. CONCLUSION: There is a significant shortfall in suitably powered studies to provide sufficient evidence for safe prescribing of AEDs to people with ID.

Prevalence and associated features of depression in women with Rett syndrome.

BACKGROUND: Little is known about depression among women with Rett syndrome (RTT) despite recent advances in knowledge about RTT. In this study, we aimed to establish the prevalence of depression among women with RTT as identified by a screening telephone interview and to explore the clinical factors associated with this. METHODS: The study employed the cross-sectional analysis of data from telephone interviews with carers of 56 women with RTT, using validated questionnaires for assessing mental health problems, challenging behaviour and RTT severity. RESULTS: Scores on the mental health assessment reached the affective/neurotic threshold in eight cases (14.3%). No significant differences were found between those reaching the threshold and those who did not in terms of severity of RTT phenotype, health problems or social circumstances. There was a significant association between screening identified depression and higher lethargy and social withdrawal. CONCLUSIONS: Screening identified depression was found among a sizeable minority of women with RTT. Further investigation is needed to establish a clinically validated prevalence of depression among this group and to identify behavioural features that would lead to prompt psychiatric assessment.

Ageing in Rett syndrome.

BACKGROUND: The aim was to gain a UK national sample of people with Rett syndrome across the age range and (1) conduct a cross-sectional comparison of age groups and (2) undertake a longitudinal follow-up. METHODS: From 308 potential participants approached to take part, a sample of 91 girls and women was achieved (29.5%). Their ages ranged from 4 to 47 years, and 71 were known to have a mutation in the methyl-CpG binding protein-2 (MECP2) gene. Seventy-two of the initial sample were followed up 16 months later, and 50 returned completed assessments (69.4%). Their ages ranged from 7 to 48 years, and 42 were MECP2 positive. Parental questionnaire measures of Rett syndrome specific characteristics, impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and self-injury were administered. RESULTS: Adaptive behaviour and behavioural characteristics of Rett syndrome were similar across age groups and, where assessed, stable over time, as were repetitive behaviours generally and self-injury. There was some suggestion of deterioration in health arising with ageing, principally contributed to by deteriorations in dental and gastro-intestinal problems both with moderate effect sizes. Indicators of mood, interest and pleasure differed significantly across age groups. The total scale score significantly deteriorated over time, with a moderate effect size. CONCLUSIONS: This study provides further evidence for the post-regression stability that characterises Rett syndrome. Emergent low mood in Rett syndrome requires further research.

Perceived 'healthiness' of foods can influence consumers' estimations of energy density and appropriate portion size.

OBJECTIVE: To compare portion size (PS) estimates, perceived energy density (ED) and anticipated consumption guilt (ACG) for healthier vs standard foods. METHODS: Three pairs of isoenergy dense (kJ per 100 g) foods-healthier vs standard cereals, drinks and coleslaws-were selected. For each food, subjects served an appropriate PS for themselves and estimated its ED. Subjects also rated their ACG about eating the food on a scale of 1 (not at all guilty) to 5 (very guilty). RESULTS: Subjects (n=186) estimated larger portions of the healthier coleslaw than that of the standard version, and perceived all healthier foods to be lower in ED than their standard alternatives, despite being isoenergy dense. Higher ACG was associated with the standard foods. Portion estimates were generally larger than recommendations and the ED of the foods was underestimated. CONCLUSIONS: The larger portions selected for the 'reduced fat' food in association with lower perceived ED and ACG suggests that such nutrition claims could be promoting inappropriate PS selection and consumption behaviour. Consumer education on appropriate portions is warranted to correct such misconceptions.

Cost of diabetic foot disease to the National Health Service in England.

AIM: To estimate the annual cost of diabetic foot care in a universal healthcare system. METHODS: National datasets and economic modelling were used to estimate the cost of diabetic foot disease to the National Health Service in England in 2010-2011. The cost of hospital admissions specific to foot disease or amputation was estimated from Hospital Episode Statistics and national tariffs. Multivariate regression analysis was used to estimate the impact of foot disease on length of stay in admissions that were not specific to foot disease or amputation. Costs in other areas were estimated from published studies and data from individual hospitals. RESULTS: The cost of diabetic foot care in 2010-2011 is estimated at £580 m, almost 0.6% of National Health Service expenditure in England. We estimate that more than half this sum (£307 m) was spent on care for ulceration in primary and community settings. Of hospital admissions with recorded diabetes, 8.8% included ulcer care or amputation. Regression analysis suggests that foot disease was associated with a 2.51-fold (95% CI 2.43-2.59) increase in length of stay.The cost of inpatient ulcer care is estimated at £219 m, and that of amputation care at £55 m. CONCLUSIONS: The cost of diabetic foot disease is substantial. Ignorance of the cost of current care may hinder commissioning of effective services for prevention and management in both community and secondary care.

Supermarket own brand foods: lower in energy cost but similar in nutritional quality to their market brand alternatives.

BACKGROUND: The present study aimed to compare the nutritional quality (NQ) and energy costs (EC) (£ MJ(-1) ) of own brand (OB) versus market brand (MB) foods in 2010 and 2012. METHODS: A list of processed foods (n = 32) was identified based on the most frequently consumed foods in the UK. Total fat, saturated fat, sugars, salt and energy density (ED) (kJ g(-1) ) in 2010 and 2012 were compared for six OB and one MB version of each food using a NQ scoring method based on the Food Standards Agency's Traffic Light System (TLS). Additional information (fruit, vegetable and nut content; protein; fibre and sodium) was recorded in 2012, and NQ was assessed using the Food Standards Agency's nutrient profiling model (NPM). The EC of the food baskets (FB) was compared in 2010 and 2012. RESULTS: There were no differences in overall NQ between OB and MB FB in 2010 (TLS, P = 0.978) or 2012 (TLS, P = 0.840; NPM, P = 0.696). However, the MB FB was highest in EC in 2010 and 2012 (both P < 0.001). There was an inverse relationship between the ED and EC of the MB foods in 2010 (r = -0.484; P = 0.005) and 2012 (r = -0.452; P = 0.009). CONCLUSIONS: The MB FB was higher in EC than the OB FB in 2010 and 2012 but not superior in overall NQ based on both the TLS and NPM.

A prospective clinical and biomechanical analysis of feet following first metatarsophalangeal joint arthrodesis for end stage hallux rigidus.

BACKGROUND: Hallux Rigidus is the result of degeneration of the 1st metatarsophalangeal joint (1st MTPJ). In end-stage hallux rigidus, treatment is mainly surgical with arthrodesis being a favourable option. Although the biomechanical effects of arthrodesis have been examined, a detailed comparison of pre- and post-operative biomechanics has yet to be conducted. RESEARCH QUESTION: Does 1st MTPJ arthrodesis positively affect foot kinematics and plantar pressure distribution? METHODS: Twelve 1st MTPJ arthrodesis were performed in patients with a mean age of 53.5 ± 5.4 years and follow up time of 6.9 ± 1.0 months. Pre- and post-operative data were collected at a CMAS (Clinical Movement Analysis Society) accredited gait laboratory using a BTS motion capture system and pedobarographic pressure plates. Patient outcome measures were also assessed using the MOXFQ. Statistical analysis was conducted using a two-way repeated measures ANOVA. RESULTS: Significant changes in stride length, cycle duration, cadence and velocity were identified following 1st MTPJ arthrodesis. A significant reduction in forefoot-hallux dorsiflexion at toe-off was identified for the operated foot from the pre-operative (20.23 ± 5.98°) to post-operative (7.56 ± 2.96°) assessment. Post-operative sagittal and transverse plane changes in the operated foot were also identified. Peak pressure and PTI results indicated significant lateralisation of load for the operated foot, but importantly this was not influenced following arthrodesis. Finally, there was a significant improvement in MOXFQ score. SIGNIFICANCE: Following 1st MTPJ fusion there is an improvement in overall gait mechanics which accompanied by the improved MOXFQ score indicates a reduction in pain and improved confidence during gait. The lack of post-operative dorsiflexion at forefoot-hallux caused load to remain lateralised and compensatory mechanisms to occur at the more proximal joints within the foot. These results provide valuable information for clinicians and will enable more accurate counselling to be provided to patients with end-stage hallux rigidus.

Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair.

Many cancers display increased expression of histone deacetylases (HDACs) and therefore transcriptionally inactive chromatin, resulting in the downregulation of genes including tumour suppressor and DNA repair genes. Histone deacetylase inhibitors (HDACi) are a heterogeneous group of epigenetic therapeutics, showing promising anticancer effects in both pre-clinical and clinical settings, in particular the effect of radiosensitisation when administered in combination with radiotherapy. Radiotherapy remains one of the most common forms of cancer treatment, leading to cell death through the induction of DNA double-strand breaks (DSBs). Cells have developed mechanisms to repair such DSB through two major pathways: non-homologous end-joining and homologous recombination. Here, we explore the current evidence for the use of HDACi in combination with irradiation, focusing on the effects of HDACi on DNA damage signalling and repair in vitro. In addition, we summarise the clinical evidence for using HDACi with radiotherapy, a growing area of interest with great potential clinical utility.

A qualitative study of carers' and professionals' views on the management of people with intellectual disability and epilepsy: a neglected population.

Little attention has been paid to the specific needs of people with intellectual disability and epilepsy despite evidence of increased prevalence of epilepsy, increased risk of complex epilepsy, and heightened use of health services among this group. In an attempt to address this gap, an online international survey was undertaken inviting health professionals and caregivers, both paid and family members, to share their views on the adequacy and quality of available treatment. This paper reports on the responses obtained from 113 individuals from the UK and Ireland. Findings revealed that professionals and carers differ in their expectations of treatment and with regard to maximizing communication during consultations. In addition, findings suggested that the potential of consultations to provide information for carers, as well as to allay concerns, may not be realized. Rescue medications were viewed favorably; however, respondents expressed less satisfaction with routine medications. These findings may reflect a failure by professionals to appropriately transfer knowledge of these treatments.

Investigating low adaptive behaviour and presence of the triad of impairments characteristic of autistic spectrum disorder as indicators of risk for challenging behaviour among adults with intellectual disabilities.

BACKGROUND: Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of impairments characteristic of autism and level of adaptive behaviour were independently associated with level of challenging behaviour among adults with intellectual disabilities. METHODS: Five datasets were merged to produce information on challenging behaviour, adaptive behaviour, presence of the triad of impairments, gender and age of 818 adults. Variables were entered into a multivariate linear regression, which also tested the interaction between the presence of the triad of impairments and level of adaptive behaviour. RESULTS: Presence of the triad of impairments, level of adaptive behaviour, their interaction, and age, but not gender, significantly and independently contributed to the prediction of challenging behaviour. Presence/absence of the triad of impairments moderated the effect of adaptive behaviour on challenging behaviour. The inverse relationship found in the absence of the triad of impairments was virtually removed when present. CONCLUSIONS: This study has shown that it is necessary to control for intercorrelation between potential risk factors for challenging behaviour and to explore how interaction between them might moderate associations.

The Sapienza University of Rome network of automated external defibrillators: a prototype webMap developed to speed access to community defibrillators and increase survival from out-of-hospital cardiac arrest.

OBJECTIVE: In Italy, only around 10% of people who experience out-of-hospital cardiac arrest (OHCA) survive. A large portion of OHCA events in public settings are characterized by an initial shockable rhythm, which requires prompt defibrillation. We aimed to create a system to quickly locate nearby public access automated external defibrillators (AEDs) on the campus of Sapienza University of Rome, the largest public university in Europe. MATERIALS AND METHODS: We developed the AED webMap through a 6-step process involving the: 1) collection of information and geographical coordinates for each AED from the university management system; 2) development of a new geolocation database; 3) integration of information contained in the new database with data provided by university departments; 4) geolocation of AEDs in the Google MyMaps environment; 5) graphic representation of all AEDs on digital map templates using specific symbols, with pop-ups containing additional information for each AED; and 6) publication of the webMap on the university website. RESULTS: The AED webMap was published on the university website (https://www.uniroma1.it/it/pagina/defibrillatori-sapienza-in-rete) and facilitates prompt identification of nearby AEDs by providing: 1) detailed AED geolocalization with interactive pop-up information for each AED, including whether the AED is located internally or externally; 2) the option to use different base maps (e.g., digital street map); 3) calculation and display of the route to reach the chosen AED; and 4) the possibility to migrate towards multiple platforms. CONCLUSIONS: The webMap can help bystanders quickly identify, locate, and reach nearby AEDs present on the campus of the largest public university in Europe, a measure that could help speed defibrillation and maximize the life-saving potential of AEDs in the event of OHCA.

COVID-19 vaccination uptake in people with epilepsy in wales.

PURPOSE: People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort. METHODS: We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations. RESULTS: There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability. CONCLUSIONS: COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.

Neutron star mass estimates from gamma-ray eclipses in spider millisecond pulsar binaries.

Reliable neutron star mass measurements are key to determining the equation of state of cold nuclear matter, but such measurements are rare. Black widows and redbacks are compact binaries consisting of millisecond pulsars and semi-degenerate companion stars. Spectroscopy of the optically bright companions can determine their radial velocities, providing inclination-dependent pulsar mass estimates. Although inclinations can be inferred from subtle features in optical light curves, such estimates may be systematically biased due to incomplete heating models and poorly understood variability. Using data from the Fermi Large Area Telescope, we have searched for gamma-ray eclipses from 49 spider systems, discovering significant eclipses in 7 systems, including the prototypical black widow PSR B1957+20. Gamma-ray eclipses require direct occultation of the pulsar by the companion, and so the detection, or significant exclusion, of a gamma-ray eclipse strictly limits the binary inclination angle, providing new robust, model-independent pulsar mass constraints. For PSR B1957+20, the eclipse implies a much lighter pulsar (1.81 ± 0.07 solar masses) than inferred from optical light curve modelling.