Publications

Background: Schizophrenia is categorized into qualitatively distinct classes, i.e. major (MNP) and simple (SNP) neurocognitive psychosis. MNP is accompanied by more severe neurocognitive deficits and symptomatology, activated immune-inflammatory and oxidative stress pathways, and induction of the tryptophan catabolite (TRYCAT) pathway with increased quinolinic acid (QA) and lowered kynurenic acid (KA) levels. Aims: To examine whether MNP and increased QA levels are associated with increased brain injury markers, including S100 calcium-binding protein B (S100B), neuroepithelial stem cell protein (Nestin), neuron-specific enolase (NSE), phosphorylated tau217 (pTau217), and glial fibrillary acidic protein (GFAP). Methods: This case-control study included 52 MNP subjects, 68 SNP subjects, and 60 healthy controls and assessed the above brain injury biomarkers and TRYCATs. Results: NSE and GFAP were significantly higher in MNP than in SNP, and in both MNP or SNP than in controls. Serum S100B levels were substantially higher in MNP than in controls and SNP. The results indicate injuries to neurofilaments in MNP and SBP, and that MNP is additionally characterized by damage to cell bodies, axons, glial cell projections, reduced neurogenesis and synaptic plasticity as compared with SNP. Increased QA levels and lowered KA predict increased pTau217, NSE and GFAP. The QA/KA ratio is the best predictor of these three brain injury markers Conclusions: These findings validate the differentiation between the two distinct subclasses with MNP being characterized by more profound injuries to brain cells and structures as compared with SNP. Increases in peripheral QA levels may contribute to these brain injuries in MNP.

Objective: To examine associations between chemokines and menstrual cycle associated symptoms (MCAS). Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days of the menstrual cycle. MCAS is diagnosed when the total daily DRSP score during the menstrual cycle is > 0.666 percentile. We assayed plasma CCL2, CCL5, CCL11, CXCL8, CXCL10, EGF, IGF-1, and PAI-1 at days 7, 14, 21 and 28 of the menstrual cycle. Results: CCL2, CCL5, CCL11 and EGF are significantly higher in women with MCAS than in those without. Increased CCL2, CXCL10, CXCL8, CCL11 and CCL5 levels are significantly associated with DRSP scores while CCL2 is the most significant predictor explaining 39.6% of the variance. The sum of the neurotoxic chemokines CCL2, CCL11 and CCL5 is significantly associated with the DRSP score and depression, physiosomatic, breast-craving and anxiety symptoms. The impact of chemokines on MCAS symptoms may differ between consecutive weeks of the menstrual cycle with CCL2 being the most important predictor of increased DRSP levels during the first two weeks, and CXCL10 or a combination of CCL2, CCL11 and CCL5 being the best predictors during week 3 and 4, respectively.Discussion: The novel case definition "MCAS" is externally validated by increased levels of uterus-associated chemokines and EGF. Those chemokines are involved in MCAS and are regulated by sex hormones and modulate endometrium functions and brain neuro-immune responses, which may underpin MCAS symptoms. As such, uterine-related chemokines may link the uterus with brain functions via a putative uterine-chemokine-brain axis.Funding Statement: This research has been supported by 1) the Ratchadaphiseksomphot Fund, Faculty of Medicine, Chulalongkorn University, grant number RA61/016; 2) Chulalongkorn University; Government Budget; and 3) the Ratchadaphiseksomphot Fund, Chulalongkorn University.Declaration of Interests: The authors have no conflict of interest with any commercial or other association in connection with the submitted article.Ethics Approval Statement: The study was approved by the Ethics Committee of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (IRB No.611/60, COA No. 1111/2017). Written informed consent was obtained from all participants prior to the study.

Sperm morphology has always been considered an important tool in evaluating a man's fertilizing potential. The objective of this multicentric study was to evaluate intra- and interindividual variability and between-laboratory variation using the same or different criteria of sperm morphology assessment. Semen samples were obtained from 20 males and 32 smears were made of all samples. Eighty coded smears (4 per patient) were sent to 8 laboratories for morphology assessment. The centers applied different classification systems (strict criteria, WHO 1987, Dusseldorf criteria) and participants were asked to analyze the 80 smears twice, with an interval of 1 week between each participant's two analyses. Intraclass correlations between repeats showed that sperm morphology can be assessed with acceptable within observer reproducibility. Expected increases in imprecision were observed up to coefficients of variation of 30% with decreasing morphology scores, regardless of the classification system used. Agreement in correct classification of samples as normal/abnormal was obtained in 80% of cases. Differences in reproducibility between slides may reflect an important source of heterogeneity due to smear preparation. These results emphasize the importance of external quality control systems to improve the value of sperm morphology assessments in the investigation of the male partner in a subfertile couple.

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson’s disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome. Multiple lines of evidence demonstrate a positive association between the degree of peripheral immune activation, inflammation and oxidative stress, gray matter atrophy, glucose hypometabolism and cerebral hypoperfusion in illness, such as multiple sclerosis, Parkinson’s disease and chronic fatigue syndrome. Most, if not all, of these abnormalities can be explained by a reduction in the numbers and function of astrocytes secondary to peripheral immune activation and inflammation. This is also true of the widespread mitochondrial dysfunction seen in otherwise normal tissue in neuroinflammatory, neurodegenerative and autoimmune diseases and in many patients with disabling, apparently idiopathic, fatigue. Given the strong association between peripheral immune activation and neuroinflammation with the genesis of fatigue the latter group of patients should be examined using FLAIR magnetic resonance imaging (MRI) and tested for the presence of peripheral immune activation. It is concluded that peripheral inflammation and immune activation, together with the subsequent activation of glial cells and mitochondrial damage, likely account for the severe levels of intractable fatigue and disability seen in many patients with neuroimmune and autoimmune diseases.This would also appear to be the case for many patients afforded a diagnosis of Chronic Fatigue Syndrome.