ISSLS PRIZE in Clinical Science 2023: comparison of degenerative MRI features of the intervertebral disc between those with and without chronic low back pain. An exploratory study of two large female populations using automated annotation.

OBJECTIVES: The relationship of degeneration to symptoms has been questioned. MRI detects apparently similar disc degeneration and degenerative changes in subjects both with and without back pain. We aimed to overcome these problems by re-annotating MRIs from asymptomatic and symptomatics groups onto the same grading system. METHODS: We analysed disc degeneration in pre-existing large MRI datasets. Their MRIs were all originally annotated on different scales. We re-annotated all MRIs independent of their initial grading system, using a verified, rapid automated MRI annotation system (SpineNet) which reported degeneration on the Pfirrmann (1-5) scale, and other degenerative features (herniation, endplate defects, marrow signs, spinal stenosis) as binary present/absent. We compared prevalence of degenerative features between symptomatics and asymptomatics. RESULTS: Pfirrmann degeneration grades in relation to age and spinal level were very similar for the two independent groups of symptomatics over all ages and spinal levels. Severe degenerative changes were significantly more prevalent in discs of symptomatics than asymptomatics in the caudal but not the rostral lumbar discs in subjects < 60 years. We found high co-existence of degenerative features in both populations. Degeneration was minimal in around 30% of symptomatics < 50 years. CONCLUSIONS: We confirmed age and disc level are significant in determining imaging differences between asymptomatic and symptomatic populations and should not be ignored. Automated analysis, by rapidly combining and comparing data from existing groups with MRIs and information on LBP, provides a way in which epidemiological and 'big data' analysis could be advanced without the expense of collecting new groups. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Attachment patterns and autobiographical episodic memory functioning: A systemic review of adult studies to advance clinical psychological science.

Patterns of insecure attachment are associated with psychopathology but the mechanisms involved remain poorly understood. Cognitive science proposes that attachment patterns are influenced by the autobiographical memory system and in turn influence its ongoing functioning. Disturbances in autobiographical memory represent cognitive risks for later emotional difficulties. We systemically reviewed 33 studies (in 28 articles) examining the association between attachment patterns and autobiographical episodic memory (AEM) in individuals from the age of 16 (i.e., from young to older adulthood). Attachment patterns were associated with key areas of AEM phenomenology, including intensity and arousal; detail, specificity, and vividness; coherence and fragmentation; and accuracy and latency. These associations appeared to be moderated by contextual and individual factors; mediated by emotional regulation and schema-based processing; linked to mental health outcomes. Attachment patterns may also influence the impact of certain AEM-based manipulations. We conclude by providing a critical discussion and a research agenda for bringing together attachment, memory, and emotion, with a view to promote mechanism-driven treatment innovation in clinical psychology.

Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab.

PURPOSE: Systemic chemotherapy including monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma (GBM). Most patients tolerated these regimens well with known side effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ- or system- specific toxicities from chemotherapy agents have never been examined by postmortem study. This is the largest cohort used to address this issue in glioma patients. METHODS: Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression. RESULTS: Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. CONCLUSION: There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma tumor progression with infiltration to brain stem and aspiration pneumonia.

Maternal early warning criteria predict postpartum severe maternal morbidity and mortality after delivery hospitalization discharge: a case-control study.

BACKGROUND: The predictors of postpartum severe maternal morbidity and mortality have not been well-described using patient-level data. OBJECTIVE: This study aimed to evaluate the application of maternal early warning criteria in the postpartum period and generate a preliminary predictive model for severe maternal morbidity and mortality occurring after delivery hospitalization discharge until 42 days postpartum. STUDY DESIGN: A retrospective case-control study was conducted from January 2013 to September 2020. Cases were identified from electronic medical records using the International Classification of Diseases, Tenth Revision codes for Centers for Disease Control and Prevention-defined severe maternal morbidity. Patients meeting the criteria for severe maternal morbidity and mortality from delivery hospitalization discharge until 42 days postpartum were matched for delivery hospital and year with the controls in an approximate 1:2 fashion. The objective was to identify the demographic and clinical risk factors during the antepartum through postpartum periods for postpartum severe maternal morbidity and mortality. Multivariable logistic regression was performed to estimate the risks, and a receiver operating characteristic curve was derived to evaluate the model. RESULTS: Ninety cases of postpartum severe maternal morbidity and mortality that occurred following delivery hospitalization discharge were identified. These were matched with 175 controls. Women with postpartum severe maternal morbidity and mortality had more postpartum assessments (mean: 1.7 vs 1.4, P=.005) and a higher frequency of maternal early warning criteria (58% [52/90] vs 2% [3/175]; P<.001) preceding the diagnosis of severe maternal morbidity and mortality than controls. Black women had higher odds of postpartum severe maternal morbidity and mortality than White women (odds ratio, 1.93; 95% confidence interval, 1.14-3.27). Women with maternal early warning criteria during postpartum assessments were more likely to experience subsequent postpartum severe maternal morbidity and mortality (odds ratio, 67.2; 95% confidence interval, 21.3-211.6) than women with no maternal early warning criteria. Although the point estimate was different in Black women (odds ratio, 161.8; 95% confidence interval, 8.9 to >999) than White women (odds ratio, 47.9; 95% confidence interval, 13.8-167.1), the effect modification between the maternal early warning criteria and race was not statistically significant (P=.93). In a multivariable model, race, body mass index, cesarean delivery, and maternal early warning criteria at postpartum assessments were associated with subsequent severe maternal morbidity and mortality, with an area under the curve of 0.905 (95% confidence interval, 0.864-0.946). CONCLUSION: Maternal early warning criteria are associated with increased odds of postpartum severe maternal morbidity and mortality. A straightforward model that includes race, body mass index, cesarean delivery, and presence of maternal early warning criteria appears to be a promising tool to identify those at risk for postpartum severe maternal morbidity and mortality following delivery hospitalization discharge. This is an important first step in improving the ability to recognize and respond to conditions preceding postpartum severe maternal morbidity. These findings should be validated in a prospective cohort.

Decoherence of photon entanglement by transmission through brain tissue with Alzheimer's disease.

The generation, manipulation and quantification of non-classical light, such as quantum-entangled photon pairs, differs significantly from methods with classical light. Thus, quantum measures could be harnessed to give new information about the interaction of light with matter. In this study we investigate if quantum entanglement can be used to diagnose disease. In particular, we test whether brain tissue from subjects suffering from Alzheimer's disease can be distinguished from healthy tissue. We find that this is indeed the case. Polarization-entangled photons traveling through brain tissue lose their entanglement via a decohering scattering interaction that gradually renders the light in a maximally mixed state. We found that in thin tissue samples (between 120 and 600 micrometers) photons decohere to a distinguishable lesser degree in samples with Alzheimer's disease than in healthy-control ones. Thus, it seems feasible that quantum measures of entangled photons could be used as a means to identify brain samples with the neurodegenerative disease.

The efficacy, challenges, and facilitators of telemedicine in post-treatment cancer survivorship care: an overview of systematic reviews.

BACKGROUND: Telemedicine services have been increasingly used to facilitate post-treatment cancer survivorship care, including improving access; monitoring health status, health behaviors, and symptom management; enhancing information exchange; and mitigating the costs of care delivery, especially since the COVID-19 pandemic. To inform guidance for the use of telemedicine in the post-COVID era, the aim of this overview of systematic reviews (SRs) was to evaluate the efficacy of, and survivor engagement in, telemedicine interventions in the post-treatment survivorship phase, and to consider implementation barriers and facilitators. METHODS: PubMed, Cochrane CENTRAL, CINAHL, Embase, and Web of Science databases were searched. SRs that examined the use of telemedicine in the post-treatment phase of cancer survivorship, published between January 2010 and April 2021, were included. Efficacy data were synthesized narratively. Implementation barriers and facilitators were synthesized using the Consolidated Framework for Implementation Research. RESULTS: Twenty-nine SRs were included. A substantive body of evidence found telemedicine to benefit the management of psychosocial and physical effects, particularly for improving fatigue and cognitive function. There was a lack of evidence on the use of telemedicine in the prevention and surveillance for recurrences and new cancers as well as management of chronic medical conditions. This overview highlights a range of diverse barriers and facilitators at the patient, health service, and system levels. CONCLUSIONS: This review highlights the benefits of telemedicine in addressing psychosocial and physical effects, but not in other areas of post-treatment cancer survivorship care. This large review provides practical guidance for use of telemedicine in post-treatment survivorship care.

Continuing clozapine treatment after a diagnosis of cardiomyopathy.

A patient in a medium secure psychiatric unit with a 19-year history of treatment-resistant schizophrenia and violence whose mental illness only responded to clozapine, was noted to have a sustained tachycardia. Echocardiography revealed mild biventricular cardiomyopathy. The patient was not significantly affected by this. Initial recommendation from Cardiology was to consider discontinuation of clozapine. It was decided, however, that the risk of worsening psychosis and resultant violence outweighed the risk of the patient's relatively mild cardiomyopathy. The patient was commenced on ramipril, and later bisoprolol. The patient no longer requires treatment in a medium secure unit and has remained on clozapine with follow-up from cardiology.

Temperature surpasses the effects of velocity and turbulence on swimming performance of two invasive non-native fish species.

Global climate change continues to impact fish habitat quality and biodiversity, especially in regard to the dynamics of invasive non-native species. Using individual aquaria and an open channel flume, this study evaluated the effects of water temperature, flow velocity and turbulence interactions on swimming performance of two lentic, invasive non-native fish in the UK, pumpkinseed (Lepomis gibbosus) and topmouth gudgeon (Pseudorasbora parva). Burst and sustained swimming tests were conducted at 15, 20 and 25°C. Acoustic Doppler velocimetry was used to measure the flume hydrodynamic flow characteristics. Both L. gibbosus and P. parva occupied the near-bed regions of the flume, conserving energy and seeking refuge in the low mean velocities flow areas despite the relatively elevated turbulent fluctuations, a behaviour which depended on temperature. Burst swimming performance and sustained swimming increased by up to 53% as temperature increased from 15 to 20°C and 71% between 15 and 25°C. Furthermore, fish test area occupancy was dependent on thermal conditions, as well as on time-averaged velocities and turbulent fluctuations. This study suggests that invasive species can benefit from the raised temperatures predicted under climate change forecasts by improving swimming performance in flowing water potentially facilitating their further dispersal and subsequent establishment in lotic environments.

An in-depth study of the associations between osteoarthritis- and osteoporosis-related phenotypes at different skeletal locations.

The relationship between OA and osteoporosis characteristics remains controversial. This study revealed that age-adjusted hand OA is associated with lower hand/arm BMD levels. Wrist fracture occurrence is associated with increased OA hand scores and low arm BMD. Conversely, age-adjusted knee and spine OA is associated with high spine, hip, and total BMDs. INTRODUCTION: Osteoarthritis (OA) and osteoporosis are two common musculoskeletal diseases which contribute a high burden of disability, yet assessments of their relationship remains controversial. The aim of this study was to clarify the association between bone mineral densities (BMD) of the hand, arm, spine, hip, and total body, and OA of the hand and knee and lumbar disc degeneration in two different ethnic groups. METHODS: Radiographic assessments of the hand, knee, and spine were collected and coded for joint space narrowing, osteophytes, and the Kellgren-Lawrence score from Chuvashian (n = 1504) and British (n = 2280) individuals. BMD measurements of standard skeletal sites were estimated by dual X-ray absorptiometry. Age- and familial-adjusted regression analyses were conducted to determine associations. RESULTS: Knee OA affection was positively associated with elevated hip, spine, and total body BMD levels (p < 0.001). Additionally, disc degeneration phenotypes showed significant positive associations with the hip, spine, and total BMD (p < 0.001). However, increased hand OA scores was significantly negatively correlated with arm and hand BMD measurements in males and females in both samples (p < 0.001). Additionally, higher hand OA scores were significantly associated with wrist fracture. CONCLUSIONS: We discovered a clear pattern of association between hand OA and low hand and arm BMD, with increased risk of wrist fracture, as well as reproducing previous associations between knee and spine OA and elevated spine, hip, and total body BMD. It appears that hand OA manifests differently in comparison to hip and knee OA.

Public health delivery in the information age: the role of informatics and technology.

AIM: Public health systems have embraced health informatics and information technology as a potential transformational tool to improve real-time surveillance systems, communication, and sharing of information among various agencies. Global pandemic outbreaks like Zika and Ebola were quickly controlled due to electronic surveillance systems enabling efficient information access and exchange. However, there is the need for a more robust technology to enhance adequate epidemic forecasting, data sharing, and effective communication. The purpose of this review was to examine the use of informatics and information technology tools and its impact on public health delivery. METHOD: Investigators searched six electronic databases. These were MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete, Cochrane Database of Systematic Reviews, COMPENDEX, Scopus, and Academic Search Premier from January 2000 to 31 March 2016. RESULTS: A total of 60 articles met the eligibility criteria for inclusion. These studies were organized into three areas as (1) definition of the term public health informatics; (2) type of public health surveillance systems and implications for public health; and (3) electronic surveillance systems functionality, capability, training, and challenges. Our analysis revealed that due to the growing expectations to provide real-time response and population-centered evidence-based public health in this information-driven age there has been a surge in informatics and information technology adoption. Education and training programs are now available to equip public health students and professionals with skills in public health informatics. However, obstacles including interoperability, data standardization, privacy, and technology transfer persist. CONCLUSION: Re-engineering the delivery of public health is necessary to meet the demands of the 21st century and beyond. To meet this expectation, public health must invest in workforce development and capacity through education and training in informatics.

A database of biological and geomorphological sea-level markers from the Last Glacial Maximum to present.

The last deglacial was an interval of rapid climate and sea-level change, including the collapse of large continental ice sheets. This database collates carefully assessed sea-level data from peer-reviewed sources for the interval 0 to 25 thousand years ago (ka), from the Last Glacial Maximum to the present interglacial. In addition to facilitating site-specific reconstructions of past sea levels, the database provides a suite of data beyond the range of modern/instrumental variability that may help hone future sea-level projections. The database is global in scope, internally consistent, and contains U-series and radiocarbon dated indicators from both biological and geomorpohological archives. We focus on far-field data (i.e., away from the sites of the former continental ice sheets), but some key intermediate (i.e., from the Caribbean) data are also included. All primary fields (i.e., sample location, elevation, age and context) possess quantified uncertainties, which-in conjunction with available metadata-allows the reconstructed sea levels to be interpreted within both their uncertainties and geological context.

Twelve-year follow-up of chronic pain in twins: Changes in environmental and genetic influence over time.

BACKGROUND: While genetic influences on chronic pain have been repeatedly demonstrated, we do not know whether these effects are stable or dynamic over time. AIMS: To determine the temporal pattern of genetic and environmental effects to individual differences in chronic pain over 12 years, we use a sample of n = 961 female twins. METHODS: Data on chronic pain were collected in 2004 (T1) and 2016 (T2) using the same comprehensive body map which divides the body into 31 distinct anatomical areas. Multivariate twin analyses for repeated measures were conducted to track changes in genetic and environmental influences. RESULTS: Heritability for chronic pain was 63% at baseline and 55% at follow-up. The best-fitting AE Cholesky model revealed one genetic factor explaining 62% of variance in chronic pain at T1 and 11% at T2. No additional genetic factors explaining the variance in chronic pain at T2 could be detected. Furthermore, a unique environmental factor (E1) explaining 37% of the variance in chronic pain at T1 and 12% at T2 and an additional environmental factor (E2) explaining 77% of the variance at T2 were found. CONCLUSION: We demonstrate for the first time that the same genetic influences are operative over time and that novel environmental factors are important in pain maintenance. The findings highlight the value of more in depth exploration of these non-shared environmental influences that could provide clues to the mechanisms behind remittance and/or maintenance of chronic pain. The identification of important environmental influences could point to novel therapeutic interventions in future. SIGNIFICANCE: The variability in chronic pain is mainly explained by new environmental factors influencing incidence, aggravation and/or chronic pain remission. Integration of these findings may provide a useful conceptual framework for the treatment and prevention of pain and pain chronification.

A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. METHODS: Based on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. KEY RESULTS: Suggestive GWAS signals (P ≤ 5.0 × 10-6 ) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P = 3.1 × 10-10 ) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. CONCLUSION & INFERENCES: Our results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

Technical note: Evaluation of fine needle aspiration cytology for the diagnosis of fatty liver in dairy cattle.

Fatty liver is a common condition affecting dairy cattle during the periparturient period, characterized by a pathological accumulation of triglycerides (TG) in the hepatocytes. The objective of this study was to evaluate the diagnostic potential of fine needle aspiration cytology in fresh liver specimens using liver TG concentrations as a gold standard. Fifty-seven liver samples from Holstein cows were collected during processing at a slaughterhouse. Tissue and fine needle aspirate samples were obtained from the parietal upper portion of the caudate lobe. Two samples of liver tissue were collected with a 16 gauge × 15 cm biopsy needle for histological and TG concentration assessment. A third sample was collected for cytology using an 18 gauge × 5.08 cm needle. The contents of the needle were transferred to a glass slide, spread, and air-dried. Liver samples were assayed by colorimetry/fluorimetry to determine TG concentrations. Concentrations of TG <2% were considered normal. Histological and cytological evaluations were conducted by 2 different pathologists blind to the visual classification. Sensitivity (Se) and specificity (Sp) were calculated. Cytology had a Se and Sp of 73 and 85%, respectively. Histopathology had a Se and Sp of 45.9 and 100%, respectively. The likelihood of having higher scores for histopathology and cytology increased as a function of liver TG content (mg/g).

Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus.

Background Hydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA). Studies of HCQ-treated patients with SLE or RA have demonstrated a positive correlation between whole-blood HCQ levels and clinical response. Such studies have involved measuring whole-blood concentrations at any given time point after HCQ ingestion assuming that steady-state concentrations would undergo limited fluctuation over a daily interval because HCQ has a long half-life. This approach might not sufficiently take into account the potential intra-patient variation in HCQ blood levels that can occur over a 24-hour period. Such variation, if significant, could affect the credibility of any concentration-response relationship provided from these previous studies. Objectives The objectives of this report are to: (a) investigate the intra-patient variation in HCQ whole-blood levels and (b) suggest an optimum time for sampling patients for future studies. Methods Six patients were recruited with cutaneous lupus erythematosus who had each been on HCQ 200 mg twice daily for at least six months, so that they were at steady-state. Each patient was fasted overnight and had standardized meals and dosing schedule. Whole blood was sampled at seven time points over 24 hours. Whole-blood HCQ levels were measured with high-performance liquid chromatography using gradient elution, fluorimetric detection and chloroquine as an internal standard. The assay had a mean inter- and intra-day coefficient of variation of 10% and 5% respectively and a limit of detection of 5ng/ml. Results HCQ levels appeared to follow a biphasic pattern over the sampling period. Maximum levels were noted a median of four hours (range 2-6) after ingestion. Median intra-patient variation between trough and peak levels, 'Cmax' ((peak - trough)/trough × 100%), was 27% (range 8-150%). Conclusions This study demonstrated that whole-blood HCQ levels vary 27% (median, range 8-150%) within an individual over a 12-hour period. Drug levels might differ between individuals because of multiple factors, including variable adherence to medication. Measuring HCQ levels for assessment of drug adherence could be valuable in the 'real-world' clinical setting. This could be assessed by taking a blood sample at any time following HCQ ingestion. If patients were found to have very low or undetectable levels of HCQ, non-adherence to HCQ should be suspected.

New catalytic strategies for α,ω-diols production from lignocellulosic biomass.

Catalytic strategies for the synthesis of 1,5-pentanediol (PDO) with 69% yield from hemicellulose and the synthesis of 1,6-hexanediol (HDO) with 28% yield from cellulose are presented. Fractionation of lignocellulosic biomass (white birch wood chips) in gamma-valerolactone (GVL)/H2O generates a pure cellulose solid and a liquid stream containing hemicellulose and lignin, which is further dehydrated to furfural with 85% yield. Furfural is converted to PDO with sequential dehydration, hydration, ring-opening tautomerization, and hydrogenation reactions. Acid-catalyzed cellulose dehydration in tetrahydrofuran (THF)/H2O produces a mixture of levoglucosenone (LGO) and 5-hydroxymethylfurfural (HMF), which are converted with hydrogen to tetrahydrofuran-dimethanol (THFDM). HDO is then obtained from hydrogenolysis of THFDM. Techno-economic analysis demonstrates that this approach can produce HDO and PDO at a minimum selling price of $4090 per ton.

Female sexual pain: Epidemiology and genetic overlap with chronic widespread pain.

BACKGROUND: Increased tender spots and lowered general pain thresholds have been observed in patients with dyspareunia. Based on this, the aim of the study was to compare the co-occurrence of female sexual pain across various pain populations and to further explore the aetiological structure underlying sexual pain by dissecting the genetic and environmental covariation among sexual pain, chronic widespread pain (CWP) and the previously reported psychological correlates of anxiety sensitivity and depression. METHODS: A multivariate twin study including 1489 female twin individuals (246 full MZ pairs, 187 full DZ pairs and 623 whose co-twin did not participate). Main outcomes measures included self-reported diagnosis of osteoarthritis and rheumatoid arthritis, and validated questionnaires for the assessment of sexual pain, CWP, depression and anxiety sensitivity. RESULTS: Sexual pain showed a small but statistically significant correlation with CWP (r = 0.08; p < 0.05), anxiety sensitivity (r = 0.15, p < 0.001) and depression (r = 0.09, p < 0.01). The heritability of sexual pain was found to be 31%. Multivariate variance component analysis revealed a genetic factor common among CWP, depression, anxiety sensitivity and sexual pain, and a second genetic factor shared between anxiety sensitivity and sexual pain only. We further detected genetic and environmental factors unique to sexual pain, explaining 24.01% and 67.24%, respectively, of the phenotypic variance. CONCLUSIONS: Our findings suggest some overlap between sexual pain and CWP and point towards a shared but complex psychophysiological aetiology underlying sexual pain. Results further highlight the influence of specific environmental and contextual stressors in the development and maintenance of sexual pain. SIGNIFICANCE: Sexual pain shares a common genetic aetiology with chronic widespread pain and the frequently reported psychological comorbidities of depression and anxiety. Overall this suggests a complex psychophysiological aetiology underlying chronic pain conditions. The high proportion of variance in sexual pain explained by environmental factors further highlights the importance of specific environmental and contextual stressors in the development and maintenance of the condition.

The effects of policy actions to improve population dietary patterns and prevent diet-related non-communicable diseases: scoping review.

Poor diet generates a bigger non-communicable disease (NCD) burden than tobacco, alcohol and physical inactivity combined. We reviewed the potential effectiveness of policy actions to improve healthy food consumption and thus prevent NCDs. This scoping review focused on systematic and non-systematic reviews and categorised data using a seven-part framework: price, promotion, provision, composition, labelling, supply chain, trade/investment and multi-component interventions. We screened 1805 candidate publications and included 58 systematic and non-systematic reviews. Multi-component and price interventions appeared consistently powerful in improving healthy eating. Reformulation to reduce industrial trans fat intake also seemed very effective. Evidence on food supply chain, trade and investment studies was limited and merits further research. Food labelling and restrictions on provision or marketing of unhealthy foods were generally less effective with uncertain sustainability. Increasingly strong evidence is highlighting potentially powerful policies to improve diet and thus prevent NCDs, notably multi-component interventions, taxes, subsidies, elimination and perhaps trade agreements. The implications for policy makers are becoming clearer.

A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population.

BACKGROUND: Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. METHODS: We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). KEY RESULTS: We identified 30 GERD suggestive risk loci (P≤5×10-5 ), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. CONCLUSIONS: We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.