Miracle-dz/UniFAR-FTUs huggingface dataset:
Region‐specific expression of immunoregulatory proteins on microglia in the healthy CNS

In accordance with a high degree of spatial organization in the central nervous system (CNS), most CNS diseases display a regional distribution. Although microglia have been established as key players in various CNS diseases, it is not yet clear whether microglia display region‐specific properties. Therefore, this study aimed to evaluate the existence of distinct microglia phenotypes in various regions of the healthy, adult mouse CNS. Using ex vivo flow cytometric analysis surface expression of CD11b, CD40, CD45, CD80, CD86, F4/80, TREM‐2b, MHCII, CXCR3, CCR9, and CCR7 were analyzed. Most of these immunoregulatory markers were found on microglia and showed significant region‐specific differences in expression levels. These findings considerably corroborate the existence of immunological diversity among microglia in the healthy, unchallenged CNS of adult mice. © 2008 Wiley‐Liss, Inc.
Analysis of the capsular polysaccharide biosynthesis locus of Porphyromonas gingivalis and development of a K1-specific polymerase chain reaction-based serotyping assay.

BACKGROUND AND OBJECTIVE Porphyromonas gingivalis is a gram-negative obligate anaerobe that is strongly associated with severe periodontitis. Previous reports showed an association of P. gingivalis capsular polysaccharide with virulence. The K1 capsular polysaccharide was found to be more immunostimulatory than the other serotypes. Our objective was to explore the genetic background of the capsule biosynthesis (K-antigen) locus in a representative group of K1 serotype strains. MATERIAL AND METHODS We used restriction fragment length polymorphism, polymerase chain reaction (PCR) and DNA sequencing to study the capsular polysaccharide locus in P. gingivalis K1 strains. For serotyping by double immunodiffusion and PCR we used 32 strains of P. gingivalis, including strains of all six known K serotypes. RESULTS All tested K1 strains showed high conservation of the capsular polysaccharide locus, although a DNA re-arrangement was found in two strains. Based on this information a K1-specific PCR-based serotyping assay was designed. The specificity and sensitivity of this test were confirmed using non-K1 P. gingivalis serotypes. CONCLUSION The capsular polysaccharide locus of P. gingivalis is conserved but may vary slightly among K1 strains. The new K1 serotyping assay presented here is much faster than double immunodiffusion and can detect K1 strains in a very selective and sensitive way. This method may therefore be clinically relevant in the detection of the virulent P. gingivalis K1 serotype.
Induction of cementogenesis and periodontal ligament regeneration by recombinant human transforming growth factor-beta3 in Matrigel with rectus abdominis responding cells.

BACKGROUND AND OBJECTIVE In primates and in primates only, the transforming growth factor-b proteins induce endochondral bone formation. Transforming growth factor-b3 also induces periodontal tissue regeneration. Two regenerative treatments using human recombinant transforming growth factor-b3 were examined after implantation in mandibular furcation defects of the nonhuman primate, Papio ursinus. MATERIAL AND METHODS Class III furcation defects were surgically created bilaterally in the mandibular first and second molars of two adult Chacma baboons (P. ursinus). Different doses of recombinant transforming growth factor-beta3 reconstituted with Matrigel matrix were implanted in the rectus abdominis muscle to induce heterotopic ossicles for subsequent transplantation to selected furcation defects. Twenty days after heterotopic implantation, periodontal defects were re-exposed, further debrided and implanted with minced fragments of induced heterotopic ossicles. Contralateral class III furcation defects were implanted directly with recombinant transforming growth factor-beta3 in Matrigel matrix with the addition of minced fragments of autogenous rectus abdominis muscle. Treated quadrants were not subjected to oral hygiene procedures so as to study the effect of the direct application of the recombinant morphogen in Matrigel on periodontal healing. Histomorphometric analyses on undecalcified sections cut from specimen blocks harvested on day 60 measured the area of newly formed alveolar bone and the coronal extension of the newly formed cementum along the exposed root surfaces. RESULTS Morphometric analyses showed greater alveolar bone regeneration and cementogenesis in furcation defects implanted directly with 75 microg of transforming growth factor-beta3 in Matrigel matrix with the addition of minced muscle tissue. CONCLUSION Matrigel matrix is an optimal delivery system for the osteogenic proteins of the transforming growth factor-beta superfamily, including the mammalian transforming growth factor-beta3 isoform. The addition of minced fragments of rectus abdominis muscle provides responding stem cells for further tissue induction and morphogenesis by the transforming growth factor-beta3 protein.
Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer cardioprotection and improve recovery of the electrically induced intracellular calcium transient during ischemia and reperfusion.

BACKGROUND AND OBJECTIVE Porphyromonas gingivalis lipopolysaccharide (LPS) is a ligand for cell surface toll-like receptors (TLR), TLR2 and TLR4 while stimulation of either leads to cardioprotection. We hypothesized that: (1) pretreatment with P. gingivalis LPS at appropriate concentrations would induce cardioprotection against injury induced by ischemia and reperfusion; and (2) P. gingivalis LPS pretreatment at cardioprotective concentrations may reduce Ca(2+) overload, which is a precipitating cause of injury, and improve recovery of contractile function. MATERIAL AND METHODS Male Sprague-Dawley rats were randomly selected to receive intraperitoneal saline or hot phenol-water-extracted P. gingivalis LPS at 0.2, 0.5, 1.0, 2.0 or 4.0 mg/kg 24 h before the experiment. The hearts were isolated and subjected to regional ischemia by coronary artery ligation followed by reperfusion. In isolated rat ventricular myocytes, the cytosolic Ca(2+) level and the electrically induced intracellular calcium (E[Ca(2+)](i)) transient, which reflects contractile function, were determined after pretreatment with a cardioprotective dose of P. gingivalis LPS. RESULTS Pretreatment with 0.5 mg/kg P. gingivalis LPS significantly reduced, while pretreatment with 1.0-4.0 mg/kg significantly increased infarct size. The Ca(2+) overload induced by ischemia-reperfusion was attenuated in myocytes from rats pretreated with 0.5 mg/kg P. gingivalis LPS. Pretreated myocytes also showed an increased amplitude of the E[Ca(2+)](i) transient, no prolongation of the time to reach the peak E[Ca(2+)](i) transient and shorter 50% decay time during reperfusion. CONCLUSION At a dosage of 0.5 mg/kg, P. gingivalis LPS confers cardioprotection against ischemia-reperfusion-induced injury and improved intracellular E[Ca(2+)](i) transient recovery, hence improving myocyte contractile recovery.
Oligodendrocyte positioning in cerebral cortex is independent of projection neuron layering

The factors affecting normal oligodendrocyte positioning in the cerebral cortex are unknown. Apart from the white matter, the highest numbers of oligodendrocytes in the rodent cortex are found in Layers V/VI, where the infragranular neurons normally reside. Few, if any, oligodendrocytes are normally found in the superficial cortical layers. To test whether or not this asymmetric positioning of oligodendrocytes is linked to the lamina positions of Layer V/VI projection neurons, mutant mice that cause neuronal layer inversion were examined. In three lines of mutant mice (Reeler, disabled‐1, and p35) examined, representing two different genetic signaling pathways, the oligodendrocyte distribution was altered from an asymmetric to a symmetric distribution pattern. Unlike cortical neurons that are inverted in these mutant mice, the lack of oligodendrocyte inversion suggests a decoupling of the genetic mechanisms governing neuronal versus oligodendrocyte patterning. We conclude that oligodendrocyte positioning is not linked to the layer positions of V/VI projection neurons. © 2008 Wiley‐Liss, Inc.
Endothelial NOS‐deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by infiltration of T cells into the central nervous system (CNS) after compromise of the blood‐brain barrier. A model used to mimic the disease in mice is experimental autoimmune encephalomyelitis (EAE). In this report, we examine the clinical and histopathological course of EAE in eNOS‐deficient (eNOS−/−) mice to determine the role of nitric oxide (NO) derived from this enzyme in the disease progression. We find that eNOS−/− mice exhibit a delayed onset of EAE that correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS underlies the T cell infiltration into the CNS. However, the eNOS−/− mice also eventually exhibit more severe EAE and delayed recovery, indicating that NO undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset, and the other neuroprotective that promotes recovery from disease exacerbation events. © 2009 Wiley‐Liss, Inc.
Oxidative injury triggers autophagy in astrocytes: The role of endogenous zinc

We have recently demonstrated that the accumulation of labile zinc in lysosomes during oxidative stress causes lysosomal membrane permeabilization (LMP) in cultured hippocampal neurons. Since autophagy involves fusion of autophagic vacuoles (AVs) with lysosomes, zinc accumulation may start in AVs. In the present study, we examined the role of endogenous zinc in H2O2‐induced autophagy and cell death in mouse astrocyte cultures. Live‐cell confocal imaging of astrocytes transfected with GFP‐LC3 revealed that the number of AVs positive for LC3 (microtubule‐associated protein 1 light chain 3) increased following exposure to H2O2 or ferrous chloride (FeCl2). Staining of RFP‐LC3‐transfected astrocytes with FluoZin‐3 indicated that the levels of labile zinc increased in AVs as well as in the cytosol and nuclei. The majority of AVs were double‐stained with LysoTracker, indicating that they were fused with lysosomes. Chelation of zinc with tetrakis [2‐pyridylmethyl]ethylenediamine (TPEN) decreased the number of AVs in H2O2‐treated astrocytes, whereas exposure to zinc increased their number, suggesting that dysregulation of zinc homeostasis is mechanistically linked to autophagy. Unexpectedly, inhibition of autophagy blocked the rise in labile zinc levels. Astrocytic death induced by H2O2 was accompanied by LMP. Autophagy inhibitors (3‐methyladenine, bafilomycin‐1) or TPEN attenuated LMP and cell death in astrocytes. These results support the possibility that endogenous zinc plays a key role in autophagy under oxidative stress in astrocytes, and suggest that autophagy is a necessary preceding event for LMP and cell death in oxidative injury. © 2009 Wiley‐Liss, Inc.
Nonpharmacological management of neonatal abstinence syndrome: a review of the literature

Abstract Background: Infants with neonatal abstinence syndrome (NAS) experience withdrawal that occurs as a result of termination of placental opioid supply following delivery. Common symptoms include restlessness, tremors, agitation and gastrointestinal disturbances. Severe NAS is often treated using opioids and/or sedatives. Although commonly employed effectively in neonatal care, there is a lack of published information regarding nonpharmacological management of the NAS infant. Objective: The purpose of this review was to summarize the current literature on nonpharmacological management of NAS. Methods: A literature search of Medline and EMBASE was performed for articles published between 2000 and June 2107. Results: Nonpharmacological management encompasses “environmental control”, “feeding methods”, “social integration”, “soothing techniques” and “therapeutic modalities”. Several interventions, including: breastfeeding, swaddling, rooming-in, environmental control and skin to skin contact have proven to be effective in managing NAS and should be incorporated into standard of care for this population (Level I–III Evidence). These interventions can be effective when offered in combination with pharmacological therapy, or as stand-alone therapy for less severe cases of NAS (Finnegan score <8). Conclusions: Given the increasing body of evidence on its efficacy and ease of implementation, nonpharmacological treatment should universally be incorporated into standard of care for NAS.
Early ultrastructural defects of axons and axon–glia junctions in mice lacking expression of Cnp1

Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating the axon, myelin also shields the axoplasm from the extracellular milieu. In the CNS, oligodendrocytes provide support for the long‐term maintenance of myelinated axons, independent of the myelin sheath. Here, we use electron microscopy and morphometric analyses to examine the evolution of axonal and oligodendroglial changes in mice deficient in 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP) and in mice deficient in both CNP and proteolipid protein (PLP/DM20). We show that CNP is necessary for the formation of a normal inner tongue process of oligodendrocytes that myelinate small diameter axons. We also show that axonal degeneration in Cnp1 null mice is present very early in postnatal life. Importantly, compact myelin formed by transplanted Cnp1 null oligodendrocytes induces the same degenerative changes in shiverer axons that normally are dysmyelinated but structurally intact. Mice deficient in both CNP and PLP develop a more severe axonal phenotype than either single mutant, indicating that the two oligodendroglial proteins serve distinct functions in supporting the myelinated axon. These observations support a model in which the trophic functions of oligodendrocytes serve to offset the physical shielding of axons by myelin membranes. © 2009 Wiley‐Liss, Inc.
Olfactory ensheathing cells: Nitric oxide production and innate immunity

Olfactory nerves extend from the nasal cavity to the central nervous system and provide therefore, a direct route for pathogenic infection of the brain. Since actual infection by this route remains relatively uncommon, powerful endogenous mechanisms for preventing microbial infection must exist, but these remain poorly understood. Our previous studies unexpectedly revealed that the unique glial cells that ensheath olfactory nerves, olfactory ensheathing cells (OECs), expressed components of the innate immune response. In this study, we show that OECs are able to detect and respond to bacterial challenge via the synthesis of nitric oxide. In vitro studies revealed that inducible nitric oxide synthase (iNOS) mRNA and protein were present in Escherichia coli‐ and Staphylococcus aureus‐incubated OECs, but were barely detectable in untreated OECs. Neuronal NOS and endothelial NOS were not expressed by OECs pre‐ and post‐bacterial incubation. Nuclear translocation of nuclear factor kappa B (NFκB), detectable in the majority of OECs 1 h following bacterial incubation, preceded iNOS induction which resulted in the production of nitric oxide. NG‐methyl‐L‐arginine significantly attenuated nitric oxide (P < 0.001) and nitrite production (P < 0.001) by OECs. In rat olfactory mucosa which was compromised by irrigation with 0.17M zinc sulfate or 0.7% Triton X‐100 to facilitate bacterial infiltration, OECs contributed to a robust synthesis of iNOS. These data strongly support the hypothesis that OECs are an essential component of the innate immune response against bacterial invasion of the central nervous system via olfactory nerves. © 2009 Wiley‐Liss, Inc.
Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia

Brief forebrain ischemia is a model of the delayed hippocampal neuronal loss seen in patients following cardiac arrest and resuscitation. Previous studies demonstrated that selective dysfunction of hippocampal CA1 subregion astrocytes occurs hours to days before delayed neuronal death. In this study we tested the strategy of directing protection to astrocytes to protect neighboring neurons from forebrain ischemia. Two well‐studied protective proteins, heat shock protein 72 (Hsp72) or superoxide dismutase 2 (SOD2), were genetically targeted for expression in astrocytes using the astrocyte‐specific human glial fibrillary acidic protein (GFAP) promoter. The expression constructs were injected stereotacticly immediately above the hippocampal CA1 region on one side of the rat brain two days prior to forebrain ischemia. Cell type specific expression was confirmed by double label immunohistochemistry. When the expression constructs were injected two days before transient forebrain ischemia, the loss of CA1 hippocampal neurons observed seven days later was significantly reduced on the injected side compared with controls. This neuroprotection was associated with significantly better preservation of astrocyte glutamate transporter‐1 immunoreactivity at 5‐h reperfusion and reduced oxidative stress. Improving the resistance of astrocytes to ischemic stress by targeting either the cytosolic or mitochondrial compartment was thus associated with preservation of CA1 neurons following forebrain ischemia. Targeting astrocytes is a promising strategy for neuronal preservation following cardiac arrest and resuscitation. © 2010 Wiley‐Liss, Inc.
Effects of L-ascorbic acid 2-phosphate magnesium salt on the properties of human gingival fibroblasts.

BACKGROUND AND OBJECTIVE L-Ascorbic acid 2-phosphate magnesium salt (APM) is an L-ascorbic acid (AsA) derivative developed to improve AsA stability and display effective biochemical characteristics. This study aimed to investigate the effects of APM on the functions and properties of human gingival fibroblasts with respect to the prevention of periodontal disease in comparison with those of AsA. MATERIAL AND METHODS Human gingival fibroblasts were incubated in the presence or absence of APM or L-ascorbic acid sodium salt (AsANa). Intracellular AsA was analysed by HPLC. Collagen synthesis was measured by ELISA and real-time RT-PCR. Intracellular reactive oxygen species (ROS) induced by hydrogen peroxide (H(2)O(2)) were quantified using a fluorescence reagent, and cell damage was estimated with calcein acetoxymethyl ester. Furthermore, intracellular ROS induced by tumor necrosis factor-α (TNF-α) were quantified, and expression of TNF-α-induced interleukin-8 expression, which increases due to inflammatory reactions, was measured by ELISA and real-time RT-PCR. RESULTS APM remarkably and continuously enhanced intracellular AsA and promoted type 1 collagen synthesis and mRNA expression. Furthermore, APM decreased cell damage through the suppression of H(2)O(2)-induced intracellular ROS and inhibited interleukin-8 production through the suppression of TNF-α-induced intracellular ROS. These effects of APM were superior to those of AsANa. CONCLUSION These results suggest that APM is more effective than AsANa in terms of intake, collagen synthesis, decreasing cell damage and inhibiting interleukin-8 expression in human gingival fibroblasts. This suggests that local application of APM can help to prevent periodontal disease.
Changing practices in mental health care: a lesson from America

Health and social care in Britain is undergoing the most profound changes in its structure and organis ation since its inception (Griffiths, 1988); indeed, some would argue that it is about to change beyond recognition. The purpose of this article is to describe contemporary developments in the delivery of such services in the USA. Given that many of the political changes here have been directly influenced by think ing and practice in that country, it is argued that there are two important lessons to be learnt. The first concerns the coordination of service delivery between different agencies, the second involves an emphasis on the delivery of acute and rehabilitation services in the community. In short the traditional distinctions between the two would be blurred.
Self-efficacy as an appraisal that moderates the coping-emotion relationship: Associations among people with rheumatoid arthritis

The way a coping strategy is expressed might depend on the nature of underlying efficacy expectations. For example, a cognitive coping strategy may have different content depending on efficacy beliefs underpinning the strategy's formulation and application. As such, self-efficacy (SE), as an appraisal, may moderate relationships between coping and outcomes: coping effects may differ depending on SE. This process was examined in 127 rheumatoid arthritis patients attending routine patient education/self-management programmes. Participants completed questionnaire measures of SE, coping, anxiety and depression at baseline and at 8 weeks follow-up. Regression analyses focused on coping and SE change variables, and their concurrent association with measures of change in anxiety and depression. Results highlighted contributions to these emotional variables from interactions between coping and SE. The nature of associations between coping and emotional outcomes was found to differ according to efficacy appraisals. This may have implications for clinical practice in that the adaptive significance of adjustment efforts may differ according to underlying SE.
Quality of Life in Hospice Versus Non-Hospice Terminally Ill Adults

The differences in subjective quality of life between terminally ill patients receiving hospice care and patients receiving palliative cancer treatments were investigated to determine whether hospice services offer an improved quality of life for this population. A convenience sample of 66 alert and oriented, terminally ill adult men and women were recruited from three Midwestern hospice and palliative care agencies. Utilizing the McGill Quality of Life questionnaire (&agr; = .89), subjective quality of life was assessed during face-to-face interviews conducted between December 2005 and March 2006. The results indicated few significant differences in subjective quality of life between the two groups, with the palliative care group scoring significantly higher on the comparative McGill Quality of Life questionnaire-Part A (t(64) = −2.12, P = . 04) and the physical symptoms (t(64) = −3.68, P = . 00) subscales. Both groups reported high scores on the support subscale (hospice M = 8.44; palliative M = 8.13), but no significant differences were found. The original hypothesis that the additional support offered to hospice patients would result in a higher subjective quality of life could not be supported by this study. To help patients achieve their greatest potential quality of life, healthcare workers must make themselves aware of the factors most likely to foster quality of life for individuals, whether that is the quiet comfort of hospice or the hope and optimism of continued treatment.