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Qin Xiang Ng,1,2 Alex Yu Sen Soh,1 Wayren Loke,2 Donovan Yutong Lim,3 Wee-Song Yeo1 1National University Hospital, National University Health System, Singapore; 2MOH Holdings Pte Ltd, Singapore; 3Institute of Mental Health, Singapore Abstract: Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal ­disorder characterized by chronic abdominal pain or discomfort and altered bowel habits. Despite the global prevalence and disease burden of IBS, its underlying pathophysiology remains unclear. Inflammation may play a pathogenic role in IBS. Studies have highlighted the persistence of mucosal inflammation at the microscopic and molecular level in IBS, with increased recruitment of enteroendocrine cells. Substantial overlaps between IBS and inflammatory bowel disease have also been reported. This review thus aimed to discuss the body of evidence pertaining to the presence of mucosal inflammation in IBS, its putative role in the disease process of IBS, and its clinical relevance. Increased mast cell density and activity in the gut may correlate with symptoms of visceral hypersensitivity. As evidenced by patients who develop postinfectious IBS, infective gastroenteritis could cause systemic inflammation and altered microbiome diversity, which in turn perpetuates a cycle of chronic, low-grade, subclinical inflammation. Apart from mucosal inflammation, neuroinflammation is probably involved in the pathophysiology of IBS via the “gut–brain” axis, resulting in altered neuroendocrine pathways and glucocorticoid receptor genes. This gives rise to an overall proinflammatory phenotype and dysregulated hypothalamic–pituitary–adrenal axis and serotonergic (5-HT) functioning, which could, at least in part, account for the symptoms of IBS. Although a definite and reproducible pattern of immune response has yet to be recognized, further research into anti-inflammatories may be of clinical value. Keywords: irritable bowel syndrome, postinfectious, inflammation, microbiome

Qin Xiang Ng,1,2 Michelle Lee Zhi Qing De Deyn,3 Nandini Venkatanarayanan,4 Collin Yih Xian Ho,2 Wee-Song Yeo,5 1Department of Medicine, National University Hospital, National University Health System, Singapore; 2MOH Holdings Pte Ltd, Singapore; 3Department of Medicine, James Cook University Hospital, Middlesbrough, UK; 4Department of Medicine, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK; 5Department of Paediatrics, National University Hospital, National University Health System, Singapore Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better.Methods: Using the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January 1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data.Results: A total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119–0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467).Conclusion: Currently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged. Keywords: SJS, TEN, epidermal necrolysis, cyclosporine, CsA, meta-analysis

We present a novel method for sensitive exosomal protein detection using organic matrix-free laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and gold nanoparticles (AuNPs) functionalized with mass tags for signal amplification (Am-tags). Target exosomes were captured by specific antibodies on AuNPs and a biochip, where the antibody-presenting AuNPs (Ab/Am-tag@AuNPs) contained excess Am-tags. LDI-TOF MS analysis revealed the mass signal of Am-tags on Ab/Am-tag@AuNPs, indicating the presence of target exosomes. Thus, the target signal was amplified by a large number of Am-tags, resulting in enhanced sensitivity. We optimized the protocol to prepare stable Ab/Am-tag@AuNPs, focusing on parameters such as the concentration and ratio of thiol molecules for AuNP functionalization, suitable solvents for the coupling reaction, and amount of antibodies conjugated to the AuNPs. Subsequently, we evaluated the ability of our method to detect exosomes isolated from three cell lines, NIH3T3, MCF7, and HeLa, using an anti-Rab5 immobilized gold chip and anti-CD63/Am-tag@AuNPs with LDI-TOF MS analysis. Calibration curves constructed for the three cell lines showed a linear relationship with an excellent limit of detection. Finally, we emphasized the versatility of our method for the quantitative detection of exosomal proteins CD63 and mucin 1 (MUC1) using two types of Am-tags. LDI-TOF MS analysis revealed the presence of CD63 and MUC1 at different expression levels in HeLa and MCF7 cancer cells. Our findings clearly indicate the potential of Ab/Am-tag@AuNPs as a sensitive and reliable approach for identifying biomarkers in exosomes, providing valuable insights into their utility in biomedical research and clinical settings., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl-CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain α-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective BCCAs and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway., (© 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Mass tags have been used for the precise identification, quantification, and characterization of macrobiomolecules and small organic molecules. Existing research has not yet demonstrated the preparation of a series of trityl-based photocleavable mass tags (PMTs) with similar structures but different molecular weights and mass variability. Herein, we introduce the design and synthesis of trityl-based in situ PMTs that generate heterolytic photocleavable cationic species upon laser irradiation. Mass variation of the PMTs was achieved via a simple conjugation reaction in the final step of synthesis. We prepared a series of PMTs with similar structures but different molecular weights and performed organic matrix-free laser desorption/ionization mass spectrometry (LDI MS) analysis. The practical applicability of the PMTs was evaluated by conjugating PMTs to oligonucleotides and utilizing them for detecting specific oligonucleotide targets combined with a mass signal amplification strategy. Quantitative aspects were also evaluated to verify the capability of the mass tags for multiplexed detection and the quantification of targets. The LDI MS analysis clearly demonstrated in situ heterolytic photocleavage that formed trityl cation peaks with high S/N ratios and high sensitivity. We strongly believe that the developed mass tags and LDI MS are useful alternatives to conventional signal transduction methods used for biosensors, such as surface plasmon resonance, electrochemical redox, and fluorescence.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a commonly used technique for analyzing large biomolecules. However, the utilization of organic matrices limits the small-molecule analysis because of the interferences in the low-mass region and the reproducibility issues. To overcome these limitations, a surface-assisted laser desorption/ionization (SALDI), which utilizes nanostructured metallic surfaces, has been developed. Herein, a novel approach for SALDI-MS was proposed using silica@gold core-shell hybrid materials with a nanogap-rich shell (SiO 2 @Au NGS), which is an emerging material due to its excellent heat-generating capabilities. The gold shell thickness was controlled by adjusting the concentration of gold precursor for the growth of gold nanoparticles. SALDI-MS measurements were performed on a layer formed by drop-casting a mixture of SiO 2 @Au NGS and analytes. At the optimized process, the gold shell thickness was observed to be 17.2 nm, which showed the highest absorbance. Based on the enhanced SALDI capability, SiO 2 @Au NGS was utilized to detect various small molecules, including amino acids, sugars, and flavonoids, and the ionization softness was confirmed with a survival yield upon fragmentation. The limits of detection, reproducibility, and salt tolerance of SiO 2 @Au NGS demonstrate its potential as an effective and reliable SALDI material for small-molecule analyses.

The typical textile dyeing process calls for a wide range of operational parameters, and it has always been difficult to pinpoint which of these qualities is the most important in dyeing performance. Consequently, this research used a combined design of experiments and machine learning prediction models' method to offer a sustainable and beneficial reactive cotton fabric dyeing process. To be more precise, we built a least square support vector regression (LSSVR) model based on Taguchi's statistical orthogonal design (L 27 ) to predict exhaustion percentage (E%), fixation rate (F%), and total fixation efficiency (T%) and color strength (K/S) in the reactive cotton dyeing process. The model's prediction accuracy was assessed using many measures, including root mean square error (RMSE), mean absolute error (MAE), and the coefficient of determination (R 2 ). Principal component regression (PCR), partial least square regression (PLSR), and fuzzy modelling were some of the other types of regression models used to compare results. Our findings reveal that the LSSVR model greatly outperformed competing models in predicting the E%, F%, T%, and K/S. This is shown by the LSSVR model's much smaller RMSE and MAE values. Overall, it provided the highest possible R 2 values, which reached 0.9819., (© 2023. The Author(s).)

Despite the widespread interest in electrospinning technology, very few simulation studies have been conducted. Thus, the current research produced a system for providing a sustainable and effective electrospinning process by combining the design of experiments with machine learning prediction models. Specifically, in order to estimate the diameter of the electrospun nanofiber membrane, we developed a locally weighted kernel partial least squares regression (LW-KPLSR) model based on a response surface methodology (RSM). The accuracy of the model's predictions was evaluated based on its root mean square error (RMSE), its mean absolute error (MAE), and its coefficient of determination (R 2 ). In addition to principal component regression (PCR), locally weighted partial least squares regression (LW-PLSR), partial least square regression (PLSR), and least square support vector regression model (LSSVR), some of the other types of regression models used to verify and compare the results were fuzzy modelling and least square support vector regression model (LSSVR). According to the results of our research, the LW-KPLSR model performed far better than other competing models when attempting to forecast the membrane's diameter. This is made clear by the much lower RMSE and MAE values of the LW-KPLSR model. In addition, it offered the highest R 2 values that could be achieved, reaching 0.9989., (© 2023. The Author(s).)

The regulation of membrane protein activity for cellular functions is critically dependent on the composition of phospholipid membranes. Cardiolipin, a unique phospholipid found in bacterial membranes and mitochondrial membranes of eukaryotes, plays a crucial role in stabilizing membrane proteins and maintaining their function. In the human pathogen Staphylococcus aureus, the SaeRS two-component system (TCS) controls the expression of key virulence factors essential for the bacterium's virulence. The SaeS sensor kinase activates the SaeR response regulator via phosphoryl transfer to bind its gene target promoters. In this study, we report that cardiolipin is critical for sustaining the full activity of SaeRS and other TCSs in S. aureus. The sensor kinase protein SaeS binds directly to cardiolipin and phosphatidylglycerol, enabling SaeS activity. Elimination of cardiolipin from the membrane reduces SaeS kinase activity, indicating that bacterial cardiolipin is necessary for modulating the kinase activities of SaeS and other sensor kinases during infection. Moreover, the deletion of cardiolipin synthase genes cls1 and cls2 leads to reduced cytotoxicity to human neutrophils and lower virulence in a mouse model of infection. These findings suggest a model where cardiolipin modulates the kinase activity of SaeS and other sensor kinases after infection to adapt to the hostile environment of the host and expand our knowledge of how phospholipids contribute to membrane protein function.

Given the carcinogenic properties of formaldehyde-based chemicals, an alternative method for resin-finishing cotton textiles is urgently needed. Therefore, the primary objective of this study is to introduce a sustainable resin-finishing process for cotton fabric via an industrial procedure. For this purpose, Bluesign® approved a formaldehyde-free Knittex RCT® resin was used, and the process parameters were designed and optimized according to the Taguchi L 27 method. XRD analysis confirmed the crosslinking formation between resin and neighboring molecules of cotton fabric, as no change in the cellulose crystallization phase. Several machine learning models were built in a sequence to predict the crease recovery angle (CRA), tearing strength (TE) and whiteness index (WI). Assessment of modelling was evaluated through the use of various metrics such as root mean square error (RMSE), mean absolute error (MAE), and the coefficient of determination (R 2 ). Results were compared to those from other regression models, such as principal component regression (PCR), partial least squares regression (PLSR), and fuzzy modelling. Based on the results of our research, the LSSVR model predicted the CRA, TE, and WI with substantially more accuracy than other models, as shown by the fact that its RMSE and MAE values were significantly lower. In addition, it offered the greatest possible R 2 values, reaching up to 0.9627., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Staphylococcus aureus is a ubiquitous Gram-positive bacterium and an opportunistic human pathogen. S. aureus pathogenesis relies on a complex network of regulatory factors that adjust gene expression. Two important factors in this network are CodY, a repressor protein responsive to nutrient availability, and the SaeRS two-component system (TCS), which responds to neutrophil-produced factors. Our previous work revealed that CodY regulates the secretion of many toxins indirectly via Sae through an unknown mechanism. We report that disruption of codY results in increased levels of phosphorylated SaeR (SaeR~P) and that codY mutant cell membranes contain a higher percentage of branched-chain fatty acids (BCFAs) than do wild-type membranes, prompting us to hypothesize that changes to membrane composition modulate the activity of the SaeS sensor kinase. Disrupting the lpdA gene encoding dihydrolipoyl dehydrogenase, which is critical for BCFA synthesis, significantly reduced the abundance of SaeR, phosphorylated SaeR, and BCFAs in the membrane, resulting in reduced toxin production and attenuated virulence. Lower SaeR levels could be explained in part by reduced stability. Sae activity in the lpdA mutant could be complemented genetically and chemically with exogenous short- or full-length BCFAs. Intriguingly, lack of lpdA also alters the activity of other TCSs, suggesting a specific BCFA requirement managing the basal activity of multiple TCSs. These results reveal a novel method of posttranscriptional virulence regulation via BCFA synthesis, potentially linking CodY activity to multiple virulence regulators in S. aureus. IMPORTANCE Two-component systems (TCSs) are an essential way that bacteria sense and respond to their environment. These systems are usually composed of a membrane-bound histidine kinase that phosphorylates a cytoplasmic response regulator. Because most of the histidine kinases are embedded in the membrane, lipids can allosterically regulate the activity of these sensors. In this study, we reveal that branched-chain fatty acids (BCFAs) are required for the activation of multiple TCSs in Staphylococcus aureus. Using both genetic and biochemical data, we show that the activity of the virulence activator SaeS and the phosphorylation of its response regulator SaeR are reduced in a branched-chain keto-acid dehydrogenase complex mutant and that defects in BCFA synthesis have far-reaching consequences for exotoxin secretion and virulence. Finally, we show that mutation of the global nutritional regulator CodY alters BCFA content in the membrane, revealing a potential mechanism of posttranscriptional regulation of the Sae system by CodY.

Objectives: This research aims to apply an auditory display for tumor imaging using fluorescence data, discuss its feasibility for in vivo tumor evaluation, and check its potential for assisting enhanced cancer perception. Methods: Xenografted mice underwent fluorescence imaging after an injection of cy5.5-glucose. Spectral information from the raw data was parametrized to emphasize the near-infrared fluorescence information, and the resulting parameters were mapped to control a sound synthesis engine in order to provide the auditory display. Drag−click maneuvers using in-house data navigation software-generated sound from regions of interest (ROIs) in vivo. Results: Four different representations of the auditory display were acquired per ROI: (1) audio spectrum, (2) waveform, (3) numerical signal-to-noise ratio (SNR), and (4) sound itself. SNRs were compared for statistical analysis. Compared with the no-tumor area, the tumor area produced sounds with a heterogeneous spectrum and waveform, and featured a higher SNR as well (3.63 ± 8.41 vs. 0.42 ± 0.085, p < 0.05). Sound from the tumor was perceived by the naked ear as high-timbred and unpleasant. Conclusions: By accentuating the specific tumor spectrum, auditory display of fluorescence imaging data can generate sound which helps the listener to detect and discriminate small tumorous conditions in living animals. Despite some practical limitations, it can aid in the translation of fluorescent images by facilitating information transfer to the clinician in in vivo tumor imaging.

Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.

Kidney failure, one of the most prevalent diseases in the world and with increasing incidence, is associated with substantial morbidity and mortality. Currently available modes of kidney replacement therapy include dialysis and kidney transplantation. Though kidney transplantation is the preferred and ideal mode of kidney replacement therapy, this modality, however, is not without its risks. Kidney transplant recipients are constantly at risk of complications associated with immunosuppression, namely, opportunistic infections (e.g., Epstein-Barr virus and cytomegalovirus infections), post-transplant lymphoproliferative disorder , and complications associated with immunosuppressants (e.g., calcineurin inhibitor- and corticosteroid-associated new onset diabetes after transplantation and calcineurin inhibitor-associated nephrotoxicity). Transplantation tolerance, an acquired state in which immunocompetent recipients have developed donor-specific unresponsiveness, may be the Holy Grail in enabling optimal allograft survival and obviating the risks associated with immunosuppression in kidney transplant recipients. This review aims to discuss the biomarkers available to predict, identify, and define the transplant immune tolerant state and various tolerance induction strategies. Regrettably, pediatric patients have not been included in any tolerance studies and this should be the focus of future studies., (© 2021. IPNA.)

Novel (Z)-3-((4,6-diphenylpyrimidin-2-ylamino)methylene)-2,3-dihydrochromen-4-one derivatives were designed and synthesized to find chemotherapeutic agents. Derivative 9 was selected based on its clonogenicity against cancer cells and synthetic yield for further biological experiments. It showed decreases in aurora kinase A, B, and C phosphorylation from western blot analysis. Derivative 9 upregulated the expression of G1 cell cycle inhibitory proteins including p21 and p27, and G1 progressive cyclin D1, and downregulated G1-to-S progressive cyclins, resulting in cell cycle arrest at the G1/S boundary. It stimulated the cleavage of caspase-9, -3, -7, and poly (ADP-ribose) polymerase, resulting in triggering apoptosis through a caspase-dependent pathway. In addition, derivative 9 inhibited in vivo tumor growth in a syngeneic tumor implantation mouse model. The findings of this study suggest that derivative 9 can be considered as a lead compound for chemotherapeutic agents., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the Gram-positive pathogen Staphylococcus aureus , FtsH, a membrane-bound metalloprotease, plays a critical role in bacterial virulence and stress resistance. This protease is also known to sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics; however, the molecular mechanism is not known. Here, by the analysis of FtsH substrate mutants, we found that FtsH sensitizes MRSA specifically to β-lactams by degrading YpfP, the enzyme synthesizing the anchor molecule for lipoteichoic acid (LTA). Both the overexpression of FtsH and the disruption of ypfP -sensitized MRSA to β-lactams were observed. The knockout mutation in ftsH and ypfP increased the thickness of the cell wall. The β-lactam sensitization coincided with the production of aberrantly large LTA molecules. The combination of three mutations in the rpoC , vraB, and SAUSA300&#95;2133 genes blocked the β-lactam-sensitizing effect of FtsH. Murine infection with the ypfP mutant could be treated by oxacillin, a β-lactam antibiotic ineffective against MRSA; however, the effective concentration of oxacillin differed depending on the S. aureus strain. Our study demonstrated that the β-lactam sensitizing effect of FtsH is due to its digestion of YpfP. It also suggests that the larger LTA molecules are responsible for the β-lactam sensitization phenotype, and YpfP is a viable target for developing novel anti-MRSA drugs.

Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has anti-inflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Titanium tetrachloride (TiCl₄) as an alternative coagulant to remove organic matters and nutrients from the effluent of the secondary wastewater treatment was evaluated by comparison of removal efficiency of total phosphorous to Al- and Fe-based coagulants. Also, the surface characteristics, elemental contents, and crystallinity of the TiO₂ produced from wastewater sludge flocculated with TiCl₄ coagulant were investigated depending on the calcination temperatures. The more dosages of coagulants were injected, the greater concentrations of the cations (Al +3 , Fe +3 , Ti +4 ) and hydrogen ions (H + ) resulted in the lower pH. Also, TiCl₄ formed larger and heavier flocs than other coagulants and resulted in greater T-P removal efficiencies with reduced amounts of dosage. The phase change of anatase and rutile crystalline structures of TiO₂ incinerated from wastewater sludges of TiCl₄ coagulant was observed at relatively high calcination temperatures due to the existence of mixtures of organic matters, nutrients, and various impurities in the wastewater sludges of TiCl₄ coagulant. Both C and P atoms were found to be mainly doped in/on TiO₂ and the C and P atom originated from residual carbon of the settled organic matters and phosphorus nutrients present in effluents from sewage treatment plant, respectively. Therefore, 600-800 °C is the optimal calcination temperatures for TiO₂ produced from TiCl₄ coagulant flocculated with effluents from sewage treatment plant.

Although psychological factors are known to affect bladder and bowel control, the occurrence of functional urinary disorders in patients with psychiatric disorders has not been well-studied or described. A higher prevalence of functional lower urinary tract disorders have also been reported amongst patients with obsessive-compulsive (OC) disorders. A systematic literature search of PubMed, EMBASE, OVID Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found five observational studies on the topic. Unfortunately, as only one study had a (healthy) control group, a meta-analytic approach was not possible. Overall, patients with OC symptoms appeared to have increased occurrence of functional urinary symptoms, e.g., overactive bladder, increase in urgency, frequency, incontinence and enuresis. This was even more common amongst patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) or Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) as opposed to patients with OCD alone. Several biological and behavioural mechanisms and treatment approaches were discussed. However, as the current evidence base was significantly limited and had moderate to serious risk of bias, no strong inferences could be drawn. Further well-designed cohort studies are necessary to better elucidate the observed associations and their management.

Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities in vitro and in vivo . There is growing commercial interest in the application of astaxanthin in nutraceuticals and cosmeceuticals, due to its purported photoprotective, DNA repair, antioxidant, and anti-inflammatory benefits. This systematic review therefore aimed to summarize current clinical evidence on the effects of astaxanthin supplementation on skin health. Using the following combinations of broad Major Exploded Subject Headings (MesH) terms or text words [astaxanthin OR AST OR ASX OR carotenoid OR xanthophyll] AND [skin OR derm*], a comprehensive search of PubMed, EMBASE, Medline, Clinicaltrials.gov, and Google Scholar databases found a total of eleven clinical studies. There were six randomized, placebo-controlled, double-blind trials, while the rest were prospective, open-label studies. In many of the randomized, controlled trials reviewed, AST supplementation improved skin texture, appearance (wrinkles), and moisture content at the end of the study period. AST also appeared to protect against UV-induced skin damage. No serious adverse events were reported in any of the studies. However, most available studies had a relatively small sample size and were conducted on healthy Japanese females. Many of the studies were also funded by commercial entities, with potential conflicts of interests. This was difficult to account for in our analyses. Overall, there is some clinical data to support the benefits of astaxanthin supplementation (in the range of 3 to 6 mg/d) on skin health, especially for photoaged skin.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available athttp://dx.doi.org/10.21037/qims-20-929). The authors have no conflicts of interest to declare.

In recent months, there are increasing reports of a Kawasaki disease-like syndrome in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed 'Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS)' in the UK. Debate is ongoing regarding the nature of these pro-inflammatory syndromes. We herein propose that the platelet count may, at least in part, be able to help us differentiate between the two aforementioned syndromes. In a recent report, compared to a historical 'classical' Kawasaki disease (KD) cohort, patients with PIMS-TS had significantly lower platelet counts (188 vs 383 g/L, p < 0.0001). A possible explanation for this is their difference in underlying immunopathogenesis. In KD, the fundamental pathogenesis is thought to be immune complex-mediated, hence, the use of intravenous immunoglobulin (IVIg) which competes with the immunoglobulin Fc receptors (FcRs) on inflammatory cells, preventing the activation of these cells and thereby ameliorating the inflammatory response. If left untreated, these immune complexes activates the inflammatory cells (including monocytes and neutrophils), which also results in recruitment of platelets, resulting in the thrombocytosis we commonly see in KD. These immune complexes may also bind to platelets directly via FcRs on platelet membranes. In contrast, in viral-associated hyperinflammatory syndromes (e.g. PIMS-TS or MIS-C), there are mediators being secreted in the process of eradication of the virus (mainly to stimulate CD8+ cells to kill viral infected cells), which would inadvertently suppress bone marrow function and activate platelets, culminating in thrombocytopenia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mass spectrometry (MS) is an ideal tool for analyzing multiple types of (bio)molecular information simultaneously in complex biological systems. In addition, MS provides structural information on targets, and can easily discriminate between true analytes and background. Therefore, imaging mass spectrometry (IMS) enables not only visualization of tissues to give positional information on targets but also allows for molecular analysis of targets by affording the molecular weights. Matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) MS is particularly effective and is generally used for IMS. However, the requirement for an organic matrix raises several limitations that get in the way of accurate and reliable images and hampers imaging of small molecules such as drugs and their metabolites. To overcome these problems, various organic matrix-free LDI IMS systems have been developed, mostly utilizing nanostructured surfaces and inorganic nanoparticles as an alternative to the organic matrix. This minireview highlights and focuses on the progress in organic matrix-free LDI IMS and briefly discusses the use of other IMS techniques such as desorption electrospray ionization, laser ablation electrospray ionization, and secondary ion mass spectrometry. [BMB Reports 2020; 53(7): 349-356].

Yemen has been faced with the worst cholera epidemic of modern times, with more than 1 million suspected cases and 3000 deaths at the time of writing. This problem is largely due to the longstanding civil war between pro-government forces and the Houthi armed movement, which has severely damaged already vulnerable sanitation and healthcare facilities and systems in the country. It is further compounded by a dire lack of basic amenities, chronic malnutrition, and unfavourable weather conditions. Another contributory component may be aerial transfer by cholera-infected chironomid insects. To contain the spread of cholera in Yemen, a nation-wide armistice should be negotiated, and national and local committees must be convened to coordinate efforts on the ground. Community isolation facilities with proper sanitation, reliable disposal systems, and a clean water supply should be set up to isolate and treat sick patients. The continuity of vaccination programmes should be ensured. Public health campaigns to educate local communities about good hygiene practices and nutrition are also necessary. The One Health paradigm emphasizes a multi-sectoral and transdisciplinary understanding and approach to prevent and mitigate the threat of communicable diseases. This paradigm is highly applicable to the ongoing cholera crisis in Yemen, as it demands a holistic and whole-of-society approach at the local, regional, and national levels. The key stakeholders and warring parties in Yemen must work towards a lasting ceasefire during these trying times, especially given the extra burden from the mounting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak worldwide.

We report the acid-assisted photolysis of the trimethyl lock system which has long been harnessed for a variety of applications such as drug delivery, cellular imaging, enzyme activity assays, and surface patterning. By mass spectrometric analysis, we found that photoinduced intramolecular cyclization and the ensuing release of the pendant groups of the trimethyl lock on the self-assembled monolayers proceeded cleanly in the presence of HCl, to give a high yield., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we investigated the correlation between curcumin and glutathione (GSH) levels in mammalian cells using gold nanoparticles (AuNPs) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). GSH exists in high concentration in the cytosol and acts as a major antioxidant and reducing agent in organisms. Previous studies showed that curcumin, a well-known antioxidant with anti-inflammatory, anti-proliferative, and anti-carcinogenic activities, affects GSH levels in mammalian cells. However, the correlation between their levels remains controversial and has not yet been completely elucidated. This study used our recent strategy of GSH quantification, where GSH in cell lysate is captured on maleimide groups of AuNPs and analyzed using MALDI-TOF MS with isotopomer GSH (GSH*)-conjugated AuNPs as an internal standard. The comparison between GSH and GSH* relative intensities allows the quantitation of GSH in cells. In this way, GSH levels in mammalian cells were investigated after incubation with curcumin at various concentrations with or without oxidative stress. We observed that intracellular GSH levels were affected by curcumin in a concentration-dependent manner with oxidative stress; GSH levels decrease at a lower curcumin concentration, which can be recovered at increased curcumin concentrations. We also found that the GSH level increased at all curcumin concentrations after a certain incubation time. We believe our strategy can be commonly used to determine GSH levels in cells that are treated differently with various exogenous stimulants like reactive oxygen species, biofunctional natural products, and drug candidates. Graphical abstract.

In bacteria, chromosomal DNA resides in the cytoplasm, and most transcription factors are also found in the cytoplasm. However, some transcription factors, called membrane-bound transcription factors (MTFs), reside in the cytoplasmic membrane. Here, we report the identification of a new MTF in the Gram-positive pathogen Staphylococcus aureus and its regulation by the protease FtsH. The MTF, named MbtS ( m embrane- b ound t ranscription factor of S taphylococcus aureus ), is encoded by SAUSA300&#95;2640 and predicted to have an N-terminal DNA binding domain and three transmembrane helices. The MbtS protein was degraded by membrane vesicles containing FtsH or by the purified FtsH. MbtS bound to an inverted repeat sequence in its promoter region, and the DNA binding was essential for its transcription. Transcriptional comparison between the ftsH deletion mutant and the ftsH mbtS double mutant showed that MbtS could alter the transcription of over 200 genes. Although the MbtS protein was not detected in wild-type (WT) cells grown in a liquid medium, the protein was detected in some isolated colonies on an agar plate. In a murine model of a skin infection, the disruption of mbtS increased the lesion size. Based on these results, we concluded that MbtS is a new S. aureus MTF whose activity is proteolytically regulated by FtsH. IMPORTANCE Staphylococcus aureus is an important pathogenic bacterium causing various diseases in humans. In the bacterium, transcription is typically regulated by the transcription factors located in the cytoplasm. In this study, we report an atypical transcription factor identified in S. aureus Unlike most other transcription factors, the newly identified transcription factor is located in the cytoplasmic membrane, and its activity is proteolytically controlled by the membrane-bound AAA+ protease FtsH. The newly identified MTF, named MbtS, has the potential to regulate the transcription of over 200 genes. This study provides a molecular mechanism by which a protease affects bacterial transcription and illustrates the diversity of the bacterial transcriptional regulation., (Copyright © 2020 American Society for Microbiology.)

Many developed countries are experiencing a rapidly "greying" population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo-controlled, double-blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects., (© 2019 John Wiley & Sons, Ltd.)

Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits.

Background: Depression is a growing public health problem that affects over 350 million people globally and accounts for approximately 7.5% of healthy years lost due to disability. Escitalopram, one of the first-line medications for the treatment of depression, is a selective serotonin reuptake inhibitor and one of the most commonly prescribed antidepressant medications worldwide. Although thought to be generally safe and with minimal drug-drug interactions, we herein present an unusual case of cholestatic liver injury, likely secondary to escitalopram initiation., Case Summary: A 56-year-old Chinese lady presented with fever and cholestatic liver injury two weeks after initiation of escitalopram for the treatment of psychotic depression. Physical examination was unremarkable. Further investigations, including a computed tomography scan of the abdomen and pelvis and tests for hepatitis A, B and C and for autoimmune liver disease were unyielding. Hence, a diagnosis of escitalopram-induced liver injury was made. Upon stopping escitalopram, repeat liver function tests showed downtrending liver enzymes with eventual normalization of serum aspartate aminotransferase and alanine aminotransferase one-week post-discharge., Conclusion: Clinicians should be aware of the possibility of escitalopram-induced liver injury when initiating depressed patients on antidepressant treatment. This requires extra vigilance as most patients may remain asymptomatic. Measurement of liver function tests could be considered after initiation of antidepressant treatment, especially in patients with pre-existing liver disease., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Irritable bowel syndrome (IBS) is a prevalent and debilitating gastrointestinal condition. Research has reported persistent, low-grade mucosal inflammation and significant overlaps between patients with IBS and those with dyspepsia, suggesting a possible pathogenic role of Helicobacter pylori ( H. pylori ) in IBS. This study therefore aimed to provide the first systematic review and meta-analysis on the association between H. pylori infection and IBS., Aim: To investigate the association between H. pylori infection and IBS., Methods: Using the keywords " H. pylori OR Helicobacter OR Helicobacter pylori OR infection" AND "irritable bowel syndrome OR IBS", a preliminary search of PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Web of Science, Google Scholar and WanFang databases yielded 2924 papers published in English between 1 January 1960 and 1 June 2018. Attempts were also made to search grey literature., Results: A total of 13 clinical studies were systematically reviewed and nine studies were included in the final meta-analysis. Random-effects meta-analysis found a slight increased likelihood of H. pylori infection in patients with IBS, albeit this was not statistically significant (pooled odds ratio 1.47, 95% confidence interval: 0.90-2.40, P = 0.123). It must also be acknowledged that all of the available studies reported only crude odd ratios. H. pylori eradication therapy also does not appear to improve IBS symptoms. Although publication bias was not observed in the funnel plot, there was a high degree of heterogeneity amongst the studies included in the meta-analysis ( I 2 = 87.38%)., Conclusion: Overall, current evidence does not support an association between IBS and H. pylori infection. Further rigorous and detailed studies with larger sample sizes and after H. pylori eradication therapy are warranted., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript. All the authors have no conflict of interest related to the manuscript., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: Competing interestsThe BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

Background: The elucidation of the biological roles of individual active compounds in terms of their in vivo bio-distribution and bioactivity could provide crucial information to understand how natural compounds work together as treatments for diseases., Purpose: We examined the functional roles of Byakangelicin (Byn) to improve the brain accumulation of active compounds, e.g., umbelliferone (Umb), curcumin (Cur), and doxorubicin (Dox), and consequently to enhance their biological activities., Methods: Active compounds were administered intravenously to mice, with or without Byn, after which organs were isolated and visualized for their ex vivo fluorescence imaging to determine the bio-distribution of each active compound in vivo. For the in vivo bioactivity, Cur, either with or without Byn, was administered to a lipopolysaccharide (LPS)-induced neuro-inflammation model for 5 days, and its anti-inflammatory effects were examined by ELISA using a brain homogenate and serum., Results: We successfully demonstrated that the levels of active compounds (Umb, Cur, and Dox) in the brain, lung, and pancreas were greatly elevated by the addition of Byn via direct ex vivo fluorescence monitoring. In addition, sufficient accumulation of the active compound, Cur, greatly reduced LPS-induced neuro-inflammation in vivo., Conclusion: Byn could serve as a modulator to allow improved brain accumulation of diverse active compounds (Umb, Cur, and Dox) and enhanced therapeutic effects., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background and objectives : Worldwide, the number of caesarean sections performed has increased exponentially. Some studies have reported better pain control and lower postoperative requirements for opioids when intravenous (IV) paracetamol was administered preoperatively. This meta-analysis thus aimed to investigate the utility of preoperative IV paracetamol for post-caesarean analgesia. Materials and Methods: By using the keywords (paracetamol OR acetaminophen) AND [cesarea* OR caesarea* OR cesaria* OR caesaria*], a systematic literature search was conducted using PubMed, Medline, Embase, Google Scholar and ClinicalTrials.gov databases for papers published in English between January 1, 1960 and March 1, 2019. Grey literature was searched as well. Results: Seven clinical trials were reviewed, while five randomized, placebo-controlled, double-blind studies were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, there was a significant reduction in postoperative opioid consumption and pain score in the group that received preoperative IV paracetamol, compared to placebo, as the standardized mean difference (SMD) were -0.460 (95% CI -0.828 to -0.092, p = 0.014) and -0.719 (95% CI: -1.31 to -0.13, p = 0.018), respectively. However, there was significant heterogeneity amongst the different studies included in the meta-analysis (I 2 = 70.66%), perhaps owing to their diverse protocols. Some studies administered IV paracetamol 15 min before induction while others gave it before surgical incision. Conclusion: This is the first review on the topic. Overall, preoperative IV paracetamol has convincingly demonstrated useful opioid-sparing effects and it also appears safe for use at the time of delivery. It should be considered as a component of an effective multimodal analgesic regimen. Future studies could be conducted on other patient groups, e.g., those with multiple comorbidities or chronic pain disorders, and further delineate the optimal timing to administer the drug preoperatively., Competing Interests: The authors declare no conflict of interest.

Mannitol-1-phosphate dehydrogenase (M1PDH) is a key enzyme in Staphylococcus aureus mannitol metabolism, but its roles in pathophysiological settings have not been established. We performed comprehensive structure-function analysis of M1PDH from S. aureus USA300, a strain of community-associated methicillin-resistant S. aureus , to evaluate its roles in cell viability and virulence under pathophysiological conditions. On the basis of our results, we propose M1PDH as a potential antibacterial target. In vitro cell viability assessment of Δ mtlD knockout and complemented strains confirmed that M1PDH is essential to endure pH, high-salt, and oxidative stress and thus that M1PDH is required for preventing osmotic burst by regulating pressure potential imposed by mannitol. The mouse infection model also verified that M1PDH is essential for bacterial survival during infection. To further support the use of M1PDH as an antibacterial target, we identified dihydrocelastrol (DHCL) as a competitive inhibitor of S. aureus M1PDH ( Sa M1PDH) and confirmed that DHCL effectively reduces bacterial cell viability during host infection. To explain physiological functions of Sa M1PDH at the atomic level, the crystal structure of Sa M1PDH was determined at 1.7-Å resolution. Structure-based mutation analyses and DHCL molecular docking to the Sa M1PDH active site followed by functional assay identified key residues in the active site and provided the action mechanism of DHCL. Collectively, we propose Sa M1PDH as a target for antibiotic development based on its physiological roles with the goals of expanding the repertory of antibiotic targets to fight antimicrobial resistance and providing essential knowledge for developing potent inhibitors of Sa M1PDH based on structure-function studies. IMPORTANCE Due to the shortage of effective antibiotics against drug-resistant Staphylococcus aureus , new targets are urgently required to develop next-generation antibiotics. We investigated mannitol-1-phosphate dehydrogenase of S. aureus USA300 ( Sa M1PDH), a key enzyme regulating intracellular mannitol levels, and explored the possibility of using Sa M1PDH as a target for developing antibiotic. Since mannitol is necessary for maintaining the cellular redox and osmotic potential, the homeostatic imbalance caused by treatment with a Sa M1PDH inhibitor or knockout of the gene encoding Sa M1PDH results in bacterial cell death through oxidative and/or mannitol-dependent cytolysis. We elucidated the molecular mechanism of Sa M1PDH and the structural basis of substrate and inhibitor recognition by enzymatic and structural analyses of Sa M1PDH. Our results strongly support the concept that targeting of Sa M1PDH represents an alternative strategy for developing a new class of antibiotics that cause bacterial cell death not by blocking key cellular machinery but by inducing cytolysis and reducing stress tolerance through inhibition of the mannitol pathway., (Copyright © 2019 Nguyen et al.)

Background : Autism spectrum disorder (ASD) is a complex developmental condition typically characterized by deficits in social and communicative behaviors as well as repetitive patterns of behaviors. Despite its prevalence (affecting 0.1% to 1.8% of the global population), the pathogenesis of ASD remains incompletely understood. Patients with ASD are reported to have more frequent gastrointestinal (GI) complaints. There is some anecdotal evidence that probiotics are able to alleviate GI symptoms as well as improve behavioral issues in children with ASD. However, systematic reviews of the effect of prebiotics/probiotics on ASD and its associated symptoms are lacking. Methods : Using the keywords (prebiotics OR probiotics OR microbiota OR gut) AND (autism OR social OR ASD), a systematic literature search was conducted on PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases. The inclusion criteria were original clinical trials, published in English between the period 1st January 1988 and 1st February 2019. Results : A total of eight clinical trials were systematically reviewed. Two clinical trials examined the use of prebiotic and/or diet exclusion while six involved the use of probiotic supplementation in children with ASD. Most of these were prospective, open-label studies. Prebiotics only improved certain GI symptoms; however, when combined with an exclusion diet (gluten and casein free) showed a significant reduction in anti-sociability scores. As for probiotics, there is limited evidence to support the role of probiotics in alleviating the GI or behavioral symptoms in children with ASD. The two available double-blind, randomized, placebo-controlled trials found no significant difference in GI symptoms and behavior. Conclusion : Despite promising preclinical findings, prebiotics and probiotics have demonstrated an overall limited efficacy in the management of GI or behavioral symptoms in children with ASD. In addition, there was no standardized probiotics regimen, with multiple different strains and concentrations of probiotics, and variable duration of treatments.

Background: A lack of consensus exists as to the timing of kidney biopsy in children with steroid-dependent nephrotic syndrome (SDNS) where minimal change disease (MCD) predominates. This study aimed at examining the applicability of a biomarker-assisted risk score model to select SDNS patients at high risk of focal segmental glomerulosclerosis (FSGS) for biopsy., Methods: Fifty-five patients with SDNS and biopsy-proven MCD (n = 40) or FSGS (n = 15) were studied. A risk score model was developed with variables consisting of age, sex, eGFR, suPAR levels and percentage of CD8 + memory T cells. Following multivariate regression analysis, total risk score was calculated as sum of the products of odds ratios and corresponding variables. Predictive cut-off point was determined using receiver operator characteristics (ROC) curve analysis., Results: Plasma suPAR levels in FSGS patients were significantly higher, while percentage of CD45RO + CD8 + CD3 + was significantly lower than in MCD patients and controls. ROC analysis suggests the risk score model with threshold score of 16.7 (AUC 0.84, 95% CI 0.72-0.96) was a good predictor of FSGS on biopsy. The 100% PPV cut-off was >24.0, while the 100% NPV was <13.3., Conclusion: A suPAR and CD8 + memory T cell percentage-based risk score model was developed to stratify SDNS patients for biopsy and for predicting FSGS.