Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence.

BACKGROUND: The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. OBJECTIVE: This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. STUDY DESIGN: In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. RESULTS: Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval, -467 to -98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval, -7.3 to -1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval, -8501 to -1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval, -1501 to -246; P<.01), the villous area (-1.5 mm2; 95% confidence interval, -2.7 to -0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval, -8201 to -2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval, -1.1 to -0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. CONCLUSION: Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Missed Antimicrobial Stewardship Opportunities for Hospitalized Patients with Urinary Tract Infections Receiving Ceftriaxone.

Background: Ceftriaxone is a commonly utilized antibiotic for the treatment of urinary tract infections (UTI) despite the limited literature supporting its use. Opportunities for antimicrobial stewardship (ASP), including IV-to-PO conversions and de-escalation of therapy, are often missed in the hospital setting. Objective: The study reported here describes the utilization of ceftriaxone in patients admitted to the hospital and treated for UTIs in a large health system, focusing on opportunities for IV-to-PO conversion of antibiotic therapy. Methods: This was a multi-center, retrospective, descriptive study conducted in a large health system. Patients admitted from January 2019 to July 2019 were included for analysis if they were 18 years or older at admission, diagnosed with acute cystitis, acute pyelonephritis, or unspecified UTI, and received two or more doses of ceftriaxone. The primary outcome was to evaluate the percentage of patients who were eligible for conversion from IV ceftriaxone to oral antibiotics while admitted to the hospital based on the defined criteria for automatic pharmacist conversion in the health system. Percentage of urine cultures with susceptibility to cefazolin, the duration of antibiotic therapy in the hospital, and an evaluation of oral antibiotics prescribed at discharge were also recorded. Results: A total of 300 patients were included; 88% met the pre-specified criteria for IV-to-PO conversion, but only 12% were converted from IV-to-PO antibiotics during hospitalization. Approximately 65% of patients remained on IV ceftriaxone until discharge, at which time they were converted to a PO antibiotic, most commonly fluoroquinolones followed by third-generation cephalosporins. Conclusion: Patients admitted to the hospital and receiving treatment with ceftriaxone for UTI were infrequently converted to oral therapy prior to discharge despite meeting criteria for automatic pharmacist IV-to-PO conversion. Findings highlight opportunities to contribute to antimicrobial stewardship initiatives across the health system and the importance of tracking and reporting results to frontline providers.

How Postbaccalaureate Career Changer and Traditional Medical Students Differ Academically.

OBJECTIVE: This retrospective descriptive study compared the academic performance of postbaccalaureate career changer students with that of traditional students during the classroom-based, science-dominated early years of medical school. Earlier studies documented the eventual success of nontraditional medical students, although we found little information specific to the medical school performance of career changers. Our objective was to determine whether postbaccalaureate career changer medical students perform differently from traditionally prepared medical students in the science-dominated early years of medical school classroom education. METHODS: This study analyzed the admission data and academic performance of medical students at the University of Central Florida College of Medicine across 8 years (N = 630). Differences in performance were assessed using examination grades from the first 2 years of medical school, and US Medical Licensing Examination (USMLE) Step 1 and Step 2 scores. RESULTS: Statistically significant differences were found between traditional and career changer students for all science modules in year 1, and 4 of the 5 modules in year 2. Traditional students performed better on USMLE Step 1. Significant differences between the groups disappeared by USMLE Step 2. CONCLUSIONS: Career changer medical students show a small, persistent academic lag in the first 2 years of medical school and on USMLE Step 1 scores. By USMLE Step 2 the difference disappears. Similar undergraduate grade point averages and Medical College Admission Test scores suggest that science exposure, not ability may explain these differences. An unexpected finding is the number of career changer students is not increasing proportional to the proliferation of postbaccalaureate programs in the United States. This study may benefit student advisors and residency directors, and, it is hoped, provide reassurance to career changer students.

Personalized Therapeutic Cocktail of Wild Environmental Phages Rescues Mice from Acinetobacter baumannii Wound Infections.

Multidrug-resistant bacterial pathogens are an increasing threat to public health, and lytic bacteriophages have reemerged as a potential therapeutic option. In this work, we isolated and assembled a five-member cocktail of wild phages against Acinetobacter baumannii and demonstrated therapeutic efficacy in a mouse full-thickness dorsal infected wound model. The cocktail lowers the bioburden in the wound, prevents the spread of infection and necrosis to surrounding tissue, and decreases infection-associated morbidity. Interestingly, this effective cocktail is composed of four phages that do not kill the parent strain of the infection and one phage that simply delays bacterial growth in vitro via a strong but incomplete selection event. The cocktail here appears to function in a combinatorial manner, as one constituent phage targets capsulated A. baumannii bacteria and selects for loss of receptor, shifting the population to an uncapsulated state that is then sensitized to the remaining four phages in the cocktail. Additionally, capsule is a known virulence factor for A. baumannii, and we demonstrated that the emergent uncapsulated bacteria are avirulent in a Galleria mellonella model. These results highlight the importance of anticipating population changes during phage therapy and designing intelligent cocktails to control emergent strains, as well as the benefits of using phages that target virulence factors. Because of the efficacy of this cocktail isolated from a limited environmental pool, we have established a pipeline for developing new phage therapeutics against additional clinically relevant multidrug-resistant pathogens by using environmental phages sourced from around the globe.

Environmental impacts of different crop rotations in terms of soil compaction.

Avoiding soil compaction caused by agricultural management is a key aim of sustainable land management, and the soil compaction risk should be considered when assessing the environmental impacts of land use systems. Therefore this project compares different crop rotations in terms of soil structure and the soil compaction risk. It is based on a field trial in Germany, in which the crop rotations (i) silage maize (SM) monoculture, (ii) catch crop mustard (Mu)_sugar beet (SB)-winter wheat (WW)-WW, (iii) Mu_SM-WW-WW and (iv) SB-WW-Mu_SM are established since 2010. Based on the cultivation dates, the operation specific soil compaction risks and the soil compaction risk of the entire crop rotations are modelled at two soil depths (20 and 35 cm). To this end, based on assumptions of the equipment currently used in practice by a model farm, two scenarios are modelled (100 and 50% hopper load for SB and WW harvest). In addition, after one complete rotation, in 2013 and in 2014, the physical soil parameters saturated hydraulic conductivity (kS) and air capacity (AC) were determined at soil depths 2-8, 12-18, 22-28 and 32-38 cm in order to quantify the soil structure. At both soil depths, the modelled soil compaction risks for the crop rotations including SB (Mu_SB-WW-WW, SB-WW-Mu_SM) are higher (20 cm: medium to very high risks; 35 cm: no to medium risks) than for those without SB (SM monoculture, Mu_SM-WW-WW; 20 cm: medium risks; 35 cm: no to low risks). This increased soil compaction risk is largely influenced by the SB harvest in years where soil water content is high. Halving the hopper load and adjusting the tyre inflation pressure reduces the soil compaction risk for the crop rotation as a whole. Under these conditions, there are no to low soil compaction risks for all variants in the subsoil (soil depth 35 cm). Soil structure is mainly influenced in the topsoil (2-8 cm) related to the cultivation of Mu as a catch crop and WW as a preceding crop. Concerning kS, Mu_SB-WW-WW (240 cm d(-1)) and Mu_SM-WW-WW (196 cm d(-1)) displayed significantly higher values than the SM monoculture (67 cm d(-1)), indicating better structural stability and infiltration capacity. At other soil depths, and for the parameter AC, there are no systematic differences in soil structure between the variants. Under the circumstances described, all crop rotations investigated are not associated with environmental impacts caused by soil compaction.

The Use of Intraperitoneal Ampicillin in a Patient With Enterococcus faecalis Peritonitis.

INTRODUCTION: Peritoneal dialysis (PD) - associated peritonitis is a serious complication of peritoneal dialysis (PD). The 2022 International Society of Peritoneal Dialysis (ISPD) guidelines do not recommend intraperitoneal (IP) ampicillin for treatment of Enterococcal PD - associated peritonitis. To date, there is no in vivo data to support use of IP ampicillin for the treatment of Enterococcus faecalis. CASE DESCRIPTION: A 69-year-old man with a past medical history of end stage kidney disease (ESKD) requiring continuous cycling peritoneal dialysis (CCPD) was admitted to the hospital and treated for peritonitis with E. faecalis. The patient's CCPD prescription was 2.5% Dianeal with 5 total exchanges. IP ampicillin was added to the first 4 exchanges and additional ampicillin was added to the last fill. The patient successfully completed the treatment course with clinical cure. DISCUSSION: The use of IP ampicillin for E. faecalis peritonitis is controversial and previously lacked compelling clinical evidence for or against its use. This case demonstrates treatment of peritonitis using a modified dosing strategy with ampicillin added to each CCPD exchange and last fill. The loss of ampicillin antimicrobial activity reported in vitro with E. faecalis was not supported by this case.

Adenylate kinase release as a high-throughput-screening-compatible reporter of bacterial lysis for identification of antibacterial agents.

Adenylate kinase (AK) is a ubiquitous intracellular enzyme that is released into the extracellular space upon cell lysis. We have shown that AK release serves as a useful reporter of bactericidal agent activity and can be exploited for antimicrobial screening purposes. The AK assay exhibits improved sensitivity over that of growth-based assays and can detect agents that are active against bacteria in clinically relevant growth states that are difficult to screen using conventional approaches, such as small colony variants (SCV) and bacteria within established biofilms. The usefulness of the AK assay was validated by screening a library of off-patent drugs for agents that exhibit antimicrobial properties toward a variety of bacterial species, including Escherichia coli and all members of the "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The assay detected antibiotics within the library that were expected to be active against the organism screened. Moreover, 38 drugs with no previously reported antibacterial activity elicited AK release. Four of these were acquired, and all were verified to exhibit antimicrobial activity by standard susceptibility testing. Two of these molecules were further characterized. The antihistamine, terfenadine, was active against S. aureus planktonic, SCV population, and biofilm-associated cells. Tamoxifen, an estrogen receptor antagonist, was active toward E. faecium in vitro and also reduced E. faecium pathogenesis in a Galleria mellonella infection model. Our data demonstrate that the AK assay provides an attractive screening approach for identifying new antimicrobial agents. Further, terfenadine and tamoxifen may represent novel antimicrobial drug development scaffolds.

Liability and maternal immunization: in utero injury claims in the VICP.

Generally, under the National Childhood Vaccine Injury Act of 1986 (Vaccine Act), vaccine administrators and manufacturers are shielded from medical malpractice or products liability actions stemming from vaccine-related injuries and deaths. That said, as generous as these protections may be, they have boundaries, some of which are clear and others of which are unsettled. This is particularly so for in utero injuries stemming from immunization of pregnant women. The issue of whether in utero injuries are afforded such protections, vis á vis compensation by the National Vaccine Injury Compensation Program (VICP) under the Vaccine Act, has not definitively been resolved by the courts. Short of a decision by the Court of Appeals for the Federal Circuit or a statutory amendment by Congress specifically addressing this issue, the uncertainty remains.

Evaluation of Pseudomonas aeruginosa pathogenesis and therapeutics in military-relevant animal infection models.

Modern combat-related injuries are often associated with acute polytrauma. As a consequence of severe combat-related injuries, a dysregulated immune response results in serious infectious complications. The gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that often causes life-threatening bloodstream, lung, bone, urinary tract, and wound infections following combat-related injuries. The rise in the number of multidrug-resistant P. aeruginosa strains has elevated its importance to civilian clinicians and military medicine. Development of novel therapeutics and treatment options for P. aeruginosa infections is urgently needed. During the process of drug discovery and therapeutic testing, in vivo testing in animal models is a critical step in the bench-to-bedside approach, and required for Food and Drug Administration approval. Here, we review current and past literature with a focus on combat injury-relevant animal models often used to understand infection development, the interplay between P. aeruginosa and the host, and evaluation of novel treatments. Specifically, this review focuses on the following animal infection models: wound, burn, bone, lung, urinary tract, foreign body, and sepsis.

Synergistic Killing and Re-Sensitization of Pseudomonas aeruginosa to Antibiotics by Phage-Antibiotic Combination Treatment.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a serious health threat. Bacteriophage-antibiotic combination therapy is a promising candidate for combating these infections. A 5-phage P. aeruginosa cocktail, PAM2H, was tested in combination with antibiotics (ceftazidime, ciprofloxacin, gentamicin, meropenem) to determine if PAM2H enhances antibiotic activity. Combination treatment in vitro resulted in a significant increase in susceptibility of MDR strains to antibiotics. Treatment with ceftazidime (CAZ), meropenem, gentamicin, or ciprofloxacin in the presence of the phage increased the number of P. aeruginosa strains susceptible to these antibiotics by 63%, 56%, 31%, and 81%, respectively. Additionally, in a mouse dorsal wound model, seven of eight mice treated with a combination of CAZ and PAM2H for three days had no detectable bacteria remaining in their wounds on day 4, while all mice treated with CAZ or PAM2H alone had ~107 colony forming units (CFU) remaining in their wounds. P. aeruginosa recovered from mouse wounds post-treatment showed decreased virulence in a wax worm model, and DNA sequencing indicated that the combination treatment prevented mutations in genes encoding known phage receptors. Treatment with PAM2H in combination with antibiotics resulted in the re-sensitization of P. aeruginosa to antibiotics in vitro and a synergistic reduction in bacterial burden in vivo.

Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis.

Acinetobacter baumannii is an emerging bacterial pathogen of considerable health care concern. Nonetheless, relatively little is known about the organism's virulence factors or their regulatory networks. Septicemia and ventilator-associated pneumonia are two of the more severe forms of A. baumannii disease. To identify virulence factors that may contribute to these disease processes, genetically diverse A. baumannii clinical isolates were evaluated for the ability to proliferate in human serum. A transposon mutant library was created in a strain background that propagated well in serum and screened for members with decreased serum growth. The results revealed that disruption of A. baumannii phospholipase D (PLD) caused a reduction in the organism's ability to thrive in serum, a deficiency in epithelial cell invasion, and diminished pathogenesis in a murine model of pneumonia. Collectively, these results suggest that PLD is an A. baumannii virulence factor.

Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations.

Acinetobacter baumannii is well adapted to the hospital environment, where infections caused by this organism are associated with significant morbidity and mortality. Genetic determinants of antimicrobial resistance have been described extensively, yet the mechanisms by which A. baumannii regulates antibiotic resistance have not been defined. We sought to identify signals encountered within the hospital setting or human host that alter the resistance phenotype of A. baumannii. In this regard, we have identified NaCl as being an important signal that induces significant tolerance to aminoglycosides, carbapenems, quinolones, and colistin upon the culturing of A. baumannii cells in physiological NaCl concentrations. Proteomic analyses of A. baumannii culture supernatants revealed the release of outer membrane proteins in high NaCl, including two porins (CarO and a 33- to 36-kDa protein) whose loss or inactivation is associated with antibiotic resistance. To determine if NaCl affected expression at the transcriptional level, the transcriptional response to NaCl was determined by microarray analyses. These analyses highlighted 18 genes encoding putative efflux transporters that are significantly upregulated in response to NaCl. Consistent with this, the effect of NaCl on the tolerance to levofloxacin and amikacin was significantly reduced upon the treatment of A. baumannii with an efflux pump inhibitor. The effect of physiological concentrations of NaCl on colistin resistance was conserved in a panel of multidrug-resistant isolates of A. baumannii, underscoring the clinical significance of these observations. Taken together, these data demonstrate that A. baumannii sets in motion a global regulatory cascade in response to physiological NaCl concentrations, resulting in broad-spectrum tolerance to antibiotics.

Preventing emergency department visits and hospitalizations for asthma by use of oral corticosteroids at home: are we adhering to national guidelines?

BACKGROUND: Oral corticosteroids (OCS) in the home management of asthma exacerbations have been recommended in the NIH/NHLBI guidelines since 1991. As a routine component of written action plans, OCS treatment at home is associated with reduced emergency department (ED) visits and hospitalizations as well as decreased mortality. METHODS: A literature search of English language journals from 1991 to 2009 was performed using several databases, including PubMed, EMBASE, and SCOPUS. We assessed studies that evaluated adherence to national guidelines for home management of asthma exacerbations. RESULTS: Our review of the literature found that several studies reveal that a small percentage (<3-26%) of patients are receiving OCS at home to manage asthma exacerbations prior to an ED visit. Additional studies were found showing very low use of written action plans, strongly suggesting lack of OCS for home management of asthma exacerbations. CONCLUSIONS: Despite evidence of reduced ED visits and hospitalizations and the recommendations of national and international guidelines, the home use of OCS in managing asthma exacerbations remains unacceptably low. New strategies are needed to ensure home use of OCS as part of written action plans to prevent ED visits and hospitalizations for asthma exacerbations.

Stability of Porcine reproductive and respiratory syndrome virus at ambient temperatures.

The stability of Porcine reproductive and respiratory syndrome virus (PRRSV) was evaluated for temperatures appropriate to laboratory and field settings. Four North American (type 2) isolates (ATCC VR-2332, JA-142, MN-184, and Ingelvac(R) PRRS ATP vaccine virus) in cell culture medium (pH 7.5) were held at 1 of 4 temperatures (4, 10, 20, and 30 degrees C) and sampled over time. Samples were tested for infectious virus and total PRRSV RNA using median tissue culture infectious dose and quantitative reverse transcription polymerase chain reaction, respectively. The rate of loss of infectious virus was expressed in terms of the time required for virus concentration to decline by one half (i.e., half-life [T(1/2)]). Statistical analysis found that temperature, but not virus isolate, had a significant effect on T(1/2), and a single nonlinear regression model was derived to predict T(1/2) for temperatures between 0 and 50 degrees C: T(1/2) = 243.54 e((-0.109*TEMP)). In contrast to changes over time in the concentration of infectious virus, no change in the concentration of quantitative reverse transcription polymerase chain reaction-detectable PRRSV was detected at any temperature and contact time. This information will be of interest to persons working in laboratory or field situations in which the control of PRRSV is important.

Characterization of Acinetobacter baumannii Copper Resistance Reveals a Role in Virulence.

Acinetobacter baumannii is often highly drug-resistant and causes severe infections in compromised patients. These infections can be life threatening due to limited treatment options. Copper is inherently antimicrobial and increasing evidence indicates that copper containing formulations may serve as non-traditional therapeutics against multidrug-resistant bacteria. We previously reported that A. baumannii is sensitive to high concentrations of copper. To understand A. baumannii copper resistance at the molecular level, herein we identified putative copper resistance components and characterized 21 strains bearing mutations in these genes. Eight of the strains displayed a copper sensitive phenotype (pcoA, pcoB, copB, copA/cueO, copR/cusR, copS/cusS, copC, copD); the putative functions of these proteins include copper transport, oxidation, sequestration, and regulation. Importantly, many of these mutant strains still showed increased sensitivity to copper while in a biofilm. Inductively coupled plasma mass spectrometry revealed that many of these strains had defects in copper mobilization, as the mutant strains accumulated more intracellular copper than the wild-type strain. Given the crucial antimicrobial role of copper-mediated killing employed by the immune system, virulence of these mutant strains was investigated in Galleria mellonella; many of the mutant strains were attenuated. Finally, the cusR and copD strains were also investigated in the murine pneumonia model; both were found to be important for full virulence. Thus, copper possesses antimicrobial activity against multidrug-resistant A. baumannii, and copper sensitivity is further increased when copper homeostasis mechanisms are interrupted. Importantly, these proteins are crucial for full virulence of A. baumannii and may represent novel drug targets.

Impact of Frequent Administration of Bacteriophage on Therapeutic Efficacy in an A. baumannii Mouse Wound Infection Model.

The spread of multidrug antibiotic resistance (MDR) is a widely recognized crisis in the treatment of bacterial infections, including those occurring in military communities. Recently, the World Health Organization published its first ever list of antibiotic-resistant "priority pathogens" - a catalog of 12 families of bacteria that pose the greatest threat to human health with A. baumannii listed in the "Priority 1: Critical" category of pathogens. With the increasing prevalence of antibiotic resistance and limited development of new classes of antibiotics, alternative antimicrobial therapies are needed, with lytic bacteriophage (phage) specifically targeted against each of the high priority bacterial infections as a potential approach currently in development toward regulatory approval for clinical use. Balb/c mice were prophylactically administered PBS or phage selected against A. baumannii strain AB5075. After 3 weeks, mice were anesthetized, wounded (dorsal), and challenged topically with AB5075. Following infection, mice were subsequently treated with PBS or phage for three consecutive days, and evaluated for 3 weeks to assess the safety and efficacy of the phage treatment relative to the control. We assessed mortality, bacterial burden, time to wound closure, systemic and local cytokine profiles, alterations in host cellular immunity, and finally presence of neutralizing antibodies to the phage mixture. In our study, we found that prophylactic phage administration led to a significant reduction in monocyte-related cytokines in serum compared to mice given PBS. However, we detected no significant changes to circulating blood populations or immune cell populations of secondary lymphoid organs compared to PBS-treated mice. Following prophylactic phage administration, we detected a marked increase in total immunoglobulins in serum, particularly IgG2a and IgG2b. Furthermore, we determined that these antibodies were able to specifically target phage and effectively neutralize their ability to lyse their respective target. In regards to their therapeutic efficacy, administration of phage treatment effectively decreased wound size of mice infected with AB5075 without adverse effects. In conclusion, our data demonstrate that phage can serve as a safe and effective novel therapeutic agent against A. baumannii without adverse reactions to the host and pre-exposure to phage does not seem to adversely affect therapeutic efficacy. This study is an important proof of concept to support the efforts to develop phage as a novel therapeutic product for treatment of complex bacterial wound infections.

Complete Genome Sequences of 10 Phages Lytic against Multidrug-Resistant Pseudomonas aeruginosa.

We report the genome sequences of 10 Pseudomonas aeruginosa phages studied for their potential for formulation of a therapeutic cocktail; they represent the families Myoviridae, Podoviridae, and Siphoviridae Genome sizes ranged from 43,299 to 88,728 nucleotides, with G+C contents of 52.1% to 62.2%. The genomes contained 68 to 168 coding sequences.

Rifampin hepatotoxicity associated with treatment of latent tuberculosis infection.

BACKGROUND: To determine the occurrence of hepatotoxicity associated with rifampin treatment of latent tuberculosis infection in patients from a public health tuberculosis clinic. METHODS: Evaluation of rifampin hepatotoxicity in adults aged >or=18 years from a database maintained from June 2001 to May 2007 in a public health department clinic. Rifampin 600 mg daily for 4 months was prescribed. Hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels more than 3 times the upper limit of normal (ULN) with symptoms or more than 5 times the ULN without symptoms. RESULTS: Rifampin therapy was initiated in 348 patients. Among 205 patients with evaluable data, 4 (1.95%, 95% confidence interval: 0%-4.33%) had AST or ALT levels >5 times the ULN (2 patients at 1 month and 2 patients at 3 months). Three of these patients had elevated AST/ALT at baseline; 1 had hepatitis C and 1 had an unconfirmed history of hepatitis. Adherence to clinic visits and prescribed treatment was poor. CONCLUSIONS: Rifampin hepatotoxicity associated with treatment of latent tuberculosis infection is rare. Our report suggests that hepatotoxicity is more likely in patients with baseline hepatic dysfunction and the need for increased vigilance in monitoring transaminases in these patients.

Precarious sleep? Nonstandard work, gender, and sleep disturbance in 31 European countries.

Despite the advent of precarious work, little is known about how this form of employment can generate disparities in sleep outcomes. We extend existing work by providing a theoretical framework linking different measures of work precarity to sleep problems. We argue that the association between objective precarious working conditions and sleep disturbance is channeled through and mediated by subjective work precarity. We further argue that gender moderates the relationship between objective and subjective work precarity. We test this theoretical framework using the 2010 European Working Conditions Survey. Our results indicate that objective precarious working conditions undermine sleep by promoting the subjective experience of insecurity. Furthermore, the indirect effect of objective precarious work on sleep disturbance through subjective employment insecurity varies by gender: compared to women in similar working conditions, men report higher levels of subjective precarity. This research makes important contributions to the literatures on the health consequences of nonstandard work and social determinants of well-being.