Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries.

BACKGROUND: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. METHODS: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. RESULTS: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. CONCLUSIONS: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Specific metabolic syndrome components predict cognition and social functioning in people with type 2 diabetes mellitus and severe mental disorders.

OBJECTIVE: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and transdiagnostic perspectives. METHODS: Metabolic syndrome components and neurocognitive and social functioning were assessed in 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL), elevated blood pressure (BP), and elevated fasting glucose (FPG); the remaining participants comprised the No-MetS group. Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No-MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 - 0.03). In both groups, the most robust associations between MetS components and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cognition and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). CONCLUSIONS: Specific MetS components are significantly associated with cognitive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cognition and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle-based therapeutic interventions targeted at that group hold the potential to improve health outcomes.

A Cofactor-Based Mechanism for the Origin of the Genetic Code.

The origin of the genetic code is probably the central problem of the studies on the origin of life. The key question to answer is the molecular mechanism that allows the association of the amino acids with their triplet codons. We proposed that the codon-anticodon duplex located in the acceptor stem of primitive tRNAs would facilitate the chemical reactions required to synthesize cognate amino acids from simple amino acids (glycine, valine, and aspartic acid) linked to the 3' acceptor end. In our view, various nucleotide-A-derived cofactors (with reactive chemical groups) may be attached to the codon-anticodon duplex, which allows group-transferring reactions from cofactors to simple amino acids, thereby producing the final amino acid. The nucleotide-A-derived cofactors could be incorporated into the RNA duplex (helix) by docking Adenosine (cofactor) into the minor groove via an interaction similar to the A-minor motif, forming a base triple between Adenosine and one complementary base pair of the duplex. Furthermore, we propose that this codon-anticodon duplex could initially catalyze a self-aminoacylation reaction with a simple amino acid. Therefore, the sequence of bases in the codon-anticodon duplex would determine the reactions that occurred during the formation of new amino acids for selective binding of nucleotide-A-derived cofactors.

Torsade de pointes associated with chloroquine, hydroxychloroquine, and azithromycin: a retrospective analysis of individual case safety reports from VigiBase.

PURPOSE: To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches. METHODS: The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated. RESULTS: One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34). CONCLUSIONS: The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.

Possible Ancestral Functions of the Genetic and RNA Operational Precodes and the Origin of the Genetic System.

The origin of genetic systems is the central problem in the study of the origin of life for which various explanatory hypotheses have been presented. One model suggests that both ancestral transfer ribonucleic acid (tRNA) molecules and primitive ribosomes were originally involved in RNA replication (Campbell 1991). According to this model the early tRNA molecules catalyzed their own self-loading with a trinucleotide complementary to their anticodon triplet, while the primordial ribosome (protoribosome) catalyzed the transfer of these terminal trinucleotides from one tRNA to another tRNA harboring the growing RNA polymer at the 3´-end.Here we present the notion that the anticodon-codon-like pairs presumably located in the acceptor stem of primordial tRNAs (Rodin et al. 1996) (thus being and remaining, after the code and translation origins, the major contributor to the RNA operational code (Schimmel et al. 1993)) might have originally been used for RNA replication rather than translation; these anticodon and acceptor stem triplets would have been involved in accurately loading the 3'-end of tRNAs with a trinucleotide complementary to their anticodon triplet, thus allowing the accurate repair of tRNAs for their use by the protoribosome during RNA replication.We propose that tRNAs could have catalyzed their own trinucleotide self-loading by forming catalytic tRNA dimers which would have had polymerase activity. Therefore, the loading mechanism and its evolution may have been a basic step in the emergence of new genetic mechanisms such as genetic translation. The evolutionary implications of this proposed loading mechanism are also discussed.

Cataracts and statins. A disproportionality analysis using data from VigiBase.

The basis of the association between statin use and cataract has been explored using the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) through January 2019. The reporting odds ratios (RORs) as a measure of disproportionality for reported cataracts and individual statins have been calculated. Subgroup analyses according statin lipophilicity, sex, and age groups have been performed. Moreover, RORs have been calculated for non-statin lipid lowering drugs. An increased disproportionality have been found for most individual statins lovastatin: [ROR: 14.80, 95% confidence interval (CI): 13.30, 16.46)], atorvastatin (ROR: 3.48, 95% CI 3.19-3.80), pravastatin (ROR: 3.15, 95% CI: 2.54-3.90), rosuvastatin (ROR: 2.90, 95% CI: 2.53-3.31), simvastatin (ROR: 2.27, 95%CI: 1.99-2.60), fluvastatin (ROR: 2.03, 95% CI: 1.33-3.08) and statins (overall) ROR: 3.66, 95% CI:3.46-3.86). Increased disproportionality for cataract and statins (drug-class) have been found regardless of statin lipophilicity, sex and group age (more or less than 65 years old). No disproportionality was found for other lipid-lowering drugs (ezetimibe, fibrates or PCSK9 inhibitors). These findings suggest an increased risk of cataract associated with statins as a drug-class. Further studies to characterize the risk are advised. Benefits and potential harms should be considered before starting treatment with statins.

Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders.

Inverse comorbidity is a lower-than-expected probability of disease occuring in individuals who have been diagnosed with other medical conditions. Emerging evidence points to inverse cancer comorbidity in people with certain CNS disorders. In this Opinion article, we discuss the evidence for this intriguing association and possible underlying mechanisms. We believe that this association is an invaluable opportunity to gain insight into the pathogenesis of these diseases, and understanding why certain individuals with CNS disorders are protected against many different types of cancer could help to develop new and improved treatments.

Rates and predictors of relapse in first-episode non-affective psychosis: a 3-year longitudinal study in a specialized intervention program (PAFIP).

Relapses may represent a critical hazard in schizophrenia spectrum disorders as they are associated with an increased risk of a clinical and functional deterioration. Preventing relapse after recovering from a first psychotic episode has become a major challenge due to its critical impact on lifelong functionality. This study explored the rate of first and second relapses and the predictors associated with these relapses in a large cohort of non-affective psychosis patients during a period of 3 years after the first break of the illness. From February 2001 to May 2014, sociodemographic and clinical data from an epidemiological cohort of 341 non-affective first-episode psychosis patients at risk of relapse were analysed at a specialized early intervention service. Logistic regression, Cox regression, and Kaplan-Meier survival analyses were performed to compare non-relapsed and relapsed patients. One hundred and sixty-six (48.7%) individuals relapsed at least once. Median time to relapse was 17.0 months in non-adherent patients and 40.0 months in adherent patients (log-rankχ 2: 51.36; p < 0.001). Non-adherence to medication (odds ratio-OR 2.979; p < 0.001), schizophrenia diagnosis (OR 2.173; p = 0.002), and age of onset (OR 1.020; p = 0.033) were the main predictors of the first relapse. Fifty-six subjects experienced a second relapse (33.73%) predicted by diagnosis (OR 1.975; p = 0.074), age of onset (OR 1.078; p = 0.003), and positive symptoms (OR 0.863; p = 0.03), but not adherence. Non-adherence is the main predictive factor of first relapse after a first episode of psychosis. Second relapses were not often and not related to modifiable factors, suggesting that multiple relapsed patients may comprise a subgroup with a higher biological risk.

Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.

There is epidemiological evidence that patients with certain Central Nervous System (CNS) disorders have a lower than expected probability of developing some types of Cancer. We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Cancers, and that are deregulated in opposite directions. We conducted transcriptomic meta-analyses of three CNS disorders (Alzheimer's disease, Parkinson's disease and Schizophrenia) and three Cancer types (Lung, Prostate, Colorectal) previously described with inverse comorbidities. A significant overlap was observed between the genes upregulated in CNS disorders and downregulated in Cancers, as well as between the genes downregulated in CNS disorders and upregulated in Cancers. We also observed expression deregulations in opposite directions at the level of pathways. Our analysis points to specific genes and pathways, the upregulation of which could increase the incidence of CNS disorders and simultaneously lower the risk of developing Cancer, while the downregulation of another set of genes and pathways could contribute to a decrease in the incidence of CNS disorders while increasing the Cancer risk. These results reinforce the previously proposed involvement of the PIN1 gene, Wnt and P53 pathways, and reveal potential new candidates, in particular related with protein degradation processes.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

BACKGROUND: Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. METHODS AND FINDINGS: Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints. CONCLUSIONS: In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment. REVIEW REGISTRATION: PROSPERO CRD42014014404.

Diagnosis and neurocognitive profiles in first-episode non-affective psychosis patients.

This study explored whether there are distinguishable neurocognitive profiles in diagnostic subgroups of first-episode non-affective psychosis (FEP) patients. Four hundred and eighty-seven individuals with diagnoses of non-affective psychosis disorders were evaluated 6 months after first contact with psychiatric services. Individuals with schizophrenia (n = 257), schizophreniform (n = 141), brief psychotic disorder (n = 54), and psychosis not otherwise specified (n = 35) were compared on baseline neuropsychological variables using analyses of variance and covariance with potential clinical, premorbid, and sociodemographic confounders. The brief psychotic disorder subgroup was the least impaired on global cognitive function, in particular when compared to the schizophrenia subgroup, and specifically on executive function, processing speed, and motor dexterity domains. However, with the exception of the processing speed domain, profile differences could be explained by sex, age, psychotic and negative symptoms, years of education, and premorbid IQ. These results suggest processing speed as a diagnostic marker for brief psychotic disorder in FEP patients. Further, there are quantitative and qualitative differences across the schizophrenia spectrum disorders subgroups, indicating different profiles with varying degrees of deficit.

How does family intervention improve the outcome of people with schizophrenia?

BACKGROUND: There is strong evidence of the efficacy of family psychosocial interventions for schizophrenia, but evidence of the role played by the attitudes of relatives in the therapeutic process is lacking. METHOD: To study the effect of a family intervention on family attitudes and to analyse their mediating role in the therapeutic process 50 patients with schizophrenia and their key relatives undergoing a trial on the efficacy of a family psychosocial intervention were studied by means of the Affective Style Coding System, the Scale of Empathy, and the Relational Control Coding System. Specific statistical methods were used to determine the nature of the relationship of the relatives' attitudes to the outcome of family intervention. RESULTS: Family psychosocial intervention was associated with a reduction in relatives' guilt induction and dominance and an improvement in empathy. Empathy and lack of dominance were identified as independent mediators of the effect of family psychosocial intervention. The change in empathy and dominance during the first 9 months of the intervention predicted the outcome in the following 15 months. CONCLUSION: Relatives' empathy and lack of dominance are mediators of the beneficial effect of family psychosocial intervention on patient's outcome.

Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors.

Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.

Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies.

BACKGROUND: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ). METHOD: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. RESULTS: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ). CONCLUSION: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.

Efficiency assessment of follow-up methodology of patients with knee replacement to predict post-surgical functionality: a protocol for randomised control PROKnee trial.

INTRODUCTION: Even when total knee arthroplasty (TKA) is an extended treatment, most patients experience a suboptimal evolution after TKA. The objectives of this study are the following: (1) to determine the effectiveness of two different prosthesis stabilisation systems on the functionality in activities of daily life, and (2) to determine prognostic biomarkers of knee prosthesis function based on radiological information, quantification of cytokines, intra-articular markers and biomechanical functional evaluation to predict successful evolution. METHODS AND ANALYSIS: The PROKnee trial was designed as a randomised controlled patient-blinded trial with two parallel groups that are currently ongoing. The initial recruitment will be 99 patients scheduled for their first TKA, without previous prosthesis interventions in lower limbs, who will be randomly divided into two groups that differed in the stabilisation methodology incorporated in the knee prosthesis: the MEDIAL-pivot group and the CENTRAL-pivot group. The maximum walking speed will be reported as the primary outcome, and the secondary results will be patient-reported questionnaires related to physical status, cognitive and mental state, radiological test, laboratory analysis and biomechanical instrumented functional performance, such as the 6-minute walking test, timed up-and-go test, gait, sit-to-stand, step-over, and ability to step up and down stairs. All the results will be measured 1 week before TKA and at 1.5, 3, 6 and 12 months after surgery. ETHICS AND DISSEMINATION: All procedures were approved by the Ethical Committee for Research with Medicines of the University Clinical Hospital of Valencia on 8 October 2020 (order no. 2020/181). Participants are required to provide informed consent for the study and for the surgical procedure. All the data collected will be treated confidentially since they will be blinded and encrypted. The results from the trial will be published in international peer-reviewed scientific journals, regardless of whether these results are negative or inconclusive. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04850300).

Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels.

Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η2p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η2p = 0.06) and C-reactive protein (CRP) (p = 0.03; η2p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.

Inflammation and weight change related to neurocognitive and functional impairment in diabetes and psychiatric disorders.

INTRODUCTION: Obesity is a global pandemic associated with various cardio-metabolic and psychiatric disorders. Neurocognitive and functional deficits have been associated with several somatic and psychiatric disorders. Adiposity-related inflammation has recently emerged as a key risk factor for neurocognitive and functional impairments. This prospective transdiagnostic study aimed to investigate the role of adiposity-related inflammatory markers in neurocognitive and functional outcomes associated with weight changes. METHODS: Peripheral blood inflammatory and oxidative stress biomarkers and neurocognitive and functional performance were assessed twice over 1 year in 165 individuals, including 30 with schizophrenia, 42 with bipolar disorder, 35 with major depressive disorder, 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls. Participants were stratified by body mass index into categories of type 2 obesity (T2OB; n=30), type 1 obesity (T1OB; n=42), overweight (OW; n=53), and average weight (NW; n=40). Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Compared with NW, T2OB and T1OB were significantly associated with impaired neurocognitive and functional performance (p<0.01; η2p=0.06-0.12) and higher levels of C-reactive protein and platelets (PLT) (p<0.01; η2p=0.08-0.16), with small-to-moderate effect sizes. IL-6, IL-10, and PLT were key factors for detecting significant weight changes in T1OB and T2OB over time. Regression models revealed that inflammatory and oxidative stress biomarkers and cellular adhesion molecules were significantly associated with neurocognitive and functional performance (p<0.05). DISCUSSION: Obesity is characterized by neurocognitive and functional impairments alongside low-grade systemic inflammation. Adiposity-related inflammatory biomarkers may contribute to neurocognitive and functional decline in individuals with T2DM and psychiatric disorders. Our data suggest that these biomarkers facilitate the identification of specific subgroups of individuals at higher risk of developing obesity.

Psychometric behaviour of the strengths and difficulties questionnaire (SDQ) in the Spanish national health survey 2006.

BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is a tool to measure the risk for mental disorders in children. The aim of this study is to describe the diagnostic efficiency and internal structure of the SDQ in the sample of children studied in the Spanish National Health Survey 2006. METHODS: A representative sample of 6,773 children aged 4 to 15 years was studied. The data were obtained using the Minors Questionnaire in the Spanish National Health Survey 2006. The ROC curve was constructed and calculations made of the area under the curve, sensitivity, specificity and the Youden J indices. The factorial structure was studied using models of exploratory factorial analysis (EFA) and confirmatory factorial analysis (CFA). RESULTS: The prevalence of behavioural disorders varied between 0.47% and 1.18% according to the requisites of the diagnostic definition. The area under the ROC curve varied from 0.84 to 0.91 according to the diagnosis. Factor models were cross-validated by means of two different random subsamples for EFA and CFA. An EFA suggested a three correlated factor model. CFA confirmed this model. A five-factor model according to EFA and the theoretical five-factor model described in the bibliography were also confirmed. The reliabilities of the factors of the different models were acceptable (>0.70, except for one factor with reliability 0.62). CONCLUSIONS: The diagnostic behaviour of the SDQ in the Spanish population is within the working limits described in other countries. According to the results obtained in this study, the diagnostic efficiency of the questionnaire is adequate to identify probable cases of psychiatric disorders in low prevalence populations. Regarding the factorial structure we found that both the five and the three factor models fit the data with acceptable goodness of fit indexes, the latter including an externalization and internalization dimension and perhaps a meaningful positive social dimension.Accordingly, we recommend studying whether these differences depend on sociocultural factors or are, in fact, due to methodological questions.

The screen for cognitive impairment in psychiatry: diagnostic-specific standardization in psychiatric ill patients.

BACKGROUND: The Screen for Cognitive Impairment in Psychiatry (SCIP) is a simple and easy to administer scale developed for screening cognitive deficits. This study presents the diagnostic-specific standardization data for this scale in a sample of schizophrenia and bipolar I disorder patients. METHODS: Patients between 18 and 55 years who are in a stable phase of the disease, diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar I disorder were enrolled in this study. RESULTS: The SCIP-S was administered to 514 patients (57.9% male), divided into two age groups (18-39 and 40-55 years) and two educational level groups (less than and secondary or higher education). The performance of the patients on the SCIP-S is described and the transformed scores for each SCIP-S subtest, as well as the total score on the instrument, are presented as a percentile, z-score, T-scores, and IQ quotient. CONCLUSIONS: We present the first jointly developed benchmarks for a cognitive screening test exploring functional psychosis (schizophrenia and bipolar disorder), which provide increased information about patient's cognitive abilities. Having guidelines for interpreting SCIP-S scores represents a step forward in the clinical utility of this instrument and adds valuable information for its use.

Myopericarditis Associated with the Novavax COVID-19 Vaccine (NVX-CoV2373): A Retrospective Analysis of Individual Case Safety Reports from VigiBase.

BACKGROUND: Myocarditis and pericarditis have been associated most notably with mRNA vaccines, but the association with a recently authorized adjuvated vaccine (NVX-CoV2373) is controversial. OBJECTIVE: The aim was to analyze the cases of myocarditis and pericarditis in association with NVX-CoV2373 reported to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase), applying disproportionality analyses. PATIENTS AND METHODS: The main characteristics of the ICSRs reporting myopericarditis with NVX-CoV2373 have been summarized. Reporting odds ratios (RORs) as a measure of disproportionality for reported myopericarditis (November 1967-August 2022) have been calculated for NVX-CoV2373; mRNA and adenoviral vector-based vaccines were also included as a reference. RESULTS: In total, 61 ICSRs included NVX-CoV2373. Most of the reports originated in Australia (50; 82.0%); 24 (39.3%) were considered serious. None of them were fatal. The median age of individuals was 35.5 years old, and most were males (38; 62.3%). Chest pain was the most common co-reported event 43 (70.5%). The median induction period was 3 days after immunization. Increased disproportionality for myopericarditis was found for NVX-CoV2373 (ROR 14.47, 95% confidence interval [CI] 11.22-18.67) and mRNA vaccines: BNT162b2 (ROR 17.15, 95% CI 16.88-17.42) and mRNA-1273 (ROR 6.92, 95% CI 6.77-7.08). Higher values were found in males. The adenoviral vector-based vaccine Ad26.COV2.S showed slightly increased disproportionality (ROR 1.83, 95% CI 1.70-1.98), whereas no increased disproportionality was found for ChAdOx1. CONCLUSIONS: NVX-CoV2373 vaccine showed a similar increased disproportionality as mRNA vaccines. More evidence from controlled studies is necessary; however, a precautionary approach is warranted. Healthcare professionals should be aware of the potential occurrence of myopericarditis with this new vaccine.