Immunophenotyping schizophrenia subtypes stratified by antipsychotic response.

Immune dysfunction has been proposed to play a role in the pathophysiology behind the development and persistence of psychosis. Current immunophenotyping studies are limited by small sample sizes and the number of immune markers investigated. Pharmacological subtypes in schizophrenia based on antipsychotic response have been proposed, but few studies have investigated immunophenotypes in treatment-resistant schizophrenia.

Association between treatment resistance and cognitive function in schizophrenia.

Introduction: Treatment-resistant schizophrenia (TRS) affects around 30% of individuals with schizophrenia. About half of the patients with TRS who are treated with clozapine do not show a meaningful clinical response, that is, clozapine resistance. To date, the relationship between cognitive function and treatment response categories is not entirely clear.

Predictors of functioning in treatment-resistant schizophrenia: the role of negative symptoms and neurocognition.

Introduction: Predictors of functioning are well-studied in schizophrenia, but much less so in treatment-resistant schizophrenia (TRS). In this study, we aim to investigate contributions of schizophrenia symptom domains and neurocognition to predict functioning in a TRS population (n = 146).

Methods: Participants were assessed on the Positive and Negative Syndrome Scale (PANSS), to calculate scores for five symptom factors (Positive, Negative, Cognitive, Depressive and Hostility) and two negative symptom constructs (Diminished Expressivity (DE), and Social Anhedonia (SA) as part of the Motivation and Pleasure-related dimension), based on a previously validated model, modified in accordance with EPA guidelines on negative symptoms assessment.

Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.

Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells.

Pyogenic liver abscesses in peritoneal dialysis patients: A single-centre retrospective case series.

Peritoneal dialysis (PD)-related infection rates have improved, but serious complications such as liver abscesses remain an issue, posing unique management challenges including safety of continuing PD versus early PD catheter removal. Current literature describing this is unfortunately limited. This study aims to describe the characteristics, management and outcomes of liver abscesses in PD patients from a retrospective review of prevalent PD patients on follow-up at Tan Tock Seng Hospital between 1st January 2016 and 30th June 2021.

Deconstructing the genetic architecture of treatment-resistant schizophrenia in East Asian ancestry.

Background: Treatment-resistant schizophrenia (TRS) affects a substantial proportion of patients who do not respond adequately to antipsychotic medications, yet the underlying biological mechanism remains poorly understood. This study investigates the link between the genetic predisposition to schizophrenia and TRS.

Methods: 857 individuals diagnosed with schizophrenia were divided into TRS (n = 142) and non-TRS (n = 715) based on well-defined TRS criteria.

Obsessive-compulsive symptoms and disorder in clozapine-treated schizophrenia.

Background: Obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) are commonly reported in patients with schizophrenia. Furthermore, the use of clozapine in treatment-resistant schizophrenia has been thought to induce or aggravate these disorders. To date, there is a paucity of research regarding the prevalence and associated factors.

Once-daily versus divided dosing regimens of clozapine: A cross-sectional study in Singapore.

Introduction: Clozapine is recognized as the gold standard medication for treatment-resistant schizophrenia. Despite the general recommendation of administering in a divided dosing regimen, clozapine is often prescribed once daily at night in clinical practice. This study aims to compare patient characteristics, psychiatric symptoms, side effects, and plasma concentration of clozapine between once-daily dosing and divided dosing regimens.

Synthesis of portimines reveals the basis of their anti-cancer activity.

Marine-derived cyclic imine toxins, portimine A and portimine B, have attracted attention because of their chemical structure and notable anti-cancer therapeutic potential. However, access to large quantities of these toxins is currently not feasible, and the molecular mechanism underlying their potent activity remains unknown until now. To address this, a scalable and concise synthesis of portimines is presented, which benefits from the logic used in the two-phase terpenoid synthesis along with other tactics such as exploiting ring-chain tautomerization and skeletal reorganization to minimize protecting group chemistry through self-protection.

The Impact of Clozapine Delay on Clinical Outcomes in Schizophrenia.

Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes. This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks.

Anger and Dementia Caregiving: A Systematic Review of the Effects of Anger and Hostility on Caregivers' Physical Health.

Background: Anger is commonly experienced by family caregivers of people living with dementia yet its effect on caregivers' physical health remains unknown.

Objective: The primary aim of this study was to systematically review current evidence on the effects of anger and hostility on caregivers' physical health.

Methods: We searched Medline, EMBASE, PubMed, and PsycINFO up to January 2022.

Novel Coronavirus Main Protease Di- and Tripeptide Inhibitors for Treating COVID-19.

COVID-19 is a highly infectious disease caused by SARS-CoV-2. First reported in December 2019, it rapidly escalated into a global pandemic, resulting in over 6.3 million fatalities by July 4, 2022.

When Objective Ambivalence Predicts Subjective Ambivalence: An Affect-Cognition Matching Perspective.

Understanding when people are likely to feel ambivalent is important, as ambivalence is associated with key attitude outcomes, such as attitude-behavior consistency. Interestingly, the presence of conflicting positive and negative reactions (objective ambivalence) is weakly related to feeling conflicted (subjective ambivalence). We tested a novel situation that can influence the correspondence between objective and subjective ambivalence: whether a message and a recipient's topic match in affective versus cognitive orientation.

Metabolic syndrome and cardiovascular risk between clozapine and non-clozapine antipsychotic users with schizophrenia.

Introduction: Clozapine use is associated with higher risks of metabolic side effects and cardiovascular diseases (CVD). Thus, this study aims to establish and compare the cardiometabolic profiles between non-clozapine antipsychotic and clozapine users with schizophrenia.

Methods: Data from 88 non-clozapine and 166 clozapine users were extracted from existing databases - demographics, medications, smoking and medical histories, anthropometric parameters, serum lipid and fasting glucose levels.

Novel Halomethylketone Azadipeptides for Treating COVID-19.

COVID-19 is a highly infectious disease caused by the SARS-CoV-2 coronavirus. It rapidly escalated into a global pandemic, causing more than 6 million fatalities by March 2022, a little over 2 years since its emergence in December 2019. The first peptidomimetic coronavirus main protease inhibitor, nirmatrelvir, was granted Emergency Use Authorization by the U.

A comparison of arteriovenous fistula failure between Malaysian and Australian and New Zealand participants enrolled in the FAVOURED trial.

Aim: To describe and compare de novo arteriovenous fistula (AVF) failure rates between Australia and New Zealand (ANZ), and Malaysia.

Background: AVFs are preferred for haemodialysis access but are limited by high rates of early failure.

Methods: A post hoc analysis of 353 participants from ANZ and Malaysia included in the FAVOURED randomised-controlled trial undergoing de novo AVF surgery was performed.

Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer.

Unlabelled: Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) in multiple cancers. Here, we discovered that besides its well-established role in DNA repair, MSH2 exerts a novel epigenomic function in gastric cancer. Unbiased CRISPR-based mass spectrometry combined with genome-wide CRISPR functional screening revealed that in early-stage gastric cancer MSH2 genomic binding is not randomly distributed but rather is associated specifically with tumor-associated super-enhancers controlling the expression of cell adhesion genes.

Long-Distance Repression by Human Silencers: Chromatin Interactions and Phase Separation in Silencers.

Three-dimensional genome organization represents an additional layer in the epigenetic regulation of gene expression. Active transcription controlled by enhancers or super-enhancers has been extensively studied. Enhancers or super-enhancers can recruit activators or co-activators to activate target gene expression through long-range chromatin interactions.

Polarization of Attitudes as a Function of Mortality Salience: A Meta-Cognitive Analysis.

Background: The present study analyzes how attitudes can polarize after reminders of death in the context of persuasion, and proposes that a meta-cognitive process (i.e., self-validation) can serve as a compensatory coping mechanism to deal with mortality salience.

Defensive Confidence and Certainty in Unchanged Attitudes: The Role of Affect-Cognition Matching.

Despite much prior research on matching appeals to the affective-cognitive orientation of attitudes, little attention has focused on the consequences of affect-cognition (mis)matching when individuals resist persuasion. We propose that unlike a matched attack, an attack that is mismatched to the affective-cognitive orientation of attitudes would result in low defensive confidence individuals holding onto their unchanged attitudes with less certainty than high defensive confidence individuals. As hypothesized, low defensive confidence participants were less certain after an affective than a cognitive attack for a cognitive issue (Study 1), and the opposite was true for an affective issue (Study 2).