Highly conserved bifidobacteria in the human gut: Bifidobacterium longum subsp. longum as a potential modulator of elderly innate immunity.

Aging is a physiological and immunological process involving the deterioration of human health, characterised by the progressive alteration of organs and their functions. The speed and extent of such decline are dependent on lifestyle, environment, and genetic factors. Moreover, with advancing age, humans become progressively more fragile and prone to acute and chronic diseases. Although the intestinal microbiota is predisposed to perturbations that accompany aging and frailty, it is generally accepted that the gut microbiota engages in multiple interactions that affect host health throughout the host life span. In the current study, an exhaustive in silico investigation of gut-associated bifidobacteria in healthy individuals from birth to old age revealed that Bifidobacterium longum subsp. longum is the most prevalent member, especially during infancy and in centenarians. Moreover, B. longum subsp. longum genome reconstruction and strain tracing among human gut microbiomes allowed the identification of prototypes of this taxon in the human gut microbiota of healthy elderly individuals. Such analyses guided culturomics attempts to isolate B. longum subsp. longum strains that matched the genomic content of B. longum subsp. longum prototypes from healthy elderly individuals. The molecular effects of selected B. longum subsp. longum strains on the human host were further investigated using in vitro microbe-host interactions, revealing differences in the host immune system transcriptome, with a reduction in gene expression of inflammation-related cytokines. These intriguing findings support the potential anti-aging effects of elderly associated prototypes of B. longum subsp. longum.

Measurement of Direct-Photon Cross Section and Double-Helicity Asymmetry at sqrt[s]=510 GeV in p[over →]+p[over →] Collisions.

We present measurements of the cross section and double-helicity asymmetry A_{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510 GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510 GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

Comparison of patient characteristics and treatment approaches for femoral and inguinal hernias utilizing dynamic ultrasound at a single institution.

PURPOSE: To assess the differences in management approach to femoral versus inguinal hernias and to identify patient characteristics associated with each hernia type. METHODS: Imaging studies for patients who had undergone dynamic ultrasound evaluation for the symptom of groin pain between January 1, 2010, and March 31, 2019, at a single institution Musculoskeletal Department were analyzed. Positive femoral hernia imaging studies were compared to studies for inguinal hernias and matching medical records for imaging studies were analyzed. Association of patient characteristics (age, sex, smoking, diabetes) with hernia type was assessed. Primary outcomes were surgical versus non-surgical approach, type of surgery, number of follow-up visits, and pain resolution. RESULTS: A total of 1319 patients presented with groin pain and were assessed with dynamic ultrasound (534 female; 785 male; mean [± SD] age 48.2 ± 16.5). While 409 (31.0%) patients had a femoral hernia detected, 666 (50.6%) had an inguinal hernia detected (p < .05). Significantly more inguinal hernias were surgically repaired than femoral hernias (65.0% vs 53.9% p = .008), and more inguinal hernias than femoral hernias were treated with open surgery (71.0% vs 57.7%; p = .014). Patients with femoral hernias had significantly more follow-up clinic visits than patients with inguinal hernias (mean [± SD] 2.65 ± 4.80 vs 1.76 ± 1.27; p = .010). No difference in the percentage of patients who had pain resolution was observed (82.2% inguinal vs 75.0% femoral; p = .13). CONCLUSIONS: Femoral hernias were managed more conservatively than inguinal hernias at our institution.

Probing Gluon Spin-Momentum Correlations in Transversely Polarized Protons through Midrapidity Isolated Direct Photons in p

Studying spin-momentum correlations in hadronic collisions offers a glimpse into a three-dimensional picture of proton structure. The transverse single-spin asymmetry for midrapidity isolated direct photons in p^{↑}+p collisions at sqrt[s]=200 GeV is measured with the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). Because direct photons in particular are produced from the hard scattering and do not interact via the strong force, this measurement is a clean probe of initial-state spin-momentum correlations inside the proton and is in particular sensitive to gluon interference effects within the proton. This is the first time direct photons have been used as a probe of spin-momentum correlations at RHIC. The uncertainties on the results are a 50-fold improvement with respect to those of the one prior measurement for the same observable, from the Fermilab E704 experiment. These results constrain gluon spin-momentum correlations in transversely polarized protons.

Diverse cellular morphologies during lumen maturation in Anopheles gambiae larval salivary glands.

Mosquitoes are the greatest animal threat to human health, causing hundreds of millions of infections and around 1 million deaths each year. All mosquito-borne pathogens must traverse the salivary glands (SGs) to be transmitted to the next host, making this organ an ideal target for interventions. The adult SG develops from precursor cells located in the larval SG duct bud. Characterization of the larval SG has been limited. We sought to better understand larval SG architecture, secretion and gene expression. We developed an optimized method for larval SG staining and surveyed hundreds of larval stage 4 (L4) SGs using fluorescence confocal microscopy. Remarkable variation in SG cell and chromatin organization differed among individuals and across the L4 stage. Lumen formation occurred during L4 stage through secretion likely involving a coincident cellular apical lipid enrichment and extracellular vesicle-like structures. Meta-analysis of microarray data showed that larval SG gene expression is divergent from adult SGs, more similar to larval gastric cecae, but different from other larval gut compartments. This work highlights the variable cell architecture of larval Anopheles gambiae SGs and provides candidate targets for genetic strategies aiming to disrupt SGs and transmission of mosquito-borne pathogens.

Erratum: Evolution of π

This corrects the article DOI: 10.1103/PhysRevLett.109.152301.

Concordance between health administrative data and survey-derived diagnoses for mood and anxiety disorders.

OBJECTIVE: To assess whether estimates of survey structured interview diagnoses of mood and anxiety disorders were concordant with diagnoses of these disorders obtained from health administrative data. METHODS: All Ontario respondents to the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH) were linked to health administrative databases at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Survey structured interview diagnoses were compared with health administrative data diagnoses obtained using a standardized algorithm. We used modified Poisson regression analyses to assess whether socio-demographic factors were associated with concordance between the two measures. RESULTS: Of the 4157 Ontarians included in our sample, 20.4% had either a structured interview diagnosis (13.9%) or health administrative diagnosis (10.4%) of a mood or anxiety disorder. There was high discordance between measures, with only 19.4% agreement. Migrant status, age, employment, and income were associated with discordance between measures. CONCLUSIONS: Our findings indicate that previous estimates of the 12-month prevalence of mood and anxiety disorders in Ontario may be underestimating the true prevalence, and that population-based surveys and health administrative data may be capturing different groups of people. Understanding the limitations of data commonly used in epidemiologic studies is a key foundation for improving population-based estimates of mental disorders.

Nuclear Dependence of the Transverse Single-Spin Asymmetry in the Production of Charged Hadrons at Forward Rapidity in Polarized p+p, p+Al, and p+Au Collisions at sqrt[s_{NN}]=200 GeV.

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively charged hadrons in polarized p^{↑}+p, p^{↑}+Al, and p^{↑}+Au collisions at sqrt[s_{NN}]=200 GeV. The measurements have been performed at forward rapidity (1.4<η<2.4) over the range of transverse momentum (1.8

Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow.

Does the body give the brain an attentional boost? Examining the relationship between attentional and cardiac gating.

Studies on mind-body interactions have largely focused on how mental states modulate bodily physiological responses. Increasing evidence suggests that bodily states also modulate mental states. Here we investigated how both may be integrated in the brain at the resolution of a heartbeat, examining how phasic fluctuations of peripheral blood pressure and central attentional resources combine to influence cognition. We examined the effects of cardiac phase on the performance of two simultaneous tasks: a go/no-go letter detection task where targets were concurrently presented on background faces and a short-term memory face discrimination task. Short-term memory for the background face was better when the initial face was encoded during the systole rather than diastole phase and when it was paired with a target rather than a distractor. There was no significant interaction between cardiac phase and letter detection. These data suggest that peripheral blood pressure and central attention independently regulate cognitive performance.

Measurements of Multiparticle Correlations in d+Au Collisions at 200, 62.4, 39, and 19.6 GeV and p+Au Collisions at 200 GeV and Implications for Collective Behavior.

Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d+Au collisions at sqrt[s_{NN}]=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrt[s_{NN}]=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.

Nuclear Dependence of the Transverse-Single-Spin Asymmetry for Forward Neutron Production in Polarized p+A Collisions at sqrt[s_{NN}]=200 GeV.

During 2015, the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized p+p collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in p+p collisions predicts only a moderate atomic-mass-number (A) dependence. In contrast, the asymmetries observed at RHIC in p+A collisions showed a surprisingly strong A dependence in inclusive forward neutron production. The observed asymmetry in p+Al collisions is much smaller, while the asymmetry in p+Au collisions is a factor of 3 larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed A dependence.

Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan.

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

Do Riparian Buffers Protect Stream Invertebrate Communities in South American Atlantic Forest Agricultural Areas?

We investigated the influence and relative importance of insecticides and other agricultural stressors in determining variability in invertebrate communities in small streams in intensive soy-production regions of Brazil and Paraguay. In Paraguay we sampled 17 sites on tributaries of the Pirapó River in the state of Itapúa and in Brazil we sampled 18 sites on tributaries of the San Francisco River in the state of Paraná. The riparian buffer zones generally contained native Atlantic forest remnants and/or introduced tree species at various stages of growth. In Brazil the stream buffer width was negatively correlated with sediment insecticide concentrations and buffer width was found to have moderate importance in mitigating effects on some sensitive taxa such as mayflies. However, in both regions insecticides had low relative importance in explaining variability in invertebrate communities, while various habitat parameters were more important. In Brazil, the percent coverage of soft depositional sediment in streams was the most important agriculture-related explanatory variable, and the overall stream-habitat score was the most important variable in Paraguay streams. Paraguay and Brazil both have laws requiring forested riparian buffers. The ample forested riparian buffer zones typical of streams in these regions are likely to have mitigated the effects of pesticides on stream invertebrate communities. This study provides evidence that riparian buffer regulations in the Atlantic Forest region are protecting stream ecosystems from pesticides and other agricultural stressors. Further studies are needed to determine the minimum buffer widths necessary to achieve optimal protection.

Global Prevalence of Elder Abuse: A Meta-analysis and Meta-regression.

OBJECTIVE: Elder abuse is increasingly recognised as a global public health and social problem. There has been limited inter-study comparison of the prevalence and risk factors for elder abuse. This study aimed to estimate the pooled and subtype prevalence of elder abuse worldwide and identify significant associated risk factors. METHODS: We conducted a meta-analysis and meta-regression of 34 population-based and 17 non-population-based studies. RESULTS: The pooled prevalences of elder abuse were 10.0% (95% confidence interval, 5.2%-18.6%) and 34.3% (95% confidence interval, 22.9%-47.8%) in population-based studies and third party- or caregiver-reported studies, respectively. Being in a marital relationship was found to be a significant moderator using random-effects model. CONCLUSIONS: This meta-analysis revealed that third parties or caregivers were more likely to report abuse than older abused adults. Subgroup analyses showed that females and those resident in non-western countries were more likely to be abused. Emotional abuse was the most prevalent elder abuse subtype and financial abuse was less commonly reported by third parties or caregivers. Heterogeneity in the prevalence was due to the high proportion of married older adults in the sample. Subgroup analysis showed that cultural factors, subtypes of abuse, and gender also contributed to heterogeneity in the pooled prevalence of elder abuse.

Prenatal alcohol exposure and prenatal stress differentially alter glucocorticoid signaling in the placenta and fetal brain.

Adverse intrauterine environments increase vulnerability to chronic diseases across the lifespan. The hypothalamic-pituitary-adrenal (HPA) axis, which integrates multiple neuronal signals and ultimately controls the response to stressors, may provide a final common pathway linking early adversity and adult diseases. Both prenatal alcohol exposure (PAE) and prenatal stress (PS) induce a hyperresponsive HPA phenotype in adulthood. As glucocorticoids are pivotal for the normal development of many fetal tissues including the brain, we used animal models of PAE and PS to investigate possible mechanisms underlying fetal programing of glucocorticoid signaling in the placenta and fetal brain at gestation day (GD) 21. We found that both PAE and PS dams had higher corticosterone (CORT) levels than control dams. However, 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme levels were increased in PAE and unchanged in PS placentae, although there were no differences in 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) levels. Moreover, only PAE fetuses showed decreased body weight and increased placental weight, and hence a lower fetal/placental weight ratio, a marker of placenta efficiency, compared to all other prenatal groups. Importantly, PAE and PS differentially altered corticosteroid receptor levels in placentae and brains. In the PS condition, maternal CORT was negatively correlated with both 11ß-HSD1 and mineralocorticoid receptor (MR) protein levels in male and female placentae, whereas in the PAE condition, there were trends for a positive correlation between maternal CORT and 11ß-HSD1, regardless of sex, and a negative correlation between maternal alcohol intake and MR in male placentae. In fetal brains, sexually dimorphic changes in MR and glucocorticoid receptor (GR) levels, and the MR/GR ratio seen in C fetuses were absent in PAE and PS fetuses. In addition, PS but not PAE female fetuses had higher MR and lower GR expression levels in certain limbic areas compared to C female fetuses. Thus the similar adult HPA hyperresponsive phenotype in PAE and PS animals likely occurs through differential effects on glucocorticoid signaling in the placenta and fetal brain.

Species at Risk (SPEAR) index indicates effects of insecticides on stream invertebrate communities in soy production regions of the Argentine Pampas.

We investigated relationships among insecticides and aquatic invertebrate communities in 22 streams of two soy production regions of the Argentine Pampas over three growing seasons. Chlorpyrifos, endosulfan, cypermethrin, and lambda-cyhalothrin were the insecticides most frequently detected in stream sediments. The Species at Risk (SPEAR) pesticide bioassessment index (SPEARpesticides) was adapted and applied to evaluate relationships between sediment insecticide toxic units (TUs) and invertebrate communities associated with both benthic habitats and emergent vegetation habitats. SPEARpesticides was the only response metric that was significantly correlated with total insecticide TU values for all three averaged data sets, consistently showing a trend of decreasing values with increasing TU values (r2=0.35 to 0.42, p-value=0.001 to 0.03). Although pyrethroids were the insecticides that contributed the highest TU values, toxicity calculated based on all insecticides was better at predicting changes in invertebrate communities than toxicity of pyrethroids alone. Crustaceans, particularly the amphipod Hyalella spp., which are relatively sensitive to pesticides, played a large role in the performance of SPEARpesticides, and the relative abundance of all crustaceans also showed a significant decreasing trend with increasing insecticide TUs for two of three data sets (r2=0.30 to 0.57, p-value=0.003 to 0.04) examined. For all data sets, total insecticide TU was the most important variable in explaining variance in the SPEARpesticides index. The present study was the first application of the SPEAR index in South America, and the first one to use it to evaluate effects of pesticides on invertebrate communities associated with aquatic vegetation. Although the SPEAR index was developed in Europe, it performed well in the Argentine Pampas with only minor modifications, and would likely improve in performance as more data are obtained on traits of South American taxa, such as pesticide sensitivity and generation time.

MAP3K11/GDF15 axis is a critical driver of cancer cachexia.

BACKGROUND: Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. METHODS: Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non-cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. RESULTS: Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour-produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. CONCLUSIONS: The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome.

Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients.

BACKGROUND: Cancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes. METHODS: We measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores. RESULTS: GDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both). CONCLUSION: GDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss.