Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Discov Ment Health ; 4(1): 8, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38453827

ABSTRACT

Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.

2.
BMC Psychiatry ; 24(1): 27, 2024 01 06.
Article in English | MEDLINE | ID: mdl-38184524

ABSTRACT

BACKGROUND: People with severe COVID anxiety have poor mental health and impaired functioning, but the course of severe COVID anxiety is unknown and the quality of evidence on the acceptability and impact of psychological interventions is low. METHODS: A quantitative cohort study with a nested feasibility trial. Potential participants aged 18 and over, living in the UK with severe COVID anxiety, were recruited online and from primary care services. We examined levels of COVID anxiety in the six months after recruitment, and factors that influenced this, using linear regression. Those scoring above 20 on the short Health Anxiety Inventory were invited to participate in a feasibility trial of remotely delivered Cognitive Behavioural Therapy for Health Anxiety (CBT-HA). Exclusion criteria were recent COVID-19, current self-isolation, or current receipt of psychological treatment. Key outcomes for the feasibility trial were the level of uptake of CBT-HA and the rate of follow-up. RESULTS: 204 (70.2%) of 285 people who took part in the cohort study completed the six month follow-up, for whom levels of COVID anxiety fell from 12.4 at baseline to 6.8 at six months (difference = -5.5, 95% CI = -6.0 to -4.9). Reductions in COVID anxiety were lower among older people, those living with a vulnerable person, those with lower baseline COVID anxiety, and those with higher levels of generalised anxiety and health anxiety at baseline. 36 (90%) of 40 participants enrolled in the nested feasibility trial were followed up at six months. 17 (80.9%) of 21 people in the active arm of the trial received four or more sessions of CBT-HA. We found improved mental health and social functioning among those in the active, but not the control arm of the trial (Mean difference in total score on the Work and Social Adjustment Scale between baseline and follow up, was 9.7 (95% CI = 5.8-13.6) among those in the active, and 1.0 (95% C.I. = -4.6 to 6.6) among those in the control arm of the trial. CONCLUSIONS: While the mental health of people with severe COVID anxiety appears to improve over time, many continue to experience high levels of anxiety and poor social functioning. Health anxiety is highly prevalent among people with severe COVID anxiety and may provide a target for psychological treatment. TRIAL REGISTRATION: Retrospectively registered at ISRCTN14973494 on 09/09/2021.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Humans , Anxiety/therapy , Cohort Studies , Feasibility Studies , United Kingdom/epidemiology
3.
BJPsych Bull ; 48(1): 51-56, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36632805

ABSTRACT

AIMS AND METHOD: With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021. RESULTS: Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment. CLINICAL IMPLICATIONS: PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.

4.
Personal Ment Health ; 18(1): 19-31, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37674476

ABSTRACT

Poor quality sleep is common for people who have a diagnosis of personality disorder (PD). Core cognitive and behavioral features of PD may cause and perpetuate poor sleep, but to date, no review has collated the evidence on the efficacy of interventions to improve sleep quality for people with PD. Structured searches for interventional studies among adults with PD and reporting validated measures of sleep quality were conducted up to November 2022 in multiple databases. Single-case reports were excluded. Study quality was assessed with standardized risk of bias tools. Unreported data was sought systematically from authors. This review was pre-registered with an international prospective register of systematic reviews (PROSPERO) (CRD42021282105). Of the 3503 identified studies, nine met inclusion criteria, representing a range of psychological, pharmaceutical, and other interventions and outcome measures. Meta-analytic methods were not feasible because of the serious risk of bias in all studies, and results were therefore synthesized narratively. There is limited and low-quality evidence of the effects of a variety of interventions to improve the sleep quality of people living with PD. Further research might consider specifically including people diagnosed with PD in trials of sleep interventions and using sleep outcome measures in trials of established PD treatments.


Subject(s)
Sleep Quality , Adult , Humans , Systematic Reviews as Topic
5.
Case Rep Ophthalmol ; 14(1): 692-697, 2023.
Article in English | MEDLINE | ID: mdl-38090107

ABSTRACT

Introduction: We present a unique case of iris chafing syndrome in a patient with a complex ophthalmologic history after successful placement of a single-piece in-the-bag intraocular lens (IOL) in an eye with healthy zonular support. Case Presentation: A patient with a previous history of multiple retinal surgeries presented with pain and elevated intraocular pressure (IOP) secondary to retained viscoelastic material in the anterior chamber. Following removal of the viscoelastic material in clinic, the patient underwent a combined cataract and glaucoma surgery. Subsequently, the patient developed signs and symptoms of iris chafing syndrome. Anterior segment imaging revealed the cause to be iridociliary adhesion causing an elimination of the sulcus space. Iris chafing syndrome was suspected when the patient presented post-operatively with changes in vision and anterior chamber inflammation. New iris transillumination defects present at the edge of the optic and haptic of the 1-piece lens helped confirm the diagnosis of UGH. Upon further investigation with gonioscopy, ultrasound biomicroscopy and anterior segment optical coherence tomography, it was determined that the patient had iridociliary adhesions. These adhesions eliminated the sulcus space, which resulted in iris chafing. The patient opted for conservative medical management. Best-corrected distance visual acuity remained stable at 20/100 and IOP remained well controlled. Conclusion: A complex ocular history of multiple retinal surgeries and retained viscoelastic material in the anterior chamber resulted in adhesions of the ciliary processes to the iris, leading to UGH syndrome in a patient with an otherwise unremarkable placement of a single-piece in-the-bag IOL.

6.
Molecules ; 28(24)2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38138459

ABSTRACT

Herein we describe a novel route to indole derivatives from a variety of N-substituted 2-alkenylanilines. This route features three operationally simple steps: (1) oxidation to convert N-substituted 2-alkenylanilines into epoxide intermediates, (2) intramolecular cyclization, and (3) the acid-catalyzed elimination of water.

7.
J Clin Psychopharmacol ; 43(6): 498-506, 2023.
Article in English | MEDLINE | ID: mdl-37930201

ABSTRACT

PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-). METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02). IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.


Subject(s)
Antipsychotic Agents , Depressive Disorder, Treatment-Resistant , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Humans , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Depression/drug therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Depressive Disorder, Treatment-Resistant/complications , Personality Disorders/drug therapy , Personality Disorders/chemically induced , Personality Disorders/complications , Quetiapine Fumarate/pharmacology , Quetiapine Fumarate/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/chemically induced , Sleep Quality , Sleep Wake Disorders/drug therapy
8.
J Am Soc Mass Spectrom ; 34(7): 1235-1247, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37254938

ABSTRACT

This is the second of two manuscripts describing how general linear modeling (GLM) of a selection of the most abundant normalized fragment ion abundances of replicate mass spectra from one laboratory can be used in conjunction with binary classifiers to enable specific and selective identifications with reportable error rates of spectra from other laboratories. Here, the proof-of-concept uses a training set of 128 replicate cocaine spectra from one crime laboratory as the basis of GLM modeling. GLM models for the 20 most abundant fragments of cocaine were then applied to 175 additional test/validation cocaine spectra collected in more than a dozen crime laboratories and 716 known negative spectra, which included 10 spectra of three diastereomers of cocaine. Spectral similarity and dissimilarity between the measured and predicted abundances were assessed using a variety of conventional measures, including the mean absolute residual and NIST's spectral similarity score. For each spectral measure, GLM predictions were compared to the traditional exemplar approach, which used the average of the cocaine training set as the consensus spectrum for comparisons. In unsupervised models, EASI provided better than a 95% true positive rate for cocaine with a 0% false positive rate. A supervised binary logistic regression model provided 100% accuracy and no errors using EASI-predicted abundances of only four peaks at m/z 152, 198, 272, and 303. Regardless of the measure of spectral similarity, error rates for identifications using EASI were superior to the traditional exemplar/consensus approach. As a supervised binary classifier, EASI was more reliable than using Mahalanobis distances.

9.
J Am Soc Mass Spectrom ; 34(7): 1248-1262, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37255332

ABSTRACT

This study aims to resolve one of the longest-standing problems in mass spectrometry, which is how to accurately identify an organic substance from its mass spectrum when a spectrum of the suspected substance has not been analyzed contemporaneously on the same instrument. Part one of this two-part report describes how Rice-Ramsperger-Kassel-Marcus (RRKM) theory predicts that many branching ratios in replicate electron-ionization mass spectra will provide approximately linear correlations when analysis conditions change within or between instruments. Here, proof-of-concept general linear modeling is based on the 20 most abundant fragments in a database of 128 training spectra of cocaine collected over 6 months in an operational crime laboratory. The statistical validity of the approach is confirmed through both analysis of variance (ANOVA) of the regression models and assessment of the distributions of the residuals of the models. General linear modeling models typically explain more than 90% of the variance in normalized abundances. When the linear models from the training set are applied to 175 additional known positive cocaine spectra from more than 20 different laboratories, the linear models enabled ion abundances to be predicted with an accuracy of <2% relative to the base peak, even though the measured abundances vary by more than 30%. The same models were also applied to 716 known negative spectra, including the diastereomers of cocaine: allococaine, pseudococaine, and pseudoallococaine, and the residual errors were larger for the known negatives than for known positives. The second part of the manuscript describes how general linear regression modeling can serve as the basis for binary classification and reliable identification of cocaine from its diastereomers and all other known negatives.

10.
BMC Psychiatry ; 23(1): 117, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36810010

ABSTRACT

BACKGROUND: Anxiety about COVID-19 is common. For most people this is an appropriate response to the loss of livelihoods and loved-ones, disruptions to social networks, and uncertainty about the future. However, for others these anxieties relate to contracting the virus itself, a phenomenon termed COVID anxiety. Little is known about the characteristics of people with severe COVID anxiety or the impact it has on their daily lives. METHODS: We conducted a two-phase cross-sectional survey of people aged 18 or over who were living in United Kingdom, self-identified as anxious about COVID-19, and had a score of ≥9 on the Coronavirus Anxiety Scale. We recruited participants nationally through online adverts and locally via primary care services in London. Data on demographic and clinical factors were used in multiple regression modelling to examine the greatest contributors to functional impairment, poor health-related quality of life and protective behaviours in this sample of individuals with severe COVID anxiety. RESULTS: We recruited 306 people with severe COVID anxiety between January and September 2021. Most were female (n = 246, 81.2%); they had a median age of 41 (range = 18-83). The majority of participants also had generalised anxiety (n = 270, 91.5%), depression (n = 247, 85.5%), and a quarter (n = 79, 26.3%) reported a physical health condition which put them at increased risk of hospitalisation with COVID-19. Half had severe social dysfunction (n = 151, 52.4%). One in ten reported never leaving their home, one in three washed all items brought into their house, one in five washed their hands constantly, and one in five of those with children reported not sending them to school because of fears of COVID-19. Increasing co-morbid depressive symptoms best explained functional impairment and poor quality of life after controlling for other factors. CONCLUSIONS: This study highlights the high degree of co-occuring mental health problems, and the extent of functional impairment and poor health-related quality of life among people with severe COVID anxiety. Further research is needed to establish the course of severe COVID anxiety as the pandemic progresses, and steps that can be taken to support people who experience this distress.


Subject(s)
COVID-19 , Child , Adult , Humans , Female , Male , Cross-Sectional Studies , Quality of Life , Social Interaction , Depression/etiology , Anxiety/etiology
11.
Environ Sci Technol ; 56(24): 17965-17976, 2022 12 20.
Article in English | MEDLINE | ID: mdl-36459429

ABSTRACT

Granular activated carbon (GAC) is used to sorb a broad range of halogenated contaminant classes, but spent GAC disposal is costly. Taking advantage of GAC's conductivity, this study evaluated the conversion of the GAC to cathodes for electrochemical reductive dehalogenation of 15 halogenated alkanes and alkenes exhibiting a diversity of structures (type of halogen, number of halogens, functional groups) and including contaminants of practical importance (e.g., trichloroethylene). Alkane degradation rates increased with the number of halogens and in the order: chlorine < bromine < iodine. Quantitative structure-activity relationships (QSARs) correlating experimental first-order degradation rate constants for alkanes with molecular descriptors associated with an outer-sphere one-electron transfer calculated using density functional theory indicated that correlations with molecular descriptors improved in the order: aqueous phase reduction potentials (E0,aq) < energy of the substrate's lowest unoccupied molecular orbital (ELUMO) < Marcus theory activation free energies (ΔG‡) ∼ gas-phase standard reduction free energies (ΔG0,gas). Chlorinated alkene degradation rates increased with decreasing number of chlorines, and QSAR correlations were opposite those of alkanes, indicating a different reaction mechanism. Degradation timescales ranged from 1 min to 3 h with halides as predominant products. These results suggest that the electrochemical reduction of halogenated alkanes and alkenes can be used to regenerate spent GAC.


Subject(s)
Alkanes , Charcoal , Alkenes , Halogens/chemistry , Chlorine , Electrodes
12.
Curr Opin Psychiatry ; 35(3): 192-199, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35579873

ABSTRACT

PURPOSE OF REVIEW: There is increasing interest in the links between exposure to air pollution and a range of health outcomes. The association with mental health however is much less established. This article reviews developments in the field over the past 12 months, highlighting the evidence for causation, associations between multiple air pollutants and mental health outcomes, and assesses the challenges of researching this topic. RECENT FINDINGS: Increasingly rigorous methods are being applied to the investigation of a broader range of mental health outcomes. These methods include basic science, neuroimaging, and observational studies representing diverse geographical locations. Cohort studies with linked high-resolution air pollutant exposure data are common, facilitating advanced analytic methods. To date, meta-analyses have demonstrated small and significant positive associations between long-term exposure to fine particulate matter and depressive symptoms and cognitive decline. Methodological complexities in measuring exposure and outcome pose ongoing difficulties for the field. SUMMARY: Literature on this topic has recently seen an appreciable expansion. Work that better estimates daily exposure, controls for complex confounders, and is driven by hypotheses founded in candidate causal mechanisms would help clarify associations, and inform targeted interventions and policymakers.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Humans , Mental Health , Particulate Matter/adverse effects , Particulate Matter/analysis
13.
BJPsych Open ; 8(2): e63, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35256037

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has high morbidity and mortality in older adults and people with dementia. Infection control and prevention measures potentially reduce transmission within hospitals. AIMS: We aimed to replicate our earlier study of London mental health in-patients to examine changes in clinical guidance and practice and associated COVID-19 prevalence and outcomes between COVID-19 waves 1 and 2 (1 March to 30 April 2020 and 14 December 2020 to 15 February 2021). METHOD: We collected the 2 month period prevalence of wave 2 of COVID-19 in older (≥65 years) in-patients and those with dementia, as well as patients' characteristics, management and outcomes, including vaccinations. We compared these results with those of our wave 1 study. RESULTS: Sites reported that routine testing and personal protective equipment were available, and routine patient isolation on admission occurred throughout wave 2. COVID-19 infection occurred in 91/358 (25%; 95% CI 21-30%) v. 131/344, (38%; 95% CI 33-43%) P < 0.001 in wave 1. Hospitals identified more asymptomatic carriers (26/91; 29% v. 16/130; 12%) and fewer deaths (12/91; 13% v. 19/131; 15%; odds ratio = 0.92; 0.37-1.81) compared with wave 1. The patient vaccination uptake rate was 49/58 (85%). CONCLUSIONS: Patients in psychiatric in-patient settings, mostly admitted without known SARS-CoV-2 infection, had a high risk of infection compared with people in the community but lower than that during wave 1. Availability of infection control measures in line with a policy of parity of esteem between mental and physical health appears to have lowered within-hospital COVID-19 infections and deaths. Cautious management of vulnerable patient groups including mental health patients may reduce the future impact of COVID-19.

15.
Ultrasound Med Biol ; 48(3): 480-487, 2022 03.
Article in English | MEDLINE | ID: mdl-34872787

ABSTRACT

The aim of the study was to assess the feasibility of using a superb microvascular imaging-based vascular index (SMI-VI) for evaluating adult hepatic steatosis. We prospectively compared liver parenchyma SMI-VI (color pixels/total pixels in the region of interest), portal vein velocity, hepatic artery Doppler parameters (peak systolic velocity, end diastolic velocity, resistive index) and serum lipid and alanine aminotransferase (ALT) levels between 16 normal livers and 34 steatotic livers using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as the reference. On the basis of a two-tailed t-test, differences in SMI-VI, portal vein velocity, MRI-PDFF and ALT between normal (MRI-PDFF <5%) and steatotic (MRI-PDFF ≥5%) livers were statistically significant (p < 0.02), whereas hepatic artery Doppler parameters and triglyceride levels were not (p > 0.05). We observed an inverse correlation of SMI-VI with MRI-PDFF (r = -0.88). With 0.19 as the best cutoff value, the area under the receiver operating characteristic curve, sensitivity and specificity of SMI-VI for determining ≥mild (MRI-PDFF ≥5%) non-alcoholic fatty liver disease (NAFLD) were 0.95, 96% and 94%, respectively. Our results indicate the feasibility of using SMI-VI to assess adult hepatic steatosis. SMI-VI is a potential surrogate marker in the screening for NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Alanine Transaminase , Feasibility Studies , Humans , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging/methods , Non-alcoholic Fatty Liver Disease/diagnosis
16.
BMJ Open ; 12(9): e059321, 2022 09 07.
Article in English | MEDLINE | ID: mdl-36691181

ABSTRACT

INTRODUCTION: Some people are so anxious about COVID-19 that it impairs their functioning. However, little is known about the course of severe COVID-19 anxiety or what can be done to help people who experience it. METHODS AND ANALYSIS: Cohort study with a nested feasibility trial with follow-up at 3 and 6 months. We recruited 306 people who were aged 18 and over, lived in the UK and had severe COVID-19 anxiety (indicated by a score of 9 or more on the Coronavirus Anxiety Scale (CAS)). To take part in the nested feasibility trial, participants also had to have a score of 20 or more on the Short Health Anxiety Inventory. We excluded people from the trial if they had had COVID-19 within the previous 4 weeks, if they were currently self-isolating or if they were already receiving psychological treatment.We publicised the study nationally through adverts, social media and posts on message boards. We also recruited participants via clinicians working in primary and secondary care NHS services in London. All those in the active arm will be offered 5-10 sessions of remotely delivered modified cognitive-behavioural therapy for health anxiety (CBT-HA). We will examine the proportion of participants who remain above threshold on the CAS at 3 and 6 months and factors that influence levels of COVID-19 anxiety over 6 months using mixed effects logistic regression. The key feasibility metrics for the nested trial are the level of uptake of CBT-HA and the rate of follow-up. ETHICS AND DISSEMINATION: Approved by Leicester Central Research Ethics Committee (reference: 20/EM/0238). The results of the study will be published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ISRCTN14973494.


Subject(s)
COVID-19 , Cognitive Behavioral Therapy , Humans , Adult , Adolescent , Feasibility Studies , Cohort Studies , Anxiety , Cognitive Behavioral Therapy/methods , United Kingdom
17.
Metabolites ; 11(11)2021 Nov 20.
Article in English | MEDLINE | ID: mdl-34822450

ABSTRACT

Histone deacetylases (HDACs) are epigenetic enzymes that play a central role in gene regulation and are sensitive to the metabolic state of the cell. The cross talk between metabolism and histone acetylation impacts numerous biological processes including development and immune function. HDAC inhibitors are being explored for treating cancers, viral infections, inflammation, neurodegenerative diseases, and metabolic disorders. However, how HDAC inhibitors impact cellular metabolism and how metabolism influences their potency is unclear. Discussed herein are recent applications and future potential of systems biology methods such as high throughput drug screens, cancer cell line profiling, single cell sequencing, proteomics, metabolomics, and computational modeling to uncover the interplay between metabolism, HDACs, and HDAC inhibitors. The synthesis of new systems technologies can ultimately help identify epigenomic and metabolic biomarkers for patient stratification and the design of effective therapeutics.

18.
mSphere ; 6(5): e0062921, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34585964

ABSTRACT

Antibiotics are a major risk factor for Clostridioides difficile infections (CDIs) because of their impact on the microbiota. However, nonantibiotic medications such as the ubiquitous osmotic laxative polyethylene glycol 3350 (PEG 3350) also alter the microbiota. Clinicians also hypothesize that PEG helps clear C. difficile. But whether PEG impacts CDI susceptibility and clearance is unclear. To examine how PEG impacts susceptibility, we treated C57BL/6 mice with 5-day and 1-day doses of 15% PEG in the drinking water and then challenged the mice with C. difficile 630. We used clindamycin-treated mice as a control because they consistently clear C. difficile within 10 days postchallenge. PEG treatment alone was sufficient to render mice susceptible, and 5-day PEG-treated mice remained colonized for up to 30 days postchallenge. In contrast, 1-day PEG-treated mice were transiently colonized, clearing C. difficile within 7 days postchallenge. To examine how PEG treatment impacts clearance, we administered a 1-day PEG treatment to clindamycin-treated, C. difficile-challenged mice. Administering PEG to mice after C. difficile challenge prolonged colonization up to 30 days postchallenge. When we trained a random forest model with community data from 5 days postchallenge, we were able to predict which mice would exhibit prolonged colonization (area under the receiver operating characteristic curve [AUROC] = 0.90). Examining the dynamics of these bacterial populations during the postchallenge period revealed patterns in the relative abundances of Bacteroides, Enterobacteriaceae, Porphyromonadaceae, Lachnospiraceae, and Akkermansia that were associated with prolonged C. difficile colonization in PEG-treated mice. Thus, the osmotic laxative PEG rendered mice susceptible to C. difficile colonization and hindered clearance. IMPORTANCE Diarrheal samples from patients taking laxatives are typically rejected for Clostridioides difficile testing. However, there are similarities between the bacterial communities from people with diarrhea and those with C. difficile infections (CDIs), including lower diversity than the communities from healthy patients. This observation led us to hypothesize that diarrhea may be an indicator of C. difficile susceptibility. We explored how osmotic laxatives disrupt the microbiota's colonization resistance to C. difficile by administering a laxative to mice either before or after C. difficile challenge. Our findings suggest that osmotic laxatives disrupt colonization resistance to C. difficile and prevent clearance among mice already colonized with C. difficile. Considering that most hospitals recommend not performing C. difficile testing on patients taking laxatives, and laxatives are prescribed prior to administering fecal microbiota transplants via colonoscopy to patients with recurrent CDIs, further studies are needed to evaluate if laxatives impact microbiota colonization resistance in humans.


Subject(s)
Clostridioides difficile/drug effects , Clostridioides difficile/physiology , Clostridium Infections/drug therapy , Gastrointestinal Microbiome/drug effects , Laxatives/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Clindamycin/therapeutic use , Clostridium Infections/microbiology , Clostridium Infections/prevention & control , Disease Susceptibility , Feces/microbiology , Female , Gastrointestinal Microbiome/physiology , Mice , Mice, Inbred C57BL , Polyethylene Glycols/therapeutic use , RNA, Ribosomal, 16S/analysis
19.
Environ Sci Technol ; 54(24): 16176-16185, 2020 12 15.
Article in English | MEDLINE | ID: mdl-33269915

ABSTRACT

Reverse osmosis (RO) treatment of municipal wastewater effluent is becoming more common as water reuse is implemented in water-stressed regions. Where RO concentrate is discharged with limited dilution, concentrations of trace organic contaminants could pose risks to aquatic ecosystems. To provide a low-cost option for removing trace organic compounds from RO concentrate, a pilot-scale treatment system comprising open-water unit-process wetlands with and without ozone pretreatment was studied over a 2-year period. A suite of ecotoxicologically relevant organic contaminants was partially removed via photo- and bio-transformations, including ß-adrenergic blockers, antivirals, antibiotics, and pesticides. Biotransformation rates were as fast as or up to approximately 50% faster than model predictions based upon data from open-water wetlands that treated municipal wastewater effluent. Phototransformation rates were comparable to or as much as 60% slower than those predicted by models that accounted for light penetration and scavenging of reactive oxygen species. Several compounds were transformed during ozone pretreatment that were poorly removed in the open-water wetland. The combined treatment system resulted in a decrease in the risk quotients of trace organic contaminants in the RO concentrate, but still dilution may be required to protect sensitive species from urban-use pesticides with low environmental effect concentrations.


Subject(s)
Ozone , Water Pollutants, Chemical , Water Purification , Ecosystem , Osmosis , Waste Disposal, Fluid , Wastewater , Water , Wetlands
20.
Water Res ; 176: 115744, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32251944

ABSTRACT

This study evaluated ozone treatment to address concerns regarding the discharge to marine waters of chemical contaminants and pathogens in reverse osmosis (RO) concentrates generated during the potable reuse of municipal wastewaters. Previous studies indicated that contaminants can be sorted into five groups based on their reaction rate constants with ozone and hydroxyl radical to predict degradation of chemical contaminants during ozonation of municipal effluents. Spiking representatives of each group into five RO concentrate samples, this study demonstrated that the same contaminant grouping scheme could be used to predict contaminant degradation during ozonation of RO concentrates, despite the higher concentrations of ozone and hydroxyl radical scavengers. The predictive capability of the contaminant grouping scheme was further validated for four contaminants of concern in RO concentrates, including the pesticides fipronil and imidacloprid, and the metal chelates Ni-EDTA and Cu-EDTA. After measuring their ozone and hydroxyl radical reaction rate constants, these compounds were assigned to contaminant groups, and their degradation during ozonation matched predictions. Addition of 300 mg/L CaO at pH 11 achieved partial removal of the native nickel and copper by precipitation. Ozone pretreatment further enhanced precipitation of nickel, but not copper. Ozonation achieved 5-log inactivation of MS2 in all five concentrate samples at 1.18 mg O3/mg DOC. Ozonation at 0.9 mg O3/mg DOC formed 139-451 µg/L bromate. Pretreatment of RO concentrates with chlorine and ammonia reduced bromate formation by a maximum of 48% but increased total halogenated DBP concentrations from 20 µg/L to 36 µg/L. Regardless, neither bromate nor trihalomethane concentrations exceeded threshold concentrations of concern for discharge to marine waters.


Subject(s)
Ozone , Pesticides , Water Pollutants, Chemical , Water Purification , Metals , Osmosis , Wastewater
SELECTION OF CITATIONS
SEARCH DETAIL
...