Novel indices reveal that pollinator exposure to pesticides varies across biological compartments and crop surroundings.

Declines in insect pollinators have been linked to a range of causative factors such as disease, loss of habitats, the quality and availability of food, and exposure to pesticides. Here, we analysed an extensive dataset generated from pesticide screening of foraging insects, pollen-nectar stores/beebread, pollen and ingested nectar across three species of bees collected at 128 European sites set in two types of crop. In this paper, we aimed to (i) derive a new index to summarise key aspects of complex pesticide exposure data and (ii) understand the links between pesticide exposures depicted by the different matrices, bee species and apple orchards versus oilseed rape crops. We found that summary indices were highly correlated with the number of pesticides detected in the related matrix but not with which pesticides were present. Matrices collected from apple orchards generally contained a higher number of pesticides (7.6 pesticides per site) than matrices from sites collected from oilseed rape crops (3.5 pesticides), with fungicides being highly represented in apple crops. A greater number of pesticides were found in pollen-nectar stores/beebread and pollen matrices compared with nectar and bee body matrices. Our results show that for a complete assessment of pollinator pesticide exposure, it is necessary to consider several different exposure routes and multiple species of bees across different agricultural systems.

Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Conservative Kidney Management: When, Why, and For Whom?

Deciding between dialysis and conservative kidney management (CKM) in an elderly or seriously ill person with kidney failure is complex and requires shared decision making. Patients and families look to their nephrologist to provide an individualized recommendation that aligns with patient-centered goals. For a balanced and considered decision to be made, dialysis should not be the default and nephrologists need to be familiar with relevant prognostic information including survival, symptom burden, functional trajectory, and quality of life with dialysis and with CKM. CKM is a holistic, proactive, and multidisciplinary treatment for kidney failure. For some elderly comorbid patients, CKM improves symptom burden and aligns with quality-of-life goals, with modest or no loss of longevity. CKM can be provided by a nephrologist alone but ideally is managed through partnership with a dedicated supportive or palliative care service embedded within the nephrology practice. Treatment decisions are best discussed early in the disease trajectory and occur over many consultations, and nephrologists should be upskilled in communication to better support patients and families in these important conversations. Nephrologists should remain actively involved in their patients' care through to end-of-life care.

Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels.

BACKGROUND: Nonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction. AIM: We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate. METHODS: Six infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS). RESULTS: Average plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable. CONCLUSION: KD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine.

Multi-Omic Analyses Reveal Bifidogenic Effect and Metabolomic Shifts in Healthy Human Cohort Supplemented With a Prebiotic Dietary Fiber Blend.

Dietary fiber, a nutrient derived mainly from whole grains, vegetables, fruits, and legumes, is known to confer a number of health benefits, yet most Americans consume less than half of the daily recommended amount. Convenience and affordability are key factors determining the ability of individuals to incorporate fiber-rich foods into their diet, and many Americans struggle to access, afford, and prepare foods rich in fiber. The objective of this clinical study was to test the changes in microbial community composition, human metabolomics, and general health markers of a convenient, easy to use prebiotic supplement in generally healthy young participants consuming a diet low in fiber. Twenty healthy adults participated in this randomized, placebo-controlled, double-blind, crossover study which was registered at clinicaltrials.gov as NCT03785860. During the study participants consumed 12 g of a prebiotic fiber supplement and 12 g of placebo daily as a powder mixed with water as part of their habitual diet in randomized order for 4 weeks, with a 4-week washout between treatment arms. Fecal microbial DNA was extracted and sequenced by shallow shotgun sequencing on an Illumina NovaSeq. Plasma metabolites were detected using liquid chromatography-mass spectrometry with untargeted analysis. The phylum Actinobacteria, genus Bifidobacterium, and several Bifidobacterium species (B. bifidum, B. adolescentis, B. breve, B. catenulatum, and B. longum) significantly increased after prebiotic supplementation when compared to the placebo. The abundance of genes associated with the utilization of the prebiotic fiber ingredients (sacA, xfp, xpk) and the production of acetate (poxB, ackA) significantly changed with prebiotic supplementation. Additionally, the abundance of genes associated with the prebiotic utilization (xfp, xpk), acetate production (ackA), and choline to betaine oxidation (gbsB) were significantly correlated with changes in the abundance of the genus Bifidobacterium in the prebiotic group. Plasma concentrations of the bacterially produced metabolite indolepropionate significantly increased. The results of this study demonstrate that an easy to consume, low dose (12 g) of a prebiotic powder taken daily increases the abundance of beneficial bifidobacteria and the production of health-promoting bacteria-derived metabolites in healthy individuals with a habitual low-fiber diet. Clinical Trial Registration: www.clinicaltrials.gov/, identifier: NCT03785860.

Agri-environment scheme nectar chemistry can suppress the social epidemiology of parasites in an important pollinator.

Emergent infectious diseases are one of the main drivers of species loss. Emergent infection with the microsporidian Nosema bombi has been implicated in the population and range declines of a suite of North American bumblebees, a group of important pollinators. Previous work has shown that phytochemicals found in pollen and nectar can negatively impact parasites in individuals, but how this relates to social epidemiology and by extension whether plants can be effectively used as pollinator disease management strategies remains unexplored. Here, we undertook a comprehensive screen of UK agri-environment scheme (AES) plants, a programme designed to benefit pollinators and wider biodiversity in agricultural settings, for phytochemicals in pollen and nectar using liquid chromatography and mass spectrometry. Caffeine, which occurs across a range of plant families, was identified in the nectar of sainfoin (Onobrychis viciifolia), a component of UK AES and a major global crop. We showed that caffeine significantly reduces N. bombi infection intensity, both prophylactically and therapeutically, in individual bumblebees (Bombus terrestris), and, for the first time, that such effects impact social epidemiology, with colonies reared from wild-caught queens having both lower prevalence and intensity of infection. Furthermore, infection prevalence was lower in foraging bumblebees from caffeine-treated colonies, suggesting a likely reduction in population-level transmission. Combined, these results show that N. bombi is less likely to be transmitted intracolonially when bumblebees consume naturally available caffeine, and that this may in turn reduce environmental prevalence. Consequently, our results demonstrate that floral phytochemicals at ecologically relevant concentrations can impact pollinator disease epidemiology and that planting strategies that increase floral abundance to support biodiversity could be co-opted as disease management tools.

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder.

BACKGROUND: Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD. METHODS: Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo-continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel-wise CBF comparisons were set at threshold of p < 0.05 cluster-corrected for multiple comparisons, voxel-level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions. RESULTS: Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate-induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions. CONCLUSIONS: This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

Flagellum Removal by a Nectar Metabolite Inhibits Infectivity of a Bumblebee Parasite.

Plant phytochemicals can act as natural "medicines" for animals against parasites [1-3]. Some nectar metabolites, for example, reduce parasite infections in bees [4-7]. Declining plant diversity through anthropogenic landscape change [8-11] could reduce the availability of medicinal nectar plants for pollinators, exacerbating their decline [12]. Existing studies are, however, limited by (1) a lack of mechanistic insights into how phytochemicals affect pollinator diseases and (2) the restriction to few, commercially available chemicals, thereby potentially neglecting plants with the biggest antiparasitic effects. To rapidly identify plants with the greatest potential as natural bee medicines, we developed a bioactivity-directed fractionation assay for nectar metabolites. We evaluated 17 important nectar plants against the bumblebee pathogen Crithidia bombi (Trypanosomatidae) [13-17]. The most bioactive species was heather (Calluna vulgaris), the second most productive UK nectar plant [10]. We identified 4-(3-oxobut-1-enylidene)-3,5,5-trimethylcyclohex-2-en-1-one (callunene) from heather nectar as a potent inhibitor of C. bombi. Wild bumblebees (Bombus terrestris) foraging on heather ingest callunene at concentrations causing complete C. bombi inhibition. Feeding on callunene was prophylactic against infections. We show that C. bombi establishes infections by flagellar anchoring to the ileum epithelium. Short-term callunene exposure induced flagellum loss in C. bombi choanomastigotes, resulting in a loss of infectivity. We conclude that plant secondary metabolites can disrupt parasite flagellum attachment, revealing a mechanism behind their prophylactic effects. The decline of heathlands [18-21] reduces the availability of natural bee "medicine" and could exacerbate the contribution of diseases to pollinator declines. VIDEO ABSTRACT.

Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study.

BACKGROUND: Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals. METHODS: Twenty-four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm3 ), voxel-level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7). RESULTS: Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p < 0.001). CONCLUSIONS: Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.

Retrospective chart review to assess domains of quality of death (recognition of dying, appropriate limitations, symptom monitoring, anticipatory prescribing) of patients dying in the acute hospital under the care of a nephrology service with renal supportive care support over time.

AIM: To explore the quality of deaths in an acute hospital under a nephrology service at two teaching hospitals in Sydney with renal supportive care services over time. METHODS: Retrospective chart review of all deaths in the years 2004, 2009 and 2014 at St George Hospital (SGH) and in 2014 at the Concord Repatriation General Hospital. Domains assessed were recognition of dying, invasive interventions, symptom assessment, anticipatory prescribing, documentation of spiritual needs and bereavement information for families. End-of-life care plan (EOLCP) use was also evaluated at SGH. RESULTS: Over 90% of patients were recognized to be dying in all 3 years at SGH. Rates of interventions in the last week of life were low and did not differ across the 3 years. There was a significant increase in the prescription of anti-psychotic, anti-emetic and anti-cholinergic medication over the years at SGH. Use of EOLCP was significantly higher at SGH, and their use improved several quality domains. Of all deaths, 68% were referred to palliative care at SGH and 33% at Concord Repatriation General Hospital (not significant). Cessation of observations and non-essential medications and documentation of bereavement information given to families was low across both sites in all years, although this significantly improved when EOLCP were used. CONCLUSION: While acute teams are good at recognizing dying, they need support to care for dying patients. The use of EOLCP in acute services can facilitate improvements in caring for the dying. Renal supportive care services need time to become embedded in the culture of the acute hospital.

Older people with hip fracture transferred to intermediate care: outcomes in an integrated health and social care model.

Following surgery for hip fracture almost a quarter of patients do not return directly to their usual residence, using the resources within intermediate care and enablement. This was a retrospective cohort study involving 156 Salford residents admitted with hip fracture in 2015. Linked health data were collected on those discharged to intermediate care vs home in terms of readmissions, mortality, lengths of stay, delayed transfers of care, diagnoses of delirium and pre-existing forms of dementia. The median duration of the continuous care episode in the intermediate care cohort, inclusive of readmissions to hospital, was 52 days. There was a 26% (n=20) readmission rate from intermediate care. Readmission rates at 120 days were higher among those discharged to intermediate care vs home (OR 3.21, 95% CI 1.37-7.54, p=0.007) and among those with a form of dementia (OR 4.76, 95% CI 1.79-12.63, p=0.0017). Patients with delirium during their acute admission were more likely to be discharged to intermediate care (OR 5.43, 95% CI 2.36-12.47, p=0.0001) and were less likely to ultimately be discharged home (OR 6.40, 95% CI 2.25-18.21, p=0.0005), as were those with some form of dementia (OR 6.60, 95% CI 1.97-22.08, p=0.002). Measurement of the entire care episode demonstrates significant lengths of stay. Medium term readmission rates are higher in those discharged to intermediate care. Delirium and dementia are associated with higher readmission rates and lower rates of discharge to own home. It is imperative that a whole pathway approach to commissioning hip fracture services is established.

Effect of ICD Therapies on Mortality in the OMNI Trial.

BACKGROUND: Analyses from primary prevention trials on implantable cardioverter defibrillator (ICD) therapy have shown an association between shocks and increased mortality. Recent data suggest a similar association with antitachycardia pacing (ATP). OBJECTIVE: The OMNI study is an observational study of pacemaker and ICD use. We aim to examine associations between ICD therapies and mortality in this setting. METHODS: A total of 2,255 OMNI patients with ICDs were included. Treated episodes were classified as appropriate or inappropriate. Patients were assigned into 1 of 3 groups depending on whether the episode required ATP only, single shock, or multiple shocks, and then followed for all-cause mortality. Additionally, we aimed to determine the frequency with which inappropriate ATP precipitated ventricular arrhythmias that led to shock, since this has been suggested as a mechanism of harm. RESULTS: Over a mean follow-up of 39 ± 19 months, there were a total of 470 deaths (21%). Compared to patients with no treated episodes, patients with appropriate therapy had greater risk of death. Hazard ratios were 1.46 (95% confidence interval [CI] 1.05-2.02; P = 0.023) for the ATP-only group, 2.11 (95% CI 1.51-2.96; P < 0.001) for the single-shock group, and 2.55 (95% CI 1.43-4.57; P = 0.002) for the multishock group. There was no significant association between any type of inappropriate therapy and increased mortality. We identified only 7 instances of inappropriate ATP precipitating ventricular arrhythmia resulting in shock. CONCLUSIONS: Patients receiving appropriate therapy of all types had increased mortality compared to those with no episodes. Furthermore, inappropriate ATP rarely precipitates ventricular arrhythmias.

Simulation of biological therapies for degenerated intervertebral discs.

The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs.

Effects of natural organic matter on calcium and phosphorus co-precipitation.

Phosphorus (P), calcium (Ca) and natural organic matter (NOM) naturally occur in all aquatic ecosystems. However, excessive P loads can cause eutrophic or hyper-eutrophic conditions in these waters. As a result, P regulation is important for these impaired aquatic systems, and Ca-P co-precipitation is a vital mechanism of natural P removal in many alkaline systems, such as the Florida Everglades. The interaction of P, Ca, and NOM is also an important factor in lime softening and corrosion control, both critical processes of drinking water treatment. Determining the role of NOM in Ca-P co-precipitation is important for identifying mechanisms that may limit P removal in both natural and engineered systems. The main goal of this research is to assess the role of NOM in inhibiting Ca and P co-precipitation by: (1) measuring how Ca, NOM, and P concentrations affect NOM's potential inhibition of co-precipitation; (2) determining the effect of pH; and (3) evaluating the precipitated solids. Results showed that Ca-P co-precipitation occurs at pH 9.5 in the presence of high natural organic matter (NOM) (≈30 mg L(-1)). The supersaturation of calcite overcomes the inhibitory effect of NOM seen at lower pH values. Higher initial P concentrations lead to both higher P precipitation rates and densities of P on the calcite surface. The maximum surface density of co-precipitated P on the precipitated calcite surface increases with increasing NOM levels, suggesting that NOM does prevent the co-precipitation of Ca and P.

Method for controlled mitochondrial perturbation during phosphorus MRS in children.

UNLABELLED: Insulin resistance is increasingly prevalent in children and may be related to muscle mitochondrial dysfunction, necessitating development of mitochondrial assessment techniques. Recent studies used phosphorus magnetic resonance spectroscopy (P-MRS), a noninvasive technique appealing for clinical research. P-MRS requires exercise at a precise percentage of maximum volitional contraction (MVC). MVC measurement in children, particularly in those with a disease, is problematic because of variability in perception of effort and motivation. We therefore developed a method to predict MVC using maximal calf muscle cross-sectional area (MCSA) to assure controlled and reproducible muscle metabolic perturbations. METHODS: Data were collected from 66 sedentary 12- to 20-yr-old participants. Plantarflexion MVC was assessed using an MRI-compatible exercise treadle device. MCSA of the calf muscles were measured from magnetic resonance images. Data from the first 26 participants were used to model the relation between MVC and MCSA (predicted MVC = 24.763 + 0.0047 MCSA). This model was then applied to the subsequent 40 participants. RESULTS: MVC versus model-predicted mean MVC was 43.9 ± 0.8 kg versus 44.2 ± 1.81 (P = 0.90). P-MRS results when predicted and MVC were similar showed expected changes during MVC-based exercise. In contrast, MVC was markedly lower than predicted in four participants and produced minimal metabolic perturbation. Upon repeat testing, these individuals could perform their predicted MVC with coaching, which produced expected metabolic perturbations. CONCLUSIONS: Compared with using MVC testing alone, using magnetic resonance imaging to predict muscle strength allows for a more accurate and standardized P-MRS protocol during exercise in children. This method overcomes a major obstacle in assessing mitochondrial function in youths. These studies have importance as we seek to determine the role of mitochondrial function in youths with insulin resistance and diabetes and response to interventions.

Development of auditory event-related potentials in infants prenatally exposed to methadone.

Developmental features of the P2 auditory ERP in a change detection paradigm were examined in infants prenatally exposed to methadone. Opiate dependent pregnant women maintained on methadone replacement therapy were recruited during pregnancy (N = 60). Current and historical alcohol and substance use, SES, and psychiatric status were assessed with a maternal interview during the third trimester. Medical records were used to collect information regarding maternal medications, monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol exposures. Between birth and 4 months infant ERP change detection performance was evaluated on one occasion with the oddball paradigm (.2 probability oddball) using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed increased P2 amplitude at Fz and effective change detection performance at P2 not seen in the newborn group. Developmental maturation of amplitude and stimulus discrimination for P2 has been reported in developing infants at all of the ages tested and data reported here in the older infants are consistent with typical development. However, it has been previously reported that the P2 amplitude difference is detectable in neonates; therefore, absence of a difference in P2 amplitude between stimuli in the 4-15 days group may represent impaired ERP performance by neonatal abstinence syndrome or prenatal methadone exposure.

White matter abnormalities and working memory impairment in systemic lupus erythematosus.

OBJECTIVE/BACKGROUND: Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy in SLE. METHODS: We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using magnetic resonance spectroscopy, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter. RESULTS: Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant when we considered disease duration and left frontal white matter Ch/Cr against total PASAT score and total dyads. CONCLUSIONS: Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.

Pyelonephritis: what are the present day causative organisms and antibiotic susceptibilities?

AIM: Infections of the lower urinary tract and acute pyelonephritis are commonly encountered in clinical practice. Widespread usage of antibiotics and changing susceptibility profiles of uropathogens requires regular review of treatment guidelines to meet these challenges. We aimed to better understand the prevalence of uropathogens and emerging antibiotic resistance in patients with pyelonephritis requiring hospital admission. METHODS: In this single centre, 12-year retrospective observational study, we reviewed case notes and urine culture results of 249 patients admitted with acute pyelonephritis under the care of the nephrology department, along with 46,660 urine samples with positive isolates from the emergency department (ED) during the same period. The prevalence of uropathogens, their antibiotic susceptibilities and emerging resistance patterns to commonly used antibiotics were studied. Antibiotic susceptibilities were also reviewed in line with the currently recommended national guidelines for empiric therapy. RESULTS: We found the most prevalent uropathogen to be Escherichia coli. Approximately 50% of E. coli infections were resistant to ampicillin. First and third generation cephalosporin resistance was <5%, however, the latter has increased over the last decade and is more prevalent in the elderly. Enterococcus faecalis was associated with less than 10% of cases of lower urinary tract infections and no case of pyelonephritis. CONCLUSION: Antibiotic resistance of uropathogens to commonly used antibiotics is increasing with time and there is a need for hospitals to review their recommended guidelines for empiric therapy in line with local patterns of uropathogens and antibiotic susceptibilities.