A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank.

BACKGROUND: Common types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203 309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. METHODS: A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. RESULTS: We identified three genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10-11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10-10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10-8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). CONCLUSIONS: We have identified three loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.

Changes in RT-PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS-CoV-2: Report of two cases.

The implications of the menstrual cycle for disease susceptibility, development, and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are largely unknown. Here, we describe two women infected with SARS-CoV-2 whose real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT-PCR test results were positive during the first menstrual period before admission, but turned negative during hospitalization, and then were positive again during the second menstrual period after hospital discharge. Another one also developed a fever again on the first day of her menstrual period after hospital discharge. RT-PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. The cases indicate sex hormones may play an important role in SARS-CoV-2 infection. For women with history of exposure to SARS-CoV-2, the management protocol should include assessment of the menstrual status.

Perioperative management of patients with suspected or confirmed COVID-19: review and recommendations for perioperative management from a retrospective cohort study.

BACKGROUND: Current guidelines for perioperative management of coronavirus disease 19 (COVID-19) are mainly based on extrapolated evidence or expert opinion. We aimed to systematically investigate how COVID-19 affects perioperative management and clinical outcomes, to develop evidence-based guidelines. METHODS: First, we conducted a rapid literature review in EMBASE, MEDLINE, PubMed, Scopus, and Web of Science (January 1 to July 1, 2020), using a predefined protocol. Second, we performed a retrospective cohort analysis of 166 women undergoing Caesarean section at Tongji Hospital, Wuhan during the COVID-19 pandemic. Demographic, imaging, laboratory, and clinical data were obtained from electronic medical records. RESULTS: The review identified 26 studies, mainly case reports/series. One large cohort reported greater mortality in elective surgery patients diagnosed after, rather than before surgery. Higher 30 day mortality was associated with emergency surgery, major surgery, poorer preoperative condition and surgery for malignancy. Regional anaesthesia was favoured in most studies and personal protective equipment (PPE) was generally used by healthcare workers (HCWs), but its use was poorly described for patients. In the retrospective cohort study, duration of surgery, oxygen therapy and hospital stay were longer in suspected or confirmed patients than negative patients, but there were no differences in neonatal outcomes. None of the 262 participating HCWs was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when using level 3 PPE perioperatively. CONCLUSIONS: When COVID-19 is suspected, testing should be considered before non-urgent surgery. Until further evidence is available, HCWs should use level 3 PPE perioperatively for suspected or confirmed patients, but research is needed on its timing and specifications. Further research must examine longer-term outcomes. CLINICAL TRIAL REGISTRATION: CRD42020182891 (PROSPERO).

Photocatalytically Stable Superhydrophobic and Translucent Coatings Generated from PDMS-Grafted-SiO2/TiO2@PDMS with Multiple Applications.

In this paper, we present a highly efficient, cost-effective, and widely applicable functionalized SiO2/TiO2-polymer based coating to fabricate a translucent, fluorine-free, chemically stable, photocatalytic active, self-healable superhydrophobic coating, which consisted of two mixed functionalized particles (MFP) and polydimethylsiloxane (PDMS) in a proper ratio. Both SiO2 and TiO2 powders were functionalized with PDMS brushes to achieve superhydrophobicity. To maximally optimize its properties, including superhydrophobicity, transparency, and photocatalytic activity, the ratios between MFP with PDMS were carefully studied and optimized. Glass slides coated with this mixed coating (MC) showed translucence with a transparency of 75%. It also presented superior photocatalytic activity and strong UV resistance that could repeatedly degrade organic oil pollutants as many as 50 times, while still maintaining superhydrophobicity even upon exposure to UV light with a high intensity of 80 mW/cm2 for as long as 36 h. When low-surface-tension oils such as dodecane wetted the MC surface, it showed excellent slippery performance and could quickly repel strong acid/alkali/hot water and even very corrosive liquids such as aqua regia. MC achieved extremely stable underoil superhydrophobicity (toward liquids including water, strong acid and base, hot water, etc.) and self-cleaning properties, not only in oils at room temperature but also in a scalded oil environment. Moreover, MC showed self-healable performance after recycled plasma treatment. The stainless steel mesh coated with MC was also used to highly efficiently separate oil-water mixtures. Moreover, harsher liquids including strong acid/alkali solutions/hot water/ice water-oil mixtures could also be successfully separated by the coated mesh. This coating was believed to largely broaden both indoor and outdoor applications for superhydrophobic surfaces.

Genetic and Environmental Risk for Chronic Pain and the Contribution of Risk Variants for Major Depressive Disorder: A Family-Based Mixed-Model Analysis.

BACKGROUND: Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study. METHODS AND FINDINGS: Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum ß = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum ß = 5.68 x 10-2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum ß = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum ß = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes. CONCLUSIONS: Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. METHODS AND RESULTS: A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. CONCLUSIONS: We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

Development and external validation of multivariable risk models to predict incident and resolved neuropathic pain: a DOLORisk Dundee study.

Neuropathic pain is difficult to treat, and an understanding of the risk factors for its onset and resolution is warranted. This study aimed to develop and externally validate two clinical risk models to predict onset and resolution of chronic neuropathic pain. Participants of Generation Scotland: Scottish Family Health Study (GS; general Scottish population; n = 20,221) and Genetic of Diabetes Audit and Research in Tayside Scotland (GoDARTS; n = 5236) were sent a questionnaire on neuropathic pain and followed- -up 18 months later. Chronic neuropathic pain was defined using DN4 scores (≥ 3/7) and pain for 3 months or more. The models were developed in GS using logistic regression with backward elimination based on the Akaike information criterion. External validation was conducted in GoDARTS and assessed model discrimination (ROC and Precision-Recall curves), calibration and clinical utility (decision curve analysis [DCA]). Analysis revealed incidences of neuropathic pain onset (6.0% in GS [236/3903] and 10.7% in GoDARTS [61/571]) and resolution (42.6% in GS [230/540] and 23.7% in GoDARTS [56/236]). Psychosocial and lifestyle factors were included in both onset and resolved prediction models. In GoDARTS, these models showed adequate discrimination (ROC = 0.636 and 0.699), but there was evidence of miscalibration (Intercept = - 0.511 and - 0.424; slope = 0.623 and 0.999). The DCA indicated that the models would provide clinical benefit over a range of possible risk thresholds. To our knowledge, these are the first externally validated risk models for neuropathic pain. The findings are of interest to patients and clinicians in the community, who may take preventative or remedial measures.

A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.

Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test (metaUSAT) software for genetically correlated phenotypes (N = 397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and four loci were newly suggested. The LDL receptor related protein 1 (LRP1)-Signal Transducer and Activator of Transcription 6 (STAT6)-S hort chain D ehydrogenase/R eductase family 9C member 7 (SDR9C7) region in chromosome 12 was the most significantly associated locus with a leading p value of 1.24 × 10-62 of rs11172113. The One Cut homeobox 2 (ONECUT2) gene locus in chromosome 18 was the strongest signal among the four new loci with a p value of 1.29 × 10-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more variants for headaches. This study has paved way for a large GWAS meta-analysis involving cohorts of different while genetically correlated headache phenotypes. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00078-7.

Reciprocal interaction between depression and pain: results from a comprehensive bidirectional Mendelian randomization study and functional annotation analysis.

ABSTRACT: To understand a putative causal link for depression and pain, we retrieved summary statistics from genome-wide association studies conducted for pain at 7 different body sites (N = 151,922-226,683) and major depression disorder (MDD, Ncase/control = 246,363/561,190). We conducted a bidirectional Mendelian randomization analysis using distinct genome-wide association studies-identified single nucleotide polymorphisms for each trait as instrumental variables and performed several sensitivity analyses to verify Mendelian randomization assumptions. We also conducted functional annotation analysis using 396 tissue-specific annotations from the roadmap project. Across 7 different body sites, genetic predisposition to depression was associated with pain at the neck/shoulder (odds ratio [OR] = 1.08 per one log-unit increase in depression risk, 95% confidence interval [CI]: 1.06-1.10), back (OR = 1.05, 95% CI: 1.04-1.07), abdominal/stomach (OR = 1.03, 95% CI: 1.02-1.04), as well as headache (OR = 1.10, 95% CI: 1.07-1.12), but not with pain on the face, hip, and knee. In the reverse direction, genetically instrumented multisite chronic pain (OR = 1.78 per one increment in the number of pain site, 95% CI: 1.51-2.11) and headache (OR = 1.55 per one log-unit increase in headache risk, 95% CI = 1.13-2.10) were associated with MDD. Functional annotation analysis showed differential clustering patterns where depression clustered closely with headache and neck/shoulder pain, exhibiting substantial brain tissue enrichment. Our study indicates that depression is a causal risk factor for headache and pain localized at neck/shoulder, back, and abdominal/stomach, rather than pain at face, hip, and knee, and suggests common neurological pathologies underlying the development of depression, headache, and neck/shoulder pain.

Axial length of myopia: a review of current research.

Myopia, or nearsightedness, is a worldwide common type of refractive error. It is a non-life-threatening disorder with huge social and economic consequences due to its increasing prevalence. Axial length (AL) is the primary determinant of non-syndromic myopia. It is a parameter representing the combination of anterior chamber depth, lens thickness and vitreous chamber depth of the eye. AL can also be treated as an endophenotype of myopia and may provide extra advantages in the investigation of its genetic basis. The study of AL will not only identify the determinants of eye elongation, but also provide aetiological evidence for myopia. The purpose of this review is to outline the current state of AL research. Epidemiological evidence, genetic determinants, the relationship with other eye components and relative animal models of AL are summarised.

Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility.

Importance: Neuropathic pain (NP) has important clinical and socioeconomic consequences for individuals and society. Increasing evidence indicates that genetic factors make a significant contribution to NP, but genome-wide association studies (GWASs) are scant in this field and could help to elucidate susceptibility to NP. Objective: To identify genetic variants associated with NP susceptibility. Design, Setting, and Participants: This genetic association study included a meta-analysis of GWASs of NP using 3 independent cohorts: ie, Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS); Generation Scotland: Scottish Family Health Study (GS:SFHS); and the United Kingdom Biobank (UKBB). Data analysis was conducted from April 2018 to December 2019. Exposures: Individuals with NP (ie, case participants; those with pain of ≥3 months' duration and a Douleur Neuropathique en 4 Questions score ≥3) and individuals with no pain (ie, control participants) with or without diabetes from GoDARTS and GS:SFHS were identified using validated self-completed questionnaires. In the UKBB, self-reported prescribed medication and hospital records were used as a proxy to identify case participants (patients recorded as receiving specific anti-NP medicines) and control participants. Main Outcomes and Measures: GWAS was performed using linear mixed modeling. GWAS summary statistics were combined using fixed-effect meta-analysis. A total of 51 variants previously shown to be associated with NP were tested for replication. Results: This study included a total of 4512 case participants (2662 [58.9%] women; mean [SD] age, 61.7 [10.8] years) and 428 489 control participants (227 817 [53.2%] women; mean [SD] age, 62.3 [11.5] years) in the meta-analysis of 3 cohorts with European descent. The study found a genome-wide significant locus at chromosome 12q23.1, which mapped to SLC25A3 (rs369920026; odds ratio [OR] for having NP, 1.68; 95% CI, 1.40-2.02; P = 1.30 × 10-8), and a suggestive variant at 13q14.2 near CAB39L (rs7992766; OR, 1.09; 95% CI, 1.05-1.14; P = 1.22 × 10-7). These mitochondrial phosphate carriers and calcium binding genes are expressed in brain and dorsal root ganglia. Colocalization analyses using expression quantitative loci data found that the suggestive variant was associated with expression of CAB39L in the brain cerebellum (P = 1.01 × 10-14). None of the previously reported variants were replicated. Conclusions and Relevance: To our knowledge, this was the largest meta-analyses of GWAS to date. It found novel genetic variants associated with NP susceptibility. These findings provide new insights into the genetic architecture of NP and important information for further studies.

Cohort profile: DOLORisk Dundee: a longitudinal study of chronic neuropathic pain.

PURPOSE: Neuropathic pain is a common disorder of the somatosensory system that affects 7%-10% of the general population. The disorder places a large social and economic burden on patients as well as healthcare services. However, not everyone with a relevant underlying aetiology develops corresponding pain. DOLORisk Dundee, a European Union-funded cohort, part of the multicentre DOLORisk consortium, was set up to increase current understanding of this variation in onset. In particular, the cohort will allow exploration of psychosocial, clinical and genetic predictors of neuropathic pain onset. PARTICIPANTS: DOLORisk Dundee has been constructed by rephenotyping two pre-existing Scottish population cohorts for neuropathic pain using a standardised 'core' study protocol: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) (n=5236) consisting of predominantly type 2 diabetics from the Tayside region, and Generation Scotland: Scottish Family Health Study (GS:SFHS; n=20 221). Rephenotyping was conducted in two phases: a baseline postal survey and a combined postal and online follow-up survey. DOLORisk Dundee consists of 9155 participants (GoDARTS=1915; GS:SFHS=7240) who responded to the baseline survey, of which 6338 (69.2%; GoDARTS=1046; GS:SFHS=5292) also responded to the follow-up survey (18 months later). FINDINGS TO DATE: At baseline, the proportion of those with chronic neuropathic pain (Douleur Neuropathique en 4 Questions questionnaire score ≥3, duration ≥3 months) was 30.5% in GoDARTS and 14.2% in Generation Scotland. Electronic record linkage enables large scale genetic association studies to be conducted and risk models have been constructed for neuropathic pain. FUTURE PLANS: The cohort is being maintained by an access committee, through which collaborations are encouraged. Details of how to do this will be available on the study website (http://dolorisk.eu/). Further follow-up surveys of the cohort are planned and funding applications are being prepared to this effect. This will be conducted in harmony with similar pain rephenotyping of UK Biobank.

Sex- and age-specific genetic analysis of chronic back pain.

ABSTRACT: Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as "Back pain for 3+ months" in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and 7 nonoverlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in 4 independent cohorts. Four loci demonstrated single nucleotide polymorphism-by-sex interaction, although none of them were formally replicated. Single nucleotide polymorphism-explained heritability was higher in females (0.079 vs 0.067, P = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838 ± 0.041, different from 1 with P = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858 ± 0.049 in younger people vs 0.544 ± 0.157 in older people; P = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.

Herpes Zoster and Postherpetic Neuralgia in an Elderly Patient with Critical COVID-19: A Case Report.

Critical patients with COVID-19 are thought to be at high risk of developing chronic pain. However, the exact nature and mechanisms of COVID-19-related chronic pain remain largely unknown. Here, we describe clinical features, treatments and outcome of herpes zoster as well as postherpetic neuralgia in a 70-year-old woman with critical COVID-19. The patient had a history of type 2 diabetes and myasthenia gravis. She developed herpes zoster in the right 10 to 12 lumbar dermatomes in the recovery period of COVID-19. Intravenous (250 mg 3 times a day) and then oral (400 mg 5 times a day) acyclovir was used for antiviral therapy. Pregabalin (75 mg orally twice a day) and ibuprofen was used for analgesia. Her skin lesions resolved 21 days after the onset of rash. However, she continued to have persistent pain in the same dermatomal distribution. After the dosage of pregabalin was increased to 150 mg orally twice a day, her pain was partially relieved. During the telephone follow-up 4 months after herpes zoster eruption, the patient still complained intermittent pain in the right 10 to 12 lumbar dermatomes. Our case draws attention to postherpetic neuralgia in COVID-19 patients and provides a targeted suggestion for this kind of patients.

Treatment of solitary hepatocellular carcinoma up to 2 cm: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: In recent years, there has been considerable uncertainty about the optimal treatment option for very early hepatocellular carcinoma (HCC) with tumor size less than 2 cm. Therefore, we performed a systematic review and meta-analysis to evaluate the outcomes of the different treatments. METHODS: This study was designed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). PubMed, EMBASE, and Cochrane library were searched for calculating the survival rates, and the "time to event" method was used to compare the outcomes of liver resection (LR) and radiofrequency ablation (RFA). All studies focusing on the treatment of solitary HCC up to 2 cm by different techniques were included in our analysis. The Hazard ratios (HR) and 95% confidence intervals (CI) derived from multivariate and univariate analysis were utilized to assess the treatment risks. RESULTS: We included 32 studies in our systematic review. The median 5-year overall survival (OS) and recurrence-free survival rate (RFS) for LR were 73% and 47%, respectively, and those for RFA were 73% and 43%, respectively. RFA was found to be associated with increased risk of mortality and recurrence compared to LR (HR = 1.61, 95% CI: 1.35-1.92, P < .0001 for OS and HR = 1.75, 95% CI: 1.56-1.96, P < .0001 for RFS). CONCLUSION: Our meta-analysis demonstrated that LR is superior to RFA in the treatment of solitary HCC up to 2 cm, with reduction in mortality and recurrence risk and improved long-term outcome.

Core-Shell Graphitic Carbon Nitride/Zinc Phytate as a Novel Efficient Flame Retardant for Fire Safety and Smoke Suppression in Epoxy Resin.

Novel core-shell graphitic carbon nitride/zinc phytate (g-C3N4/PAZn) flame retardant was simple synthetized using two-dimensional g-C3N4 and bio-based PAZn by self-assembly and incorporated into epoxy resin (EP) for improving the fire safety. The flame retardance and smoke suppression were investigated by cone calorimetry. The results indicated that g-C3N4/PAZn-EP displayed outstanding flame retardancy and smoke suppression, for example, the peak heat release rate and peak smoke production rate decreased by 71.38% and 25%, respectively. Furthermore, the flame retardancy mechanism was further explored by char residue and thermal stability analysis. It can be predicted that g-C3N4/PAZn will provide valuable reference about bio-based flame retardant.

Genetic correlations between pain phenotypes and depression and neuroticism.

Correlations between pain phenotypes and psychiatric traits such as depression and the personality trait of neuroticism are not fully understood. In this study, we estimated the genetic correlations of eight pain phenotypes (defined by the UK Biobank, n = 151,922-226,683) with depressive symptoms, major depressive disorders and neuroticism using the the cross-trait linkage disequilibrium score regression (LDSC) method integrated in the LD Hub. We also used the LDSC software to calculate the genetic correlations among pain phenotypes. All pain phenotypes, except hip pain and knee pain, had significant and positive genetic correlations with depressive symptoms, major depressive disorders and neuroticism. All pain phenotypes were heritable, with pain all over the body showing the highest heritability (h2 = 0.31, standard error = 0.072). Many pain phenotypes had positive and significant genetic correlations with each other indicating shared genetic mechanisms. Our results suggest that pain, neuroticism and depression share partially overlapping genetic risk factors.

Author Correction: Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A genome-wide association study implicates that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity.

Background: Diabetic maculopathy is a form of diabetic retinopathy. The visual acuity of one third of patients with diabetic maculopathy will be affected. The purpose of this study was to identify genetic contributors of diabetic maculopathy with decreased visual acuity based on a genome-wide association approach using a well-defined Scottish diabetic cohort. Methods: We used linked e-health records of diabetic patients to define our cases and controls. The cases in this study were defined as type 2 diabetic patients who had ever been recorded in the linked e-health records as having maculopathy (observable or referable) in at least one eye and whose visual acuity of the eye was recorded to have decreased between the first and the last visual acuity record of that eye in the longitudinal e-health records. The controls were defined as a type 2 diabetic individual who had never been diagnosed with maculopathy or retinopathy in the linked e-health records. Anyone who had laser photocoagulation treatment was also excluded from the controls. A standard genome-wide association approach was applied. Results: Overall, we identified 469 cases and 1,374 controls within the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. We found that the P value of rs9966620 in the TTC39C gene was 4.13x10-8, which reached genome-wide significance. Conclusions: We suggest that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity. This needs to be confirmed by further replication studies and functional studies.