Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis.

Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-ß while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient's PBMCs.

Amoxicillin impact on pathophysiology induced by short term high salt diet in mice.

Current evidence emerging from both human and animal models confirms that high-salt diet consumption over a period modulates the gut ecology and subsequently accelerates the development of the pathophysiology of many metabolic diseases. The knowledge of short-term intake of a high-salt diet (HSD) on gut microbiota and their role in the progression of metabolic pathogenesis and the consequence of a typical course of common antibiotics in this condition has yet not been investigated. The present study elicited this knowledge gap by studying how the gut microbiota profile changes in mice receiving HSD for a short period followed by Amoxicillin treatment on these mice in the last week to mimic a typical treatment course of antibiotics. In this study, we provided a standard chow diet (CD) and HSD for 3 weeks, and a subset of these mice on both diets received antibiotic therapy with Amoxicillin in the 3rd week. We measured the body weight of mice for 3 weeks. After 21 days, all animals were euthanised and subjected to a thorough examination for haemato-biochemical, histopathological, and 16S rRNA sequencing, followed by bioinformatics analysis to determine any changes in gut microbiota ecology. HSD exposure in mice for short duration even leads to a significant difference in the gut ecology with enrichment of specific gut microbiota crucially linked to developing the pathophysiological features of metabolic disease-related inflammation. In addition, HSD treatment showed a negative impact on haemato-biochemical parameters. However, Amoxicillin treatment in HSD-fed mice restored the blood-biochemical markers near to control values and reshaped gut microbiota known for improving the pathophysiological attributes of metabolic disease related inflammation. This study also observed minimal and insignificant pathological changes in the heart, liver, and kidney in HSD-fed mice.

The reliability and validity of DSM 5 diagnostic criteria for neurocognitive disorder and relationship with plasma neurofilament light in a down syndrome population.

The validity of dementia diagnostic criteria depends on their ability to distinguish dementia symptoms from pre-existing cognitive impairments. The study aimed to assess inter-rater reliability and concurrent validity of DSM-5 criteria for neurocognitive disorder in Down syndrome. The utility of mild neurocognitive disorder as a distinct diagnostic category, and the association between clinical symptoms and neurodegenerative changes represented by the plasma biomarker neurofilament light were also examined. 165 adults with Down syndrome were included. Two clinicians independently applied clinical judgement, DSM-IV, ICD-10 and DSM-5 criteria for dementia (or neurocognitive disorder) to each case. Inter-rater reliability and concurrent validity were analysed using the kappa statistic. Plasma neurofilament light concentrations were measured for 55 participants as a marker of neurodegeneration and between group comparisons calculated. All diagnostic criteria showed good inter-rater reliability apart from mild neurocognitive disorder which was moderate (k = 0.494). DSM- 5 criteria had substantial concurrence with clinical judgement (k = 0.855). When compared to the no neurocognitive disorder group, average neurofilament light concentrations were higher in both the mild and major neurocognitive disorder groups. DSM-5 neurocognitive disorder criteria can be used reliably in a Down syndrome population and has higher concurrence with clinical judgement than the older DSM-IV and ICD-10 criteria. Whilst the inter-rater reliability of the mild neurocognitive disorder criteria was modest, it does appear to identify people in an early stage of dementia with underlying neurodegenerative changes, represented by higher average NfL levels.

Selection of animal models for COVID-19 research.

The researcher community across the globe is on a search for a promising animal model that closely mimics the clinical manifestation of SARS-CoV-2. Though some developments were seen such as serial adaptation in various animal species or the creation of genetically engineered models, a suitable animal model remains elusive. A model that could display the severity of human illness and can be used for the fast-track evaluation of potential drugs as well as for the clinical trials of vaccines is an urgent need of the hour. In the light of huge information generated on SARS-CoV-2 and daily updates received from the research community, we have chosen to review the current status of animal models of SARS-CoV-2 in encompassing the areas of viral replication, transmission, active/passive immunization, clinical disease, and pathology. The review is intended to help the researchers in the selection of appropriate animal models for SARS CoV-2 research in the fight against the current global pandemic.

Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.

Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.

Antigen peptide transporter 1 is involved in the development of fructose-induced hepatic steatosis in mice.

BACKGROUND AND AIM: The purpose of this study is to assess whether the decrease in CD8 cells has any role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we therefore used antigen peptide transporter 1 (TAP1(-/-)) mice that cannot transport major histocompatibility complex class I antigens onto the cell surface resulting in failure of the generation of CD8 cells. METHODS: Wild-type C57Bl/6J and TAP1(-/-) mice were fed with 30% fructose solution for 8 weeks. The percentage of CD4, CD8 cells in peripheral blood mononuclear cells, and liver were sorted by fluorescence-activated cell sorting in both control and fructose-treated mice. Bodyweight, histopathological changes, oil red O staining, glucose tolerance test, intraperitoneal insulin tolerance test, serum levels of triglycerides, cholesterol, aspartate aminotransferase, and alanine aminotransferase were also evaluated. Quantitative real-time polymerase chain reaction was performed to determine the expression of specific genes involved in development of fatty changes in the liver. RESULTS: Chronic consumption of fructose in TAP1(-/-) mice did not develop NAFLD, insulin resistance, or change in level of CD8 cells. Moreover, there was delay in relative expression levels of genes involved in development of NAFLD in fructose-treated TAP1(-/-) mice. CONCLUSION: Taken together, the data suggest that TAP1(-/-) -deficient mice displayed reduced levels of CD8 cells that have a vital role in the initiation and propagation of liver inflammation and is a casual role in the beginning of fructose-induced liver damage as well as insulin resistance in mice.

A psychiatric intensive care unit for older adults: an interval comparison of admissions.

BACKGROUND: Published information on psychiatric intensive care provision and requirements of older adults is limited. This audit aims to describe and compare demographic data, clinical characteristics and outcomes of patients admitted to a Scottish regional psychiatric intensive care unit (PICU) for older adults during two 18-month periods five years apart. METHOD: Data on all patients admitted to the PICU for older adults during the two sample periods, commencing 2001 and 2006 respectively, were collected prospectively by the clinical care team, and included information on previous psychiatric contact and detentions under mental health legislation, diagnoses, cognitive ratings, reasons for transfer to the PICU, treatments and outcomes. Continuous variables were subject to statistical analyses. RESULTS: Twenty-one and 20 male patients were admitted during the 2001 and 2006 cohorts respectively, with equivalent mean ages of 72.9 years. The majority of patients were married, diagnosed with dementia, with similar levels of previous psychiatric admissions and detentions under mental health legislation. The commonest reason for transfer to the PICU was physical aggression. The 2006 cohort exhibited shorter inpatient stays prior to transfer to, and shorter durations of stay in, the PICU. CONCLUSIONS: The PICU for older adults provides a function similar to the PICU for general adults. The cohorts were similar on most recorded variables, with noted differences possibly reflecting increased awareness and acceptance of the service, reduced tolerance by staff of aggressive behaviors by patients, and enhanced community services in the region. These perceptions warrant further study and clarification.

Effects of ketamine and thiopentone anesthesia on serum lipid parameters in adult bonnet monkeys (Macaca radiata).

We investigated the effect of anesthesia on serum lipid parameters in adult bonnet macaques (Macaca radiata). We treated 10 animals with ketamine hydrochloride (15 mg/kg intramuscularly) and, on the next day, thiopentone sodium (25 mg/kg intravenously). Blood samples were obtained before and after anesthetic treatment. Serum cholesterol, triglycerides, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were measured by autoanalyzer. Ketamine anesthesia significantly decreased serum cholesterol and HDL levels, whereas thiopentone significantly reduced triglycerides and VLDL and increased HDL values. Although the effects of ketamine hydrochloride and thiopentone sodium on serum biochemical values have been reported, no literature addressing the effect of anesthesia on lipid parameters in bonnet macaques is available. These findings will be useful in designing experiments assessing pathologic and toxicologic changes in serum lipid parameters and interpreting data obtained from adult bonnet monkeys.