Spatial and Depth Profiling of Agricultural Formulations in Leaf Tissue Using LAESI Mass Spectrometry.

Formulating agrochemical products involves combining several chemical components, including the active ingredient(s), to obtain a final product with desirable efficacy. A formulated product incorporates additional components to modulate properties that enhance the efficacy of the active(s) by modifying physical properties such as viscosity, hydrophobicity, miscibility, and others. In plants, understanding the formulation's ability to spread on tissues and penetrate through the outer layer is critical in evaluating the efficacy of the final product. We have previously demonstrated the use of mass spectrometry imaging to determine spreadability. In this study, we show that laser ablation electrospray mass spectrometry (LAESI-MS) can be a valuable tool to assess the penetrability of formulations into the leaf tissues by selectively sampling various layers of leaf tissue by manipulating the laser intensity and analyzing the ablated material using a mass spectrometer. Using this technique, we were able to identify a formulation composition that can improve the penetration and uptake of active ingredients.

Genomic analysis of azithromycin-resistant Salmonella from food animals at slaughter and processing, and retail meats, 2011-2021, United States.

IMPORTANCE: Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones.

High burden of sexually transmitted infections among under-resourced populations in the Dominican Republic.

Background: Sexually transmitted infections (STIs) are a major health issue, exacerbated by limited financial and infrastructural resources in developing countries. Methods: Prevalence of STIs was assessed in two urban centers of the Dominican Republic (DR) among populations at high risk for STIs: pregnant youth, men who have sex with men (MSM), trans women (TG), batey residents, female sex workers, and people living with human immunodeficiency virus (HIV). We conducted a cross-sectional survey and biological specimen collection to screen for Chlamydia trachomatis, Neisseria gonorrhea, Mycoplasma genitalium, Trichomonas vaginalis (trichomoniasis), Treponema pallidum (syphilis), HIV, hepatitis B and C, and human papillomavirus (HPV) among at-risk populations between 2015 and 2018. Ureaplasma urealyticum testing was also conducted even though it is not considered a STI. A non-probability community sample was recruited. Descriptive statistics examined the prevalence of STIs by population. Results: A total of 1991 subjects participated in the study. The median age was 26 years (range: 18-65). Most participants were female (65.3%), heterosexual (76.7%), and were not partnered (55.7%). Most of the participants reported unprotected vaginal sex in the last 6 months (54%); among MSM and TG almost half of the participants reported unprotected anal sex in the last 6 months and 17.6% reported drug use in the last 6 months. Almost half of the participants (49%) tested positive for one or more STIs. The most prevalent STI was Chlamydia trachomatis (12.8%), and human papillomavirus (11.9%). Among transgender women, 65.3% tested positive for an STI, 64.8% of female sex workers tested positive for an STI, and 53.8% of pregnant adolescents tested positive for an STI. Conclusion: There is a high prevalence of STIs among key and under resourced populations in the DR. Our findings highlight the need to conduct further research to optimize prevention and care strategies for structurally vulnerable and under resourced populations in the DR.

Development of core competencies for field veterinary epidemiology training programs.

A workforce with the adequate field epidemiology knowledge, skills and abilities is the foundation of a strong and effective animal health system. Field epidemiology training is conducted in several countries to meet the increased global demand for such a workforce. However, core competencies for field veterinary epidemiology have not been identified and agreed upon globally, leading to the development of different training curricula. Having a set of agreed core competencies can harmonize field veterinary epidemiology training. The Food and Agriculture Organization of the United Nations (FAO) initiated a collective, iterative, and participative process to achieve this and organized two expert consultative workshops in 2018 to develop core competencies for field veterinary epidemiology at the frontline and intermediate levels. Based on these expert discussions, 13 competencies were identified for the frontline and intermediate levels. These competencies were organized into three domains: epidemiological surveillance and studies; field investigation, preparedness and response; and One Health, communication, ethics and professionalism. These competencies can be used to facilitate the development of field epidemiology training curricula for veterinarians, adapted to country training needs, or customized for training other close disciplines. The competencies can also be useful for mentors and employers to monitor and evaluate the progress of their mentees, or to guide the selection process during the recruitment of new staff.

Modification of a Quadrupole/Orbitrap/Linear Quadrupole Ion Trap Tribrid Mass Spectrometer for Diagnostic Gas-Phase Ion-Molecule Reactions.

Tandem mass spectrometry based on diagnostic gas-phase ion-molecule reactions represents a robust method for functional group identification in unknown compounds. To date, most of these reactions have been studied using unit-resolution instruments, such as linear quadrupole ion traps and triple quadrupoles, which cannot be used to obtain elemental composition information for the species of interest. In this study, a high-resolution mass spectrometer, a quadrupole/orbitrap/linear quadrupole ion trap tribrid, was modified by installing a portable reagent inlet system to obtain high-resolution data for ion-molecule reactions. Examination of a previously published test system, the reaction between protonated 1,1'-sulfonyldiimizadole with 2-methoxypropene, demonstrated the ability to perform ion-molecule reactions on the modified tribrid mass spectrometer. High-resolution data were obtained for ion-molecule reactions of three isobaric ions (protonated glycylalanine, protonated glutamine, and protonated lysine) with diethylmethoxyborane. On the basis of these data, the isobaric ions can be differentiated based on both their measured accurate mass as well as the different product ions they generated upon the ion-molecule reactions. In a different experiment, analyte ions were subjected to collision-induced dissociation (CID), and the structures of the resulting fragment ions were examined via diagnostic ion-molecule reactions. This experiment allows for the functional group interrogation of fragment ions and can be used to improve the understanding of the structures of fragment ions generated in the gas phase.

Investigation of fragmentation pathways of protonated 2-methoxypyrimidine derivatives.

Several representative pyrimidine derivatives were selected to undergo electrospray ionization (ESI) followed by collision-induced dissociation tandem mass spectrometry (CID MS/MS) experiments. Two competitive pathways were found to govern the formation of major fragment ions from protonated species of these molecules. The pathways were largely affected by the 2-O-methyl group but not significantly influenced by the substitution on C-5 site of the pyrimidine ring. These findings were supported by both deuterium labeling CID MS/MS experiments and theoretical calculations. The deuterium labeled pyrimidine ion molecules were generated in-source in ESI from the fully deuterated hydrazinyl pyrimidines, which were readily obtained through hydrogen/deuterium (H/D) exchange when dissolved in deuterium oxide (D2 O).

Participatory and Transdisciplinary Studies of Brucella Infection in Humans and Animals in Yunnan Province, China-Lessons Learned.

Brucellosis is an important zoonosis occurring globally. In addition to the risk for disease in humans, the disease causes production losses, since the disease in livestock is characterized by abortion and other reproductive failures. The disease is a public health concern in China, but no information is available on knowledge, perception and awareness of potential risk groups such as farmers, butchers and animal health workers; yet successful control requires compliance of those affected groups to be effective. Following the principles of the Ecohealth approach, emphasis was given to participation of all relevant stakeholders, use of qualitative and quantitative tools, and cross-sectorial collaboration. Data collection included on-farm questionnaires (N = 192) and collection of bulk milk samples of goat (N = 40), cattle (N = 45) and buffalo (N = 41) from farms, as well as serum samples (N = 228) from humans. Milk samples were tested with an ELISA for presence of antibodies, while a serum agglutination test was used for human samples. Qualitative work included 17 focus group discussion (FGD) with villagers and 47 in-depth interviews (IDI) with village animal health workers, doctors, and butchers, focused on knowledge, perception and awareness on zoonoses including brucellosis. Results from questionnaires indicate that abortions are a common problem; cattle with abortion history are kept for further insemination and the milk still consumed or sold. Antibodies against Brucella were detected in cows' (5/45) and goats' (1/40) milk samples, and in human samples (5/126) in Yiliang, while in Mangshi, all buffalo (N = 41) and humans (N = 102) were negative. FGD and IDI results showed an alarmingly low knowledge and awareness on zoonoses; particularly, low awareness about brucellosis was noted, even among the professional groups. Collaboration between village animal health workers and doctors was uncommon. No confirmed brucellosis cases were found in retrospective investigation of hospital and veterinary stations. This study demonstrates the presence of brucellosis in livestock and humans in Yunnan, indicating a non-negligible risk for humans. It is also made apparent that there is a need for increased awareness among both farmers and professionals in order to reduce the risk of zoonotic transmissions.

Genotypic and Phenotypic Characterization of Incompatibility Group FIB Positive Salmonella enterica Serovar Typhimurium Isolates from Food Animal Sources.

Salmonella enterica is one of the most common bacterial foodborne pathogens in the United States, causing illnesses that range from self-limiting gastroenteritis to more severe, life threatening invasive disease. Many Salmonella strains contain plasmids that carry virulence, antimicrobial resistance, and/or transfer genes which allow them to adapt to diverse environments, and these can include incompatibility group (Inc) FIB plasmids. This study was undertaken to evaluate the genomic and phenotypic characteristics of IncFIB-positive Salmonella enterica serovar Typhimurium isolates from food animal sources, to identify their plasmid content, assess antimicrobial resistance and virulence properties, and compare their genotypic isolates with more recently isolated S. Typhimurium isolates from food animal sources. Methods: We identified 71 S. Typhimurium isolates that carried IncFIB plasmids. These isolates were subjected to whole genome sequencing and evaluated for bacteriocin production, antimicrobial susceptibility, the ability to transfer resistance plasmids, and a subset was evaluated for their ability to invade and persist in intestinal human epithelial cells. Results: Approximately 30% of isolates (n = 21) displayed bacteriocin inhibition of Escherichia coli strain J53. Bioinformatic analyses using PlasmidFinder software confirmed that all isolates contained IncFIB plasmids along with multiple other plasmid replicon types. Comparative analyses showed that all strains carried multiple antimicrobial resistance genes and virulence factors including iron acquisition genes, such as iucABCD (75%), iutA (94%), sitABCD (76%) and sitAB (100%). In 17 cases (71%), IncFIB plasmids, along with other plasmid replicon types, were able to conjugally transfer antimicrobial resistance and virulence genes to the susceptible recipient strain. For ten strains, persistence cell counts (27%) were noted to be significantly higher than invasion bacterial cell counts. When the genome sequences of the study isolates collected from 1998-2003 were compared to those published from subsequent years (2005-2018), overlapping genotypes were found, indicating the perseverance of IncFIB positive strains in food animal populations. This study confirms that IncFIB plasmids can play a potential role in disseminating antimicrobial resistance and virulence genes amongst bacteria from several food animal species.

Perceived Importance of Health Concerns Among Lesbian, Gay, Bisexual, and Transgender Adults in a National, Probability-Based Phone Survey, 2017.

Perceptions of the importance of health problems can drive advocacy, policy change, resource distribution, and individual behaviors. However, little is known about how lesbian, gay, bisexual, and transgender (LGBT), that is, sexual and gender minority (SGM) adults view the health problems facing SGM populations. In a 2017 national, probability-based survey of U.S. SGM adults (N = 453), we asked respondents to identify the most serious health problem facing SGM people today. Participants also rated the seriousness of five specific health problems (HIV/AIDS, suicide, hate crimes, harmful alcohol use, tobacco use). Analyses accounted for the complex sampling design and were stratified by gender identity. One quarter of U.S. SGM adults identified the most serious health problem facing SGM people to be HIV/AIDS (95% confidence interval [20.3, 31.2]). More respondents stated there were no serious LGBT health differences compared with straight/cisgender adults (4.2%, confidence interval [2.6, 5.9]) than identified tobacco use, hate crimes, chronic diseases, cancer, or suicide as the most serious. Importance ratings differed by gender and tobacco/alcohol use were perceived as less serious compared with HIV/AIDS, suicide, and hate crimes. Attention paid to HIV/AIDS by the SGM public, while important, may hinder efforts to address chronic diseases and other health issues affecting SGM people.

Risk, Resilience, and Smoking in a National, Probability Sample of Sexual and Gender Minority Adults, 2017, USA.

Background. There are well-documented inequities in smoking between sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, and transgender [LGBT]) and straight and cisgender people. However, there is less information about risk for and resilience against smoking among SGM people. Such information is critical for understanding etiology and developing interventions. Aims. To conduct a within-group assessment of risks and resiliencies relating to smoking status. Method. In 2017, we conducted a cross-sectional telephone survey with a national, probability-based sample of SGM adults (N = 453). We assessed theory-informed risks (adverse childhood events, substance use-oriented social environment, mental distress, stigma, discrimination, social isolation, and identity concealment) and resiliencies (advertising skepticism, identity centrality, social support, and SGM community participation). We applied survey weights, standardized predictor variables, and fit logistic regression models predicting smoking status. We stratified by age and SGM identity. Results. Patterns of risk and resilience differ by age and identity. Effects were consistently in the same direction for all groups for participating in substance use-oriented social environments, pointing to a potential risk factor for all groups. Advertising skepticism and having people you can talk to about being LGBTQ were potential protective factors. Discussion. Intervention development should address risk and resilience that differs by SGM identity. Additionally, our findings suggest interventionists should consider theoretical frameworks beyond minority stress. Conclusion. While much of the literature has focused on the role of stress from stigma and discrimination in tobacco use, addressing social norms and bolstering protective factors may also be important in SGM-targeted interventions.

Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension.

Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B-cell populations was determined in a reduced utero-placental perfusion pressure (RUPP) model of preeclampsia. Anti-murine CD20 monoclonal antibody (5 mg/kg, Clone 5D2) or corresponding mu IgG2a isotype control was administered intraperitoneally to timed pregnant Sprague-Dawley rats on gestation day (GD)10 and 13. RUPP or sham control surgeries were performed on GD14, and mean arterial pressure (MAP) was measured on GD19 from a carotid catheter. As anticipated, RUPP surgery increased MAP and heart rate and decreased mean fetal and placental weight. However, anti-CD20 treatment did not affect these responses. On GD19, B-cell populations were enumerated in the blood, peritoneal cavity, spleen, and placenta with flow cytometry. B1 and B2 cells were not significantly increased following RUPP. Anti-CD20 depleted B1 and B2 cells in peritoneum and circulation but depleted only B2 lymphocytes in spleen and placenta, with no effect on circulating or peritoneal IgM. Overall, these data do not exclude a role for antibodies produced by B cells before depletion but indicate the presence of B lymphocytes in the last trimester of pregnancy is not critical for placental ischemia-induced hypertension.NEW & NOTEWORTHY The adaptive and innate immune systems are implicated in hypertension, including the pregnancy-specific hypertensive condition preeclampsia. However, the mechanism of immune system dysfunction leading to pregnancy-induced hypertension is unresolved. In contrast to previous reports, this study reveals that the presence of classic B2 lymphocytes and peritoneal and circulating B1 lymphocytes is not required for development of hypertension following third trimester placental ischemia in a rat model of pregnancy-induced hypertension.

Interactions between the complement and endothelin systems in normal pregnancy and following placental ischemia.

Preeclampsia is characterized by new onset hypertension and fetal growth restriction and is associated with aberrant activation of the innate immune complement system and stressed or ischemic placenta. Previous studies have suggested a role for both endothelin and complement system activation products in new onset hypertension in pregnancy, but inter-relationships of the pathways are unclear. We hypothesized that complement activation following placental ischemia stimulates the endothelin pathway to cause hypertension and impair fetal growth. The Reduced Uterine Perfusion Pressure (RUPP) model results in hypertension and fetal growth restriction in a pregnant rat due to placental ischemia caused by mechanical obstruction of blood flow to uterus and placenta. The effect of inhibitor of complement activation soluble Complement Receptor 1 (sCR1) and endothelin A receptor (ETA) antagonist atrasentan on hypertension, fetal weight, complement activation (systemic circulating C3a and local C3 placental deposition) and endothelin [circulating endothelin and message for preproendothelin (PPE), ETA and endothelin B receptor (ETB) in placenta] in the RUPP rat model were determined. Following placental ischemia, sCR1 attenuated hypertension but increased message for PPE and ETA in placenta, suggesting complement activation causes hypertension via an endothelin independent pathway. With ETA antagonism the placental ischemia-induced increase in circulating C3a was unaffected despite inhibition of hypertension, indicating systemic C3a alone is not sufficient. In normal pregnancy, inhibiting complement activation increased plasma endothelin but not placental PPE message. Atrasentan treatment increased fetal weight, circulating endothelin and placental ETA message, and unexpectedly increased local complement activation in placenta (C3 deposition) but not C3a in circulation, suggesting endothelin controls local placental complement activation in normal pregnancy. Atrasentan also significantly decreased message for endogenous complement regulators Crry and CD55 in placenta and kidney in normal pregnancy. Results of our study indicate that complement/endothelin interactions differ in pregnancies complicated with placental ischemia vs normal pregnancy, as well as locally vs systemically. These data clearly illustrate the complex interplay between complement and endothelin indicating that perturbations of either pathway may affect pregnancy outcomes.

Questions associated with the development of novel drugs intended for the treatment of bacterial infections in veterinary species.

The emergence of multi-drug resistant bacteria has limited therapeutic options for the treatment of bacterial diseases in both human and veterinary medicine. This has resulted in an urgent need for novel agents to treat infectious diseases. Veterinary medicine is further constrained by the need to ensure that our emerging therapeutics have minimal or no impact on resistance in human pathogens. Thus, there has recently been increased attention given to the development of alternative treatments for infectious disease in animals. The domain of alternative therapies, which includes antimicrobial peptides, bacteriophages, probiotics, and immunomodulators, provides a means to directly inhibit the ability of a pathogen to damage the host while optimally, not imposing a selective pressure favouring antibiotic resistance. However, it is recognized that bacterial pathogens have the capability of expressing a variety of virulence factors, necessitating a clear understanding of the specific target for that therapeutic intervention. This manuscript explores the various virulence mechanisms, the potential utility of developing novel anti-virulence agents for counteracting the expression of diseases associated with veterinary species, and some of the unique regulatory hurdles to be addressed within the framework of a new animal drug application. We conclude with the public health concerns to be considered as these agents are integrated into the veterinary therapeutic arsenal. Our hope is that this manuscript will provide a platform to stimulate discussions on the critical questions that need to be addressed.

Impact of co-carriage of IncA/C plasmids with additional plasmids on the transfer of antimicrobial resistance in Salmonella enterica isolates.

BACKGROUND: Antimicrobial resistance in Salmonella enterica is often plasmid encoded. A key resistance plasmid group is the incompatibility group (Inc) A/C plasmids that often carry multiple resistance determinants. Previous studies showed that IncA/C plasmids were often co-located with other plasmids. The current study was undertaken to evaluate the impact of plasmid co-carriage on antimicrobial resistance and plasmid transfer. METHODS: A total of 1267 Salmonella isolates, representing multiple serotypes and sources were previously subjected to susceptibility testing and 251 isolates with resistance to at least 5 antimicrobial agents were identified for further study. Each isolate was subjected to PCR-based replicon typing, and those with IncA/C plasmids were selected for plasmid isolation, PCR-based mapping of IncA/C plasmid backbone genes, and conjugation assays to evaluate resistance plasmid transferability. RESULTS: Of the 87 identified IncA/C positive isolates, approximately 75% carried a plasmid with another identified replicon type, with the most common being I1 (39%), FIA, FIIA, FIB and HI2 (each 15%). PCR-based mapping indicated significant diversity in IncA/C backbone content, especially in regions encoding transfer-associated and hypothetical proteins. Conjugation experiments showed that nearly 68% of the isolates transferred resistance plasmids, with 90% containing additional identified plasmids or larger (>50 kb) non-typeable plasmids. CONCLUSIONS: The majority of IncA/C-positive strains were able to conjugally transfer antimicrobial resistance to the recipient, encoded by IncA/C and/or co-carried plasmids. These findings highlight the importance of co-located plasmids for resistance dissemination either by directly transferring resistance genes or by potentially providing the needed conjugation machinery for IncA/C plasmid transfer.

Alveolarides: Antifungal Peptides from Microascus alveolaris Active against Phytopathogenic Fungi.

Three novel cyclodepsipeptides, alveolarides A (1), B (2), and C (3), each possessing the rare 2,3-dihydroxy-4-methyltetradecanoic acid unit and a ß-phenylalanine amino acid residue, along with the known peptide scopularide were isolated and identified from the culture broth of Microascus alveolaris strain PF1466. The pure compounds were evaluated for biological activity, and alveolaride A (1) provided strong in vitro activity against the plant pathogens Pyricularia oryzae, Zymoseptoria tritici, and Ustilago maydis. Moderate activity of alveolaride A was observed under in planta conditions against Z. tritici, Puccinia triticina, and Phakopsora pachyrhizi. Structures of 1, 2, and 3 were determined by detailed analysis of NMR (1D and 2D) and mass spectrometry data. The partial absolute configuration of alveolaride A (1) was established.

Effect of nicotine on placental ischemia-induced complement activation and hypertension in the rat.

Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia-reperfusion injury in kidney and liver. Prior studies indicated that complement activation was critical for placental ischemia-induced hypertension in a rat model. Thus, it was hypothesized here that nicotine was responsible for the protective effect of cigarette smoking in preeclampsia and would attenuate placental ischemia-induced systemic complement activation and hypertension. The Reduced Utero-placental Perfusion Pressure (RUPP) model in the pregnant rat was employed to induce placental ischemia, resulting in complement activation, fetal resorptions, and hypertension. On gestation day (GD)14, nicotine (1 mg/kg) or saline was administered via subcutaneous injection prior to RUPP surgery and daily through GD18. On GD19, placental ischemia significantly increased mean arterial pressure (MAP) in saline injected animals. However, the placental ischemia-induced increase in blood pressure was not evident in nicotine-treated animals and nicotine treatment significantly increased MAP variability. Circulating C3a was measured as an indicator of complement activation and increased C3a in RUPP compared to Sham persisted with nicotine treatment, as did fetal resorptions. These data suggested to us that nicotine may contribute to the decreased risk of preeclampsia with cigarette smoking, but this protective effect was confounded by additional effects of nicotine on the cardiovascular system.

Effects of low concentrations of erythromycin, penicillin, and virginiamycin on bacterial resistance development in vitro.

Distillers grains are co-products of the corn ethanol industry widely used in animal feed. We examined the effects of erythromycin, penicillin, and virginiamycin at low concentrations reflective of those detected in distillers grains on bacterial resistance selection. At 0.1 µg/ml erythromycin, macrolide-resistant mutants were induced in one Campylobacter coli and one Enterococcus faecium strain, while these strains plus three additional C. coli, one additional E. faecium, and one C. jejuni also developed resistance when exposed to 0.25 µg/ml erythromycin. At 0.5 µg/ml erythromycin, a total of eight strains (four Campylobacter and four Enterococcus) obtained macrolide-resistant mutants, including two strains from each genus that were not selected at lower erythromycin concentrations. For penicillin, three of five E. faecium strains but none of five Enterococcus faecalis strains consistently developed resistance at all three selection concentrations. Virginiamycin at two M1:S1 ratios did not induce resistance development in four out of five E. faecium strains; however, increased resistance was observed in the fifth one under 0.25 and 0.5 µg/ml virginiamycin selections. Although not yet tested in vivo, these findings suggest a potential risk of stimulating bacterial resistance development in the animal gut when distillers grains containing certain antibiotic residues are used in animal feed.

From apelin to exercise: emerging therapies for management of hypertension in pregnancy.

Studies over the last couple of decades have provided exciting new insights into mechanisms underlying the pathogenesis of preeclampsia. In addition, several novel and innovative molecules and ideas for management of the syndrome have also come forth. While our basic understanding of the initiating events of preeclampsia continues to be placental ischemia/hypoxia stimulating the release of a variety of factors from the placenta that act on the cardiovascular and renal systems, the number of candidate pathways for intervention continues to increase. Recent studies have identified apelin and its receptor, APJ, as an important contributor to the regulation of cardiovascular and fluid balance that is found to be disrupted in preeclampsia. Likewise, continued studies have revealed a critical role for the complement arm of the innate immune system in placental ischemia induced hypertension and in preeclampsia. Finally, the recent increase in animal models for studying hypertensive disorders of pregnancy has provided opportunities to evaluate the potential role for physical activity and exercise in a more mechanistic fashion. While the exact quantitative importance of the various endothelial and humoral factors that mediate vasoconstriction and elevation of arterial pressure during preeclampsia remains unclear, significant progress has been made. Thus, the goal of this review is to discuss recent efforts towards identifying therapies for hypertension during pregnancy that derive from work exploring the apelinergic system, the complement system as well as the role that exercise and physical activity may play to that end.

Regulatory Considerations for the Approval of Drugs Against Histomoniasis (Blackhead Disease) in Turkeys, Chickens, and Game Birds in the United States.

Histomoniasis, commonly referred to as blackhead disease, is a serious threat to the turkey and game bird industries worldwide, and it is having an increasingly negative impact on the chicken industry as well. The Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM), charged with the approval and regulation of new animal drugs in the United States, understands the rising need for the availability of therapeutic options against histomoniasis. CVM has actively engaged in discussions with the poultry industry, academic institutions, and animal health companies regarding the current status of histomoniasis in the United States and varied success of past and current management, prophylactic, and therapeutic interventions that have been used against the disease. As effective options against the disease are severely limited, CVM encourages the poultry industry, academic institutions, and animal health companies to work together to research and develop viable management, prophylactic, and therapeutic strategies, such as litter management, deworming programs, vaccines or other biologics, novel technologies, and animal drugs. CVM also recognizes the potential challenges that the poultry industry, academic institutions, and animal health companies may encounter while working towards the approval of safe and effective drug products for the treatment and control of histomoniasis. With that recognition, CVM encourages interested parties to begin discussions with CVM early in order to align research of the drug product against histomoniasis with the drug approval requirements, such that it leads to the approval of a new animal drug in an efficient and expedient manner. This article provides information about the FDA's regulatory process for the approval of new animal drugs in the United States, with especial emphasis on drug products for the treatment and control of histomoniasis in turkeys, chickens, and game birds.