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1.

Background

Recent studies break with traditional opinion that the lower respiratory tract is sterile, and increasingly focus on the lung microbiome and disease. Smoking, as an important etiology of inflammatory lung disease, was considered as a factor influencing lung microbiome variations in our study, and we aimed to study the effect of smoking on inflammation and microbial diversity and community.

Methods

Forty male mice were selected and randomly divided into a smoking and a non-smoking group. Mice in the smoking group were exposed to smoke smog for 2?h/day for 90?days. Blood and lung tissues were obtained after the experiment, and ELISA was used to measure interleukin-6 and C reactive protein concentrations. 16S rRNA gene quantification and sequencing technology were used to compare microbial diversity and community between the two groups. SAS 9.1 and R software were used to analyze the data.

Results

Thirty-six mice survived, and the weight of the smoking group increased more slowly than that of the non-smoking group. Denser inflammation and congestion were observed in the lungs of the smoking mice compared with the non-smoking group Higher microbial diversity was observed in the smoking group, and Enterobacter, Acidimicrobiales_norank, and Caulobacteraceae_Unclassified genus were significantly more abundant in the non-smoking group (P?<?0.001).

Conclusions

Smoking altered microbial diversities and communities in the lower respiratory tract of mice. Microbial variation should be considered in future studies focusing on smoking-induced inflammatory disease.
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2.

Background

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.

Methods

Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.

Results

Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.

Conclusions

Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.
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3.

Background

Options for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel?, a high molecular weight polymer being developed as a contraceptive device for men.

Methods

Sixteen adult male rhesus monkeys received intravas injections of Vasalgel, consisting of 25% styrene maleic acid in dimethyl sulfoxide. After a one-week recovery, males were returned to outdoor group housing, which included at least 3 and up to 9 intact, breeding females with a successful reproductive history.

Results

Treated males have had no conceptions since Vasalgel injections. All males were housed with intact females for at least one breeding season and seven have been almost continually housed with females for 2 years. Complications were minor and included one incident of incorrect placement of Vasalgel into the vas deferens and the development of a sperm granuloma in one animal. Three unilateral vasectomies were performed, one was necessary for incorrect placement of Vasalgel, the other two were elective.

Conclusions

Intravas injection of Vasalgel in sexually mature adult male rhesus monkeys was effective in preventing conception in a free-living, group environment. Complications were few and similar to those associated with traditional vasectomy.
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4.

Background

Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal (HPA)-axis and glucocorticoid secretions in relation to behavioral performances. The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may also affect social interactions and social-living per se, where adequate physiological and behavioral responses are essential to cope with unstable social environmental conditions.

Methods

Effects of diets high in PUFAs or SFAs and a control diet were investigated in male and female guinea pigs after 60 days of supplementation. Plasma fatty acid patterns served as an indicator of the general fatty acid status. HPA-axis activities, determined by measuring saliva cortisol concentrations, social behaviors, and hierarchy ranks were analyzed during group housing of established single-sexed groups and during challenging social confrontations with unfamiliar individuals of the other groups.

Results

The plasma PUFA:SFA ratio was highest in PUFA supplemented animals, with female levels significantly exceeding males, and lowest in SFA animals. SFA males and females showed increased saliva cortisol levels and decreased aggressiveness during group housing, while sociopositive behaviors were lowest in PUFA males. Males generally showed higher cortisol increases in response to the challenging social confrontations with unfamiliar individuals than females. While increasing cortisol concentrations were detected in control and PUFA animals, no such effect was found in SFA animals. During social confrontations, PUFA males showed higher levels of agonistic and sociopositive behaviors and also gained higher dominance ranks among males, which was not detected for females.

Conclusions

While SFAs seemingly impaired cortisol responses and social behaviors, PUFAs enabled adequate behavioral responses in male individuals under stressful new social environmental conditions. This sex-specific effect was possibly related to a general sex difference in the n-3 PUFA bioavailability and cortisol responses, which may indicate that males are more susceptible to changing environmental conditions, and shows how dietary fatty acids can shape social systems.
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5.

Background

This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males.

Methods

We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995–2008.

Results

Median age at presentation was 66,7 ± 10,9 years. Average follow-up was 63 ± 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ýnvasive ductal carcinoma was the most frequent pathologic type (70% of cases).

Conclusion

Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.
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6.

Background

Sexual dimorphism in blood pressure has been associated with differential expression of the angiotensin II (AII) receptors and with activity of the nervous system. It is generally accepted that ageing affects kidney function as well as autonomic nervous system and hormonal balance. Given that hypertension is more prevalent in men than women until women reach their seventh decade, we hypothesised that females would be relatively protected from adverse effects of ageing compared to males and that this would be mediated by the protective effect of ovarian steroids.

Methods

Intact and gonadectomised male and female normotensive Wistar rats aged 6, 12 and 18 months were used to study renal function, blood pressure, heart rate, and blood pressure variability.

Results

We observed that intact females had lower levels of proteinuria and higher (12.5%) creatinine clearance compared to intact males and that this difference was abolished by castration but not by ovariectomy. Ovariectomy resulted in a change by 9% in heart rate, resulting in similar cardiovascular parameters to those observed in males or gonadectomised males. Spectral analysis of systolic blood pressure revealed that high-frequency power spectra were significantly elevated in the females vs. males and were reduced by ovariectomy.

Conclusions

Taken altogether, the results show that females are protected from age-related declining renal function and to a lesser extent from rising blood pressure in comparison to males. Whilst ovariectomy had some deleterious effects in females, the strongest effects were associated with gonadectomy in males, suggesting a damaging effect of male hormones.
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7.

Background

The aim of this study was to examine the necessity of early intervention for students with potential bulimia by investigating how the eating attitudes of college students change and examining the relation between bulimic symptoms and depressive symptoms or the ability to cope with stress.

Methods

The study participants were students who entered Hiroshima University in 2014. This study was conducted at two time points: Time-1 in 2014 and Time-2 in 2017. The Eating Attitudes Test-26 (EAT-26), Bulimic Inventory Test, Edinburgh (BITE), Beck Depression Inventory-II (BDI-II), and Coping Inventory for Stressful Situations (CISS) were administered at Times 1 and 2, and the responses were compared between the time points. Next, we compared the BDI-II scores of the BITE improved and worsened groups. In addition, we divided the participants into a clinical group, subthreshold group, and healthy group based on the BITE score at Time-1to compared their depressive symptoms and the ability to cope with stress.

Results

Significantly higher BITE and BDI-II scores were recorded for both males and females at Time-2 than at Time-1. The BDI-II score at Time-1 was significantly higher in the BITE worsened group than in the BITE improved group. The BDI-II scores at Time-1 were significantly higher for both males and females in the subthreshold group than in the healthy group. Furthermore, significantly higher CISS-T and CISS-E scores were recorded at Time-1 for females in the subthreshold group than for females in the healthy group.

Conclusions

Based on these results, intervention for students the subthreshold group is important, and the key to intervention may be to address not only eating behaviors but also depressive symptoms and stress coping.

Trial registration

UMIN000029474 Registered 9 October, 2017 (retrospectively).
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8.

Background

The objective of this study was to assess whether sex-specific differences in fetal and infant growth exist.

Methods

This study was embedded in the Generation R Study, a population-based prospective birth cohort. In total, 8556 live singleton births were included. Fetal growth was assessed by ultrasound. During the first trimester, crown-rump-length (CRL) was measured. In the second and third trimester of pregnancy head circumference (HC), abdominal circumference (AC) and femur length (FL) were assessed. Information on infant growth during the first 2 years of life was obtained from Community Health Centers and included HC, body weight and length.

Results

In the first trimester, male CRL was larger than female CRL (0.12 SD [95% CI 0.03,0.22]). From the second trimester onwards, HC and AC were larger in males than in females (0.30 SD [95% CI 0.26,0.34] and 0.09 SD [95% CI 0.05,0.014], respectively). However, FL in males was smaller compared to female fetuses (0.21 SD [95% CI 0.17,0.26]). Repeated measurement analyses showed a different prenatal as well as postnatal HC growth pattern between males and females. A different pattern in body weight was observed with a higher body weight in males until the age of 12 months where after females have a higher body weight.

Conclusions

Sex affects both fetal as well as infant growth. Besides body size, also body proportions differ between males and females with different growth patterns. This sexual dimorphism might arise from differences in fetal programming with sex specific health differences as a consequence in later life.
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9.

Background

The ability to direct the cellular response by means of biomaterial surface topography is important for biomedical applications. Substrate surface topography has been shown to be an effective cue for the regulation of cellular response. Here, the response of human aortic endothelial cells to nanoporous anodic alumina and macroporous silicon with collagen and fibronectin functionalization has been studied.

Methods

Confocal microscopy and scanning electron microscopy were employed to analyse the effects of the material and the porosity on the adhesion, morphology, and proliferation of the cells. Cell spreading and filopodia formation on macro- and nanoporous material was characterized by atomic force microscopy. We have also studied the influence of the protein on the adhesion.

Results

It was obtained the best results when the material is functionalized with fibronectin, regarding cells adhesion, morphology, and proliferation.

Conclusion

These results permit to obtain chemical modified 3D structures for several biotechnology applications such as tissue engineering, organ-on-chip or regenerative medicine.
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10.

Background

A recent review article suggests that elimination of infused crystalloid fluid might occur faster in females than in males. To study this question, a population kinetic analysis was performed to compare the turnover of buffered Ringer’s solution when infused at different rates in males and females.

Methods

Data were retrieved from seven series of experiments where 44 intravenous infusions of Ringer’s acetate had been given to female volunteers and 67 to male volunteers. Frequent measurements of the blood hemoglobin and the urinary excretion were used as input in a kinetic two-volume model with micro-constants and covariates, using a nonlinear mixed effects software. The key outcome measure was the rate of irreversible elimination of infused fluid, which was expressed as the half-life, obtained as the excreted urine divided by the modeled plasma volume expansion over time.

Results

The half-life amounted to 24 min (95 % confidence interval, 21–27) in the females and 38 min (33–42) in the males. The urinary excretion differed somewhat less than suggested by these figures during the experimental period (3–4 h) because the plasma volume became less expanded in the females. This was due to that fluid that had been distributed peripheral tissues (the interstitium) returned slightly more slowly to the central fluid space (the plasma) in the females. Gender did not serve as a statistically significant covariate to other rate constants in the kinetic model.

Conclusions

The half-life of infused Ringer’s acetate was 60 % longer in healthy male volunteers than in female volunteers.
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11.

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.
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12.

Background

This study aimed to construct a biological age assessment formula for the Chinese population and to explore the effectiveness of double filtration plasmapheresis for anti-ageing and longevity.

Methods

915 subjects were recruited, including 584 (63.8%) males and 331 females (36.2%). Male age was 50.94±10.60 (mean±SD), and female age was 51.20±11.84 (mean±SD). 34 blood markers were detected in the laboratory. The ageing biomarkers were determined by statistical correlation analysis and redundancy analysis, and the biological age assessment formula was established by multiple linear regression analysis. Paired sample T test was used to analyse the elimination effect of double filtration plasmapheresis on aging biomarkers.

Results

Based on the comprehensive blood test and analysis, the ageing biomarkers were screened, and the male and female biological age assessment formulas were established. Then, the elimination of ageing biomarkers by double filtration plasmapheresis was examined. Double filtration plasmapheresis can eliminate ageing biomarkers, with an average of 4.47?years decrease in age for males and 8.36?years for females.

Conclusion

So, biological age provides a scientific tool for assessing ageing, and double filtration plasmapheresis is safe and might be effective for anti-ageing and longevity. However, the effect of plasmapheresis is expected to be transient, so further studies are needed to plan the number and range of the plasmapheresis procedures necessary to consistently lower the parameters under study.
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13.

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.
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14.

Introduction

In the past 20+ years, several studies of bovine embryo production showed how the ratio of male to female embryos changes if embryos are made in vivo or in vitro. It is known that in in vitro systems, the sex ratio is in favor of males when there are high levels of glucose, and favors females when the principal energetic substrate is one other than glucose, like citrate.

Objectives

The aim of this study was to evaluate the embryo metabolism during three important periods of in vitro development: the early development (from day 1 until day 3), the middle of culture (day 3 until day 5), and later development (day 5 until day 7).

Methods

To obtain this information we evaluated the spent medium from each time period by 1H NMR.

Results

Our results confirm that embryo metabolism is different between sexes. The new information obtained by identifies markers that we can use to predict the embryo sex.

Conclusion

These results open a new, non-invasive method to evaluate sex of the embryos before the transfer. In the first period of embryo culture, valine concentration is good indicator (66.7% accurate), while in the last phase of culture, pyruvate depletion is the best marker (64% accurate) to evaluate the sex of the embryo.
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15.

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.
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16.

Introduction

In some fish species, it is difficult to distinguish mature females from immature females or females that have already spawned via appearance or other convenient methods. Few studies have investigated plasma metabolite profiling for the prediction of fish maturation.

Objectives

We investigated the comprehensive metabolic profiles of plasma among immature females and mature females ready to spawn, as well as already spawned breeders of blunt snout bream (Megalobrama amblycephala). The purpose of this study was to screen out potential biomarkers for sexually mature female M. amblycephala compared to immature female individuals and already spawned breeders.

Methods

Three groups were set up in this study, which included 1-year-old immature females, 2-year-old sexually mature females ready to spawn and successfully spawned females of M. amblycephala. Plasma samples were collected to investigate comprehensive metabolic profiles through UPLC-MS/MS based on a metabolomics analysis method.

Results

According to multivariate and univariate statistical analysis, plasma metabolite profiles of the three groups were clearly separated. The differential plasma metabolites from three hormone related pathways including the GnRH signaling pathway, steroid hormone biosynthesis and steroid biosynthesis, were analyzed. A total of 29 metabolites were identified as differential biomarkers associated with the female maturation status.

Conclusion

The identified potential biomarkers could be useful in separating mature M. amblycephala from immature individuals or ovulation-induced female individuals, which would allow for more effective artificial breeding. The results may contribute to a better understanding of the maturation mechanisms of fish in the aspect of metabolomics.
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17.

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.
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18.

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.
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19.

Background

In the recent years, a role of the immune system in Huntington’s disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease.

Results

As compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers?≥?20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection.

Conclusions

These data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking.
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20.

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.
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