Long-distance swimming by African lions in Uganda.

Earth's most imperiled and iconic wildlife are facing tough decisions under increasing human pressure and limited resources. Swimming across rivers and water bodies filled with high densities of predators may be one such example. In African lions Panthera leo, previous water crossings (recorded in the peer-reviewed and gray literature, on film, and found using Google Search, and YouTube) have recorded distances ranging from <10 to 100 m, with some resulting in mortality by Nile Crocodiles Crocodylis niloticus. However, we observed a coalition of male lions swimming >1 km across Uganda's Kazinga channel located in the Queen Elizabeth National Park six times, and recorded this behavior on film on February 1st 2024. We speculate that three factors could be driving these lions to take long-distance swims with a high density of crocodiles and hippos Hippopotamus amphibius, namely (1) the lack of lionesses in this ecosystem, (2) intraspecific fights over territory with other male coalitions, and (3) the only other land connection giving lions access to the peninsula is a small road bridge with a strong human presence.

Phylogenomic analyses and comparative genomics of Pseudomonas syringae associated with almond (Prunus dulcis) in California.

We sequenced and comprehensively analysed the genomic architecture of 98 fluorescent pseudomonads isolated from different symptomatic and asymptomatic tissues of almond and a few other Prunus spp. Phylogenomic analyses, genome mining, field pathogenicity tests, and in vitro ice nucleation and antibiotic sensitivity tests were integrated to improve knowledge of the biology and management of bacterial blast and bacterial canker of almond. We identified Pseudomonas syringae pv. syringae, P. cerasi, and P. viridiflava as almond canker pathogens. P. syringae pv. syringae caused both canker and foliar (blast) symptoms. In contrast, P. cerasi and P. viridiflava only caused cankers, and P. viridiflava appeared to be a weak pathogen of almond. Isolates belonging to P. syringae pv. syringae were the most frequently isolated among the pathogenic species/pathovars, composing 75% of all pathogenic isolates. P. cerasi and P. viridiflava isolates composed 8.3 and 16.7% of the pathogenic isolates, respectively. Laboratory leaf infiltration bioassays produced results distinct from experiments in the field with both P. cerasi and P. syringae pv. syringae, causing significant necrosis and browning of detached leaves, whereas P. viridiflava conferred moderate effects. Genome mining revealed the absence of key epiphytic fitness-related genes in P. cerasi and P. viridiflava genomic sequences, which could explain the contrasting field and laboratory bioassay results. P. syringae pv. syringae and P. cerasi isolates harboured the ice nucleation protein, which correlated with the ice nucleation phenotype. Results of sensitivity tests to copper and kasugamycin showed a strong linkage to putative resistance genes. Isolates harbouring the ctpV gene showed resistance to copper up to 600 µg/ml. In contrast, isolates without the ctpV gene could not grow on nutrient agar amended with 200 µg/ml copper, suggesting ctpV can be used to phenotype copper resistance. All isolates were sensitive to kasugamycin at the label-recommended rate of 100µg/ml.

Codesign of remote data collection for chronic management of pediatric home mechanical ventilation.

INTRODUCTION: Outpatient monitoring of children using invasive home mechanical ventilation (IHMV) is recommended, but access to care can be difficult. This study tested if remote (home-based) data collection was feasible and acceptable in chronic IHMV management. METHODS: A codesign study was conducted with an IHMV program, home nurses, and English- and Spanish-speaking parent-guardians of children using IHMV (0-17 years; n = 19). After prototyping, parents used a remote patient monitoring (RPM) bundle to collect patient heart rate, respiratory rate (RR), oxygen saturation, end-tidal carbon dioxide (EtCO2 ), and ventilator pressure/volume over 8 weeks. User feedback was analyzed using qualitative methods and the System Usability Scale (SUS). Expected marginal mean differences within patient measures when awake, asleep, or after a break were calculated using mixed effects models. RESULTS: Patients were a median 2.9 years old and 11 (58%) took breaks off the ventilator. RPM data were entered on a mean of 83.7% (SD ± 29.1%) weeks. SUS scores were 84.8 (SD ± 10.5) for nurses and 91.8 (SD ± 10.1) for parents. Over 90% of parents agreed/strongly agreed that RPM data collection was feasible and relevant to their child's care. Within-patient comparisons revealed that EtCO2 (break-vs-asleep 2.55 mmHg, d = 0.79 [0.42-1.15], p < .001; awake-vs-break 1.48, d = -0.49 [0.13-0.84], p = .02) and RR (break-vs-asleep 16.14, d = 2.12 [1.71-2.53], p < .001; awake-vs-break 3.44, d = 0.45 [0.10-0.04], p = .03) were significantly higher during ventilator breaks. CONCLUSIONS: RPM data collection in children with IHMV was feasible, acceptable, and captured clinically meaningful vital sign changes during ventilator breaks, supporting the clinical utility of RPM in IHMV management.

Predictors for invasive home mechanical ventilation duration in bronchopulmonary dysplasia.

BACKGROUND: Children with bronchopulmonary dysplasia (BPD) who require invasive home mechanical ventilation (IHMV) are medically vulnerable and experience high caregiving and healthcare costs. Predictors for duration of IHMV in children with BPD remain unclear, which can make prognostication and decision-making challenging. METHODS: A retrospective cohort study of children with BPD requiring IHMV was conducted from independent children's hospital records (2005-2021). The primary outcome was IHMV duration, defined as time from initial discharge home on IHMV until cessation of positive pressure ventilation (day and night). Two new variables were included: discharge age corrected for tracheostomy (DACT) (chronological age at discharge minus age at tracheostomy) and level of ventilator support at discharge (minute ventilation per kg per day). Univariable Cox regression was performed with variables of interest compared to IHMV duration. Significant nonlinear factors (p < 0.05) were included in the multivariable analysis. RESULTS: One-hundred-and-nineteen patients used IHMV primarily for BPD. Patient median index hospitalization lasted 12 months (interquartile range [IQR] 8.0,14.4). Once home, half of the patients were weaned off IHMV by 36.0 months and 90% by 52.2 months. Being Hispanic/Latinx ethnicity (hazard ratio [HR] 0.14 (95% confidence interval [CI] 0.04, 0.53), p < 0.01) and having a higher DACT were associated with increased IHMV duration (HR 0.66 (CI 0.43, 0.98), p < 0.05). CONCLUSIONS: Disparity in IHMV duration exists among patients using IHMV after prematurity. Prospective multisite studies that further investigate new analytic variables, such as DACT and level of ventilator support, and address standardization of IHMV care are needed to create more equitable IHMV management strategies.

Timing of Violence Exposure and Girls' Temperament Stability From Childhood to Adolescence.

Individual differences in temperament (e.g., negative emotionality) are robust early predictors of emotional and behavioral health. Although temperament is often conceptualized as relatively stable across the lifespan, evidence suggests that it may change over time as a function of social context. Extant studies have been limited by cross-sectional or short-term longitudinal designs that have precluded tests of stability as well as factors that may influence stability across developmental periods. In addition, few studies have tested the impact of social contexts that are common for children living in urban and under-resourced environments, such as exposure to community violence. In the present study we hypothesized that levels of negative emotionality, activity, and shyness would decrease across development from childhood to mid-adolescence as a function of early exposure to violence in the Pittsburgh Girls Study, a community study of girls enriched for families living in low-resourced neighborhoods. Temperament was assessed by parent- and teacher-report on the Emotionality Activity Sociability Shyness Temperament Survey in childhood (5-8-years-old), early-adolescence (11-years-old), and mid-adolescence (15-years-old). Violence exposure (e.g., victim of or witness to violent crime, exposure to domestic violence) was assessed annually via child and parent report. Results showed that on average, combined caregiver and teacher reports of negative emotionality and activity level exhibited small but significant reductions from childhood to adolescence, whereas shyness remained stable. Violence exposure in early adolescence predicted increases in negative emotionality and shyness by mid-adolescence. Violence exposure was not associated with stability of activity level. Our findings suggest that exposure to violence, particularly in early adolescence, amplifies individual differences in shyness and negative emotionality, underlying an important pathway of risk for developmental psychopathology.

Natural Recombination among Type I Restriction-Modification Systems Creates Diverse Genomic Methylation Patterns among Xylella fastidiosa Strains.

Xylella fastidiosa is an important bacterial plant pathogen causing high-consequence diseases in agricultural crops around the world. Although as a species X. fastidiosa can infect many host plants, there is significant variability between strains regarding virulence on specific host plant species and other traits. Natural competence and horizontal gene transfer are believed to occur frequently in X. fastidiosa and likely influence the evolution of this pathogen. However, some X. fastidiosa strains are difficult to manipulate genetically using standard transformation techniques. Several type I restriction-modification (R-M) systems are encoded in the X. fastidiosa genome, which may influence horizontal gene transfer and recombination. Type I R-M systems themselves may undergo recombination, exchanging target recognition domains (TRDs) between specificity subunits (hsdS) to generate novel alleles with new target specificities. In this study, several conserved type I R-M systems were compared across 129 X. fastidiosa genome assemblies representing all known subspecies and 32 sequence types. Forty-four unique TRDs were identified among 50 hsdS alleles, which are arrayed in 31 allele profiles that are generally conserved within a monophyletic cluster of strains. Inactivating mutations were identified in type I R-M systems of specific strains, showing heterogeneity in the complements of functional type I R-M systems across X. fastidiosa. Genomic DNA methylation patterns were characterized in 20 X. fastidiosa strains and associated with type I R-M system allele profiles. Overall, these data suggest hsdS genes recombine among Xylella strains and/or unknown donors, and the resulting TRD reassortment establishes differential epigenetic modifications across Xylella lineages. IMPORTANCE Economic impacts on agricultural production due to X. fastidiosa have been severe in the Americas, Europe, and parts of Asia. Despite a long history of research on this pathogen, certain fundamental questions regarding the biology, pathogenicity, and evolution of X. fastidiosa have still not been answered. Wide-scale whole-genome sequencing has begun to provide more insight into X. fastidiosa genetic diversity and horizontal gene transfer, but the mechanics of genomic recombination in natural settings and the extent to which this directly influences bacterial phenotypes such as plant host range are not well understood. Genome methylation is an important factor in horizontal gene transfer and bacterial recombination that has not been comprehensively studied in X. fastidiosa. This study characterizes methylation associated with type I restriction-modification systems across a wide range of X. fastidiosa strains and lays the groundwork for a better understanding of X. fastidiosa biology and evolution through epigenetics.

Trends in delivery hospitalizations with pregestational and gestational diabetes mellitus and associated outcomes: 2000-2019.

BACKGROUND: Pregestational diabetes mellitus and its associated risks may be increasing in the obstetrical population. OBJECTIVE: This study aimed to characterize the trends in delivery hospitalizations with pregestational diabetes mellitus, the prevalence of chronic diabetes complications, and the risk for adverse outcomes. STUDY DESIGN: This repeated, cross-sectional study used the United States National Inpatient Sample to identify delivery hospitalizations with pregestational diabetes mellitus between 2000 and 2019. Trends in delivery hospitalizations with pregestational diabetes mellitus were assessed using joinpoint regression to determine the average annual percent change. Trends in chronic diabetes complications, including chronic kidney disease, neuropathy, peripheral vascular disease, and diabetic retinopathy, were also analyzed. The risk for adverse obstetrical outcomes was compared between patients with and those without pregestational diabetes mellitus using adjusted logistic regression models that were adjusted for demographic, clinical, and hospital characteristics with adjusted odds ratios with 95% confidence intervals as measures of association. RESULTS: Of 76.7 million delivery hospitalizations, 179,885 (0.23%) had type 1 diabetes mellitus, 430,544 (0.56%) had type 2 diabetes mellitus, and 99,327 (0.13%) had unspecified diabetes mellitus. From 2000 to 2019, the prevalence of diabetes mellitus increased from 1.8 to 7.3 per 1000 deliveries for type 2 diabetes mellitus (average annual percent change, 8.0%; 95% confidence interval, 6.9%-9.2%), from 1.5 to 3.2 per 1000 deliveries for unspecified diabetes mellitus (average annual percent change, 3.9%; 95% confidence interval, 1.4%-6.3%), and from 2.7 in 2000 to 2.8 per 1000 deliveries (average annual percent change, 0.2%; 95% confidence interval, -0.8% to 1.3%) for type 1 diabetes mellitus. The prevalence of chronic diabetes mellitus complications increased from 2.7% to 5.6% over the study period (average annual percent change, 5.9%; 95% confidence interval, 3.7%-8.0%). Pregestational diabetes mellitus was associated with severe maternal morbidity, cesarean delivery, hypertensive disorders of pregnancy, preterm birth, and shoulder dystocia. CONCLUSION: Pregestational diabetes mellitus increased over the study period, driven by a quadrupling in the prevalence of type 2 diabetes mellitus. Notably, the prevalence of chronic diabetes mellitus complications doubled concomitantly. Pregestational diabetes mellitus was associated with a range of adverse outcomes. These findings are further evidence that pregestational diabetes mellitus is an important contributor to maternal risk and that optimizing diabetes care in women of childbearing age will continue to be of major public health importance.

At-home end-tidal carbon dioxide measurement in children with invasive home mechanical ventilation.

BACKGROUND: Carbon dioxide concentration trending is used in chronic management of children with invasive home mechanical ventilation (HMV) in clinical settings, but options for end-tidal carbon dioxide (EtCO2 ) monitoring at home are limited. We hypothesized that a palm-sized, portable endotracheal capnograph (PEC) that measures EtCO2 could be adapted for in-home use in children with HMV. METHODS: We evaluated the internal consistency of the PEC by calculating an intraclass correlation coefficient of three back-to-back breaths by children (0-17 years) at baseline health in the clinic. Pearson's correlation was calculated for PEC EtCO2 values with concurrent mean values of in-clinic EtCO2 and transcutaneous CO2 (TCM) capnometers. The Bland-Altman test determined their level of agreement. Qualitative interviews and surveys assessed usability and acceptability by family-caregivers at home. RESULTS: CO2 values were collected in awake children in varied activity levels and positions (N = 30). The intraclass correlation coefficient for the PEC was 0.95 (p < 0.05). The correlation between the PEC and in-clinic EtCO2 device was 0.85 with a mean difference of -3.8 mmHg and precision of ±1.1 mmHg. The correlation between the PEC and the clinic TCM device was 0.92 with a mean difference of 0.2 mmHg and precision of ±1.0. Family-caregivers (N = 10) trialed the PEC at home; all were able to obtain measurements at home while children were awake and sometimes asleep. CONCLUSIONS: A portable, noninvasive device for measuring EtCO2 was feasible and acceptable, with values that trend similarly to currently in-practice, outpatient models. These devices may facilitate monitoring of EtCO2 at home in children with invasive HMV.

Insights Regarding Resistance of 'Nemaguard' Rootstock to the Bacterium Xylella fastidiosa.

'Nemaguard' is a commonly used rootstock for almond and stone fruits due to resistance to nematodes and enhanced scion vigor. Nemaguard also happens to be resistant to strains of Xylella fastidiosa that cause almond leaf scorch disease. Previous research showed that prior to June-budding, this rootstock can prevent infection of almond nursery stock by X. fastidiosa. Further, the rootstock also promotes recovery from infection in susceptible almond scions. Objectives of this study were to 1) compare movement and bacterial populations of X. fastidiosa in almond and Nemaguard, 2) determine whether the metabolic profile of infected versus noninfected plants of each species correspond with differences in pathogen distribution, and 3) evaluate the impact of feeding on Nemaguard on transmission efficiency and pathogen populations in insects. Results showed limited or no movement of X. fastidiosa beyond the point of mechanical inoculation in Nemaguard, whereas X. fastidiosa was detected in susceptible almond and isolated from plant samples distal to the point of inoculation. Large differences in the concentration of phenolic compounds between Nemaguard and almond were also found, although this was not impacted by infection status. After acquiring X. fastidiosa from infected plants, vector access periods of up to 14 days on Nemaguard neither reduced pathogen populations in vectors nor reduced transmission efficiency of X. fastidiosa to susceptible plants when compared with similar vector-access periods on susceptible grapevines. Results suggest Nemaguard, in spite of having high phenolic concentrations in its xylem, does not directly impact X. fastidiosa survival and that future research should focus on identification of potential physical traits that prevent bacterial attachment, multiplication, or movement within the plant.

Short Communication:Outcomes of Dual Versus Triple Antiretroviral Drug Regimens Among Virally Suppressed Adults in the DC Cohort.

This study explored virological outcomes of two-drug (2DRs) and three-drug (3DRs) antiretroviral regimens in adults with HIV in the DC Cohort. We analyzed 310 treatment-experienced adults with sustained HIV RNA ≤50 copies/mL at baseline, 53 of whom switched to 2DRs and 257 continued 3DRs. Adults on 2DRs and 3DRs had similar demographics (median age 53.3 years, 76.8% cisgender male, 76.1% Black). Adults on 2DRs had more participants with ≥2 comorbidities (62.3% vs. 42.8%, p = .019), had a longer time since HIV diagnosis (median years 20.4 vs. 13.2, p = .017), and received the regimen of interest for a shorter duration (median years 1.3 vs. 3.3, p < .001) compared with adults on 3DRs. Adults receiving 2DRs had a higher, although nonsignificant, risk for virological failure (two consecutive HIV RNA ≥50 copies/mL) at 24 months follow-up than adults on 3DRs (6.7% vs. 1.7%, respectively; p = .10). Future analysis of the effectiveness of 2DRs is needed.

Access to direct-acting antivirals for hepatitis C-negative transplant recipients receiving organs from hepatitis C-viremic donors.

PURPOSE: A barrier to using organs from hepatitis C virus (HCV)-viremic donors is the high cost of direct-acting antivirals (DAAs) and concerns about access for recipients after transplantation. The purpose of this study was to evaluate access, cost, and timing for HCV DAAs following transplantation. METHODS: This was a single-center, retrospective study of HCV-negative adult transplant recipients from June 2017 to December 2019 who received grafts from HCV-viremic and/or HCV-seropositive individuals and became HCV viremic after transplantation. RESULTS: Between June 2017 and December 2019, there were 60 HCV-negative transplant recipients who became viremic after receiving grafts from HCV-viremic or HCV-seropositive donors. Thirty-eight patients met the inclusion criteria (n = 25 with liver transplants, n = 6 with lung transplants, n = 4 with simultaneous liver and kidney transplants, and n = 3 with kidney transplants). Of these patients, 23 had commercial insurance, 13 had Medicare, and 2 had Medicaid. All patients ultimately received insurance coverage for treatment; however, 36 (95%) required prior authorization and 9 (24%) required appeals to obtain insurance coverage. The median time from DAA prescription to insurance approval was 6 days. The median time from transplantation to start of treatment was 29 days (range, 0-84 days). Patients with Medicaid insurance had a significantly longer time to insurance approval (31.5 vs 6 days, P = 0.007). The average out-of-pocket cost to patients was less than $10 a month after patient assistance. All patients who completed treatment and 12-week follow-up after treatment achieved a sustained virologic response (n = 36). CONCLUSION: In this study, all HCV-negative recipients who developed HCV following transplantation had access to DAA therapy, with the majority starting treatment in the first month after transplantation.

What MFTs should know about nutrition, psychosocial health, and collaborative care with nutrition professionals.

Despite sufficient evidence on the role of nutrition in psychosocial health, Marriage and Family Therapists lack the knowledge for sufficient assessment and referrals in treatment. The purpose of this article is to orient MFTs to human metabolism and the effects of various nutrients, or lack thereof, on the psychosocial health in their clients. The roles of several micronutrients and macronutrients will be described as well as the effects of eating patterns and overall metabolic health on mental health. Finally, implications for MFTs as sole practitioners, domains for assessment and psychoeducation, and recommendations for collaborating with nutrition professionals will be discussed.

Microbe Profile: Xylella fastidiosa - a devastating agricultural pathogen with an endophytic lifestyle.

Xylella fastidiosa is a vector-borne plant vascular pathogen that has caused devastating disease outbreaks in diverse agricultural crops worldwide. A major global quarantine pathogen, X. fastidiosa can infect hundreds of plant species and can be transmitted by many different xylem sap-feeding insects. Several decades of research have revealed a complex lifestyle dependent on adaptation to the xylem and insect environments and interactions with host plant tissues.

Feasibility of a Digital Intervention to Promote Healthy Weight Management among Postpartum African American/Black Women.

The study aim was to implement and evaluate the feasibility of a culturally informed ("BeFAB") app for African American/Black women to address postpartum weight. Women (n = 136; mean age = 27.8 ± 5.4; mean BMI = 32.5 ± 4.3) were recruited from postpartum units, and randomly assigned to receive BeFAB (n = 65) or usual care (n = 71) for 12 weeks. App content included didactic lessons delivered via a virtual coach, app-based messages, goal setting and tracking, and edutainment videos. Feasibility outcomes included recruitment, retention and engagement, and self-reported acceptability. Behavioral (i.e., diet, physical activity), psychosocial (i.e., stress, coping, support, self-efficacy) and weight outcomes were also examined. Recruitment goals were met, but attrition was high, with 56% retention at 12 weeks. Approximately half of participants accessed the app and set a goal ≥one time, but <10% reported achieving a nutrition or activity goal. Among study completers, ≥60% found the app content at least somewhat helpful. Within-group changes for BeFAB among completers were found for increased moderate-to-vigorous physical activity and decreased fruit/vegetable intake and weight. Findings indicate initial feasibility of recruiting postpartum women to participate in a digital healthy body weight program but limited use, reflecting low acceptability and challenges in engagement and retention. Future research is needed on strategies to engage and retain participants in postpartum interventions.

Accumulation of Good Intentions: How Individual Practice Guidelines Lead to Polypharmacy in the Treatment of Patients with Polytrauma.

Polytrauma clinical triad (PCT) is the comorbid occurrence of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and pain after trauma. No clinical practice guidelines for postacute care of patients with PCT currently exist; instead, clinical practice guidelines have been published for the three conditions (TBI, PTSD, and pain) as distinct clinical entities. Using multiple, individual practice guidelines for a patient with PCT may lead to unintended prescription of multiple and potentially adversely interacting medications (ie, polypharmacy). Polypharmacy, especially that which includes central nervous system-acting medications, may lead to overdose, suicidality, and chronic symptomatology. Current individual guidelines for each condition of PCT do not address how to coordinate care for the polytraumatic diagnosis. The purpose of this Practice Management piece is to describe the unintended consequences of polypharmacy in patients with PCT and to discuss mitigation approaches including rational prescribing, nonpharmacologic alternatives, and interdisciplinary coordination.

Diversity in Academic Otolaryngology: An Update and Recommendations for Moving From Words to Action.

OBJECTIVES: (1) To investigate the state of diversity and inclusion initiatives in otolaryngology-head and neck surgery (OHNS) as compared to general surgery and (2) assess their effects on female representation in these programs. METHODS: The websites of OHNS residency programs, general surgery residency programs, and their associated academic medical institutions were indexed for content related to diversity and inclusion (D&I) initiatives. Gender data were gathered and used as a proxy for identity diversity. RESULTS: All programs surveyed (N = 198) have D&I programs at the institutional level and have an office of D&I (or equivalent program). However, only 18% of general surgery programs and 19% of otolaryngology programs have additional department-level D&I initiatives. There was an increase in the proportion of female residents across all residency programs if the program mentioned D&I on their website (44% vs 38%, P = .004) and if the program reported a D&I initiative (45% vs 38%, P < .001). CONCLUSION: Despite the ACGME's recent emphasis on the importance of recruiting and retaining a diverse physician workforce, the minority of otolaryngology residency programs advertise any concerted, department-level efforts toward increasing D&I at their residency program. General surgery programs have a significantly higher proportion of female department chairs and higher mean proportion of female residents when compared to OHNS. Programs that mention the diversity of their residents or faculty on the program website and programs with their own D&I initiatives have a higher mean proportion of female residents.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Grapevine phenolic compounds influence cell surface adhesion of Xylella fastidiosa and bind to lipopolysaccharide.

Bacterial phytopathogen Xylella fastidiosa specifically colonizes the plant vascular tissue through a complex process of cell adhesion, biofilm formation, and dispersive movement. Adaptation to the chemical environment of the xylem is essential for bacterial growth and progression of infection. Grapevine xylem sap contains a range of plant secondary metabolites such as phenolics, which fluctuate in response to pathogen infection and plant physiological state. Phenolic compounds are often involved in host-pathogen interactions and influence infection dynamics through signaling activity, antimicrobial properties, and alteration of bacterial phenotypes. The effect of biologically relevant concentrations of phenolic compounds coumaric acid, gallic acid, epicatechin, and resveratrol on growth of X. fastidiosa was assessed in vitro. None of these compounds inhibited bacterial growth, but epicatechin and gallic acid reduced cell-surface adhesion. Cell-cell aggregation decreased with resveratrol treatment, but the other phenolic compounds tested had minimal effect on aggregation. Expression of attachment (xadA) and aggregation (fimA) related genes were altered by presence of the phenolic compounds, consistent with observed phenotypes. All four of the phenolic compounds bound to purified X. fastidiosa lipopolysaccharide (LPS), a major cell-surface component. Information regarding the impact of chemical environment on pathogen colonization in plants is important for understanding the infection process and factors associated with host susceptibility.