Slow weight gain is associated with increased periodic breathing in healthy infants

To investigate the hypothesis that weight gain can influence periodic breathing in healthy infants, we prospectively studied, by nocturnal pneumogram technique, respiration and heart rate in 99 full-term infants during the first month of life. Eighty-eight infants had a repeat study at about 2 months of age. Pneumograms were analyzed visually for percent periodic breathing (%PB), and by computer for mean respiratory rate and mean heart rate. We found a median %PB of 0.9 initially and of 0.3 at about 2 months of age. The 95th percentile was 13.5 at 2 weeks and 7.3 at 2 months, higher than previously reported. Between the two ages tested, %PB was inversely correlated with weight gain (P < 0.001, (0.03, respectively). Infants with greater weight gain had a greater fall in %PB (P < 0.03). We conclude that in the first 2 months of life, slow weight gain is associated with increased periodic breathing. Pediatr Pulmonol. 1994; 17:22–25. © 1994 Wiley-Liss, Inc.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

Fulminant hepatic failure

Opinion statement The rare but potentially devastating clinical syndrome of fulminant hepatic failure has as its components severe encephalopathy and finally cerebral edema, hemodynamic instability, renal failure, coagulopathy, profound metabolic disturbances and a particular susceptibility to bacterial and fungal infection. Despite advances in medical management, fulminant hepatic failure in its most severe form carries a high mortality rate unless urgent orthotopic liver transplantation is carried out. However, availability of cadaveric donor organs is limited and, due to the rapidly progressive clinical course in many cases, a substantial proportion of patients will die or develop contraindications to transplantation before the procedure can be performed. Consequently, recent interest has centred on living donor transplantation and the possibility of providing temporary liver support, either through auxiliary partial organ transplantation, extracorporeal perfusion or transplantation of hepatocytes, to allow time for either a liver graft to become available or native liver regeneration, on which spontaneous survival ultimately depends, to occur.     

Glycopeptide insensitive Staphylococcus aureus subdural empyema treated with linezolid and rifampicin

A 4-year-old boy had surgical debulking of a cerebral astrocytoma followed by chemotherapy. He developed a subdural empyema with a teicoplanin and methicillin resistant Staphylococcus aureus. He was successfully treated with surgical drainage and 6 weeks of antibiotic therapy which included linezolid, rifampicin and metronidazole. Linezolid may be successful in treating other CNS infections caused by antibiotic resistant gram-positive organisms.     

Antimicrobial treatment options for neurosurgical ventricular shunt infections in children from 1993 to 2012: a systematic review

Purpose

The aim of this systematic review was to review studies that existed from 1993 to 2012 regarding antimicrobial treatment options of paediatric neurosurgical shunt.

Methods

Studies were identified from MEDLINE, Scopus and Cochrane databases using a search strategy that was registered on the PROSPERO database. Studies were included if they had two or more patients, aged less than 18 years, and also specified the organism and antimicrobial treatment that was used.

Results

The search yielded 2,985 articles, and 76 articles were suitable for full review. In the final qualitative analysis, only eight studies were included, involving 86 participants. The most common antimicrobial regimens for Gram-positive infections was intravenous and intrathecal vancomycin (n?=?7), followed by intravenous vancomycin monotherapy.

Conclusion

This systematic review has shown that there are no prospective randomised studies of antimicrobial treatment options for paediatric neurosurgical patients in the last 20 years, and larger prospective studies are urgently required for this serious infection. There is some limited case series showing the benefits of certain antimicrobials such as vancomycin and ceftriaxone, but a larger case series or randomised controlled trial is required, particularly to establish the benefit, if any, of additional intraventricular antimicrobials.     

Palmitate-TLR4 signaling regulates the histone demethylase,JMJD3, in macrophages and impairs diabetic wound healing

Chronic macrophage inflammation is a hallmark of type 2 diabetes (T2D) and linked to the development of secondary diabetic complications. T2D is characterized by excess concentrations of saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) by which SFAs control inflammation is unknown. Using monocyte-macrophages isolated from human blood and murine models, we demonstrate that palmitate (C16:0), the most abundant circulating SFA in T2D, increases expression of the histone demethylase, Jmjd3. Upregulation of Jmjd3 results in removal of the repressive histone methylation (H3K27me3) mark on NFκB-mediated inflammatory gene promoters driving macrophage-mediated inflammation. We identify that the effects of palmitate are fatty acid specific, as laurate (C12:0) does not regulate Jmjd3 and the associated inflammatory profile. Further, palmitate-induced Jmjd3 expression is controlled via TLR4/MyD88-dependent signaling mechanism, where genetic depletion of TLR4 (Tlr4^−/−) or MyD88 (MyD88^−/−) negated the palmitate-induced changes in Jmjd3 and downstream NFκB-induced inflammation. Pharmacological inhibition of Jmjd3 using a small molecule inhibitor (GSK-J4) reduced macrophage inflammation and improved diabetic wound healing. Together, we conclude that palmitate contributes to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy may represent a novel treatment for nonhealing diabetic wounds.     

Type D personality and cardiovascular reactivity to acute stress: The mediating effects of social support and negative social relationships

Type D personality has been consistently associated with adverse cardiovascular health with atypical cardiovascular reactions to psychological stress one potential underlying mechanism. As Type D individuals have been noted to report lower social support and greater perceptions of negativity in social interactions, this study examined if the association between Type D personality and cardiovascular reactivity was mediated by these social relationships. A sample of 195 undergraduate students (138 female) participated in this observational study, where they completed measures assessing Type D personality (DS14), social support, and perceptions of negative social relationships (National Institute of Health social relationship scales), before undergoing a traditional cardiovascular reactivity protocol. Systolic and diastolic blood pressure (SBP; DBP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were monitored throughout. ANCOVAs and regressions indicated that Type D personality was associated with lower cardiovascular reactivity to a mental arithmetic stressor. Furthermore, mediation analyses (process macro) indicated that the relationship between Type D personality and cardiovascular reactivity was mediated via increased perceptions of negative social relationships, as well as lower levels of social support. Apart from a significant association between Type D personality and increased HR reactivity, all results failed to withstand adjustment for the individual effects of negative affect (NA) and social inhibition (SI) in controlled analyses. Overall, these findings suggest that the predictive utility of Type D personality on cardiovascular reactivity above and beyond the individual effects of NA and SI is limited, and may vary depending on the cardiovascular parameter of focus.     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

Electrochemical Synthesis of Zinc Oxide Nanostructures on Flexible Substrate and Application as an Electrochemical Immunoglobulin-G Immunosensor

Immunoglobulin G (IgG), a type of antibody, represents approximately 75% of serum antibodies in humans, and is the most common type of antibody found in blood circulation. Consequently, the development of simple, fast and reliable systems for IgG detection, which can be achieved using electrochemical sandwich-type immunosensors, is of considerable interest. In this study we have developed an immunosensor for human (H)-IgG using an inexpensive and very simple fabrication method based on ZnO nanorods (NRs) obtained through the electrodeposition of ZnO. The ZnO NRs were treated by electrodepositing a layer of reduced graphene oxide (rGO) to ensure an easy immobilization of the antibodies. On Indium Tin Oxide supported on Polyethylene Terephthalate/ZnO NRs/rGO substrate, the sandwich configuration of the immunosensor was built through different incubation steps, which were all optimized. The immunosensor is electrochemically active thanks to the presence of gold nanoparticles tagging the secondary antibody. The immunosensor was used to measure the current density of the hydrogen development reaction which is indirectly linked to the concentration of H-IgG. In this way the calibration curve was constructed obtaining a logarithmic linear range of 10–1000 ng/mL with a detection limit of few ng/mL and good sensitivity.     

More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins

Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.