ABSTRACT
BACKGROUND: Metabolism dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease. Few MAFLD predictions are simple and accurate. We examined the predictive performance of the albumin-to-glutamyl transpeptidase ratio (AGTR), plasma atherogenicity index (AIP), and serum uric acid to high-density lipoprotein cholesterol ratio (UHR) for MAFLD to design practical, inexpensive, and reliable models. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle dataset, which contained 12,654 participants, was filtered and randomly separated into internal validation and training sets. This study examined the relationships of the AGTR and AIP with MAFLD using binary multifactor logistic regression. We then created a MAFLD predictive model using the training dataset and validated the predictive model performance with the 2017-2018 NHANES and internal datasets. RESULTS: In the total population, the predictive ability (AUC) of the AIP, AGTR, UHR, and the combination of all three for MAFLD showed in the following order: 0.749, 0.773, 0.728 and 0.824. Further subgroup analysis showed that the AGTR (AUC1 = 0.796; AUC2 = 0.690) and the combination of the three measures (AUC1 = 0.863; AUC2 = 0.766) better predicted MAFLD in nondiabetic patients. Joint prediction outperformed the individual measures in predicting MAFLD in the subgroups. Additionally, the model better predicted female MAFLD. Adding waist circumference and or BMI to this model improves predictive performance. CONCLUSION: Our study showed that the AGTR, AIP, and UHR had strong MAFLD predictive value, and their combination can increase MAFLD predictive performance. They also performed better in females.
Subject(s)
Non-alcoholic Fatty Liver Disease , Uric Acid , Humans , Female , Nutrition Surveys , Albumins , Cholesterol, HDL , gamma-GlutamyltransferaseABSTRACT
BACKGROUND AND AIMS: The relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and mortality in individuals with diabetes remains uncertain. This study aimed to explore the relationship between serum UHR and all-cause and cardiovascular disease (CVD) mortality in adults with diabetes. METHODS AND RESULTS: A total of 5,665 patients with diabetes were enrolled from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Mortality data were determined through the National Death Index (NDI) until December 31, 2019. The multivariate hazard ratio (HR) and 95% confidence interval (CI) were examined by Cox proportional risk modeling and threshold effects analysis. Stratified analyses were conducted to identify the populations with high-risk mortality. Among the participants with diabetes, 1,088 all-cause mortality, containing 310 CVD mortality occurred. Following adjustment for multivariate, higher UHR was significantly and nonlinearly associated with increased all-cause mortality (HR 1.02, 95% CI 1.02-1.02) and CVD mortality (HR 1.03, 95% CI 1.03-1.03). Furthermore, a U-shaped relationship between UHR and all-cause and CVD mortality, with a plateau at 12.57% for all-cause mortality and 9.86% for CVD mortality. Below the inflection points, a higher UHR was associated with a 4% reduced risk for all-cause mortality. Conversely, exceeding the inflection points, a 4% higher risk for all-cause and a 3% higher risk for CVD mortality associated with elevated UHR. CONCLUSIONS: Nonlinearity of UHR with all-cause and CVD mortality was observed in adults with diabetes in the United States, with thresholds identified at 12.57% for all-cause and 9.86% for CVD mortality respectively.
Subject(s)
Biomarkers , Cardiovascular Diseases , Cause of Death , Cholesterol, HDL , Diabetes Mellitus , Nutrition Surveys , Uric Acid , Humans , Male , Uric Acid/blood , Female , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Middle Aged , Cholesterol, HDL/blood , Risk Assessment , United States/epidemiology , Adult , Biomarkers/blood , Diabetes Mellitus/blood , Diabetes Mellitus/mortality , Diabetes Mellitus/diagnosis , Time Factors , Aged , Prognosis , Predictive Value of Tests , Risk Factors , Cross-Sectional StudiesABSTRACT
OBJECTIVE: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. METHODS: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. RESULTS: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. CONCLUSION: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.
Subject(s)
Cholesterol, HDL , Glucuronidase , Klotho Proteins , Nutrition Surveys , Uric Acid , Humans , Uric Acid/blood , Male , Female , Middle Aged , Glucuronidase/blood , Cholesterol, HDL/blood , Cross-Sectional Studies , Adult , Aged , ROC CurveABSTRACT
Pancreatic cancer patients have poor survival rates and are frequently treated using gemcitabine (Gem). However, initial tumor sensitivity often gives way to rapid development of resistance. Gem-based drug combinations are employed to increase efficacy and mitigate resistance, but our understanding of molecular-level drug interactions, which could assist in the development of more effective therapeutic regimens, is limited. Global quantitative proteomic analysis could provide novel mechanistic insights into drug combination interactions, but it is challenging to achieve high-quality quantitative proteomics analysis of the large sample sets that are typically required for drug combination studies. Here, we investigated molecular-level temporal interactions of Gem with BGJ398 (infigratinib), a recently approved pan-FGFR inhibitor, in multiple treatment groups (N = 42 samples) using IonStar, a robust large-scale proteomics method that employs well-controlled, ultrahigh-resolution MS1 quantification. A total of 5514 proteins in the sample set were quantified without missing data, requiring >2 unique peptides/protein, <1% protein false discovery rate (FDR), <0.1% peptide FDR, and CV < 10%. Functional analysis of the differentially altered proteins revealed drug-dysregulated processes such as metabolism, apoptosis, and antigen presentation pathways. These changes were validated experimentally using Seahorse metabolic assays and immunoassays. Overall, in-depth analysis of large-scale proteomics data provided novel insights into possible mechanisms by which FGFR inhibitors complement and enhance Gem activity in pancreatic cancers.
Subject(s)
Pancreatic Neoplasms , Proteome , Humans , Proteome/analysis , Proteomics/methods , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , Gemcitabine , Peptides/analysis , Apoptosis , Drug Therapy, Combination , Drug Combinations , Cell Line, Tumor , Pancreatic NeoplasmsABSTRACT
Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models recapitulate tumor-stroma interactions, but the conventional antibody-based immunoassay is inadequate to discriminate tumor and stromal proteins. Here, we describe a species-deconvolved proteomics approach embedded in IonStar that can unambiguously quantify the tumor (human-derived) and stromal (mouse-derived) proteins in PDX samples, enabling unbiased investigation of tumor and stromal proteomes with excellent quantitative reproducibility. With this strategy, we studied tumor-stroma interactions in PDAC PDXs that responded differently to Gemcitabine combined with nab-Paclitaxel (GEM+PTX) treatment. By analyzing 48 PDX animals 24 h/192 h after treatment with/without GEM+PTX, we quantified 7262 species-specific proteins under stringent cutoff criteria, with high reproducibility. For the PDX sensitive to GEM+PTX, the drug-dysregulated proteins in tumor cells were involved in suppressed oxidative phosphorylation and the TCA cycle, and in the stroma, inhibition of glycolytic activity was predominant, suggesting a relieved reverse Warburg effect by the treatment. In GEM+PTX-resistant PDXs, protein changes suggested extracellular matrix deposition and activation of tumor cell proliferation. Key findings were validated by immunohistochemistry (IHC). Overall, this approach provides a species-deconvolved proteomic platform that could advance cancer therapeutic studies by enabling unbiased exploration of tumor-stroma interactions in the large number of PDX samples required for such investigations.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Animals , Humans , Mice , Carcinoma, Pancreatic Ductal/drug therapy , Cell Line, Tumor , Gemcitabine , Heterografts , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Pancreatic Neoplasms/pathology , Proteomics , Reproducibility of ResultsABSTRACT
Microbial life present in the marine environment has to be able to adapt to rapidly changing and often extreme conditions. This makes these organisms a putative source of commercially interesting compounds since adaptation provides different biochemical routes from those found in their terrestrial counterparts. In this work, the goal was the identification of a marine bacterium isolated from a sample taken at a shallow water hydrothermal vent and of its red product. Genomic, lipidomic, and biochemical approaches were used simultaneously, and the bacterium was identified as Serratia rubidaea. A high-throughput screening strategy was used to assess the best physico-chemical conditions permitting both cell growth and production of the red product. The fatty acid composition of the microbial cells was studied to assess adaptation at the lipid level under stressful conditions, whilst several state-of-the-art techniques, such as DSC, FTIR, NMR, and Ultra-High Resolution Qq-Time-of-Flight mass spectrometry, were used to characterize the structure of the pigment. We hypothesize that the pigment, which could be produced by the cells up to 62 °C, is prodigiosin linked to an aliphatic compound that acts as an anchor to keep it close to the cells in the marine environment.
Subject(s)
Hydrothermal Vents , Water , Serratia , Prodigiosin/chemistryABSTRACT
Persons at clinical high-risk for psychosis (CHR) are characterised by specific neurocognitive deficits. However, the course of neurocognitive performance during the prodromal period and over the onset of psychosis remains unclear. The aim of this meta-analysis was to synthesise results from follow-up studies of CHR individuals to examine longitudinal changes in neurocognitive performance. Three electronic databases were systematically searched to identify articles published up to 31 December 2021. Thirteen studies met inclusion criteria. Study effect sizes (Hedges' g) were calculated and pooled for each neurocognitive task using random-effects meta-analyses. We examined whether changes in performance between baseline and follow-up assessments differed between: (1) CHR and healthy control (HC) individuals, and (2) CHR who did (CHR-T) and did not transition to psychosis (CHR-NT). Meta-analyses found that HC individuals had greater improvements in performance over time compared to CHR for letter fluency (g = -0.32, p = 0.029) and digit span (g = -0.30, p = 0.011) tasks. Second, there were differences in longitudinal performance of CHR-T and CHR-NT in trail making test A (TMT-A) (g = 0.24, p = 0.014) and symbol coding (g = -0.51, p = 0.011). Whilst CHR-NT improved in performance on both tasks, CHR-T improved to a lesser extent in TMT-A and had worsened performance in symbol coding over time. Together, neurocognitive performance generally improved in all groups at follow-up. Yet, evidence suggested that improvements were less pronounced for an overall CHR group, and specifically for CHR-T, in processing speed tasks which may be a relevant domain for interventions aimed to enhance neurocognition in CHR populations.
Subject(s)
Cognition Disorders , Psychotic Disorders , Humans , Neuropsychological Tests , Disease Progression , Psychotic Disorders/psychology , Prodromal Symptoms , Longitudinal StudiesABSTRACT
BACKGROUND: Certain migrant groups are more likely to develop a psychotic disorder compared to the native-born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra-high risk for psychosis (UHR) compared to native-born young people and whether migrant status was associated with the risk of transition to a full-threshold psychotic disorder. METHODS: The cohort included all young people aged 15-24 who were identified as UHR at a specialist clinic over a five-year period (2012-16). Australian census data were used to obtain the at-risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. RESULTS: 467 young people were identified as UHR, of which 13.5% (n = 63) were born overseas. First-generation migrants were 2.6-fold less likely to be identified as UHR compared to Australian-born young people (IRR = 0.39, 95% CI [0.30, 0.51], P < 0.001). There was no difference between migrant and native-born young people in their risk of transitioning to a psychotic disorder (HR = 0.90, 95% CI [0.39, 2.08], P = 0.81). CONCLUSIONS: UHR first-generation migrants may be under-accessing mental health services.
Subject(s)
Emigrants and Immigrants/statistics & numerical data , Health Services Accessibility , Mental Health Services , Psychotic Disorders/diagnosis , Adolescent , Africa South of the Sahara/ethnology , Africa, Northern/ethnology , Age Factors , Asia, Southeastern/ethnology , Australia , Disease Progression , Emigrants and Immigrants/psychology , Female , Humans , Male , Middle East/ethnology , Psychotic Disorders/ethnology , Psychotic Disorders/psychology , Risk , Risk Assessment , Young AdultABSTRACT
PURPOSE OF REVIEW: This review will aim to summarize the current body of epidemiological, clinical and therapeutic knowledge concerning specific co-occurrence of obsessive-compulsive symptoms (OCSs) and schizophrenia spectrum disorder. RECENT FINDINGS: Almost 30% of the patients with schizophrenia display OCS, and three main contexts of emergence are identified: prodromal symptoms of schizophrenia, co-occurrence of OCS and schizophrenia and antipsychotics-induced OCS. Recent clinical studies show that patients with SZ and OCS have more severe psychotic and depressive symptoms, higher suicidality and lower social functioning. A recent cognitive investigation found that OCS and delusions share specific metacognitive profiles, particularly through a heightened need to control thoughts. Finally, a recent cross-sectional study of clozapine-induced OCS found a dose-response relationship between clozapine and OCS. OCS appeared reliably as linked to poorer outcomes among patients with schizophrenia. However, the specific clinical value of OCS among other prodromal symptoms of schizophrenia remains unknown.
Subject(s)
Obsessive-Compulsive Disorder/complications , Schizophrenia/complications , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Clozapine/administration & dosage , Clozapine/adverse effects , Clozapine/therapeutic use , Cross-Sectional Studies , Humans , Obsessive-Compulsive Disorder/chemically induced , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/epidemiology , Prodromal Symptoms , Schizophrenia/drug therapy , Schizophrenia/epidemiologyABSTRACT
OBJECTIVE: About one-third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis (FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. METHOD: Retrospective study comparing duration of hospital admission, referral-to-diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high-risk service (n = 164) to patients with FEP who initially presented to conventional mental health services (n = 2779). Regression models were performed, controlling for several confounders. RESULTS: FEP patients who had presented to a high-risk service spent 17 fewer days in hospital [95% CI: -33.7 to (-0.3)], had a shorter referral-to-diagnosis time [B coefficient -74.5 days, 95% CI: -101.9 to -(47.1)], a lower frequency of admission [IRR: 0.49 (95% CI: 0.39-0.61)] and a lower likelihood of compulsory admission [OR: 0.52 (95% CI: 0.34-0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. CONCLUSION: Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic.
Subject(s)
Episode of Care , Patient Outcome Assessment , Psychotic Disorders/psychology , Psychotic Disorders/therapy , Adolescent , Adult , Early Diagnosis , Female , Hospitalization/statistics & numerical data , Humans , Male , Mental Health Services , Prodromal Symptoms , Psychotic Disorders/diagnosis , Retrospective StudiesABSTRACT
BACKGROUND: Psychiatric disorders are consistent with the gene x environment model, and non-specific environmental factors such as childhood trauma, urbanity, and migration have been implicated. All of these factors have in common to dysregulate the biological pathways involved in response to stress. Stress is a well-known precipitating factor implicated in psychiatric disorders such as depression, bipolar disorder, anxiety, and possibly schizophrenia. More precisely, psychosocial stress induces dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and could modify neurotransmission, which raises the question of the involvement of stress-related biological changes in psychotic disorders. Indeed, the literature reveals dysregulation of the HPA axis in schizophrenia. This dysregulation seems to be present in the prodromal phases (UHR subjects for ultra-high risk) and early schizophrenia (FEP for first episode psychosis). Thus, and following the stress-vulnerability model, stress could act directly on psychotic onset and precipitate the transition of vulnerable subjects to a full-blown psychosis. OBJECTIVE: The present paper reviews the literature on stress and onset of schizophrenia, with consideration for the causal role vs. associated role of HPA axis dysregulation in schizophrenia and the factors that influence it, in particular during prodromal and earlier phases. We also discuss different methods developed to measure stress in humans. METHODOLOGY: We performed a bibliographic search using the keywords 'cortisol', 'glucocorticoid', 'HPA' with 'UHR', 'CHR', 'at-risk mental state', 'first episode psychosis', 'schizotypal', 'prodromal schizophrenia' in Medline, Web of Knowledge (WOS), and EBSCO completed by a screening of the references of the selected articles. RESULTS: Stress has been studied for many years in schizophrenia, either by subjective methods (questionnaires), or objective methods (standardized experimental protocols) with biological sampling and/or brain imaging methods. These methods have suggested a link between dysregulation of the HPA axis and psychotic symptoms both through abnormal basal levels of cortisol and flattened reactivity to social stress. Imaging results suggest indirect modifications, including abnormal pituitary or hippocampal volume. Several factors dysregulating the HPA axis have also been highlighted, such as consumption of drugs (i.e. cannabis), childhood trauma or genetic factors (such as COMT, or MTHFR variants). Psychological stress induces subcortical dopaminergic activation attributable to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is present in the prodromal phase (UHR) in patients who have experienced a first psychotic episode (FEP) and in siblings of schizophrenic patients. Stress dysregulation is a plausible hypothesis to understand the psychosis onset. DISCUSSION: The effect of stress on brain pathways could participate to the mechanisms underlying the onset of psychotic symptoms, both as a precipitating factor and as a marker of a predisposing vulnerability. This dysregulation fits into the gene x environment model: in subjects with genetic predispositions, stressful environmental factors can modify biological pathways implicated in psychiatric disorders, promoting the emergence of symptoms. However, many confounding factors obscure the literature, and further studies are needed in schizophrenic patients, UHR and FEP patients to clarify the precise role of stress in psychotic transition. Identification of stress biomarkers could help diagnosis and prognosis, and pave the way for specific care strategies based on stress-targeted therapies.
Subject(s)
Psychotic Disorders/physiopathology , Psychotic Disorders/psychology , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Humans , Hydrocortisone/metabolism , Hydrocortisone/physiology , Hypothalamo-Hypophyseal System/physiopathology , Pituitary-Adrenal System/physiopathology , Psychotic Disorders/etiology , Schizophrenia/metabolism , Stress, Psychological/complicationsABSTRACT
Previous findings on the capacity of Hibiscus sabdariffa (HS) polyphenols to ameliorate metabolic disturbances justify the necessity of studies oriented to find the potential metabolites responsible for such an effect. The present study examined the intestinal epithelial membrane permeability of polyphenols present in a phenolic-enriched Hibiscus sabdariffa extract (PEHS), free and encapsulated, using the Caco-2 cell line. Additionally, selected polyphenols (quercetin, quercetin-3-glucoside, quercetin-3-glucuronide, and N-feruloyltyramine) were also studied in the same absorption model. The powerful analytical platform used ultra-high-performance liquid chromatography coupled with ultra-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-ESI-UHR-Qq-TOF-MS), and enabled the characterization of seven new compounds in PEHS. In the permeation study, only a few compounds were able to cross the cell monolayer and the permeability was lower when the extract was in an encapsulated form. Pure compounds showed a moderate absorption in all cases. Nevertheless, these preliminary results may need further research to understand the complete absorption mechanism of Hibiscus polyphenols.
Subject(s)
Chromatography, High Pressure Liquid/methods , Hibiscus/chemistry , Polyphenols/pharmacokinetics , Spectrometry, Mass, Electrospray Ionization/methods , Caco-2 Cells , Humans , Permeability , Plant Extracts/chemistry , Polyphenols/analysis , Polyphenols/isolation & purificationABSTRACT
BACKGROUND AND HYPOTHESIS: Shame has been linked to the experience of psychosis, with implications for clinical outcomes, however, a meta-analysis of the relationship has not yet been conducted. This systematic review and meta-analysis aimed to examine the strength of the association between shame and psychosis, and any variations between clinical and non-clinical populations and shame type (internal vs external shame). STUDY DESIGN: Searches were conducted in CINAHL, EMBASE, PsycInfo, PubMed, Scopus, and Web of Science from the inception of the e-databases until July 2023. For inclusion, studies reported a quantitative association between psychosis and shame, or data that could be used to identify a relationship. From 11 372 unique retrieved records, 40 articles met the inclusion criteria and 38 were included in the meta-analyses. STUDY RESULTS: A significant large pooled estimate of the psychosis-shame association was identified (Zrâ =â 0.36, [95% CI: 0.28, 0.44], Pâ <â .001), indicating that higher levels of shame were associated with greater severity of psychotic symptoms. The strength of the association was similar across clinical and non-clinical populations, however, differed by type of shame and psychosis symptom measured. External shame was strongly associated with paranoia suggesting possible confounding. Only a minority of studies met the highest quality criteria. CONCLUSIONS: Shame is strongly associated with the severity of psychotic symptoms in clinical and non-clinical populations. Given the overlap with paranoia, measurement of external shame alone is not advised. Larger studies in clinical populations, with measures of a range of psychosis symptoms, are needed to better understand the relationship between shame and specific symptoms.
ABSTRACT
BACKGROUND: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging. METHODS: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231). RESULTS: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%). CONCLUSIONS: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis.
Subject(s)
Psychotic Disorders , Adolescent , Humans , Australia , Psychotic Disorders/diagnosis , Cognition , Brain/diagnostic imaging , Magnetic Resonance ImagingABSTRACT
BACKGROUND: Although ultra-high risk for schizophrenia (UHR) is related to both genetic and environment factors, the precise pathogenesis is still unknow. To date, few studies have explored the Genome-Wide Association Studies (GWAS) in UHR or HR individuals especially in Han population in China. METHODS: In this study, a GWAS analysis for 36 participants with UHR and 43 with HR were performed, and all deletion variations in 22q11 region were also compared. RESULTS: Sixteen individuals with UHR (44.4%) and none with HR converted into schizophrenia in follow-up after two years. Six loci including neurexin-1(NRXN1) (rs1045881), dopamine D1 receptor (DRD1) (rs686, rs4532), chitinase-3-like protein 1 (CHI3L1) (rs4950928), velocardiofacial syndrome (ARVCF) (rs165815), dopamine D2 receptor (DRD2) (rs1076560) were identified higher expression with significant difference in individuals converted into schizophrenia after two years. The Family with Sequence Similarity 230 Member H (FAM230H) gene in the 22q11 region were also found high expression in UHR group. CONCLUSIONS: Further expansion of sample size and validation studies are needed to explore the pathogenesis of these risk loci in UHR conversion into schizophrenia in the future.
Subject(s)
Genome-Wide Association Study , Schizophrenia , Adult , Female , Humans , Male , Young Adult , China , East Asian People , Follow-Up Studies , Genetic Predisposition to Disease/genetics , Schizophrenia/geneticsABSTRACT
AIM: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). METHODS: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side-effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. RESULTS: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side-effect assessment indicated that lithium was well-tolerated. 64% (n = 16) of participants in the lithium group were lithium-adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. CONCLUSIONS: With a side-effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort.
Subject(s)
Psychotic Disorders , Humans , Pilot Projects , Psychotic Disorders/drug therapy , Male , Female , Adolescent , Young Adult , Lithium Compounds/administration & dosage , Lithium Compounds/adverse effects , Adult , Treatment OutcomeABSTRACT
BACKGROUND: Patients with an ultra-high risk of psychosis (UHR) are more likely to transition to psychosis. Attachment style has also been associated with psychosis and other symptoms. AIMS: To review attachment styles in UHR patients and to analyze related psychosocial factors. Ours is the first systematic review of attachment in this population. METHOD: We performed a systematic review of attachment and related psychosocial factors in UHR patients following the PRISMA methodology. RESULTS: We identified five studies. The results revealed high rates of insecure attachment in this population (more than 80%). The UHR sample presented high levels of depression, anxiety, social anxiety, emotional reactivity, trauma, and poor mentalization. Premorbid social adjustment was a predictor of improvement in disorganization and negative symptoms. The rate of transition to psychosis was 10%. Attachment patterns accounted for 16.8% of the variance. This vulnerability for psychosis was also associated with poor mentalization. CONCLUSION: Early detection of patients with UHR and insecure attachment is crucial, since early intervention to address symptoms, mentalization, and attachment is feasible and may lead to an improvement in the remaining associated psychosocial related factors (secure style: better global functioning and less affective and anxious symptoms). PROSPERO ID440957.
Subject(s)
Object Attachment , Psychotic Disorders , Humans , Psychotic Disorders/psychology , Anxiety/psychology , Risk Factors , Social Adjustment , Depression/psychology , MentalizationABSTRACT
Hydrocarbon (HC) contamination in groundwater (GW) is a widespread environmental issue. Dissolved hydrocarbons in water are commonly utilized as an energy source by natural microbial communities, which can produce water soluble intermediate metabolite compounds, herein referred to as oxygen containing organic compounds (OCOCs), before achieving complete mineralization. This review aims to provide a comprehensive assessment of the literature focused on the state of the science for OCOCs detected and measured in GW samples collected from petroleum contaminated aquifers. In this review, we discuss and evaluate two hypotheses investigating OCOC formation, which are major points of contention in the freshwater oil spill community that need to be addressed. We reviewed over 150 articles compiling studies investigating OCOC formation and persistence to uncover knowledge gaps in the literature and studies that recommend quantitative and qualitative measurements of OCOCs in petroleum-contaminated aquifers. This review is essential because no consensus exists regarding specific compounds and related concerns. We highlight the knowledge gaps to progressing the discussion of hydrocarbon conversion products.
ABSTRACT
Sea spray aerosols (SSAs) are one of the largest natural sources of aerosols globally, known to affect the earth's radiation budget and to play a pivotal role in air quality and climate. The physical and chemical properties of organic components in SSA change during long-distance atmospheric transport over the ocean. To characterize the evolution of organic components during the aging process of SSA, in this study, we use a flow reactor to simulate the oxidation processes of SSA produced by authentic seawater via OH radicals (in the presence of organic gases evaporated from seawater) and to present the molecular signatures of the nascent and aged SSA. We found, under our experimental conditions, that oxidation of headspace organic gases during aging leads to significant formation of new particles and changes in the chemical constituents of SSA. In the nascent and aged SSA samples, we retained 129 and 340 products, respectively. The formation of high O/C and low carbon-number products was observed during the aging process, corresponding to functionalization and fragmentation reactions. Moreover, the significant contributions of compounds containing multiple nitrogen atoms and sulfate groups were observed in aged SSA for the first time, which can be attributed to the accretion reaction driven by OH heterogeneous oxidation and the formation of organic sulfur compounds, respectively. These findings provide additional insights into the atmospheric transformation of organic components in marine aerosols, which is important for understanding the global carbon cycle.