MS

thesisPeriventricular-intraventricular hemorrhage (PV-IVH) is a serious from of neonatal intracranial hemorrhage. This research was undertaken to determine the relationship between PV-IVH and hyperglycemia. Medical records of 57 preterm infants from the University of Utah Medical Center were examined. Data collected demonstrated a significant relationship between the occurrence of PV-IVH and hyperglycemia episode. The severity of hyperglycemia could not predict the development hydrocephalus. It was concluded that the clinical value of glucose determinations may serve to identify a PV-IVH. Further research is indicated to validate these findings and to define the specifics of the relationship between these variables

Role of leucine-rich repeat kinase 2 in severe acute pancreatitis

IntroductionIntrapancreatic activation of trypsinogen caused by alcohol or high-fat intake and the subsequent autodigestion of the pancreas tissues by trypsin are indispensable events in the development of acute pancreatitis. In addition to this trypsin-centered paradigm, recent studies provide evidence that innate immune responses triggered by translocation of intestinal bacteria to the pancreas due to intestinal barrier dysfunction underlie the immunopathogenesis of acute pancreatitis. Although severe acute pancreatitis is often associated with pancreatic colonization by fungi, the molecular mechanisms linking fungus-induced immune responses to the development of severe acute pancreatitis are poorly understood. Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein that mediates innate immune responses to fungi and bacteria. Mutations in Lrrk2 is a risk factor for Parkinson’s disease and Crohn’s disease, both of which are driven by innate immune responses to gut organisms.DiscussionIn this Minireview article, we discuss how activation of LRRK2 by the recognition of fungi induces severe acute pancreatitis

Pancreatic colonization of fungi in the development of severe acute pancreatitis

Acute pancreatitis is a common emergent disorder, a significant population of which develops the life-threatening condition, called severe acute pancreatitis (SAP). It is generally accepted that bacterial infection is associated with the development and persistence of SAP. In addition to bacterial infection, recent clinical studies disclosed a high incidence of fungal infection in patients with SAP. Moreover, SAP patients with fungal infection exhibit a higher mortality rate than those without infection. Although these clinical studies support pathogenic roles played by fungal infection in SAP, beneficial effects of prophylactic anti-fungal therapy on SAP have not been proved. Here we summarize recent clinical findings as to the relationship between fungal infection and the development of SAP. In addition, we discuss molecular mechanisms accounting for the development of SAP in the presence of fungal infection

Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta-analysis

Background: Previous studies have shown that xanthine oxidase inhibitors (XOI) might improve outcome for patients with cardiovascular disease. However, more evidence is required. Methods and results: We published a meta‐analysis of trials conducted before 2014 examining the effects of XOI on mortality in patients with cardiovascular disease. At least two further trials (N = 323 patients) have since been published. Accordingly, we repeated our analysis after a further search for randomized controlled trials of XOI in PubMed/MEDLINE, EMBASE, and Cochrane Databases. We identified eight relevant trials with 1031 patients. The average age of the patients was 61 years and 68% were men (one study did not report gender). There were 57 deaths in these eight trials, 26 in those assigned to XOI, and 31 in those assigned to the control. The updated meta‐analysis could not confirm a reduction in mortality for patients assigned to XOI compared with placebo (odds ratio 0.84) but 95% confidence intervals were wide (0.48–1.47). Conclusions: This updated meta‐analysis does not suggest that XOI exert a large reduction in mortality but also cannot exclude the possibility of substantial harm or benefit

Quantitative analysis of the binding affinity of poly(ADP-ribose) to specific binding proteins as a function of chain length

Poly(ADP-ribose) (PAR) is synthesized by poly(ADP-ribose) polymerases in response to genotoxic stress and interacts non-covalently with DNA damage checkpoint and repair proteins. Here, we present a variety of techniques to analyze this interaction in terms of selectivity and affinity. In vitro synthesized PAR was end-labeled using a carbonyl-reactive biotin analog. Binding of HPLC-fractionated PAR chains to the tumor suppressor protein p53 and to the nucleotide excision repair protein XPA was assessed using a novel electrophoretic mobility shift assay (EMSA). Long ADP-ribose chains (55-mer) promoted the formation of three specific complexes with p53. Short PAR chains (16-mer) were also able to bind p53, yet forming only one defined complex. In contrast, XPA did not interact with short polymer, but produced a single complex with long PAR chains (55-mer). In addition, we performed surface plasmon resonance with immobilized PAR chains, which allowed establishing binding constants and confirmed the results obtained by EMSA. Taken together, we developed several new protocols permitting the quantitative characterization of PAR–protein binding. Furthermore, we demonstrated that the affinity of the non-covalent PAR interactions with specific binding proteins (XPA, p53) can be very high (nanomolar range) and depends both on the PAR chain length and on the binding protein

Bispectral index-guided propofol sedation during endoscopic ultrasonography

Background/Aims Bispectral index (BIS) monitors process and display electroencephalographic data are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS). Methods This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score >8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room. Results The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged ≥75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001). Conclusions During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older

PARP1 ADP-ribosylates lysine residues of the core histone tails

The chromatin-associated enzyme PARP1 has previously been suggested to ADP-ribosylate histones, but the specific ADP-ribose acceptor sites have remained enigmatic. Here, we show that PARP1 covalently ADP-ribosylates the amino-terminal histone tails of all core histones. Using biochemical tools and novel electron transfer dissociation mass spectrometric protocols, we identify for the first time K13 of H2A, K30 of H2B, K27 and K37 of H3, as well as K16 of H4 as ADP-ribose acceptor sites. Multiple explicit water molecular dynamics simulations of the H4 tail peptide into the catalytic cleft of PARP1 indicate that two stable intermolecular salt bridges hold the peptide in an orientation that allows K16 ADP-ribosylation. Consistent with a functional cross-talk between ADP-ribosylation and other histone tail modifications, acetylation of H4K16 inhibits ADP-ribosylation by PARP1. Taken together, our computational and experimental results provide strong evidence that PARP1 modifies important regulatory lysines of the core histone tails

PENERAPAN BELAJAR KELOMPOK DALAM MENINGKATKAN PERILAKU SOSIAL ANAK DI TAMAN KANAK-KANAK ELIM RANTEPAO TANA TORAJA

TABITHA TASIK M. 2013. Penerapan Belajar Kelompok dalam Meningkatkan Perilaku Sosial Anak di Taman Kanak-Kanak Elim Rantepao Tana Toraja. Dibimbing oleh Dra.Kartini Marzuki, M.Si dan Dra.Istiani Idrus, M.Si. Program Studi Pendidikan Anak Usia Dini Fakultas Ilmu Pendidikan Universitas Negeri Makassar. Rumusan masalah penelitian adalah bagaimana penerapan belajar kelompok dapat meningkatkan kemampuan sosial anak didik di TK Elim Rantepao Tanatoraja.Tujuan penelitiana dalah untuk mengeta huimeningkatnya perilakusosial anak melalui kegiatan belajar kelompok di TK ElimRantepao. Penelitian ini merupakan penelitian kualitatif dengan jenis penelitian tindakan kelas.Penelitian ini dilaksanakan dengan dua siklus dimana setiap siklus terdiri atas tiga kali pertemuan. Prosedur penelitian tindakan kelas terdiri atas perencanaan, pelaksanaan, observasi, dan refleksi. Sasaran dan sekaligus menjadi subjek penelitian adalah anak didik kelas BIITK ElimRantepao, sebanyak 20 orang, yang terdiri dari 8 laki-laki dan 12 perempuan. Data menggunakan analisis deskriptif. Hasil penelitian menunjukkan padasiklus pertama, perilaku sosial anak dengan kegiatan belajar kelompok pada anak didik kelas BII TK Elim Rantepao Kabupaten Toraja Utara pada ketegori kurang dan meningkat pada siklus kedua rata-rata dengan kategori baik. Peningkatan tersebut dapat terlihat dari kemampuan anak didik dalam hal pergaulan anak terhadap teman-temannya, bekerjasama dalam kelompok, mauberbagi, menolong dan membantu temannya, serta dapat berinteraksi dengan teman temannya. Kesimpulan hasil penelitian yaitu terjadinya peningkatan perilaku sosial anak didik melalui penerapan belajar kelompok di kelas BII TK Elim Rantepao Kabupaten Toraja Utara