Global proteomic analyses of human cytotrophoblast differentiation/invasion.

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and as a foundation for further understanding CTB differentiation dynamics.

Hormonal Contraceptives and Mood: Review of the Literature and Implications for Future Research.

PURPOSE OF REVIEW: We examine recent studies that investigate the effects of hormonal contraception on mood in different populations of women, including women in the general population and women with diagnosed psychiatric and gynecologic disorders. We address the mechanisms of several types of hormonal contraceptives and assess how these may affect mood and gynecologic disorders. RECENT FINDINGS: The effects of hormonal contraceptives seem to be most relevant in selected subsets of women, as they may promote improved mental health in particular psychiatric disorders such as PMDD. Currently, there is no consistent evidence for negative effects of most hormonal contraceptives in the general population. Even though some studies reveal that certain individuals appear susceptible to negative mood effects from some forms of hormonal contraceptives, more research is needed to better identify these susceptible individuals.

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals.

Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastoma-associated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation.

Alterations in the Salivary Proteome and N-Glycome of Sjögren's Syndrome Patients.

We used isobaric mass tagging (iTRAQ) and lectin affinity capture mass spectrometry (MS)-based workflows for global analyses of parotid saliva (PS) and whole saliva (WS) samples obtained from patients diagnosed with primary Sjögren's Syndrome (pSS) who were enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) as compared with two control groups. The iTRAQ analyses revealed up- and down-regulation of numerous proteins that could be involved in the disease process (e.g., histones) or attempts to mitigate the ensuing damage (e.g., bactericidal/permeability increasing fold containing family (BPIF) members). An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of ß2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS). Beyond the proteome, we profiled the N-glycosites of pSS and control samples. They were enriched for glycopeptides using lectins Aleuria aurantia and wheat germ agglutinin, which recognize fucose and sialic acid/N-acetyl glucosamine, respectively. MS analyses showed that pSS is associated with increased N-glycosylation of numerous salivary glycoproteins in PS and WS. The observed alterations of the salivary proteome and N-glycome could be used as pSS biomarkers enabling easier and earlier detection of this syndrome while lending potential new insights into the disease process.

Longer Interset Rest Periods Enhance Muscle Strength and Hypertrophy in Resistance-Trained Men.

Schoenfeld, BJ, Pope, ZK, Benik, FM, Hester, GM, Sellers, J, Nooner, JL, Schnaiter, JA, Bond-Williams, KE, Carter, AS, Ross, CL, Just, BL, Henselmans, M, and Krieger, JW. Longer interset rest periods enhance muscle strength and hypertrophy in resistance-trained men. J Strength Cond Res 30(7): 1805-1812, 2016-The purpose of this study was to investigate the effects of short rest intervals normally associated with hypertrophy-type training versus long rest intervals traditionally used in strength-type training on muscular adaptations in a cohort of young, experienced lifters. Twenty-one young resistance-trained men were randomly assigned to either a group that performed a resistance training (RT) program with 1-minute rest intervals (SHORT) or a group that employed 3-minute rest intervals (LONG). All other RT variables were held constant. The study period lasted 8 weeks with subjects performing 3 total body workouts a week comprised 3 sets of 8-12 repetition maximum (RM) of 7 different exercises per session. Testing was performed prestudy and poststudy for muscle strength (1RM bench press and back squat), muscle endurance (50% 1RM bench press to failure), and muscle thickness of the elbow flexors, triceps brachii, and quadriceps femoris by ultrasound imaging. Maximal strength was significantly greater for both 1RM squat and bench press for LONG compared to SHORT. Muscle thickness was significantly greater for LONG compared to SHORT in the anterior thigh, and a trend for greater increases was noted in the triceps brachii (p = 0.06) as well. Both groups saw significant increases in local upper body muscle endurance with no significant differences noted between groups. This study provides evidence that longer rest periods promote greater increases in muscle strength and hypertrophy in young resistance-trained men.

Proteomic analysis of human follicular fluid from fertile women.

BACKGROUND: Follicular fluid is a unique biological fluid in which the critical events of oocyte and follicular maturation and somatic cell-germ cell communication occur. Because of the intimate proximity of follicular fluid to the maturing oocyte, this fluid provides a unique window into the processes occurring during follicular maturation. A thorough identification of the specific components within follicular fluid may provide a better understanding of intrafollicular signaling, as well as reveal potential biomarkers of oocyte health for women undergoing assisted reproductive treatment. In this study, we used high and low pH HPLC peptide separations followed by mass spectrometry to perform a comprehensive proteomic analysis of human follicular fluid from healthy ovum donors. Next, using samples from a second set of patients, an isobaric mass tagging strategy for quantitative analysis was used to identify proteins with altered abundances after hCG treatment. RESULTS: A total of 742 follicular fluid proteins were identified in healthy ovum donors, including 413 that have not been previously reported. The proteins belong to diverse functional groups including insulin growth factor and insulin growth factor binding protein families, growth factor and related proteins, receptor signaling, defense/immunity, anti-apoptotic proteins, matrix metalloprotease related proteins, and complement activity. In a quantitative analysis, follicular fluid samples from age-matched women undergoing in vitro fertilization oocyte retrieval were compared and 17 follicular fluid proteins were found at significantly altered levels (p < 0.05) between pre-hCG and post-hCG samples. These proteins belong to a variety of functional processes, including protease inhibition, inflammation, and cell adhesion. CONCLUSIONS: This database of FF proteins significantly extends the known protein components present during the peri-ovulatory period and provides a useful basis for future studies comparing follicular fluid proteomes in various fertility, disease, and environmental exposure conditions. We identified 17 differentially expressed proteins after hCG treatment and together these data showed the feasibility for defining biomarkers that illuminate how the ovarian follicle microenvironment is altered in various infertility-related conditions.

Evaluating the effects of preanalytical variables on the stability of the human plasma proteome.

High quality clinical biospecimens are vital for biomarker discovery, verification, and validation. Variations in blood processing and handling can affect protein abundances and assay reliability. Using an untargeted LC-MS approach, we systematically measured the impact of preanalytical variables on the plasma proteome. Time prior to processing was the only variable that affected the plasma protein levels. LC-MS quantification showed that preprocessing times <6h had minimal effects on the immunodepleted plasma proteome, but by 4 days significant changes were apparent. Elevated levels of many proteins were observed, suggesting that in addition to proteolytic degradation during the preanalytical phase, changes in protein structure are also important considerations for protocols using antibody depletion. As to processing variables, a comparison of single- vs double-spun plasma showed minimal differences. After processing, the impact ⩽3 freeze-thaw cycles was negligible regardless of whether freshly collected samples were processed in short succession or the cycles occurred during 14-17 years of frozen storage (-80 °C). Thus, clinical workflows that necessitate modest delays in blood processing times or employ different centrifugation steps can yield valuable samples for biomarker discovery and verification studies.

Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease.

OBJECTIVE: Use of estrogen-based hormone therapy (HT) as a protection from cognitive decline and Alzheimer disease (AD) is controversial, although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17ß-estradiol preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT. METHODS: Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at 2 years after randomization. RESULTS: Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention, working memory, and processing speed measures. Women who used 17ß-estradiol versus conjugated equine estrogen, whether randomized to continue or discontinue HT, showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first-degree relative. All female offspring of patients with AD declined in verbal memory; however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely because of practice effects) with continuance and declined with discontinuance of HT. CONCLUSION: Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset.

Heat stress related dairy cow mortality during heat waves and control periods in rural Southern Ontario from 2010-2012.

BACKGROUND: Heat stress is a physiological response to extreme environmental heat such as heat waves. Heat stress can result in mortality in dairy cows when extreme heat is both rapidly changing and has a long duration. As a result of climate change, heat waves, which are defined as 3 days of temperatures of 32 °C or above, are an increasingly frequent extreme weather phenomenon in Southern Ontario. Heat waves are increasing the risk for on-farm dairy cow mortality in Southern Ontario. Heat stress indices (HSIs) are generally based on temperature and humidity and provide a relative measure of discomfort which can be used to predict increased risk of on-farm dairy cow mortality. In what follows, the heat stress distribution was described over space and presented with maps. Similarly, on-farm mortality was described and mapped. The goal of this study was to demonstrate that heat waves and related HSI increases during 2010-2012 were associated with increased on-farm dairy cow mortality in Southern Ontario. Mortality records and farm locations for all farms registered in the CanWest Dairy Herd Improvement Program in Southern Ontario were retrieved for 3 heat waves and 6 three-day control periods from 2010 to 2012. A random sample of controls (2:1) was taken from the data set to create a risk-based hybrid design. On-farm heat stress was estimated using data from 37 weather stations and subsequently interpolated across Southern Ontario by geostatistical kriging. A Poisson regression model was applied to assess the on-farm mortality in relation to varying levels of the HSI. RESULTS: For every one unit increase in HSI the on-farm mortality rate across Southern Ontario increases by 1.03 times (CI95% (IRR) = (1.025,1.035); p = ≤ 0.001). With a typical 8.6 unit increase in HSI from a control period to a heat wave, mortality rates are predicted to increase by 1.27 times. CONCLUSIONS: Southern Ontario was affected by heat waves, as demonstrated by high levels of heat stress and increased on-farm mortality. Farmers should be aware of these risks, and informed of appropriate methods to mitigate such risks.

Optimistic outlook regarding maternity protects against depressive symptoms postpartum.

The transition to motherhood is a time of elevated risk for clinical depression. Dispositional optimism may be protective against depressive symptoms; however, the arrival of a newborn presents numerous challenges that may be at odds with initially positive expectations, and which may contribute to depressed mood. We have explored the relative contributions of antenatal and postnatal optimism regarding maternity to depressive symptoms in the postnatal period. Ninety-eight pregnant women underwent clinician interview in the third trimester to record psychiatric history, antenatal depressive symptoms, and administer a novel measure of optimism towards maternity. Measures of depressive symptoms, attitudes to maternity, and mother-to-infant bonding were obtained from 97 study completers at monthly intervals through 3 months postpartum. We found a positive effect of antenatal optimism, and a negative effect of postnatal disconfirmation of expectations, on depressive mood postnatally. Postnatal disconfirmation, but not antenatal optimism, was associated with more negative attitudes toward maternity postnatally. Antenatal optimism, but not postnatal disconfirmation, was associated with reduced scores on a mother-to-infant bonding measure. The relationships between antenatal optimism, postnatal disconfirmation of expectations, and postnatal depression held true among primigravidas and multigravidas, as well as among women with prior histories of mood disorders, although antenatal optimism tended to be lower among women with mental health histories. We conclude that cautious antenatal optimism, rather than immoderate optimism or frank pessimism, is the approach that is most protective against postnatal depressive symptoms, and that this is true irrespective of either mood disorder history or parity. Factors predisposing to negative cognitive assessments and impaired mother-to-infant bonding may be substantially different than those associated with depressive symptoms, a finding that merits further study.

A spatial analysis of heat stress related emergency room visits in rural Southern Ontario during heat waves.

BACKGROUND: In Southern Ontario, climate change may have given rise to an increasing occurrence of heat waves since the year 2000, which can cause heat stress to the general public, and potentially have detrimental health consequences. Heat waves are defined as three consecutive days with temperatures of 32 °C and above. Heat stress is the level of discomfort. A variety of heat stress indices have been proposed to measure heat stress (e.g., the heat stress index (HSI)), and has been shown to predict increases in morbidity and/or mortality rates in humans and other species. Maps visualizing the distribution of heat stress can provide information about related health risks and insight for control strategies. Information to inform heat wave preparedness models in Ontario was previously only available for major metropolitan areas. METHODS: Hospitals in communities of fewer than 100,000 individuals were recruited for a pilot study by telephone. The number of people visiting the emergency room or 24-hour urgent care service was collected for a total of 27 days, covering three heat waves and six 3-day control periods from 2010-2012. The heat stress index was spatially predicted using data from 37 weather stations across Southern Ontario by geostatistical kriging. Poisson regression modeling was applied to determine the rate of increased number of emergency room visits in rural hospitals with respect to the HSI. RESULTS: During a heat wave, the average rate of emergency room visits was 1.11 times higher than during a control period (IRR = 1.11, CI95% (IRR) = (1.07,1.15), p ≤ 0.001). In a univariable model, HSI was not a significant predictor of emergency room visits, but when accounting for the confounding effect of a spatial trend polynomial in the hospital location coordinates, a one unit increase in HSI predicted an increase in daily emergency rooms visits by 0.4% (IRR = 1.004, CI95%(IRR) = (1.0005,1.007), p = 0.024) across the region. One high-risk cluster and no low risk clusters were identified in the southwestern portion of the study area by the spatial scan statistic during heat waves. The high-risk cluster is located in a region with high levels of heat stress during heat waves. CONCLUSIONS: This finding will aid hospitals and rural public health units in preventing and preparing for emergencies of foreseeable heat waves. Future research is needed to assess the relation between heat stress and individual characteristics and demographics of rural communities in Ontario.

Protein composition of bronchoalveolar lavage fluid and airway surface liquid from newborn pigs.

The airway mucosa and the alveolar surface form dynamic interfaces between the lung and the external environment. The epithelial cells lining these barriers elaborate a thin liquid layer containing secreted peptides and proteins that contribute to host defense and other functions. The goal of this study was to develop and apply methods to define the proteome of porcine lung lining liquid, in part, by leveraging the wealth of information in the Sus scrofa database of Ensembl gene, transcript, and protein model predictions. We developed an optimized workflow for detection of secreted proteins in porcine bronchoalveolar lavage (BAL) fluid and in methacholine-induced tracheal secretions [airway surface liquid (ASL)]. We detected 674 and 3,858 unique porcine-specific proteins in BAL and ASL, respectively. This proteome was composed of proteins representing a diverse range of molecular classes and biological processes, including host defense, molecular transport, cell communication, cytoskeletal, and metabolic functions. Specifically, we detected a significant number of secreted proteins with known or predicted roles in innate and adaptive immunity, microbial killing, or other aspects of host defense. In greatly expanding the known proteome of the lung lining fluid in the pig, this study provides a valuable resource for future studies using this important animal model of pulmonary physiology and disease.

Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS.

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 µM and 5 µM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. AVAILABILITY OF DATA AND MATERIAL: Raw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1.

Strategies to enhance remote monitoring adherence among patients with cardiovascular implantable electronic devices.

Background: Remote monitoring (RM) of patients with cardiovascular implantable electronic devices (CIEDs) (pacemakers and implantable cardioverter-defibrillators) has a Class 1, Level of Evidence A Heart Rhythm Society recommendation. Yet RM adherence varies widely across settings, and factors associated with variation are not understood. Objective: The purpose of this study was to identify strategies for supporting RM across Veterans Health Administration (VHA) facilities. Methods: In a national evaluation, we surveyed and interviewed 27 nurses, medical instrument technicians, and advanced practice providers across 26 VHA facilities (following approximately 15,000 CIED patients). Participants were selected based on overall patient adherence by facility, which ranged from 46%-96%. Questions covered RM adherence strategies, manufacturer resources, organizational characteristics, and workflows for optimizing adherence. Results: All clinicians reported that RM adherence was extremely important (53.8%), very important (34.6%), or important (11.5%) for improving patient outcomes. High performing facilities prioritized consistent patient education about RM and evaluated nonadherence using dashboards and manufacturer web sites. High performing facilities instituted clear standard operating procedures that defined staff responsibilities and facilitated efficient contact with nonadherent patients and then family members by phone and then mail. Clinicians based at high performing facilities spent twice as many hours per week (9.1) on average managing RM adherence compared to other facilities (4.5). Effective communication (internally and with non-VHA care partners) and use of CIED manufacturer resources were essential. Facilities that were not high performing rarely used these strategies. Conclusion: Clinicians can support high RM adherence by emphasizing patient education, regularly assessing and addressing nonadherence using staff protocols, and engaging CIED manufacturers.

Mood disorders in oocyte donor candidates: brief report and implications for future research.

BACKGROUND IVF, using donor oocytes, has become increasingly common. The donation procedure carries psychiatric risks, including depression, anxiety and rarely, psychosis, and this risk increases when there is a past history of psychiatric illness. We report on the psychiatric status, at intake assessment, of a group of candidate oocyte donors. METHODS The authors reviewed clinical records of 63 women continuously presenting to a University medical center for psychiatric evaluation as part of the screening process for oocyte donation. A board certified psychiatrist administered a structured clinical interview to candidate donors, and self-report measures were obtained from 28 women. RESULTS There was a significant discrepancy between psychiatric history of depression and current mood status, as measured by both clinical interview and psychometric self-report data. Nearly one-quarter of candidate donors (22%) reported a history of major depressive disorder; however, all candidate donors denied current mood disturbance on clinical interview, and mean Beck depression inventory and profile of mood states scores were lower than expected compared with psychometric norms (P < 0.0005), epidemiological data and the recurrent nature of depressive disorders. CONCLUSIONS Candidate donors may minimize psychiatric symptoms. Given the potential for ovarian stimulation protocols to induce or exacerbate mood symptoms, and the moderate heritability of mood disorders, careful evaluation of candidate donor affective disorder history is recommended. This evaluation should focus on sensitivity to mood destabilization during times of hormonal change. Measures that examine whether a candidate donor may have a tendency to present herself in an overly favorable manner, and/or a tendency to minimize symptoms, are recommended.

Differences in verbal memory performance in postmenopausal women receiving hormone therapy: 17ß-estradiol versus conjugated equine estrogens.

OBJECTIVE: Much controversy exists and many questions remain unanswered about the effects of hormone therapy (HT) on cognition in postmenopausal women. There is growing evidence suggesting that HT compounds containing conjugated equine estrogen (CEE) have negative effects on cognition whereas 17ß-estradiol (17ß-E) either has positive or neutral effects. The present study sought to further examine this issue in a sample of postmenopausal women with risk factors for Alzheimer's disease (AD). DESIGN: Cross-sectional neuropsychological evaluation. SETTING: Academic research clinic. PARTICIPANTS: 68 healthy postmenopausal women (aged 49-68) receiving either 17ß-E or CEE for at least one year with increased risk for AD. MEASUREMENTS: Neuropsychological test battery of the cognitive domains of attention/working memory/processing speed, verbal memory, visual memory, and executive functioning. RESULTS: Multivariate analyses of variance (MANOVA) showed significantly better verbal memory performance in women receiving 17ß-E compared to women receiving CEE regardless of age, IQ, years of education, risk factors for AD (including APOE-ε4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural versus surgical menopause status. CONCLUSIONS: Verbal memory performance was better in postmenopausal women receiving 17ß-E compared to CEE in a sample population of women with risk factors for AD. Genetic risk for AD as well as other confounds did not affect this finding. The results suggest a differential effect of HT type on verbal memory, with 17ß-E being a preferential compound. Further evaluation of HT types, regimens and duration of use on cognitive performance in postmenopausal women in a controlled longitudinal design is warranted.

Rapid identification of protein biomarkers of Escherichia coli O157:H7 by matrix-assisted laser desorption ionization-time-of-flight-time-of-flight mass spectrometry and top-down proteomics.

Six protein biomarkers from two strains of Escherichia coli O157:H7 and one non-O157:H7, nonpathogenic strain of E. coli have been identified by matrix-assisted laser desorption ionization time-of-flight-time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomics. Proteins were extracted from bacterial cell lysates, ionized by MALDI, and analyzed by MS/MS. Protein biomarker ions were identified from their sequence-specific fragment ions by comparison to a database of in silico fragment ions derived from bacterial protein sequences. Web-based software, developed in-house, was used to rapidly compare the mass-to-charge (m/z) of MS/MS fragment ions to the m/z of in silico fragment ions derived from hundreds of bacterial protein sequences. A peak matching algorithm and a p-value algorithm were used to independently score and rank identifications on the basis of the number of MS/MS-in silico matches. The six proteins identified were the acid stress chaperone-like proteins, HdeA and HdeB; the cold shock protein, CspC; the YbgS (or homeobox protein); the putative stress-response protein YjbJ (or CsbD family protein); and a protein of unknown function, YahO. HdeA, HdeB, YbgS, and YahO proteins were found to be modified post-translationally with removal of an N-terminal signal peptide. Gene sequencing of hdeA, hdeB, cspC, ybgS, yahO, and yjbJ for 11 strains of E. coli O157:H7 and 7 strains of the "near-neighbor" serotype O55:H7 revealed a high degree sequence homology between these two serotypes. Although it was not possible to distinguish O157:H7 from O55:H7 from these six biomarkers, it was possible to distinguish E. coli O157:H7 from a nonpathogenic E. coli by top-down proteomics of the YahO and YbgS. In the case of the YahO protein, a single amino acid residue substitution in its sequence (resulting in a molecular weight difference of only 1 Da) was sufficient to distinguish E. coli O157:H7 from a non-O157:H7, nonpathogenic E. coli by MALDI-TOF-TOF-MS/MS, whereas this would be difficult to distinguish by MALDI-TOF-MS. Finally, a protein biomarker ion at m/z approximately 9060 observed in the MS spectra of non-O157:H7 E. coli strains but absent from MS spectra of E. coli O157:H7 strains was identified by top-down analysis to be the HdeB acid stress chaperone-like protein consistent with previous identifications by gene sequencing and bottom-up proteomics.

Rosiglitazone add-on in treatment of depressed patients with insulin resistance: a pilot study.

A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted.

Past Psychiatric Conditions as Risk Factors for Postpartum Depression: A Nationwide Cohort Study.

OBJECTIVE: To compare risk for postpartum depression across prior psychiatric diagnoses. METHODS: The deidentified Optum© Clinformatics Data Mart of national commercial insurance claims was used to identify 1,166,577 women of reproductive age with first-observed incidence of pregnancy across all 50 United States from 2003 to 2016. Women with insurance coverage for at least 6 months prior to conception and following delivery were eligible (n = 336,522). Psychiatric diagnoses prior to pregnancy were identified by ICD-9-CM and ICD-10-CM codes, including depression, anxiety and panic disorders, bipolar disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and eating disorders. Primary outcomes included postpartum depression diagnosis at 2 months and 1 year after delivery. Multiple variable logistic regression analysis assessed for independent associations between predictors and outcomes. RESULTS: Among 336,522 pregnancies, 9.4% of women were diagnosed with postpartum depression (n = 31,610). Five percent of women with no depression history developed postpartum depression, compared to 65% of women with depression prior to and during pregnancy. Among women with history of depression who were euthymic during pregnancy, 20% were diagnosed with postpartum depression. A major risk factor was a history of depression (OR = 2.7; 95% CI, 2.6-2.8; P < .001), and depression in pregnancy was a risk factor for continued depression in the postpartum period (OR = 13.1; 95% CI, 12.6-13.6; P < .001). All other psychiatric conditions, including anxiety and panic disorders, bipolar disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and eating disorders, conferred risk for postpartum depression, independent of a comorbid depression history. CONCLUSIONS: We report that all psychiatric diagnoses investigated independently increase risk for postpartum depression and suggest that care providers inquire about psychiatric history to identify and closely monitor women at increased risk for postpartum depression.

Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain.

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.