Basal and LPS-stimulated inflammatory markers and the course of individual symptoms of depression

Multiple studies show an association between inflammatory markers and major depressive disorder (MDD). People with chronic low-grade inflammation may be at an increased risk of MDD, often in the form of sickness behaviors. We hypothesized that inflammation is predictive of the severity and the course of a subset of MDD symptoms, especially symptoms that overlap with sickness behavior, such as anhedonia, anorexia, low concentration, low energy, loss of libido, psychomotor slowness, irritability, and malaise. We tested the association between basal and lipopolysaccharide (LPS)-induced inflammatory markers with individual MDD symptoms (measured using the Inventory of Depressive Symptomatology Self-Report) over a period of up to 9 years using multivariate-adjusted mixed models in 1147–2872 Netherlands Study of Depression and Anxiety (NESDA) participants. At baseline, participants were on average 42.2 years old, 66.5% were women and 53.9% had a current mood or anxiety disorder. We found that basal and LPS-stimulated inflammatory markers were more strongly associated with sickness behavior symptoms at up to 9-year follow-up compared with non-sickness behavior symptoms of depression. However, we also found significant associations with some symptoms that are not typical of sickness behavior (e.g., sympathetic arousal among others). Inflammation was not related to depression as a unified syndrome but rather to the presence and the course of specific MDD symptoms, of which the majority were related to sickness behavior. Anti-inflammatory strategies should be tested in the subgroup of MDD patients who report depressive symptoms related to sickness behavior

Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms

A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized betacoefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression.Stress-related psychiatric disorders across the life spa

Hint for a TeV neutrino emission from the Galactic Ridge with ANTARES

Interactions of cosmic ray protons, atomic nuclei, and electrons in the interstellar medium in the inner part of the Milky Way produce a γ-ray flux from the Galactic Ridge. If the γ-ray emission is dominated by proton and nuclei interactions, a neutrino flux comparable to the γ-ray flux is expected from the same sky region.Data collected by the ANTARES neutrino telescope are used to constrain the neutrino flux from the Galactic Ridge in the 1-100 TeV energy range. Neutrino events reconstructed both as tracks and showers are considered in the analysis and the selection is optimized for the search of an excess in the region |ι| < 30°, |b| < 2°. The expected background in the search region is estimated using an off-zone region with similar sky coverage. Neutrino signal originating from a power-law spectrum with spectral index ranging from Τν = 1 to 4 is simulated in both channels. The observed energy distributions are fitted to constrain the neutrino emission from the Ridge.The energy distributions in the signal region are inconsistent with the background expectation at ∼ 96% confidence level. The mild excess over the background is consistent with a neutrino flux with a power law with a spectral index 2.45+0.22-0.34 and a flux normalization dNv/dEv  = 4.0+2.7-2.0 x 1016 GeV−1 cm−2 s−1 sr−1 at 40 TeV reference energy. Such flux is consistent with the expected neutrino signal if the bulk of the observed γ-ray flux from the Galactic Ridge originates from interactions of cosmic ray protons and nuclei with a power-law spectrum extending well into the PeV energy range

Prediagnostic sex steroid hormones in relation to male breast cancer risk

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers

Search for Gamma-Ray and Neutrino Coincidences Using HAWC and ANTARES Data

In the quest for high-energy neutrino sources, the Astrophysical Multimessenger Observatory Network has implemented a new search by combining data from the High Altitude Water Cherenkov (HAWC) Observatory and the Astronomy with a Neutrino Telescope and Abyss environmental RESearch (ANTARES) neutrino telescope. Using the same analysis strategy as in a previous detector combination of HAWC and IceCube data, we perform a search for coincidences in HAWC and ANTARES events that are below the threshold for sending public alerts in each individual detector. Data were collected between 2015 July and 2020 February with a live time of 4.39 yr. Over this time period, three coincident events with an estimated false-alarm rate of &lt;1 coincidence per year were found. This number is consistent with background expectations

Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV:Results from a Case–Control Diagnostic Validation Study

We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63–0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8–86.2%) and specificity was 59.2% (95%CI: 47.3–70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4–65.1) and specificity of 71.2% (95%CI = 61.8–79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection.</p

Pilot case-control investigation of risk factors for hip fractures in the urban Indian population

<p>Abstract</p> <p>Background</p> <p>Despite the reported high prevalence of osteoporosis in India, there have been no previous studies examining the risk factors for hip fracture in the Indian population.</p> <p>Methods</p> <p>We carried out a case control investigation comprising 100 case subjects (57 women and 43 men) admitted with a first hip fracture into one of three hospitals across New Delhi. The 100 controls were age and sex matched subjects who were either healthy visitors not related to the case patients or hospital staff. Information from all subjects was obtained through a questionnaire based interview.</p> <p>Results</p> <p>There was a significant increase in the number of cases of hip fracture with increasing age. There were significantly more women (57%) than men (43%). Univariate analysis identified protective effects for increased activity, exercise, calcium and vitamin supplements, almonds, fish, paneer (cottage cheese), curd (plain yogurt), and milk. However, tea and other caffeinated beverages were significant risk factors. In women, hormone/estrogen therapy appeared to have a marginal protective effect. For all cases, decreased agility, visual impairment, long term medications, chronic illnesses increased the risk of hip fracture. The multivariate analysis confirmed a protective effect of increased activity and also showed a decrease in hip fracture risk with increasing body mass index (odds ratio (OR) 0.024, 95% confidence interval (CI) 0.006-0.10 & OR 0.81, 95% CI 0.68-0.97 respectively). Individuals who take calcium supplements have a decreased risk of hip fracture (OR 0.076; CI 0.017-0.340), as do individuals who eat fish (OR 0.094; CI 0.020-0.431), and those who eat paneer (OR 0.152; 0.031-0.741). Tea drinkers have a higher risk of hip fracture (OR 22.8; 95% CI 3.73-139.43). Difficulty in getting up from a chair also appears to be an important risk factor for hip fractures (OR 14.53; 95% CI 3.86-54.23).</p> <p>Conclusions</p> <p>In the urban Indian population, dietary calcium, vitamin D, increased body mass index, and higher activity levels have a significant protective effect on hip fracture. On the other hand, caffeine intake and decreased agility increase the risk of hip fracture. Future studies should be done in order to direct primary preventive programs for hip fracture in India.</p

Positive and Negative Regulation of Gli Activity by Kif7 in the Zebrafish Embryo

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu) protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles