Old Habits Die Hard: Dietary Habits of Migraine Patients Challenge our Understanding of Dietary Triggers

Introduction: Migraine is a multifactorial neurological disorder with a major metabolic facet. Dietary approaches represent a commonly implemented lifestyle modifying strategy in headache clinics, yet the precise relationship between diet and migraine is still a matter of debate.Materials and Methods: The study consisted of two parts: first, in a cross-sectional design, we compared alimentary habits of migraine subjects and a control group of healthy volunteers. For the second part, we prospectively evaluated patients' daily consumption of various potentially migraine-triggering foods over a two-month period in order to examine their possible association with the occurrence of a migraine attack.Results: Most migraine patients reported avoiding at least one potentially migraine-triggering food/drink from their diet. In spite of that, with the sole exemption of citrus fruits, there were no statistically significant differences with respect to consumption patterns between migraine patients and controls (including wine and chocolate). Consumption frequency over time was proportional to intake of potentially migraine-triggering foods the day before a migraine attack.Conclusion: Our results underline the need of performing trigger challenges in order to avoid falling into an association-causation fallacy when attempting to identify possible alimentary migraine triggers. Indeed, it is possible that intake of certain foods like chocolate before attacks is a consequence of pre-attack cravings or a simple coincidence facilitated by previously established dietary habits.

Justice for the Menopause: A Research Agenda

Menopause is defined by its relationship to menstruation––it is the cessation of menstruation. Medical texts identify menopause as part of the cycle of “decay” associated with female reproductive functions; early menopause is often a dreaded result of various medical treatments and a sign of disfunction. It turns out that only three types of animals experience menopause: killer whales, short-finned pilot whales, and humans, while other animals can reproduce until death. Although the precise relationship between evolutionary theory and the physical development of human menopause is still uncertain, scientists and anthropologists suggest that the “grandmother hypothesis” provides a partial explanation: older women, who can no longer produce their own children, ensure their genetic legacy by playing a critical role in helping to feed, raise, and nurture their grandchildren. The average woman will spend almost as many years “post-menopause” as they will menstruating, and they may spend four years (or more) experiencing perimenopausal symptoms, the transition time between “normal” menstruation and menopause. But legal issues relating to perimenopause, menopause, and post-menopause are just beginning to surface, prompted by the movement towards menstrual justice, feminist jurisprudence, and developments in the law of aging. This Essay is an initial effort to catalogue various legal approaches to menopause and to set out areas for further analysis. It briefly explores cultural images of menopause and post-menopausal women, including the ubiquitous hot flashes; analyzes potential legal claims for menopausal justice; and suggests the interrelationship between such approaches and social attitudes towards menopause. It suggests that “normalizing” menopause––acknowledging its realities––is one means for removing the associated stigma and “disabilities” and might result in reinterpreting existing laws and guiding future legal reforms.

The roles of photochemical and non-photochemical quenching in regulating photosynthesis depend on the phases of fluctuating light conditions

The induction and relaxation of photochemistry and non-photochemical quenching (NPQ) are not instantaneous and require time to respond to fluctuating environments. There is a lack of integrated understanding on how photochemistry and NPQ influence photosynthesis in fluctuating environments. We measured the induction and relaxation of chlorophyll a fluorescence and gas exchange in poplar and cotton at varying temperatures under saturating and fluctuating lights. When the light shifted from dark to high, the fraction of open reaction centers in photosystem II (qL) gradually increased while NPQ increased suddenly and then remained stable. Temperature significantly changed the response of qL but not that of NPQ during the dark to high light transition. Increased qL led to higher photosynthesis but their precise relationship was affected by NPQ and temperature. qL was significantly related to biochemical capacity. Thus, qL appears to be a strong indicator of the activation of carboxylase, leading to the similar dynamics between qL and photosynthesis. When the light shifted from high to low intensity, NPQ is still engaged at a high level, causing a stronger decline in photosynthesis. Our finding suggests that the dynamic effects of photochemistry and NPQ on photosynthesis depend on the phases of environmental fluctuations and interactive effects of light and temperature. Across the full spectra of light fluctuation, the slow induction of qL is a more important limiting factor than the slow relaxation of NPQ for photosynthesis in typical ranges of temperature for photosynthesis. The findings provided a new perspective to improve photosynthetic productivity with molecular biology under natural fluctuating environments.

Critical and Subcritical Anisotropic Trudinger–Moser Inequalities on the Entire Euclidean Spaces

We investigate the subcritical anisotropic Trudinger–Moser inequality in the entire space ℝ N , obtain the asymptotic behavior of the supremum for the subcritical anisotropic Trudinger–Moser inequalities on the entire Euclidean spaces, and provide a precise relationship between the supremums for the critical and subcritical anisotropic Trudinger–Moser inequalities. Furthermore, we can prove critical anisotropic Trudinger–Moser inequalities under the nonhomogenous norm restriction and obtain a similar relationship with the supremums of subcritical anisotropic Trudinger–Moser inequalities.

Baseline MMP expression in periapical granuloma and its relationship with periapical wound healing after surgical endodontic treatment

Background Matrix metalloproteinases (MMPs) catalyzes the degradation of the extracellular matrix components and have a major role in many physiological processes including wound healing. In the current study, we examined the correlation of baseline MMPs 1, 2, 7, and 9 expressions with periapical wound healing after surgical endodontic treatment. Methods 27 patients aged between 15–57 years presenting with chronic apical periodontitis or chronic apical abscess of an anterior tooth with previously attempted or failed root canal treatment were included in this study. During surgical endodontic treatment, tissue from the periapical lesion sample was collected and used for gross histopathological analysis as well as mRNA expression analysis of MMPs 1, 2, 7, and 9. Patients were recalled for follow-up after 6 and 12 months to evaluate the healing status both clinically and radiographically and healing was correlated with baseline MMP expression. Results Out of 27 patients, healing was observed in 15 patients at the end of 6 months, and patients after 12 months. Six patients showed no healing even after 12 months. Analysis of baseline MMP 1, 2, 7, and 9 expression levels with healing status showed the mean relative expression of MMP2 and MMP9 to be considerably increased in the non-healing group as compared to the healing group. Conclusion Overexpression of MMP2 and MMP9 may be considered as a potential prognostic biomarker for periapical wound healing after surgical endodontic treatment. However, further studies are desirable to establish its precise relationship with periapical wound healing.

High-order functional interactions in ageing explained via alterations in the connectome in a whole-brain model

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain's connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the age differences in high-order functional interactions can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modelling more complex forms of pathological ageing or cognitive deficits.

Self-processing in relation to emotion and reward processing in depression

Background Depression is characterised by a heightened self-focus, which is believed to be associated with differences in emotion and reward processing. However, the precise relationship between these cognitive domains is not well understood. We examined the role of self-reference in emotion and reward processing, separately and in combination, in relation to depression. Methods Adults experiencing varying levels of depression (n = 144) completed self-report depression measures (PHQ-9, BDI-II). We measured self, emotion and reward processing, separately and in combination, using three cognitive tasks. Results When self-processing was measured independently of emotion and reward, in a simple associative learning task, there was little association with depression. However, when self and emotion processing occurred in combination in a self-esteem go/no-go task, depression was associated with an increased positive other bias [b = 3.51, 95% confidence interval (CI) 1.24–5.79]. When the self was processed in relation to emotion and reward, in a social evaluation learning task, depression was associated with reduced positive self-biases (b = 0.11, 95% CI 0.05–0.17). Conclusions Depression was associated with enhanced positive implicit associations with others, and reduced positive learning about the self, culminating in reduced self-favouring biases. However, when self, emotion and reward processing occurred independently there was little evidence of an association with depression. Treatments targeting reduced positive self-biases may provide more sensitive targets for therapeutic intervention and potential biomarkers of treatment responses, allowing the development of more effective interventions.

Leptin Induced TLR4 Expression via the JAK2-STAT3 Pathway in Obesity-Related Osteoarthritis

Obesity is considered as a risk factor of osteoarthritis (OA), but the precise relationship is still poorly understood. Leptin, one of the most relevant factors secreted by adipose tissues, plays an important role in the pathogenesis of OA. Our aim was to investigate the regulation and molecular mechanism of the leptin signaling pathway in obesity-related OA. SD rats were fed with a high-fat diet (HFD) for 5, 15, and 27 weeks. The levels of leptin in serum increased from W5, while in the synovial fluid increased from W15. The histological evaluation showed that the pathological changes of OA occurred at 27 weeks rather than 5 or 15 weeks. We also found that leptin induced CD14/TLR4 activation by the JAK2-STAT3 signaling pathway to promote OA. Moreover, silencing SOCS3 enhanced leptin-induced JAK2-STAT3-CD14/TLR4 activation in rat primary chondrocytes. Our findings indicated that leptin may be one of the initiating factors of obesity-related OA. TLR4 is at least partially regulated by leptin through the JAK2-STAT3-CD14 pathway. Meanwhile, SOCS3 acting as a negative feedback inhibitor of leptin signaling presented a potential therapeutic prospect for obesity-related OA. Our study provided new evidence suggesting the key role of leptin in mediating obesity-related OA process and its underlying mechanisms.

Analysis of Test Method to Extract Material Properties From Candu Fuel Channel Spacers Made of Helical Springs

In a particular nuclear application, separation between two concentric tubes is supported by helical springs installed in the annular space. Evaluation of material degradation due to the unique operating environment requires testing of ex-service spring material. Testing is done by compressing short segments of the spring material between two surfaces as per the loading mode in operation. Nominally, the specimen behaves like multiple rings loaded uniformly in parallel, but analysis of test results based on this approximation neglects significant end effects. A detailed analysis addresses the transition from the free end boundary condition through to where the coils become confined by friction to behave like rings. The thin ring solution is compared with finite element results as well as test results. Trends from the detailed thin ring solution correspond closely to the finite element and test results. A more precise relationship between the total applied load and the maximum stress in the material is determined.

Identification of Risk Factors for Invasive Extraintestinal Pathogenic Escherichia coli (ExPEC) Disease

Background: A pathogenic group of invasive extraintestinal pathogenic (ExPEC) Escherichia coli possess the ability to infect normally sterile body sites and cause severe invasive ExPEC disease (IED). ExPEC is a leading cause of bacteremia and sepsis worldwide and is associated with older age and multidrug-resistant infections. Janssen Vaccines & Prevention is developing a novel multivalent glycoconjugate vaccine to prevent IED. We aimed to use an unbiased approach, with no prespecified potential risk factors, using machine-learning models, to screen for and identify IED risk factors for further validation. Methods: We used a patient-level prediction study design to model the probability of a patient developing IED within 14 days to 1 year from a given date based on their prior 2 years of health records. We used the Optum EHR database (~98 million subjects) in the common data model (CDM) format, with health features encoded in the following categories: conditions, procedures, drugs, healthcare visits, recent laboratory measurements, and age and gender. A gradient boosting model (XGBoost) was used with Shapley additive explanation (SHAP) values to identify which features were most important to the model’s decisions and to characterize precisely the relationship between features and outcomes (binary or continuous). Results: Study participants were aged ≥60 years at index with no previously recorded IED. Of ~6,500,000 cases included, ~8,000 had IED during the prediction window. We found that having ≥1 urinary tract infection (UTI) in the retrospective period increased the model’s probability of predicting IED for that patient, with more frequent or more recent UTIs increasing IED prediction chance (Figure 1). Higher age linearly increased the model’s likelihood of predicting that a patient would develop IED. The model also identified ≥1 inpatient or ER visit and laboratory values indicative of renal or immune dysfunction to be correlated with increased IED risk. This methodology is a generalizable approach to screening for potential risk factors for an outcome using EHR databases; it requires little to no prespecification of the health factors or precise relationship between the factors and outcome. Conclusions: Using a new, impartial methodology (with no prespecification), older age and a history of UTIs were key predictive features for IED, factors previously identified through traditional analysis, confirming the validity of the methodology. Novel features, including recent hospitalization, were shown to increase IED risk relative to existing criteria. Our findings may be used to inform the clinical development of preventive strategies.Funding: Janssen Research and DevelopmentDisclosures: None