Delayed Apoptotic Cell Clearance and Lupus-like Autoimmunity in Mice Lacking the c-mer Membrane Tyrosine Kinase

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer–deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Tracheal granulation as a cause of unrecognized airway narrowing

Tracheostomy is one of the most common elective surgical procedures performed in critically ill patients. The most frequent late complication after tracheostomy is the development of granulation tissue, a complication that may cause airway occlusion or result in airway stenosis. We report the successful management of a patient with tracheal granulation presenting as an unrecognised cause of difficulty breathing

A prospective randomized double blind study to evaluate the analgesic efficacy of low dose of intrathecal neostigmine in combination with fentanyl and bupivacaine for lower abdominal and lower limb surgery

More than 80% of patients undergoing surgical procedures under spinal anesthesia experience acute post-operative pain. The aim of the study was to compare the analgesic efficacy and side effects of addition of neostigmine to fentanyl and bupivacaine. 50 patients scheduled for elective lower abdominal and lower limb surgeries likely to finish within 3 hours, were put into two groups. 25 patients in each group aged between 18 to 60 years of either sex belonging to the ASA grade I & II. Group A was given Intrathecal Bupivacaine 12.5 mg (2.5 ml) + Fentanyl 20 µg (0.4 ml)+0.1 ml Normal Saline (Total 3 ml) and Group B was given Intrathecal Bupivacaine 12.5 mg (2.5 ml) + Fentanyl 20 µg (0.4 ml) + Neostigmine 1µg (0.1 ml) (Total 3 ml). Subjects were monitored for occurrence of any adverse events after spinal injection. We observed statistically significant difference between the two groups in the onset of sensory blockade and recovery of sensory blockade. Onset of sensory blockade was earlier in Group B and recovery time was prolonged in Group B. No difference was seen in maximal sensory blockade.&nbsp

Obstetric admissions to tertiary level intensive care unit – Prevalence, clinical characteristics and outcomes

Background and Aims: Obstetric admissions to the intensive care unit (ICU) are a subject of increasing interest, as it is an indirect indicator of maternal morbidity and mortality. The studies from areas reported to have a higher maternal mortality rate are lacking. Thus, we undertook this study to determine the prevalence pattern, clinical characteristics and outcome of obstetric patients admitted to the ICU of a tertiary care hospital. Methods: All obstetric patients (up till 42 days of delivery) admitted to the ICU from 1st October 2015 to 30th September 2016 and from 1st October 2010 to 30th September 2015 were included. Data collected for our study included demographic characteristics, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score at the time of admission, obstetric and medical history, provisional diagnosis, the reason for ICU admission, interventions required in ICU and the outcome. Results: The third trimester (46.79%) and postpartum period (40.37%) were the most common time of admission with conditions such as severe pre-eclampsia, eclampsia, HELLP syndrome (Haemolysis, elevated liver enzymes, low platelet count), antepartum haemorrhage, postpartum haemorrhage and anaemia. The mean APACHE II score was 16.89 ± 7.48 with a mortality rate of 17.76%. The mean length of stay in ICU was 3.47 ± 3.16 days, and mean length of stay in our hospital was 8.78 ± 6.76 days Conclusion: Obstetric patients recover well if treated early. A good ICU care with monitoring can save a young productive life

Assessment of malnutrition and enteral feeding practices in the critically ill: A single-centre observational study

Background and Aims: Early identification of malnutrition among hospitalised patients is essential to institute appropriate patient-specific nutritional strategies. This study was conducted to evaluate the nutritional status of medical patients at admission to the adult intensive care unit (ICU) and to identify factors which prevent attainment of daily feeding goals in them. Methods: This was a 1 year prospective, observational study on 200 medical adult ICU patients. The study was carried out based on daily documentation. The primary outcome was the nutritional status of medical Patients at admission to the adult ICU. The tests for statistical analysis used were independent t test, Chi-square test, Fisher's exact test and multivariate logistic regression analysis. Results: Out of the 200 patients in our study, 45%, 48.5% and 9% of patients had mild, moderate and severe malnutrition, respectively, corresponding to subjective global assessment (SGA) rating A,B and C, respectively. The most common reasons for non-attainment of daily feeding goals were delayed feed procurement (17.57%), and feeds being held for procedures (16.36%). The overall mean length of ICU stay was 8.63 ± 7.26 days, and the ICU mortality rate was 47.5% (95/200). Patients with SGA rating B and C at admission had higher risk of mortality in the ICU, with an adjusted odds ratio of 3.54 (95% confidence interval [CI]- 1.71–7.33, P = 0.001) and 11.11 (95% CI-2.26–54.66, P = 0.003), respectively. Conclusion: Malnutrition is commonly present at admission among medical ICU patients, and is associated with higher ICU mortality

Mechanism of Collaborative Enhancement of Binding of Paired Antibodies to Distinct Epitopes of Platelet Endothelial Cell Adhesion Molecule-1.

Monoclonal antibodies (mAbs) directed to extracellular epitopes of human and mouse Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) stimulate binding of other mAbs to distinct adjacent PECAM-1 epitopes. This effect, dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL, has been shown to enhance delivery of mAb-targeted drugs and nanoparticles to the vascular endothelium. Here we report new insights into the mechanism underlying this effect, which demonstrates equivalent amplitude in the following models: i) cells expressing a full length PECAM-1 and mutant form of PECAM-1 unable to form homodimers; ii) isolated fractions of cellular membranes; and, iii) immobilized recombinant PECAM-1. These results indicate that CEPAL is mediated not by interference in cellular functions or homophilic PECAM-1 interactions, but rather by conformational changes within the cell adhesion molecule induced by ligand binding. This mechanism, mediated by exposure of partially occult epitopes, is likely to occur in molecules other than PECAM-1 and may represent a generalizable phenomenon with valuable practical applications