The immunobiology of colitis and cholangitis in interleukin-23p19 and interleukin-17a deleted dominant negative form of transforming growth factor beta receptor type ii mice

Dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) mice, expressing a dominant negative form of TGFβ receptor II under control of the CD4 promoter, develop autoimmune colitis and cholangitis. Deficiency in interleukin (IL)-12p40 lead to a marked diminution of inflammation in both the colon and the liver. To distinguish whether IL-12p40 mediates protection by the IL-12 or IL-23 pathways, we generated an IL-23p19(-/-) dnTGFβRII strain deficient in IL-23, but not in IL-12; mice were longitudinally followed for changes in the natural history of disease and immune responses. Interestingly, IL-23p19(-/-) mice demonstrate dramatic improvement in their colitis, but no changes in biliary pathology; mice also manifest reduced T-helper (Th)17 cell populations and unchanged IFN-γ levels. We submit that the IL-12/Th1 pathway is essential for biliary disease pathogenesis, whereas the IL-23/Th17 pathway mediates colitis. To further assess the mechanism of the IL-23-mediated protection from colitis, we generated an IL-17A(-/-) dnTGFβRII strain deficient in IL-17, a major effector cytokine produced by IL-23-dependent Th17 cells. Deletion of the IL-17A gene did not affect the severity of either cholangitis or colitis, suggesting that the IL-23/Th17 pathway contributes to colon disease in an IL-17-independent manner. These results affirm that the IL-12/Th1 pathway is critical to biliary pathology in dnTGFβRII mice, whereas colitis is caused by a direct effect of IL-23. (HEPATOLOGY 2012).     

Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis

Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA(-)), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA(+)) and AMA(-) patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA(+) PBC than those observed in AMA(-) PBC patients. The portal areas from AMA(-) patients had a significant increase of cluster of differentiation (CD)5(+) cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5(+) and CD20(+) cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5(+) cells, which remain sustained and predominate over CD20(+) cells. CONCLUSION: Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC.     

A truncating mutation in B3GNT1 causes severe Walker–Warburg syndrome

Walker–Warburg syndrome (WWS) is a genetically heterogeneous form of congenital muscular dystrophy with significant brain and ocular involvement. In a multiplex consanguineous family with severe WWS phenotype, autozygome-guided sequencing of previously reported WWS genes was negative. Exome sequencing followed by autozygome filtration revealed a homozygous two-base pair insertion in B3GNT1 (NM_006876.2:c.821_822insTT), leading to premature truncation of the protein (p.Glu274Aspfs*94). Recently, two missense mutations in this gene have been reported as probably causal in a family with WWS. This report describes the first truncating mutation in B3GNT1 and confirms that this gene, which plays a role in αDG glycosylation, is a bona fide disease gene in WWS.     

Anaesthetic complications in plastic surgery

Anaesthesia related complications in plastic surgeries are fortunately rare, but potentially catastrophic. Maintaining patient safety in the operating room is a major concern of anaesthesiologists, surgeons, hospitals and surgical facilities. Circumventing preventable complications is essential and pressure to avoid these complications in cosmetic surgery is increasing. Key aspects of patient safety in the operating room are outlined, including patient positioning, airway management and issues related to some specific conditions, essential for minimizing post-operative morbidity. Risks associated with extremes of age in the plastic surgery population, may be minimised by a better understanding of the physiologic changes as well as the pre-operative and post-operative considerations in caring for this special group of patients. An understanding of the anaesthesiologist''s concerns during paediatric plastic surgical procedures can facilitate the coordination of efforts between the multiple services involved in the care of these children. Finally, the reader will have a better understanding of the perioperative care of unique populations including the morbidly obese and the elderly. Attention to detail in these aspects of patient safety can help avoid unnecessary complication and significantly improve the patients’ experience and surgical outcome.KEY WORDS: Anaesthesia, complications, plastic, surgery     

Health and wellbeing of Victorian adults with intellectual disability compared to the general Victorian population

Multiple measures of health and wellbeing of people with intellectual disability (ID) and the general Victorian population were compared using representative population level data. The sample consisted of adults with ID (N = 897) and the general Victorian population (N = 34,168) living in the state of Victoria in Australia. Proxy respondents were interviewed on behalf of people with ID, while respondents from the general Victorian population were interviewed directly. The data were weighted to reflect the age/sex/geographic distribution of the population. Results revealed that adults with ID reported higher prevalence of poor social determinants of health, behavioural risk factors, depression, diabetes, poor or fair health. A higher proportion of people with ID reported blood pressure and blood glucose checks, while a lower proportion reported cervical and breast cancer screening, compared with the general Victorian population. The survey identified areas where targeted approaches may be undertaken to improve the health outcomes of people with ID and provide an important understanding of the health and wellbeing of these Victorians.     

Accumulation of Cadmium in Transplanted Lichen Pyxine cocoes (Sw.) Nyl., with Reference to Physiochemical Variation and Kinetics of Cadmium Biosorption

Bulletin of Environmental Contamination and Toxicology - The safe utilization and risk assessment of produced water (PW) from oil and gas fields for desert irrigation have received increasing...     

Research letters

Patients with transfusion-dependent thalassemia are expected to have an unfavorable quality of life due to multiple factors. We studied the quality of life in 72 patients (age 5-39 y) with transfusion-dependent thalassemia in the era of improved care, and assessed different parameters affecting it.     

Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey

STUDY OBJECTIVE: Many people use dietary supplements or herbal products to help them sleep. We analyzed the associations between melatonin use and insomnia and between valerian use and insomnia in a representative sample of the United States population. DESIGN AND PARTICIPANTS: The data reported upon here were collected in the 2002 Alternative Health/Complementary and Alternative Medicine (CAM) Supplement to the National Health Interview Survey. This was a survey of 31,044 personal interviews that constituted an age-representative and socioeconomically representative sample of the civilian noninstitutionalized population of the United States. RESULTS: Of the survey sample, 5.9% used valerian and 5.2% used melatonin. Of those using valerian, 29.9% endorsed insomnia as 1 reason for CAM use, and, of melatonin users, 27.5% endorsed insomnia as 1 reason for CAM use. Relatively greater use occurred in individuals under age 60 years. The decision to use such substances was made in consultation with a health care provider less than half of the time. CONCLUSIONS: Large segments of the United States population used valerian or melatonin for insomnia within the year preceding the survey, and usage typically fell outside the purview of the health care system.     

Dichotomous effects of C-C chemokines in HIV-1 pathogenesis

Whilst many physiological functions of nitric oxide (NO) have been revealed so far, recent evidence proposes an essential role for NO in T lymphocyte activation and signal transduction. NO acts as a second messenger, activating soluble guanyl cyclase and participating in signal transduction pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial biogenesis in many cell types, including lymphocytes. Several studies undertaken on patients with RA and SLE have documented increased endogenous NO synthesis, although the effects of NO may be distinct. Here, we discuss recent evidence that NO contributes to T cell dysfunction in both SLE and RA by altering multiple signaling pathways in T cells. Although NO may play a physiological role in lymphocyte cell signaling, its overproduction may perturb T cell activation, differentiation and effector responses, each of which may contribute in different ways to the pathogenesis of autoimmunity.