Estudo diagnóstico dos distúrbios psicomotores primários em 36 crianças, de ambos os sexos, portadoras de deficiência mental moderada, da Escola Municipal de Paranaguá, Paraná

Orientador: Johann G. G. Melcherts HurtadoTrabalho de Graduação apresentado ao Curso de Especialização em Educação Especial da Universidade Federal do Paran

An adaptive SC line equalizer for four-wire full-duplex and multirate digital transmission

金沢大学大学院自然科学研究科情報システム金沢大学工学部An adaptive switched-capacitor (SC) line equalizer system that can be applied to four-wire full-duplex and multirate digital transmission is described. Several kinds of noises can exist in programmable high-gain SC equalizers, such as switching noise, DC offset jump, and transient response. To avoid their effects, an adaptive SC filter is proposed. Two identical SC circuits are used in parallel. An input signal is fed into both SC circuits, and output signals from both circuits are alternately sent after the above noises are eliminated. Furthermore, many different data rates can be handled by slightly modifying an equalizer circuit. A bridged-tap echo canceller and a DC offset canceller are modified so as to be applied to the proposed adaptive SC filter. A line equalizer system, that handles data rates ranging from 3.2 to 64 kb/s was designed. An LSI was fabricated using a 3-μm CMOS process. Experimental results show that noise effects are mostly eliminated, and frequency responses and eye openings are close to the designed values

Paleoenvironmental Analyses of the Buried Peat Deposit during the mid-Holocene at the Desaki Coast in Tamano City, Okayama Prefecture, Weatern Japan

The buried peat deposit was foud in the sand beach on the Desaki coast (Tamano City, Okayama Prefecture), the northeastern coast of Seto Inland Sea. In this study, we performed sulfur and diatom analyses of the deposit. The results were used along with 14C dates and the eruption age (7300 cal BP) of Kikai-Akahoya tephra (K-Ab) to derive sedimentary environments of the deposit. K-Ah was detected just below the peat deposit. At the culmination of the Jomon transgression, the peat deposit had been formed in brackish environments of salt marsh for about 300 years. In order to reconstruct local paleovegetation, we analyzed pollen, wood and plant fossils in the deposit. The results show vegetational transition from a deciduous broadleaved forest mainly of Ouercus subgen. Lepidobalanus to Pinus forest. In spite of the Holocene thermal optimum, the vegetation dominated by Ouercus subgen. Cyclobanopsis was not recognized at the Desaki site, as has been shown in many other regions of regions of western Japan. Ouercus sect. Prinus was replaced by Ouercus sect. Aegilops as the dominant section of Ouercus subgen. Lepidobalanus, suggesting early establishment of traditional rural vegetation of 'Satoyama' in Japan. However, no evidence for human agency has been obtained from the mid-Holocene archaeological sites around the Desaki site. Thus it is more likely that this vegetational transition resulted from the succession caused by natural forces such as ecological disturbance and climatic and/or endemic situations rather than by cultural deforestation

COMBINATION THERAPY OF INTRAVITREAL RANIBIZUMAB AND SUBTHRESHOLD MICROPULSE PHOTOCOAGULATION FOR MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION

Purpose: To determine the efficacy of the combination therapy of intravitreal ranibizumab (IVR) and 577-nm yellow laser subthreshold micropulse laser photocoagulation (SMLP) for macular edema secondary to branch retinal vein occlusion cystoid macular edema.Methods: Retrospective, consecutive, case–control study. Forty-six eyes of 46 patients with treatment-naive branch retinal vein occlusion cystoid macular edema were enrolled. The IVR + SMLP group consisted of 22 patients who had undergone both SMLP and IVR. Intravitreal ranibizumab group consisted of 24 patients who had undergone IVR monotherapy. Intravitreal ranibizumab therapy was one initial injection and on a pro re nata in both groups, and SMLP was performed at 1 month after IVR in the IVR + SMLP group. Preoperatively and monthly, best-corrected visual acuity and central retinal thickness were evaluated using swept source optical coherence tomography.Results: Best-corrected visual acuity and central retinal thickness significantly improved at 6 months in IVR + SMLP and IVR groups. Best-corrected visual acuity and central retinal thickness were not significantly different between the two groups at any time points. The number of IVR injections during initial 6 months in IVR group (2.3 ± 0.9) was significantly greater (P = 0.034) than that in IVR + SMLP group (1.9 ± 0.8).Conclusion: The combination therapy of IVR and SMLP can treat branch retinal vein occlusion cystoid macular edema effectively, by decreasing the frequency of IVR injections while maintaining good visual acuity

CXCR4 Negatively Regulates Keratinocyte Proliferation in IL-23-Mediated Psoriasiform Dermatitis

CXCR4 is expressed by basal keratinocytes (KCs), but little is known about its function in inflamed skin. We crossed K14-Cre and CXCR4flox/flox (f/f) transgenic mice, resulting in mice with specific loss of the CXCR4 gene in K14-expressing cells (K14-CXCR4KO), including basal KCs. K14-CXCR4KO pups had no obvious skin defects. We compared K14-CXCR4KO and CXCR4f/f control mice in an IL-23-mediated psoriasiform dermatitis model and measured skin edema, and histologic and immunohistological changes. IL-23-treated K14-CXCR4KO mice showed a 1.3-fold increase in mean ear swelling, a 2-fold increase in epidermal thickness, and greater parakeratosis. IL-23-treated wild-type (WT) mice showed weak CXCR4 expression in areas of severe epidermal hyperplasia, but strong CXCR4 expression in nonhyperplastic regions, suggesting that CXCR4 may regulate KC proliferation. To test this hypothesis, we overexpressed CXCR4 in HaCaT KC cells and treated them with IL-22 and/or CXCL12 (chemokine (C-X-C motif) ligand 12). CXCL12 blocked IL-22-mediated HaCaT cell proliferation in vitro and synergized with IL-22 in upregulating SOCS3 (suppressor of cytokine signaling 3), a key regulator of STAT3 (signal transducer and activator of transcription 3). SOCS3 was required for CXCR4-mediated growth inhibition. In human psoriatic skin, both CXCR4 and SOCS3 were upregulated in the junctional region at the border of psoriatic plaques. Thus, CXCR4 has an unexpected role in inhibiting KC proliferation and mitigating the effects of proliferative T helper type 17 cytokines

Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9–mediated progenitor cell mobilization

Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell–dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)–dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9–deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sld mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sld mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues

Polycomb-Mediated Loss of miR-31 Activates NIK-Dependent NF-κB Pathway in Adult T Cell Leukemia and Other Cancers

SummaryConstitutive NF-κB activation has causative roles in adult T cell leukemia (ATL) caused by HTLV-1 and other cancers. Here, we report a pathway involving Polycomb-mediated miRNA silencing and NF-κB activation. We determine the miRNA signatures and reveal miR-31 loss in primary ATL cells. MiR-31 negatively regulates the noncanonical NF-κB pathway by targeting NF-κB inducing kinase (NIK). Loss of miR-31 therefore triggers oncogenic signaling. In ATL cells, miR-31 level is epigenetically regulated, and aberrant upregulation of Polycomb proteins contribute to miR-31 downregulation in an epigenetic fashion, leading to activation of NF-κB and apoptosis resistance. Furthermore, this emerging circuit operates in other cancers and receptor-initiated NF-κB cascade. Our findings provide a perspective involving the epigenetic program, inflammatory responses, and oncogenic signaling

Pathway to psychiatric care in Japan: A multicenter observational study

<p>Abstract</p> <p>Background</p> <p>This study examines pathways to psychiatric care in Japan using the same method as the collaborative study carried out in 1991 under the auspices of the World Health Organization.</p> <p>Methods</p> <p>Thirteen psychiatric facilities in Japan were involved. Of the 228 patients who contacted psychiatric facilities with any psychiatric illness, eighty four visiting psychiatric facilities for the first time were enrolled. Pathways to psychiatric care, delays from the onset of illness to treatment prior to reaching psychiatrists were surveyed.</p> <p>Results</p> <p>Thirty three patients (39.4%) directly accessed mental health professionals, 32 patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via private practitioners. The patients who consulted mental health professionals as their first carers took a longer time before consulting psychiatrists than the patients who consulted non-mental health professionals as their first carers. The patients who presented somatic symptoms as their main problem experienced longer delay from the onset of illness to psychiatric care than the patients who complained about depressive or anxiety symptoms. Prior to the visit to mental health professionals, patients were rarely informed about their diagnosis and did not receive appropriate treatments from their physicians. Private practitioners were more likely to prescribe psychotropics than physicians in general hospitals, but were less likely to inform their patients of their diagnosis.</p> <p>Conclusion</p> <p>This first pathway to psychiatric care study in Japan demonstrated that referral pathway in Japan heavily relies on medical resources. The study indicates possible fields and gives indications, underlining the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders presenting with somatic and depressive symptoms in the general health care system and by private practitioners.</p

PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response