Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [11C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease.

Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use.

BACKGROUND: Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology. METHODS: Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status. RESULTS: Past-year CU (n = 22) was associated with 18.62%-19.12% higher mGlu5 availability in frontal and 14.24%-16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05%-20.62%) and limbic (15.53%-16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r's = -.47 to .66, P's = .006-.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P's = .006-.037) relative to those without CU. CONCLUSIONS: These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population.

Fibrillin-1 and asprosin, novel players in metabolic syndrome.

Fibrillin-1 is a major component of the extracellular microfibrils, where it interacts with other extracellular matrix proteins to provide elasticity to connective tissues, and regulates the bioavailability of TGFß family members. A peptide consisting of the C-terminal 140 amino acids of fibrillin-1 has recently been identified as a glucogenic hormone, secreted from adipose tissue during fasting and targeting the liver to release glucose. This fragment, called asprosin, also signals in the hypothalamus to stimulate appetite. Asprosin levels are correlated with many of the pathologies indicative of metabolic syndrome, including insulin resistance and obesity. Previous studies and reviews have addressed the therapeutic potential of asprosin as a target in obesity, diabetes and related conditions without considering mechanisms underlying the relationship between generation of asprosin and expression of the much larger fibrillin-1 protein. Profibrillin-1 undergoes obligatory cleavage at the cell surface as part of its assembly into microfibrils, producing the asprosin peptide as well as mature fibrillin-1. Patterns of FBN1 mRNA expression are inconsistent with the necessity for regulated release of asprosin. The asprosin peptide may be protected from degradation in adipose tissue. We present evidence for an alternative possibility, that asprosin mRNA is generated independently from an internal promoter within the 3' end of the FBN1 gene, which would allow for regulation independent of fibrillin-synthesis and is more economical of cellular resources. The discovery of asprosin opened exciting possibilities for treatment of metabolic syndrome related conditions, but there is much to be understood before such therapies could be introduced into the clinic.

Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.

The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic connections. We investigated this hypothesis in humans for the first time using positron emission tomography (PET) and [11C]UCB-J-a radioligand that binds to the synaptic vesicle protein 2A (SV2A) and provides an index of axon terminal density. Overall, we did not find evidence of a measurable effect on SV2A density 24 h after a single administration of ketamine in non-human primates, healthy controls (HCs), or individuals with major depressive disorder (MDD) and/or posttraumatic stress disorder (PTSD), despite a robust reduction in symptoms. A post-hoc, exploratory analysis suggests that patients with lower SV2A density at baseline may exhibit increased SV2A density 24 h after ketamine. This increase in SV2A was associated with a reduction in depression severity, as well as an increase in dissociative symptoms. These initial findings suggest that a restoration of synaptic connections in patients with lower SV2A at baseline may underlie ketamine's therapeutic effects, however, this needs replication in a larger sample. Further work is needed to build on these initial findings and further establish the nuanced pre- and post-synaptic mechanisms underpinning ketamine's therapeutic effects.

Excreted Antibiotics May Be Key to Emergence of Increasingly Efficient Antibiotic Resistance in Food Animal Production.

At a time when antibiotic resistance is seemingly ubiquitous worldwide, understanding the mechanisms responsible for successful emergence of new resistance genes may provide insights into the persistence and pathways of dissemination for antibiotic-resistant organisms in general. For example, Escherichia coli strains harboring a class A ß-lactamase-encoding gene (blaCTX-M-15) appear to be displacing strains that harbor a class C ß-lactamase gene (blaCMY-2) in Washington State dairy cattle. We cloned these genes with native promoters into low-copy-number plasmids that were then transformed into isogenic strains of E. coli, and growth curves were generated for two commonly administered antibiotics (ampicillin and ceftiofur). Both strains met the definition of resistance for ampicillin (≥32 µg/mL) and ceftiofur (≥16 µg/mL). Growth of the CMY-2-producing strain was compromised at 1,000 µg/mL ampicillin, whereas the CTX-M-15-producing strain was not inhibited in the presence of 3,000 µg/mL ampicillin or with most concentrations of ceftiofur, although there were mixed outcomes with ceftiofur metabolites. Consequently, in the absence of competing genes, E. coli harboring either gene would experience a selective advantage if exposed to these antibiotics. Successful emergence of CTX-M-15-producing strains where CMY-2-producing strains are already established, however, requires high concentrations of antibiotics that can only be found in the urine of treated animals (e.g., >2,000 µg/mL for ampicillin, based on literature). This ex vivo selection pressure may be important for the emergence of new and more efficient antibiotic resistance genes and likely for persistence of antibiotic-resistant bacteria in food animal populations. IMPORTANCE We studied the relative fitness benefits of a cephalosporin resistance enzyme (CTX-M-15) that is displacing a similar enzyme (CMY-2), which is extant in E. coli from dairy cattle in Washington State. In vitro experiments demonstrated that CTX-M-15 provides a significant fitness advantage, but only in the presence of very high concentrations of antibiotic that are only found when the antibiotic ampicillin, and to a lesser extent ceftiofur, is excreted in urine from treated animals. As such, the increasing prevalence of bacteria with blaCTX-M-15 is likely occurring ex vivo. Interventions should focus on controlling waste from treated animals and, when possible, selecting antibiotics that are less likely to impact the proximal environment of treated animals.

Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations of the Crystalline Polymorphs of the Antiviral Drug Ribavirin.

Crystal polymorphism is a common phenomenon in pharmaceutical solids and a critical issue when considering the formulation of therapeutics since multiple polymorphs may form during drug manufacturing. Low-frequency vibrational spectroscopy is sensitive to polymorphic content, and in this work, terahertz time-domain spectroscopy and low-frequency Raman spectroscopy were utilized in the study of crystalline ribavirin, a widely applicable antiviral. Characteristic spectra with numerous peaks in the sub-200 cm-1 region were obtained of the more common polymorph of ribavirin (Form II). Solid-state density functional theory (ss-DFT) simulations were then used to optimize the crystal structure of this polymorph and calculate the frequencies and spectral intensities of the lattice vibrations in the low-frequency region. The near-harmonic thermal behavior of the sample with cooling enabled excellent agreement between experiment and theory to be achieved, emphasizing the quality of the applied model, and the observed spectral peaks could be assigned to specific atomic motions in the solid. Form I and Form II polymorphs of ribavirin were both investigated with ss-DFT to understand the different aspects governing the relative stabilities of these solids. The ss-DFT simulations of the polymorph energies revealed that Form II is more stable at all temperatures due to a stronger cohesive energy than Form I; however, ribavirin in Form I has a significantly lower conformational energy. The finding of monotropism appears to conflict with the reported enantiotropism of the ribavirin polymorphs but ultimately confirms that crystal defects in the real samples greatly affect the thermodynamic relationship of the crystals.

Study on Hydration and Dehydration of Ezetimibe by Terahertz Spectroscopy with Humidity-Controlled Measurements and Theoretical Analysis.

Understanding the solid-state transitions of active pharmaceutical ingredients (APIs) is essential for quality control since differences in their forms affect the bioavailability of APIs. Terahertz (THz) frequency-domain spectroscopy is suitable for such an application since it can sensitively probe the lattice phonon modes originating in the crystal structures. THz absorption spectra were obtained for ezetimibe (EZT) and ezetimibe monohydrate (EZT-MH), which have similar crystalline structures and belong to the same space group. The observed absorption spectrum of EZT matched well with the solid-state density functional theory (ss-DFT)-simulated spectrum for the structures at 0 K and room temperature (modeled using constrained unit cell volumes). However for EZT-MH, the ss-DFT spectrum of the room-temperature structure showed better correlation with the experimental THz spectrum than that of the simulated spectrum of the 0 K structures, suggesting that the EZT-MH crystal has greater anharmonic character. Gibbs free-energy curves were calculated, and EZT-MH was found to be more stable than pure EZT and water in a broad temperature range. The hydrate stability may be influenced by the existence of more hydrogen bonds in EZT-MH. The hydration and dehydration of EZT in a pure API tablet and formulation tablets were monitored using a THz spectrometer with a humidity-controlled sample chamber. The effect of the excipient in the formulation tablet on hydration was successfully confirmed by showing that the solid-state transition of the API with excipients is significantly slower than that without it. Under a relative humidity of 60%, hydration of EZT in a pure EZT tablet occurred in 200 min, while the hydration of EZT in a formulation tablet was 50 times slower.

In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P's = 0.001-0.01) and compared with MDD individuals in three regions (P's = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P's = 0.001-0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

Spread of Nontyphoidal Salmonella in the Beef Supply Chain in Northern Tanzania: Sensitivity in a Probabilistic Model Integrating Microbiological Data and Data from Stakeholder Interviews.

East Africa is a hotspot for foodborne diseases, including infection by nontyphoidal Salmonella (NTS), a zoonotic pathogen that may originate from livestock. Urbanization and increased demand for animal protein drive intensification of livestock production and food processing, creating risks and opportunities for food safety. We built a probabilistic mathematical model, informed by prior beliefs and dedicated stakeholder interviews and microbiological research, to describe sources and prevalence of NTS along the beef supply chain in Moshi, Tanzania. The supply chain was conceptualized using a bow tie model, with terminal livestock markets as pinch point, and a forked pathway postmarket to compare traditional and emerging supply chains. NTS was detected in 36 (7.7%) of 467 samples throughout the supply chain. After combining prior belief and observational data, marginal estimates of true NTS prevalence were 4% in feces of cattle entering the beef supply and 20% in raw meat at butcheries. Based on our model and sensitivity analyses, true NTS prevalence was not significantly different between supply chains. Environmental contamination, associated with butchers and vendors, was estimated to be the most likely source of NTS in meat for human consumption. The model provides a framework for assessing the origin and propagation of NTS along meat supply chains. It can be used to inform decision making when economic factors cause changes in beef production and consumption, such as where to target interventions to reduce risks to consumers. Through sensitivity and value of information analyses, the model also helps to prioritize investment in additional research.

Factors Associated with Appropriate Gestational Weight Gain among Women with Obesity.

OBJECTIVE: This study aimed to compare attendance of nutritional counseling, dietary composition, exercise patterns, and socioeconomic factors among obese women with inappropriate gestational weight gain (iGWG) versus appropriate GWG (aGWG). STUDY DESIGN: Medicaid-eligible women receiving prenatal care at a tertiary care center from January 2013 to December 2015 were offered individualized nutritional counseling by a registered dietitian encouraging well-balanced meals and 150 min/wk of exercise. We conducted a prospective case-control study of obese women (body mass index or BMI ≥30) with a singleton gestation with iGWG (<11 or >20 pounds) versus aGWG (11-20 pounds). Dietary intake, activity level, and socioeconomic factors were compared with Chi-square, Fisher's exact, Student's t-test, and Wilcoxon Rank Sum tests as indicated, and odds ratios with 95% confidence intervals were calculated. Multivariate regression analysis for significant variables was performed. A subgroup analysis of women with BMI ≥40 was planned. RESULTS: A total of 401 women were analyzed: 78% (n = 313) with iGWG and 22% (n = 88) with aGWG. Demographics were similar between groups. Women with iGWG less frequently reported physician reinforcement of counseling and reported more physical inactivity and unemployment; there were no differences in caloric intake or macronutrient profile between groups. Multivariate regression identified physician reinforcement and employment as independent predictors of aGWG. Among women with BMI ≥40 (n = 133), those with iGWG (78%) were less likely to attend counseling, report physician reinforcement of counseling, and have adequate caloric and protein intake when compared with those with aGWG (22%). Activity level and socioeconomic factors were not different between groups. CONCLUSION: Physician reinforcement of nutritional counseling, greater activity level, and employment are associated with aGWG in women with BMI ≥30, while individualized professional nutritional counseling and dietary modifications were further associated with aGWG in women with BMI ≥40. Thus, greater focus should be placed on enhancing exposure to counseling and altering nutritional and exercise choices to optimize aGWG. KEY POINTS: · Physician reinforcement of nutritional counseling by a dietitian is crucial for obese women.. · Physical inactivity and unemployment are associated with inappropriate gestational weight gain.. · Nutritional counseling is associated with appropriate gestational weight gain in women with BMI ≥40..

Simulation and Assignment of the Terahertz Vibrational Spectra of Enalapril Maleate Cocrystal Polymorphs.

The identification of crystalline drug polymorphs using terahertz vibrational spectroscopy is a powerful approach for the nondestructive and noninvasive characterization of solid-state pharmaceuticals. However, a complete understanding of the terahertz spectra of molecular solids is challenging to obtain because of the complex nature of the low-frequency vibrational motions found in the sub-3 THz (sub-100 cm-1) range. Unambiguous assignments of the observed spectral features can be achieved through quantum mechanical solid-state simulations of crystal structures and lattice vibrations utilizing the periodic boundary condition approach. The terahertz spectra of two polymorphs of enalapril maleate are presented here to demonstrate that even large pharmaceuticals can be successfully modeled using solid-state density functional theory, including cocrystalline solids comprised of multiple distinct species. These simulations enable spectral assignments to be made, but also provide insights into the conformational and cohesion energies that contribute to the polymorph stabilities. The results reveal that the Form II polymorph of enalapril maleate is the more stable of the two under ambient conditions, and that this stability is driven by a greater intermolecular cohesion energy as compared to Form I.

Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence.

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.

Prevalence of methicillin-resistant Staphylococcus pseudintermedius on hand-contact and animal-contact surfaces in companion animal community hospitals.

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important companion animal pathogen, but few published studies have evaluated its epidemiology in primary care settings. This study determined MRSP prevalence on hand- and animal-contact surfaces in 11 small animal primary care hospitals in Washington and Idaho, USA. Overall, MRSP was isolated from at least 1 sample from 7 of 11 hospitals (64%) and from 36 of 374 total samples (10%) with no difference in prevalence between hand- and animal-contact surfaces (P = 0.51). Strain typing by pulsed-field gel electrophoresis indicated high within-hospital similarity of MRSP strains, but minimal similarity between strains from different hospitals. Indistinguishable MRSP strains were present on handand animal-contact surfaces within individual hospitals. A questionnaire was administered to a representative from each hospital. Respondents reported that animal-contact surfaces were cleaned and disinfected more frequently than hand-contact surfaces (P < 0.001). Improving hand hygiene and disinfection of hand-contact surfaces may decrease exposure of veterinary patients to MSRP.

Prévalence de Staphylococcus pseudintermedius résistant à la méthicilline sur des surfaces en contact avec les mains et des surfaces en contact avec les animaux dans des hôpitaux de première ligne pour animaux de compagnie. Staphylococcus pseudintermedius résistant à la méthicilline (MRSP) est un agent pathogène important chez les animaux de compagnie, mais peu d'études publiées ont évalué son épidémiologie dans les sites de soins de première ligne. Dans la présente étude on détermina la prévalence de MRSP sur les surfaces de contact avec les mains et les surfaces de contact avec les animaux dans 11 hôpitaux de première ligne pour animaux de compagnie dans les états de Washington et de l'Idaho, USA. De manière globale, le MRSP fut isolé à partir d'au moins un échantillon dans 7 des 11 hôpitaux (64 %) et de 36 des 374 échantillons (10 %) sans noter de différence dans la prévalence entre les contacts main-surface ou animal-surface (P = 0,51). Le typage des souches par électrophorèse en champs pulsés indiqua une similarité intra-hôpital élevée des souches de MRSP, mais une similarité minimale entre les souches provenant d'hôpitaux différents. Des souches indistinguables de MRSP étaient présentes sur les surfaces de contact avec les mains et les animaux dans un même hôpital. Un questionnaire fut soumis à un représentant de chaque hôpital. Les répondants rapportèrent que les surfaces de contact avec l'animal étaient nettoyées et désinfectées plus fréquemment que les surfaces de contact avec les mains (P < 0,001). Une amélioration de l'hygiène des mains et de la désinfection des surfaces en contacts avec les mains pourraient diminuer l'exposition de patients vétérinaires au MSRP.(Traduit par Dr Serge Messier).

Antimicrobial use policy change in pre-weaned dairy calves and its impact on antimicrobial resistance in commensal Escherichia coli: a cross sectional and ecological study.

BACKGROUND: This study is based on data collected to investigate the relation of peri-parturient events (colostrum quality, passive transfer of immunity, calving difficulty) on calf health and antimicrobial use. A component of the study was to provide feedback to farm management to identify calves at risk for disease and promote antimicrobial stewardship. At the start of the study (May 2016), a combination of enrofloxacin, penicillin, and sulfamethoxazole was the first treatment given to clinically abnormal calves. Based on feedback and interaction between study investigators, farm management and consulting veterinarians, a new policy was implemented to reduce antimicrobial use in calves. In August, the first treatment was changed to a combination of ampicillin and sulfamethoxazole. In September, the first treatment was reduced to only sulfamethoxazole. We investigated the effects of these policy changes in antimicrobial use on resistance in commensal Escherichia coli. RESULTS: We enrolled 4301 calves at birth and documented antimicrobial use until weaning. Most calves (99.4%) received antimicrobials and 70.4% received a total of 2-4 treatments. Antimicrobial use was more intense in younger calves (≤ 28 days) relative to older calves. We isolated 544 E. coli from fecal samples obtained from 132 calves. We determined resistance to 12 antimicrobials and 85% of the isolates were resistant to at least 3 antimicrobial classes. We performed latent class analysis to identify underlying unique classes where isolates shared resistance patterns and selected a solution with 4 classes. The least resistant class had isolates that were mainly resistant to only tetracycline and sulfisoxazole. The other 3 classes comprised isolates with resistance to ampicillin, chloramphenicol, aminoglycosides, sulfonamides, tetracycline, in addition to either ceftiofur; or nalidixic acid; or ciprofloxacin plus nalidixic acid and ceftiofur. Overall, E coli from younger calves and calves that received multiple treatments were more likely to have extensive resistance including resistance to fluoroquinolones and ceftiofur. In general, there was a declining trend in resistance to most antimicrobials during and after policy changes were implemented, except for ampicillin, ciprofloxacin, ceftiofur and gentamicin. CONCLUSIONS: Information feedback to farms can influence farm managers to reduce antimicrobial use and this can change endemic farm resistance patterns.

Population Structure and Antimicrobial Resistance of Canine Uropathogenic Escherichia coli.

Escherichia coli is the most common cause of human and canine urinary tract infection (UTI). Clonal groups, often with high levels of antimicrobial resistance, are a major component of the E. coli population that causes human UTI. While little is known about the population structure of E. coli that causes UTI in dogs, there is evidence that dogs and humans can share fecal strains of E. coli and that human-associated strains can cause disease in dogs. In order to better characterize the E. coli strains that cause canine UTI, we analyzed 295 E. coli isolates obtained from canine urine samples from five veterinary diagnostic laboratories and analyzed their multilocus sequence types, phenotypic and genotypic antimicrobial resistance profiles, and virulence-associated gene repertoires. Sequence type 372 (ST372), an infrequent human pathogen, was the predominant sequence type in dogs at all locations. Extended-spectrum ß-lactamase-producing isolates with blaCTX-M genes were uncommon in canine isolates but when present were often associated with sequence types that have been described in human infections. This provides support for occasional cross-host-species sharing of strains that cause extraintestinal disease and highlights the importance of understanding the role of companion animals in the overall transmission patterns of extraintestinal pathogenic E. coli.

Molecular Epidemiology of Dairy Cattle-Associated Escherichia coli Carrying blaCTX-M Genes in Washington State.

An increase in the prevalence of commensal Escherichia coli carrying blaCTX-M genes among dairy cattle was observed between 2008 and 2012 in Washington State. To study the molecular epidemiology of this change, we selected 126 blaCTX-M-positive and 126 blaCTX-M-negative isolates for determinations of the multilocus sequence types (MLSTs) and antibiotic resistance phenotypes from E. coli obtained during a previous study. For 99 isolates, we also determined the blaCTX-M alleles using PCR and sequencing and identified the replicon types of blaCTX-M-carrying plasmids. The blaCTX-M-negative E. coli isolates comprised 76 sequence types (STs) compared with 32 STs in blaCTX-M-positive E. coli isolates. The blaCTX-M-positive E. coli isolates formed three MLST clonal complexes, accounting for 83% of these isolates; 52% of blaCTX-M-negative E. coli isolates clustered into 10 clonal complexes, and the remainder were singletons. Overall, blaCTX-M-negative E. coli isolates had more diverse genotypes that were distinct to farms, whereas blaCTX-M-positive E. coli isolates had a clonal population structure and were widely disseminated on farms in both regions included in the study. Plasmid replicon types included IncI1 which predominated, followed by IncFIB and IncFIA/FIB. blaCTX-M-15 was the predominant CTX-M gene allele, followed by blaCTX-M-27 and blaCTX-M-14 There was no significant association between plasmid replicon types and bacterial STs, and neither clonal complexes nor major plasmid groups were associated with two discrete dairy-farming regions of Washington State.IMPORTANCE Infections caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli occur globally and present treatment challenges because of their resistance to multiple antimicrobial drugs. Cattle are potential reservoirs of ESBL-producing Enterobacteriaceae, and so understanding the causes of successful dissemination of blaCTX-M genes in commensal bacteria will inform future approaches for the prevention of antibiotic-resistant pathogen emergence.

Major diseases, extensive misuse, and high antimicrobial resistance of Escherichia coli in large- and small-scale dairy cattle farms in Jordan.

This study aimed to determine the major diseases, antimicrobial use, and resistance in commensal Escherichia coli in dairy cattle in Jordan. Forty-three (large, n = 21; small, n = 22) farms were surveyed. A validated questionnaire was administered to the herdsmen to elicit information about disease prevalence, antimicrobial knowledge, and antimicrobial use. In addition, fecal samples were collected from 5 lactating animals on each farm. A total of 520 E. coli isolates were tested for resistance to 12 antimicrobials. From the herdsmen's perspective, the diseases that require use of veterinary services in large and small production systems were mastitis (51.2%), metritis (51.2%), and enteritis (39.5%), and the most commonly used antimicrobials were oxytetracycline and streptomycin. Dairy herdsmen (83.7%) reported that it is easy to purchase antimicrobials without a veterinary prescription and 97.7% of them more frequently changed the antimicrobial drug rather than increasing the dose when presented with nonresponse to treatment. Escherichia coli isolates exhibited high resistance to streptomycin (47.5%), tetracycline (45.4%), and ampicillin (34.2%). Less than 10% of isolates were resistant to chloramphenicol, kanamycin, gentamicin, ciprofloxacin, and ceftriaxone. Overall, 64.6 and 37.1% of the E. coli isolates exhibited resistance to ≥1 antimicrobial and multidrug resistance (resistance to ≥3 antimicrobial classes), respectively. The isolates exhibited 107 antimicrobial resistance profiles. This study indicates that antimicrobials are frequently misused in dairies in Jordan and that resistance among commensal E. coli toward antimicrobials of human and veterinary importance is high. Therefore, educational programs for herdsmen and enacting regulations and guidelines are necessary to promote the judicious use of antimicrobials in dairy animals in Jordan.

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations.

Multidrug-resistant (MDR) Salmonella enterica can be spread from cattle to humans through direct contact with animals shedding Salmonella as well as through the food chain, making MDR Salmonella a serious threat to human health. The objective of this study was to use whole-genome sequencing to compare antimicrobial-resistant (AMR) Salmonella enterica serovars Typhimurium, Newport, and Dublin isolated from dairy cattle and humans in Washington State and New York State at the genotypic and phenotypic levels. A total of 90 isolates were selected for the study (37 S Typhimurium, 32 S Newport, and 21 S Dublin isolates). All isolates were tested for phenotypic antibiotic resistance to 12 drugs using Kirby-Bauer disk diffusion. AMR genes were detected in the assembled genome of each isolate using nucleotide BLAST and ARG-ANNOT. Genotypic prediction of phenotypic resistance resulted in a mean sensitivity of 97.2 and specificity of 85.2. Sulfamethoxazole-trimethoprim resistance was observed only in human isolates (P < 0.05), while resistance to quinolones and fluoroquinolones was observed only in 6 S Typhimurium isolates from humans in Washington State. S Newport isolates showed a high degree of AMR profile similarity, regardless of source. S Dublin isolates from New York State differed from those from Washington State based on the presence/absence of plasmid replicons, as well as phenotypic AMR susceptibility/nonsusceptibility (P < 0.05). The results of this study suggest that distinct factors may contribute to the emergence and dispersal of AMR S. enterica in humans and farm animals in different regions.IMPORTANCE The use of antibiotics in food-producing animals has been hypothesized to select for AMR Salmonella enterica and associated AMR determinants, which can be transferred to humans through different routes. Previous studies have sought to assess the degree to which AMR livestock- and human-associated Salmonella strains overlap, as well as the spatial distribution of Salmonella's associated AMR determinants, but have often been limited by the degree of resolution at which isolates can be compared. Here, a comparative genomics study of livestock- and human-associated Salmonella strains from different regions of the United States shows that while many AMR genes and phenotypes were confined to human isolates, overlaps between the resistomes of bovine and human-associated Salmonella isolates were observed on numerous occasions, particularly for S Newport. We have also shown that whole-genome sequencing can be used to reliably predict phenotypic resistance across Salmonella isolated from bovine sources.

Family Social Support Modifies the Relationships Between Childhood Maltreatment Severity, Economic Adversity and Postpartum Depressive Symptoms.

OBJECTIVES: This study examines the main and moderating effects of childhood abuse or neglect severity, income, and family social support on the presence of postpartum depressive symptoms (PDS). METHODS: Participants included 183 postpartum mothers who endorsed a history of childhood maltreatment (CM) and enrolled in a longitudinal study of mother and child outcomes. Participants completed questionnaires to assess CM severity, associated societal and maternal characteristics, and depressive symptom severity. RESULTS: The results confirm previously identified links between CM severity and PDS. Further, hierarchical linear regression analyses indicate the interaction of household income and interpersonal support from the family attenuates the relationship between CM severity and PDS. The final model accounted for 29% of the variance of PDS scores, a large effect size. CONCLUSIONS: This study is the first to demonstrate interrelationships between income and social support on resilience to postpartum psychopathology in childhood trauma-surviving women. Social support appeared to protect against PDS for all mothers in this study while income only conferred a protective effect when accompanied by family support. For clinicians, this implies the need to focus on improving family and other relationships, especially for at-risk mothers.

Development and Initial Psychometric Evaluation of the Semi-Structured Emotion Regulation Interview.

Emotion regulation (ER) strategy use has been identified as a transdiagnostic predictor of the development, maintenance, and recovery from several forms of psychopathology. However, the ER strategy use literature relies primarily on self-report measures that have several important limitations. This article describes the development and initial psychometric evaluation of a novel clinician-administered measure of ER strategy use, the Semi-Structured Emotion Regulation Interview (SERI; Lee, Weathers, & Sloan, 2016 ). The SERI was developed in a construct validation framework with emphasis on a multistage content validity process. The SERI assesses frequency and efficacy (i.e., proximal change in the targeted emotion) of 9 strategies in regulation of a specified emotion type and intensity (e.g., severe anxiety) during the past 30 days. Undergraduates (N = 68) completed a battery of self-report measures and a subsequent interview. Frequency and efficacy of each strategy was assessed separately with respect to regulation of moderate and severe anxiety and anger. Each of the assessed strategies demonstrated excellent discriminant validity. Associations between SERI and self-report measures of ER strategy use varied by target emotion type and intensity for some strategies, but not others. Implications and suggestions for future research are described.