Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic variation with concordant effects in both phenotypes shows significant SNP-based heritability enrichment, higher polygenic contribution in females, and positive covariance with mental disorders such as depression, anxiety, attention-deficit hyperactivity disorder, alcohol dependence, and autism. Conversely, genetic variation with discordant effects only contributes to schizophrenia risk in males and is negatively correlated with those disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia than vice versa. These results illustrate the genetic footprint of LNL-ISO on schizophrenia.

Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo–keto reductase 1C3 (AKR1C3) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.

Management of Impacted Teeth in Orthodontics

Introduction and Purpose: Treatment of impacted teeth in orthodontics is crucially important, as clinician is supposed to manage such cases in his/her daily practice. However, impaction cases can be so complicated especially when other factors interfere within their treatments such as anatomical locations of the impacted teeth, surgical considerations and Orthodontic Traction difficulties. The management of impacted teeth in orthodontic practice varies widely from extraction of the impacted tooth to forced orthodontic eruption. Orthodontic eruption varies between closed or open techniques that must be determined for each case, per se. Materials and Methods: One hundred fifty one impacted teeth cases were followed up, classified by their techniques as to register the results statistically. The approaches for handling the impacted teeth were open forced eruption “as window or APF Apically Positioned Flap”, closed forced eruption, negligence and extraction when indicated. Bonding with Light Cure orthodontic composite was used for all cases of forced eruption. The used Device had been Mini LED, Acteron, Li-ION 3.7V, 2500mAh. Time of Exposure 20 Second. The traction attachments had been either Titanium Button and Chain (Watted) Dentaurum, or conventional Buttons (with ligature wires or elastics). This research discusses the prognosis of impacted teeth, the approaches of the orthodontic forced eruption and when to expose, extract or even “neglect”! The article does not recommend one treatment plan for all cases, in contrary; it urges the reader to search more for innovative solutions whenever such cases come across. Results and Conclusion: It is recommended that the decision regarding orthodontic forced eruption (closed or open), or extraction be based on evaluation of each independent case. In spite of the result of this research that 126 cases of the 151 screened cases had been treated successfully by orthodontic forced eruption, but complications such ankylosis, resorption, eruption failure and periodontal pockets need to be taken into account. Another complication can often be encountered that is bonding failures, especially in closed force eruption. However, the new bonding materials and the improved techniques have helped to overcome such a problem. Finally, the more precise the location and position of the impacted tooth is known, the easier the procedure becomes.

Rare risk variants associate with epigenetic dysregulation in migraine

Migraine has a heritability of up to 65%. Genome-wide association studies (GWAS) on migraine have identified 123 risk loci, explaining only 10.6% of migraine heritability. Thus, there is a considerable genetic component not identified with GWAS. Further, the causality of the identified risk loci remains inconclusive. Rare variants contribute to the risk of migraine but GWAS are often underpowered to detect these. Whole genome sequencing is reliable for analyzing rare variants but is not frequently used in large-scale. We assessed if rare variants in the migraine risk loci associated with migraine. We used a large cohort of whole genome sequenced migraine patients (1,040 individuals from 155 families). The findings were replicated in an independent case-control cohort (2,027 migraine patients, 1,650 controls). We found rare variants (minor allele frequency<0.1%) associated with migraine in a Polycomb Response Element in the ASTN2 locus. The association was independent of the GWAS lead risk variant in the locus. The findings place rare variants as risk factors for migraine. We propose a biological mechanism by which epigenetic regulation by Polycomb Response Elements plays a crucial role in migraine etiology.

Molecular evidence of autophagy impairment as serum level of ATG13 is elevated in patients with myalgic encephalomyelitis and chronic fatigue syndrome: two independent case-control studies

Myalgic Encephalomyelitis and chronic fatigue syndrome is a multisystem illness characterized with extreme muscle fatigue associated with pain, neurocognitive impairment, and chronic inflammation. Despite intense investigation, the molecular mechanism of this disease is still unknown. Here we report two independent case-control studies to demonstrate that autophagy proteins are strongly upregulated in the serum of ME/CFS patients indicative of severe impairment in metabolic events of autophagy. Serum samples collected from two healthy and two age-matched patients were assayed for protein aggregation, screened for autophagy-related factors via an antibody array, quantified with densitometric analyses, and finally reconfirmed with ELISA analyses. Based on that double-blinded and gender-balanced study, the levels of ATG13, p62, and alpha-synuclein (α-syn) were found to be consistently elevated in the serum samples of these two ME/CFS patients. Moreover, our microglia-based oxidative stress response study and nitrite analyses indicated that serum samples of ME/CFS patients evoked the production of reactive oxygen species (ROS) and nitrite in human HMC3 microglial cells, whereas neutralization of ATG13 was shown to strongly diminish the production of ROS and nitrite demonstrating the de novo effect bloodborne autophagy factors on inducing the stress response in microglial cells. Collectively, our results indicate that the impairment of autophagy followed by upregulations of autophagy markers especially ATG13 in serum could be a pathological hallmark in ME/CFS.

Estimation of Mechanical Power Output Employing Deep Learning on Inertial Measurement Data in Roller Ski Skating

The ability to optimize power generation in sports is imperative, both for understanding and balancing training load correctly, and for optimizing competition performance. In this paper, we aim to estimate mechanical power output by employing a time-sequential information-based deep Long Short-Term Memory (LSTM) neural network from multiple inertial measurement units (IMUs). Thirteen athletes conducted roller ski skating trials on a treadmill with varying incline and speed. The acceleration and gyroscope data collected with the IMUs were run through statistical feature processing, before being used by the deep learning model to estimate power output. The model was thereafter used for prediction of power from test data using two approaches. First, a user-dependent case was explored, reaching a power estimation within 3.5% error. Second, a user-independent case was developed, reaching an error of 11.6% for the power estimation. Finally, the LSTM model was compared to two other machine learning models and was found to be superior. In conclusion, the user-dependent model allows for precise estimation of roller skiing power output after training the model on data from each athlete. The user-independent model provides less accurate estimation; however, the accuracy may be sufficient for providing valuable information for recreational skiers.

Approaches to Reduce or Eliminate the Risks of Sight Tests in Alberta

This research report is motivated by two independent case reports featuring individuals living in Alberta, Canada who experienced permanent vision loss as a result of inadequate standards of practice surrounding sight tests. Sight tests are usually performed by opticians and are conducted independently of a comprehensive eye exam. A description of the two case reports in addition to a discussion of the potential dangers of sight tests provide evidence of the public health risks associated with sight tests. To investigate potential approaches to reduce or eliminate the risks of sight tests in Alberta, we conducted a jurisdictional review examining the laws and standards of practice governing sight tests in Canada, the United States, New Zealand, and the United Kingdom. Based on the jurisdictional review, the outright prohibition of sight tests in Alberta may be the best approach to protect the public interest and reduce cases of avoidable vision loss. As seen in other Canadian provinces, alternative approaches to reduce the risk of sight tests may involve 1) developing and enforcing restrictions around the performance of sight tests or 2) developing clearly defined scenarios in which opticians can collaborate with authorized prescribers to deliver safe sight tests.

The rs2619566, rs10260404, and rs79609816 Polymorphisms Are Associated With Sporadic Amyotrophic Lateral Sclerosis in Individuals of Han Ancestry From Mainland China

The pathogenesis of sporadic amyotrophic lateral sclerosis (sALS) remains unknown; however, recent research suggests that genetic factors may play an important role. This study aimed at investigating possible genetic risk factors for the pathogenesis of sALS. In our previous study, we conducted a genome-wide association study (GWAS) in 250 sALS patients and 250 control participants of Han ancestry from mainland China (HACM) and retrospectively analyzed the previously reported candidate loci related with sALS including our GWAS investigated results. In this study, twenty-seven candidate loci that were most likely associated with sALS were selected for further analysis in an independent case/control population of 239 sALS patients and 261 control subjects of HACM ethnicity using sequenom massARRAY methodology and DNA sequencing. We discovered that the polymorphism rs2619566 located within the contactin-4 (CNTN4) gene, rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene, and rs79609816 in the inositol polyphosphate-5-phosphatase B (INPP5B) gene were strongly associated with sALS in subjects of HACM ethnicity. Subjects harboring the minor C allele of rs2619566 and the minor T allele of rs79609816 exhibited an increased risk for sALS development, while carriers of the minor C allele of rs10260404 showed a decreased risk of sALS development compared to the subjects of other genotypes. The polymorphisms of rs2619566, rs10260404, and rs79609816 may change or affect the splicing, transcription, and translation of CNTN4, DPP6, and INPP5B genes and may play roles in the pathogenesis of sALS roles in the pathogenesis of sALS.

Moduli stabilisation and the statistics of axion physics in the landscape

String theory realisations of the QCD axion are often said to belong to the anthropic window where the decay constant is around the GUT scale and the initial misalignment angle has to be tuned close to zero. In this paper we revisit this statement by studying the statistics of axion physics in the string landscape. We take moduli stabilisation properly into account since the stabilisation of the saxions is crucial to determine the physical properties of the corresponding axionic partners. We focus on the model-independent case of closed string axions in type IIB flux compactifications and find that their decay constants and mass spectrum feature a logarithmic, instead of a power-law, distribution. In the regime where the effective field theory is under control, most of these closed string axions are ultra-light axion-like particles, while axions associated to blow-up modes can naturally play the role of the QCD axion. Hence, the number of type IIB flux vacua with a closed string QCD axion with an intermediate scale decay constant and a natural value of the misalignment angle is only logarithmically suppressed. In a recent paper we found that this correlates also with a logarithmic distribution of the supersymmetry breaking scale, providing the intriguing indication that most, if not all, of the phenomenologically interesting quantities in the string landscape might feature a logarithmic distribution.