Antithrombotic Protective Effects of Arg-Pro-Gly-Pro Peptide during Emotional Stress Provoked by Forced Swimming Test in Rats.

PubMed

Grigor'eva, M E; Lyapina, L A

2017-01-01

Blood coagulation was enhanced and all factors (total, enzyme, and non-enzyme) of the fibrinolytic system were suppressed in rats in 60 min after forced swimming test. Argininecontaining tetrapeptide glyproline Arg-Pro-Gly-Pro administered prior to this test activated fibrinolysis and prevented hypercoagulation. Administration of this peptide in 5 min after swimming test also enhanced anticoagulant, fibrinolytic, and antithrombotic activity of the blood. Therefore, glyproline Arg-Pro-Gly-Pro exerted both preventive and curative effects on the hemostasis system and prevented enhancement of blood coagulation provoked by emotional stress modeled by forced swimming test.

Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus

PubMed Central

Dey, Sumanta; De, Antara; Nandy, Ashesh

2016-01-01

Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time. PMID:27279731

Preventive Strategies for Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Procedures: Evidence From a Hierarchical Bayesian Network Meta-Analysis of 124 Trials and 28 240 Patients.

PubMed

Giacoppo, Daniele; Gargiulo, Giuseppe; Buccheri, Sergio; Aruta, Patrizia; Byrne, Robert A; Cassese, Salvatore; Dangas, George; Kastrati, Adnan; Mehran, Roxana; Tamburino, Corrado; Capodanno, Davide

2017-05-01

The effectiveness of currently available effective preventive strategies for contrast-induced acute kidney injury (CIAKI) is a matter of debate. We performed a Bayesian random-effects network meta-analysis of 124 trials (28 240 patients) comparing a total of 10 strategies: saline, statin, N-acetylcysteine (NAC), sodium bicarbonate (NaHCO 3 ), NAC+NaHCO 3 , ascorbic acid, xanthine, dopaminergic agent, peripheral ischemic preconditioning, and natriuretic peptide. Compared with saline, the risk of CIAKI was reduced by using statin (odds ratio [OR], 0.42; 95% credible interval [CrI], 0.26-0.67), xanthine (OR, 0.32; 95% CrI, 0.17-0.57), ischemic preconditioning (OR, 0.48; 95% CrI, 0.26-0.87), NAC+NaHCO 3 (OR, 0.50; 95% CrI, 0.33-0.76), NAC (OR, 0.68; 95% CrI, 0.55-0.84), and NaHCO 3 (OR, 0.66; 95% CrI, 0.47-0.90). The benefit of statin therapy was consistent across multiple sensitivity analyses, whereas the efficacy of all the other strategies was questioned by restricting the analysis to high-quality trials. Overall, high heterogeneity was observed for comparisons involving xanthine and ischemic preconditioning, although the impact of NAC and xanthine was probably influenced by publication bias/small-study effect. Hydration alone was the least effective preventive strategy for CIAKI. Meta-regressions did not reveal significant associations with baseline creatinine and contrast volume. In patients with diabetes mellitus, no strategy was found to reduce the incidence of CIAKI. In patients undergoing percutaneous coronary procedures, statin administration is associated with a marked and consistent reduction in the risk of CIAKI compared with saline. Although xanthine, NAC, NaHCO 3 , NAC+NaHCO 3 , ischemic preconditioning, and natriuretic peptide may have nephroprotective effects, these results were not consistent across multiple sensitivity analyses. © 2017 American Heart Association, Inc.

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators.

PubMed

Islek, Ali; Yilmaz, Aygen; Elpek, Gulsum Ozlem; Erin, Nuray

2016-10-07

To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels. We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observed in neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis. Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects.

Childhood chronic gastritis and duodenitis: Role of altered sensory neuromediators

PubMed Central

Islek, Ali; Yilmaz, Aygen; Elpek, Gulsum Ozlem; Erin, Nuray

2016-01-01

AIM To investigate the roles of the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) in chronic gastritis and duodenitis in children. METHODS Biopsy samples from the gastric and duodenal mucosa of 52 patients and 30 control subjects were obtained. Samples were taken for pathological examination, immunohistochemical staining, enzyme activity measurements and quantitative measurements of tissue peptide levels. RESULTS We observed differential effects of the disease on peptide levels, which were somewhat different from previously reported changes in chronic gastritis in adults. Specifically, SP was increased and CGRP and VIP were decreased in patients with gastritis. The changes were more prominent at sites where gastritis was severe, but significant changes were also observed in neighboring areas where gastritis was less severe. Furthermore, the degree of changes was correlated with the pathological grade of the disease. The expression of CD10, the enzyme primarily involved in SP hydrolysis, was also decreased in patients with duodenitis. CONCLUSION Based on these findings, we propose that decreased levels of VIP and CGRP and increased levels of SP contribute to pathological changes in gastric mucosa. Hence, new treatments targeting these molecules may have therapeutic and preventive effects. PMID:27729741

Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein epitope peptide vaccine elicits specific anti-tumor immunity.

PubMed

Wang, Xiao-Ping; Wang, Qiao-Xia; Lin, Huan-Ping; Xu, Bing; Zhao, Qian; Chen, Kun

2016-11-01

Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P. This novel peptide was administered into BALB/c mice to observe the effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-γ in these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed increased granzyme B and perforin released by natural killer cells. Moreover, in vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP-expressing tumors. These results show that treatment of BALB/c mice with HSP70-P/AFP-P induced stronger T-cells responses and improved protective immunity. Our data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the treatment of AFP-expressing cancers.

Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts.

PubMed

Gary, Regina; Aigner, Michael; Moi, Stephanie; Schaffer, Stefanie; Gottmann, Anja; Maas, Stefanie; Zimmermann, Robert; Zingsem, Jürgen; Strobel, Julian; Mackensen, Andreas; Mautner, Josef; Moosmann, Andreas; Gerbitz, Armin

2018-05-09

A major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts. We have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population. CMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis. Our protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.

Atrial natriuretic peptide: a magic bullet for cancer therapy targeting Wnt signaling and cellular pH regulators.

PubMed

Serafino, A; Pierimarchi, P

2014-01-01

Atrial natriuretic peptide (ANP) is a cardiac hormone playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. In the last years, the new property ascribed to ANP of inhibiting tumor growth both in vitro and in vivo has made this peptide an attractive candidate for anticancer therapy. The molecular mechanism underlying the anti-proliferative effect of ANP has been mainly related to its interaction with the specific receptors NPRs, through which this natriuretic hormone inhibits some metabolic targets critical for cancer development, including the Ras-MEK1⁄2-ERK1⁄2 kinase cascade, functioning as a multikinase inhibitor. In this review we summarize the current knowledge on this topic, focusing on our recent data demonstrating that the antitumor activity of this natriuretic hormone is also mediated by a concomitant effect on the Wnt/β-catenin pathway and on the pH regulation ability of cancer cells, through a Frizzled-related mechanism. This peculiarity of simultaneously targeting two processes crucial for neoplastic transformation and solid tumor survival reinforces the utility of ANP for the development of both preventive and therapeutic strategies.

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents.

PubMed

Abed, Dhulfiqar Ali; Goldstein, Melanie; Albanyan, Haifa; Jin, Huijuan; Hu, Longqin

2015-07-01

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.

Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat Periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1β and TNF-α production.

PubMed

Wang, Hong-Yan; Lin, Li; Fu, Wei; Yu, Hui-Yuan; Yu, Ning; Tan, Li-Si; Cheng, Jya-Wei; Pan, Ya-Ping

2017-08-29

P-113 (AKRHHGYKRKFH-NH2) is a 12-amino-acid histidine-rich peptide derived from histatin 5 that is highly degradable in high salt concentrations and biological fluids such as serum, plasma and saliva. Nal-P-113, a novel antimicrobial peptide whose histidine residues are replaced by the bulky amino acids β-naphthylalanine, causes the antimicrobial peptide to retain its bactericidal activity even in physiological environments. This study evaluated the effect of the novel antimicrobial peptide Nal-P-113 in a rat periodontitis model and the mechanisms of action of Nal-P-113 for suppressing periodontitis. Periodontitis was induced in mandibular first molars in rats receiving a ligature and infected with Porphyromonas gingivalis. Animals were randomly divided into six groups: a, P. gingivalis W83 alone; b, P. gingivalis W83 with 6.25 μg/mL of Nal-P-113; c, P. gingivalis W83 with 25 μg/mL of Nal-P-113; d, P. gingivalis W83 with 100 μg/mL of Nal-P-113; e, P. gingivalis W83 with 400 μg/mL of Nal-P-113; and f, control without P. gingivalis W83 or Nal-P-113. Morphometric analysis was used to evaluate alveolar bone loss. Microbiological assessment of the presence of Porphyromonas gingivalis and total bacteria was performed using absolute quantitative real-time PCR and scanning electron microscopy. Gingival tissue was collected for western blot and immunohistochemical assays of IL-1β and TNF-α levels. Alveolar bone loss was inhibited by 100 μg/mL or 400 μg/mL of Nal-P-113 compared to the control group (P < 0.05). Lower amounts of P. gingivalis and total bacteria were found in groups d and e compared with group a (P < 0.05). A decrease in the levels of IL-1β and TNF-α was detected in group d and group e compared to the control group (P < 0.05). The amount of P. gingivalis was positively correlated with IL-1β and TNF-α expression in periodontal tissue (P < 0.05). Nal-P-113 exhibited protective effects on Porphyromonas gingivalis-induced periodontitis in rats by limiting the amount of bacteria and modulating IL-1β and TNF-α production. The use of Nal-P-113 in vivo might serve as a beneficial preventive or therapeutic approach for periodontitis.

[Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)].

PubMed

Dzhokhadze, T A; Buadze, T Zh; Gaĭozishvili, M N; Rogava, M A; Lazhava, T A

2013-12-01

In this paper, a comparative study of the functional genome indicators using lymphocyte cultures of patients with hypertrophic cardiomyopathy (HCM) and their first relatives. Studies conducted both in intact cultures and cultures exposed to the influence of peptide - bioregulators Epithalon, Vilon and Livagen. Last (Livagen) tested at separate and joint application with cobalt chloride salt. As indicated according to the results of the analysis, the cells of the individuals with HCM and their first relatives were characterized by higher frequency of spontaneous quantitative - structural disorders in comparison with the cells of healthy individuals. The findings suggest a different effect of bioregulators. The most effective protective action in relation normalization of functional parameters of the genome shows Epithalon for lowering the level of chromosomal instability in patients with hypertrophic cardiomyopathy and relatives of patients with HCM. On the basis of identified protective action Epithalon concludes prospects of its application in the development of preventive measures for individuals at increased risk of morbidity HCM.

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

PubMed Central

Martín-Pozuelo, Gala; González-Barrio, Rocío; Barberá, Gonzalo G.; Albalat, Amaya; García-Alonso, Javier; Mullen, William; Mischak, Harald; Periago, María Jesús

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene—which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD. PMID:27792191

A review of the design and modification of lactoferricins and their derivatives.

PubMed

Hao, Ya; Yang, Na; Teng, Da; Wang, Xiumin; Mao, Ruoyu; Wang, Jianhua

2018-06-01

Lactoferricin (Lfcin), a multifunction short peptide with a length of 25 residues, is derived from the whey protein lactoferrin by acidic pepsin hydrolysis. It has potent nutritional enhancement, antimicrobial, anticancer, antiviral, antiparasitic, and anti-inflammatory activities. This review describes the research advantages of the above biological functions, with attention to the molecular design and modification of Lfcin. In this examination of design and modification studies, research on the identification of Lfcin active derivatives and crucial amino acid residues is also reviewed. Many strategies for Lfcin optimization have been studied in recent decades, but we mainly introduce chemical modification, cyclization, chimera and polymerization of this peptide. Modifications such as incorporation of D-amino acids, acetylation and/or amidation could effectively improve the activity and stability of these compounds. Due to their wide array of bio-functions and applications, Lfcins have great potential to be developed as biological agents with multiple functions involved with nutritional enhancement, as well as disease preventive and therapeutic effects.

Preventive effect of Dendrobium candidum Wall. ex Lindl. on activated carbon-induced constipation in mice

PubMed Central

WANG, RUI; SUN, PENG; ZHOU, YALIN; ZHAO, XIN

2015-01-01

The aim of this study was to investigate the effects of Dendrobium candidum Wall. ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered D. candidum for 9 days. Body weight, defecation status, gastrointestinal (GI) transit and defecation times, in addition to the levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were used to evaluate the preventive effects of D. candidum on constipation. The laxative drug bisacodyl acted as a positive control. The time to the first defecation of a black stool for the normal, control, bisacodyl-treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126, 161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D. candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and 90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with D. candidum compared with those in the untreated control mice (P<0.05). These results demonstrate that D. candidum has preventive effects on constipation in mice, and a greater functional activity was observed when a higher concentration was administered. PMID:25574235

Preventive effect of resistant starch on activated carbon-induced constipation in mice

PubMed Central

QIAN, YU; ZHAO, XIN; KAN, JIANQUAN

2013-01-01

The aim of this study was to investigate the effects of resistant starch (RS) on activated carbon-induced constipation in ICR mice. ICR mice were fed on diet containing 15% RS of type RS2, RS3 or RS4 for 9 days. Gastrointestinal transit, defecation time and intestinal tissue histopathological sections, as well as motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were used to evaluate the preventive effects of RS on constipation. Bisacodyl, a laxative drug, was used as a positive control. The time to the first black stool defecation for normal, control, bisacodyl-treated (100 mg/kg, oral administration) and RS2-, RS3- and RS4-treated mice was 78, 208, 109, 181, 144 and 173 min, respectively. Following the consumption of RS2, RS3 and RS4 or the oral administration of bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 37.7, 52.1, 39.3 and 87.3%, respectively, of the transit in normal mice, respectively. Histopathological sections of intestinal tissue also underscored the protective effect of RS3. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with RS compared with those in the untreated control mice (P<0.05). These results demonstrate that RS has preventive effects on mouse constipation and RS3 demonstrated the best functional activity. PMID:23935751

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58

PubMed Central

Xu, Wan-Xiang; Wang, Jian; Tang, Hai-Ping; He, Ya-Ping; Zhu, Qian-Xi; Gupta, Satish K.; Gu, Shao-Hua; Huang, Qiang; Ji, Chao-Neng; Liu, Ling-Feng; Li, Gui-Ling; Xu, Cong-Jian; Xie, Yi

2016-01-01

To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs. PMID:27708433

Identification of the immunogenic epitopes of the whole venom component of the Hemiscorpius lepturus scorpion using the phage display peptide library.

PubMed

Jahdasani, Roghaye; Jamnani, Fatemeh Rahimi; Behdani, Mahdi; Habibi-Anbouhi, Mahdi; Yardehnavi, Najmeh; Shahbazzadeh, Delavar; Kazemi-Lomedasht, Fatemeh

2016-12-15

The venom of the Hemiscorpius lepturus scorpion contains mixtures of bioactive compounds that disturb biochemical and physiological functions of the victims. Hemiscorpius lepturus envenomation is recognized as a serious health concern in tropical regions. So far, there is no preventive procedure, and the main focus is on treatment of victims with an antiserum purified from hyper-immunized horses. Although antisera can neutralize the venom, they, in some cases, lead to anaphylactic shock and even death. Selection of peptides mimicking antigenic and immunogenic epitopes of toxins from random peptide libraries is a novel approach for the development of recombinant toxins and poly-epitopic vaccine. To achieve this aim, a phage display peptide library and three rounds of biopanning were performed on immobilized antibodies (IgGs) purified from the sera of hyper-immunized horses. The results show that the highest binding of the phage to immobilized horse antibodies occurred in the third round of biopanning. Over 125 individual clones carrying mimotopes of Hemiscorpius lepturus toxins were selected and subjected for sequencing. The sequencing results identified unique peptides mimicking the antigenic and immunogenic epitopes of Hemiscorpius lepturus toxins. The results of this study provide a basis for further studies and the development of a putative epitopic vaccine and a recombinant toxin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expression mapping using a retroviral vector for CD8+ T cell epitopes: definition of a Mycobacterium tuberculosis peptide presented by H2-Dd.

PubMed

Aoshi, Taiki; Suzuki, Mina; Uchijima, Masato; Nagata, Toshi; Koide, Yukio

2005-03-01

Identification of CD8+ T cell epitopes is important because detection of specific CD8+ T cells after infection or immunization requires prior knowledge of epitope specificity. Furthermore, identification of CD8+ T cell epitopes permits the development of specific preventive and therapeutic approaches to both infections and tumors. Thus far, CD8+ T cell epitopes have been identified either using an overlapping peptide library covering an entire protein, or using algorithms designed to identify likely peptides that bind to major histocompatibility complex (MHC) class I molecules. The synthesis of overlapping peptides can be prohibitively expensive, and the algorithm programs used to predict CD8+ T cell epitopes are not always accurate. Here we describe a retroviral expression system that specifically allows longer polypeptides and shorter peptides to be expressed in the cytoplasm, and thereby to be processed onto class I MHC molecules. T cells from mice that were immunized with a DNA vaccine encoding MPT-51 were probed against MHC-compatible cell lines retrovirally transduced with overlapping gene fragments encoding 120-140 amino acids of the MPT-51 molecule. After further testing of shorter peptide sequences, we identified a CD8+ T cell epitope using cell lines expressing a relatively small number of algorithm-predicted candidate epitopes. We found that one of the requirements for cell surface display of the 20-mer peptide was the need for cotranslational ubiquitination. The restriction molecule was identified as Dd following transduction with MHC class I genes followed by transduction with the oligonucleotide encoding the epitope. The retroviral expression system described here is cost-effective, particularly if the target molecule is large, and could be adapted to identifying T cell epitopes recognized in infectious disease and against tumor cell antigens.

[Doctors belonging to the Senegalese Association of Sport Medicine and doping in sports: survey on knowledge and attitudes].

PubMed

Dièye, Amadou Moctar; Diallo, Boubacar; Fall, Assane; Ndiaye, Mamadou; Cissè, Fallou; Faye, Babacar

2005-01-01

Doping in sports is as old as sports, but it grew considerably during the 20th century with the arrival in stadiums during the 1990s of amphetamines and anabolic steroids as well as such peptide hormones as erythropoietin. The international fight against doping took a giant step forward in 1999 with the creation of the world antidoping agency (WADA). This study is part of that fight. It follows an earlier survey of retail pharmacists in Senegal and aims to evaluate the knowledge about doping of doctors belonging to the Senegalese Association of Sports Medicine and to assess their attitude towards this phenomenon. Its goal is to determine how best to involve them in preventive actions. We conducted a survey in 2001 and randomly selected and interviewed 60 of the 92 doctors in the association. The questionnaire focused on three areas: their knowledge of doping, their attitudes to it, and the means of prevention that they proposed. The results showed that only 11 of the 60 doctors knew the definition of doping and 15% of doctors could not cite any family of doping products. They were aware mainly of testosterone and other anabolic steroids (84.3%), then amphetamines and other stimulants (64.7%), and finally peptide hormones (58.8%). The subjects mentioned blood doping and pharmacological manipulations as forbidden methods. They considered that the four groups of drugs most often used by athletes for doping were, in descending order, anabolic steroids, stimulants, peptide hormones and corticoids. Eighty per cent of doctors think that Senegalese athletes use doping products and that the sports most involved are football, wrestling, track and field and basketball. They also think that doping is a form of drug addiction and a public health problem. Eleven doctors (18%) said they had been contacted for information on use of doping products. The interviewees consider that the three best methods of prevention include information about side effects, unannounced urine and blood tests, and sanctions. This work shows that Senegalese athletes may use doping; it contains no direct proofs but many indirect indicators. Success against doping requires preventive activities that should be conducted jointly for trainers, sports federations and doctors of the Senegalese Association of Sports Medicine and then by all of them for athletes, who are the primary targets of any prevention campaign.

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety.

PubMed

Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

2015-07-17

Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%-2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155-195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes.

PubMed

Paparo, L; Aitoro, R; Nocerino, R; Fierro, C; Bruno, C; Canani, R Berni

2018-01-29

Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

Self-emulsifying drug delivery system improves preventive effect of curcuminoids on chronic heart failure in rats.

PubMed

Jiang, Yunbin; Wang, Junzhi; Wang, Yunhong; Ke, Xiumei; Zhang, Chuanhui; Yang, Rongping

2018-05-01

Several studies have reported the preventive or therapeutic effect of curcuminoids on chronic heart failure (CHF), but their application was limited due to low solubility and bioavailability. Our previous study indicates that self-emulsifying drug delivery system (SEDDS) improves the solubility and bioavailability of curcuminoids. Thus, the aim of this work was to investigate whether SEDDS could improve preventive effect of curcuminoids on CHF in rats. CHF model was were established by coronary artery ligation. Ninety rats were randomly and averagely divided into sham, model, low- or high-dose suspension or SEDDS of curcuminoids (66.68 or 266.68 mg/kg) groups. Hemodynamic indices were recorded by multipurpose polygraph. Serum oxidative indices, B-type natriuretic peptide (BNP) and heart weight index were determined by kits and electronic balance. Myocardial infarct area, ventricular dilatation degree and collagen volume fraction of myocardial interstitium were analyzed by Masson staining, picric acid and sirius red staining, light microscopy and image analysis system. Myocardial histopathology was observed by hematoxylin and eosin staining, Masson staining and light microscopy. Reduction of ventricular pump function, increase of BNP level and heart weight index, myocardial lipid peroxidation damage, myocardial infarction, myocardial fibrosis, and cardiac enlargement were detected or observed in model group relative to those in sham group. After treatment with suspension or SEDDS of curcuminoids, the above-mentioned pathological changes were obviously reversed relative to those in model group. Meanwhile, the ameliorative effect of SEDDS of curcuminoids was markedly better than that of suspension of curcuminoids. This work provides a valuable reference from pharmacodynamics for development of curcuminoids pharmaceutics.

Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice.

PubMed

Kossoy, George; Anisimov, Vladimir N; Ben-Hur, Herzel; Kossoy, Nadja; Zusman, Itshak

2006-01-01

The potential preventive effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on spontaneous tumorigenesis in mice was studied. One-year-old female C3H/He mice were kept for 6.5 months under standard conditions. Epitalon was injected at a dose of 0.1 microg, 5 times a week. Long-term exposure to Epitalon in small doses did not show any toxic effect. Treatment with Epitalon decreased the number of tumor-bearing mice with malignant tumors and prevented the development of metastases. Spontaneous tumors of the reproductive organs (mammary glands and ovaries) were predominant in both groups of mice (control and experimental). The mammary gland tumors were different variants of invasive ductal carcinomas. In the ovaries, granulosa-cell tumors were found. Tumors were in the minority in other organs and had benign characteristics. In control mice, metastases were found in 3 out of 9 tumor-bearing mice, all of them being from tumors of the reproductive organs. Treatment with Epitalon slowed down the development of metastases from spontaneous tumors, and no metastases were found in the experimental mice. These data highlight the antimetastatic effect of Epitalon as part of its oncostatic properties.

TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunavala-Dossabhoy, Gulshan, E-mail: gsunav@lsuhsc.edu; Palaniyandi, Senthilnathan; Richardson, Charles

2012-09-01

Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect againstmore » IR-induced salivary hypofunction. Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation. Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D{sub 0} = 4.13 {+-} 1.0 Gy; {alpha}/{beta} = 0 Gy) compared with cells transduced with the TAT peptide (D{sub 0} = 4.91 {+-} 1.0 Gy; {alpha}/{beta} = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01). Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer.« less

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

PubMed Central

Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

2015-01-01

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

High-yield, in vitro protein expression using a continuous-exchange, coupled transcription/ translation system.

PubMed

Martin, G A; Kawaguchi, R; Lam, Y; DeGiovanni, A; Fukushima, M; Mutter, W

2001-10-01

The Rapid Translation System (RTS 500) (Roche Molecular Biochemicals) is a high-yield protein expression system that utilizes an enhanced E. coli lysate for an in vitro transcription/translation reaction. In contrast to conventional transcription/translation, this system allows protein expression to continue for more than 24 h. We demonstrated the utility of the RTS 500 by expressing different soluble and active proteins that generally pose problems in cell-based expression systems. We first expressed GFP-lunasin, a fusion protein that, because of its toxicity, has been impossible to produce in whole cells. The second protein we expressed, human interleukin-2 (IL-2), is generally difficult to produce, either as the native molecule or as a GSTfusion protein, in a soluble form in bacteria. Finally, we demonstrated the capacity of the RTS 500 to co-express proteins, by the simultaneous production of GFP and CAT in a single reaction. This new technology appears to be particularly usefulfor the convenient production of preparative amounts (100-900 microg) of proteins that are toxic or insoluble in cell-based systems.

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection.

PubMed

Marcatili, Paolo; Nielsen, Martin W; Sicheritz-Pontén, Thomas; Jensen, Tim K; Schafer-Nielsen, Claus; Boye, Mette; Nielsen, Morten; Klitgaard, Kirstine

2016-12-01

Polymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections. The strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease. The extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host's capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

PubMed

Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

2013-07-09

Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

A Personal Journey of Discovery: Developing Technology and Changing Biology

NASA Astrophysics Data System (ADS)

Hood, Lee

2008-07-01

This autobiographical article describes my experiences in developing chemically based, biological technologies for deciphering biological information: DNA, RNA, proteins, interactions, and networks. The instruments developed include protein and DNA sequencers and synthesizers, as well as ink-jet technology for synthesizing DNA chips. Diverse new strategies for doing biology also arose from novel applications of these instruments. The functioning of these instruments can be integrated to generate powerful new approaches to cloning and characterizing genes from a small amount of protein sequence or to using gene sequences to synthesize peptide fragments so as to characterize various properties of the proteins. I also discuss the five paradigm changes in which I have participated: the development and integration of biological instrumentation; the human genome project; cross-disciplinary biology; systems biology; and predictive, personalized, preventive, and participatory (P4) medicine. Finally, I discuss the origins, the philosophy, some accomplishments, and the future trajectories of the Institute for Systems Biology.

Enforced OX40 Stimulation Empowers Booster Vaccines to Induce Effective CD4+ and CD8+ T Cell Responses against Mouse Cytomegalovirus Infection

PubMed Central

Panagioti, Eleni; Boon, Louis; Arens, Ramon; van der Burg, Sjoerd H.

2017-01-01

There is an imperative need for effective preventive vaccines against human cytomegalovirus as it poses a significant threat to the immunologically immature, causing congenital disease, and to the immune compromised including transplant recipients. In this study, we examined the efficacy of synthetic long peptides (SLPs) as a CD4+ and CD8+ T cell-eliciting preventive vaccine approach against mouse CMV (MCMV) infection. In addition, the use of agonistic OX40 antibodies to enhance vaccine efficacy was explored. Immunocompetent C57BL/6 mice were vaccinated in a prime-boost vaccination regiment with SLPs comprising various MHC class I- and II-restricted peptide epitopes of MCMV-encoded antigens. Enforced OX40 stimulation resulted in superior MCMV-specific CD4+ as CD8+ T cell responses when applied during booster SLP vaccination. Vaccination with a mixture of SLPs containing MHC class II epitopes and OX40 agonistic antibodies resulted in a moderate reduction of the viral titers after challenge with lytic MCMV infection. Markedly, the combination of SLP vaccines containing both MHC class I and II epitopes plus OX40 activation during booster vaccination resulted in polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD4+ and CD8+ T cell responses that were even higher in magnitude when compared to those induced by the virus, and this resulted in the best containment of virus dissemination. Our results show that the induction of strong T cell responses can be a fundamental component in the design of vaccines against persistent viral infections. PMID:28265272

Capsaicin-enriched diet ameliorates autoimmune neuritis in rats.

PubMed

Motte, Jeremias; Ambrosius, Björn; Grüter, Thomas; Bachir, Hussein; Sgodzai, Melissa; Pedreiturria, Xiomara; Pitarokoili, Kalliopi; Gold, Ralf

2018-04-24

Autoimmune neuropathies are common PNS disorders and effective treatment is challenging. Environmental influence and dietary components are known to affect the course of autoimmune diseases. Capsaicin as pungent component of chili-peppers is common in human nutrition. An influence of capsaicin on autoimmune diseases has been postulated. We tested capsaicin in the animal model of experimental autoimmune neuritis (EAN) in Lewis rat. Rats were immunized with P2-peptide and were treated with capsaicin in different preventive settings. Electrophysiological, histological, and molecular biological analyses of the sciatic nerve were performed to analyze T-cell and macrophage cell count, TRPV1, and cytokine expression. Moreover, FACS analyses including the intestinal immune system were executed. We observed an immunomodulatory effect of an early preventive diet-concept, where a physiological dosage of oral capsaicin was given 10 days before immunization in EAN. A reduced inflammation of the sciatic nerve was significant detectable clinically, electrophysiologically (CMAPs reduced in control group p < 0.01; increase of nerve conduction blocks in control group p < 0.05), histologically (significant reduction of T-cells, macrophages and demyelination), and at cytokine level. In contrast, this therapeutic effect was missing with capsaicin given from the day of immunization onwards. As possible underlying mechanism, we were able to show changes in the expression of the capsaicin receptor in the sciatic nerve and the small intestine, as well as altered immune cell populations in the small intestine. This is the first report about the immunomodulatory effect of the common nutrient, capsaicin, in an experimental model for autoimmune neuropathies.

Extracellular Zn2+ Is Essential for Amyloid β1-42-Induced Cognitive Decline in the Normal Brain and Its Rescue.

PubMed

Takeda, Atsushi; Tamano, Haruna; Tempaku, Munekazu; Sasaki, Miku; Uematsu, Chihiro; Sato, Shoko; Kanazawa, Hiroaki; Datki, Zsolt L; Adlard, Paul A; Bush, Ashley I

2017-07-26

Brain Aβ 1-42 accumulation is considered an upstream event in pathogenesis of Alzheimer's disease. However, accumulating evidence indicates that other neurochemical changes potentiate the toxicity of this constitutively generated peptide. Here we report that the interaction of Aβ 1-42 with extracellular Zn 2+ is essential for in vivo rapid uptake of Aβ 1-42 and Zn 2+ into dentate granule cells in the normal rat hippocampus. The uptake of both Aβ 1-42 and Zn 2+ was blocked by CaEDTA, an extracellular Zn 2+ chelator, and by Cd 2+ , a metal that displaces Zn 2+ for Aβ 1-42 binding. In vivo perforant pathway LTP was unaffected by perfusion with 1000 nm Aβ 1-42 in ACSF without Zn 2+ However, LTP was attenuated under preperfusion with 5 nm Aβ 1-42 in ACSF containing 10 nm Zn 2+ , recapitulating the concentration of extracellular Zn 2+ , but not with 5 nm Aβ 1-40 in ACSF containing 10 nm Zn 2+ Aβ 1-40 and Zn 2+ were not taken up into dentate granule cells under these conditions, consistent with lower affinity of Aβ 1-40 for Zn 2+ than Aβ 1-42 Aβ 1-42 -induced attenuation of LTP was rescued by both CaEDTA and CdCl 2 , and was observed even with 500 pm Aβ 1-42 Aβ 1-42 injected into the dentate granule cell layer of rats induced a rapid memory disturbance that was also rescued by coinjection of CdCl 2 The present study supports blocking the formation of Zn-Aβ 1-42 in the extracellular compartment as an effective preventive strategy for Alzheimer's disease. SIGNIFICANCE STATEMENT Short-term memory loss occurs in normal elderly and increases in the predementia stage of Alzheimer's disease (AD). Amyloid-β 1-42 (Aβ 1-42 ), a possible causing peptide in AD, is bound to Zn 2+ in the extracellular compartment in the hippocampus induced short-term memory loss in the normal rat brain, suggesting that extracellular Zn 2+ is essential for Aβ 1-42 -induced short-term memory loss. The evidence is important to find an effective preventive strategy for AD, which is blocking the formation of Zn-Aβ 1-42 in the extracellular compartment. Copyright © 2017 the authors 0270-6474/17/377253-10$15.00/0.

Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice.

PubMed

Kapuvári, Bence; Hegedüs, Rózsa; Schulcz, Ákos; Manea, Marilena; Tóvári, József; Gacs, Alexandra; Vincze, Borbála; Mező, Gábor

2016-08-01

Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g. colon carcinoma). We have previously shown that GnRH-III[(4)Lys(Ac),(8)Lys(Dau = Aoa)] bioconjugate, in which daunorubicin was attached via oxime linkage to the (8)Lys of a GnRH-III derivative, exerted significant in vivo antitumor effect on subcutaneously developed HT-29 colon tumor. In contrast, results of the study reported here indicated that this compound was not active on an orthotopically developed tumor. However, if Lys in position 4 was acylated with butyric acid instead of acetic acid, the resulting bioconjugate GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] had significant tumor growth inhibitory effect. Furthermore, it prevented tumor neovascularization, without detectable side effects. Nevertheless, the development of metastases could not be inhibited by the bioconjugate; therefore, its application in combination with a metastasis preventive agent might be necessary in order to achieve complete tumor remission. In spite of this result, the treatment with GnRH-III[(4)Lys(Bu),(8)Lys(Dau = Aoa)] bioconjugate proved to have significant benefits over the administration of free daunorubicin, which was used at the maximum tolerated dose.

An MSI tumor specific frameshift mutation in a coding microsatellite of MSH3 encodes for HLA-A0201-restricted CD8+ cytotoxic T cell epitopes.

PubMed

Garbe, Yvette; Maletzki, Claudia; Linnebacher, Michael

2011-01-01

Microsatellite instability (MSI) resulting from inactivation of the DNA mismatch repair system (MMR) characterizes a highly immunological subtype of colorectal carcinomas. Those tumors express multiple frameshift-mutated proteins which present a unique pool of tumor-specific antigens. The DNA MMR protein MSH3 is frequently mutated in MSI(+) colorectal tumors, thus making it an attractive candidate for T cell-based immunotherapies. FSP-specific CD8(+) T cells were generated from a healthy donor using reverse immunology. Those T cells specifically recognized T2 cells sensitized with the respective peptides. Specific recognition and killing of MSI(+) colorectal carcinoma cells harbouring the mutated reading frame was observed. The results obtained with T cell bulk cultures could be reproduced with T cell clones obtained from the same cultures. Blocking experiments (using antibodies and cold target inhibition) confirmed peptide as well as HLA-A0201-specificity. We identified two novel HLA-A0201-restricted cytotoxic T cell epitopes derived from a (-1) frameshift mutation of a coding A(8) tract within the MSH3 gene. These were (386)-FLLALWECSL (FSP18) and (387)-LLALWECSL (FSP19) as well as (403)-IVSRTLLLV (FSP23) and (402)-LIVSRTLLLV (FSP31), respectively. These results suggest that MSH3(-1) represents another promising MSI(+)-induced target antigen. By identifying two distinct epitopes within MSH3(-1), the sustained immunogenicity of the frameshift mutated sequence was confirmed. Our data therefore encourage further exploitation of MSH3 as a piece for peptide-based vaccines either for therapeutic or--even more important--preventive purposes.

Neuroinflammation in Alzheimer's Disease: The Preventive and Therapeutic Potential of Polyphenolic Nutraceuticals.

PubMed

Sawikr, Yousef; Yarla, Nagendra Sastry; Peluso, Ilaria; Kamal, Mohammad Amjad; Aliev, Gjumrakch; Bishayee, Anupam

2017-01-01

Brain inflammation, characterized by increased microglia and astrocyte activation, increases during aging and is a key feature of neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic impairment, induced by amyloid-β (Aβ) peptide, are at least in part mediated by microglia and astrocyte activation. Glial activation results in the sustained production of proinflammatory cytokines and reactive oxygen species, giving rise to a chronic inflammatory process. Astrocytes are the most abundant glial cells in the central nervous system and are involved in the neuroinflammation. Astrocytes can be activated by numerous factors, including free saturated fatty acids, pathogens, lipopolysaccharide, and oxidative stress. Activation of astrocytes produces inflammatory cytokines and the enzyme cyclooxygenase-2, enhancing the production of Aβ. Furthermore, the role of the receptor for advanced glycation end products/nuclear factor-κB (NF-κB) axis in neuroinflammation is in line with the nonenzymatic glycosylation theory of aging, suggesting a central role of the advanced glycation end products in the age-related cognitive and a possible role of nutraceuticals in the prevention of neuroinflammation and AD. However, modulation of P-glycoprotein, rather than antioxidant and anti-inflammatory effects, could be the major mechanism of polyphenolic compounds, including flavonoids. Curcumin, resvertrol, piperine, and other polyphenols have been explored as novel therapeutic and preventive agents for AD. The aim of this review is to critically analyze and discuss the mechanisms involved in neuroinflammation and the possible role of nutraceuticals in the prevention and therapy of AD by targeting neuroinflammation. © 2017 Elsevier Inc. All rights reserved.

Preventive and Community Medicine in Primary Care. Teaching of Preventive Medicine Vol. 5.

ERIC Educational Resources Information Center

Barker, William H., Ed.

This monograph is the result of a conference on the role of preventive and community medicine in primary medical care and education. The following six papers were presented at the conference: (1) Roles of Departments of Preventive Medicine; (2) Competency-Based Objectives in Preventive Medicine for the Family Physician; (3) Preventive Medicine…

Protective effects of vescalagin from pink wax apple [Syzygium samarangense (Blume) Merrill and Perry] fruit against methylglyoxal-induced inflammation and carbohydrate metabolic disorder in rats.

PubMed

Chang, Wen-Chang; Shen, Szu-Chuan; Wu, James Swi-Bea

2013-07-24

The unbalance of glucose metabolism in humans may cause the excessive formation of methylglyoxal (MG), which can react with various biomolecules to form the precursor of advanced glycation end products (AGEs). Vescalagin (VES) is an ellagitannin that alleviates insulin resistance in cell study. Results showed that VES reduced the value of oral glucose tolerance test, cardiovascular risk index, AGEs, and tumor necrosis factor-α contents while increasing C-peptide and d-lactate contents significantly in rats orally administered MG and VES together. The preventive effect of VES on MG-induced inflammation and carbohydrate metabolic disorder in rats was thus proved. On the basis of the experiment data, a mechanism, which involves the increase in d-lactate to retard AGE formation and the decrease in cytokine release to prevent β-cell damage, is proposed to explain the bioactivities of VES in antiglycation and in the alleviation of MG-induced carbohydrate metabolic disorder in rats.

Knowledge, practices and expectations of preventive care: a qualitative study of patients attending government general outpatient clinics in Hong Kong.

PubMed

Tam, Denise Y S; Lo, Yvonne Y C; Tsui, Wendy

2018-05-09

Evidence-based preventive care recommendations have been well established, but studies have persistently reported gaps between these recommendations and general practitioners' practices in providing preventive care. Many studies have explored factors that affect the delivery of preventive care from the perspectives of the practitioners, but relatively few have evaluated the patients' point of view. The purpose of this study was to explore patients' understanding of preventive care, the actions they were taking in terms of preventive health and their expectations from family doctors in providing preventive care. A qualitative study was conducted based on one-on-one in-depth interviews. Twenty-eight patients without chronic illnesses were purposively recruited from government general outpatient clinics in Hong Kong. The interviews took place between November 2013 and February 2014. The participants' knowledge of preventive care was limited, and their preventive practices were mostly restricted to healthy lifestyle practices. They rarely obtained individualised preventive care advice from doctors. Screening investigations were initiated after symptoms had already occurred, and the decision of what to check was arbitrary. Few of the participants knew what they wanted from their doctors in terms of preventive care. These findings show significant gaps between evidence-based preventive recommendations and patients' current knowledge and practice, and show the need for a wider spectrum of preventive care education and reliable sources to provide individualised and affordable preventive assessment and screening services. Most importantly, primary care providers must take a more proactive role to provide preventive services.

Diagnosis, pathophysiology, and management of cluster headache.

PubMed

Hoffmann, Jan; May, Arne

2018-01-01

Cluster headache is a trigeminal autonomic cephalalgia characterised by extremely painful, strictly unilateral, short-lasting headache attacks accompanied by ipsilateral autonomic symptoms or the sense of restlessness and agitation, or both. The severity of the disorder has major effects on the patient's quality of life and, in some cases, might lead to suicidal ideation. Cluster headache is now thought to involve a synchronised abnormal activity in the hypothalamus, the trigeminovascular system, and the autonomic nervous system. The hypothalamus appears to play a fundamental role in the generation of a permissive state that allows the initiation of an episode, whereas the attacks are likely to require the involvement of the peripheral nervous system. Triptans are the most effective drugs to treat an acute cluster headache attack. Monoclonal antibodies against calcitonin gene-related peptide, a crucial neurotransmitter of the trigeminal system, are under investigation for the preventive treatment of cluster headache. These studies will increase our understanding of the disorder and perhaps reveal other therapeutic targets. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ameliorating effects of HX106N, a water-soluble botanical formulation, on Aβ25-35-induced memory impairment and oxidative stress in mice.

PubMed

Lee, Doo Suk; Choi, Jinyong; Kim, Seon-Hee; Kim, Sunyoung

2014-01-01

It is well-established that amyloid β (Aβ)-induced oxidative stress plays a crucial role in Alzheimer's disease (AD) and its cognitive deficits. HX106N is a water-soluble extract prepared from a mixture of the plants Dimocarpus longan, Liriope platyphylla, Salvia miltiorrhiza, and Gastrodia elata. These ingredients are traditionally used in various plant-based medicines for the treatment of neurological disease. In this study, we examined the effects of HX106N on memory impairment and oxidative stress caused by the intracerebroventricular injection of Aβ25-35 peptide in mice. For one week prior to Aβ25-35 peptide injection and 8 d after, mice were given oral HX106N. HX106N treatment reversed the Aβ25-35-mediated decrease in alternation percentage and latency time in the Y-maze and passive avoidance tests. Mice treated with HX106N showed decreased levels of thiobarbituric acid reactive substances (TBARS), a lipid peroxidation marker. Quantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated that HX106 treatment increased levels of heme oxygenase-1 (HO-1) in the hippocampus of Aβ25-35-injected mice, while having little effect on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In the murine hippocampal neuronal cell line HT22, HX106N was found to upregulate HO-1 expression at the RNA and protein levels as well as to protect cells from glutamate-induced oxidative stress. Taken together, our data suggest that HX106N may potentially act as a preventive and/or therapeutic agent for AD.

Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis.

PubMed

Ohno, Takashi; Hattori, Youichiro; Komine, Rie; Ae, Takako; Mizuguchi, Sumito; Arai, Katsuharu; Saeki, Takeo; Suzuki, Tatsunori; Hosono, Kanako; Hayashi, Izumi; Oh-Hashi, Yoshio; Kurihara, Yukiko; Kurihara, Hiroki; Amagase, Kikuko; Okabe, Susumu; Saigenji, Katsunori; Majima, Masataka

2008-01-01

The gastrointestinal tract is known to be rich in neural systems, among which afferent neurons are reported to exhibit protective actions. We tested whether an endogenous neuropeptide, calcitonin gene-related peptide (CGRP), can prevent gastric mucosal injury elicited by ethanol and enhance healing of acetic acid-induced ulcer using CGRP knockout mice (CGRP(-/-)). The stomach was perfused with 1.6 mmol/L capsaicin or 1 mol/L NaCl, and gastric mucosal injury elicited by 50% ethanol was estimated. Levels of CGRP in the perfusate were determined by enzyme immunoassay. Gastric ulcers were induced by serosal application of absolute acetic acid. Capsaicin inhibited injured area dose-dependently. Fifty percent ethanol containing capsaicin immediately increased intragastric levels of CGRP in wild-type (WT) mice, although 50% ethanol alone did not. The protective action of capsaicin against ethanol was completely abolished in CGRP(-/-). Preperfusion with 1 mol/L NaCl increased CGRP release and reduced mucosal damage during ethanol perfusion. However, 1 mol/L NaCl was not effective in CGRP(-/-). Healing of ulcer elicited by acetic acid in CGRP(-/-) mice was markedly delayed, compared with that in WT. In WT, granulation tissues were formed at the base of ulcers, and substantial neovascularization was induced, whereas those were poor in CGRP(-/-). Expression of vascular endothelial growth factor was more markedly reduced in CGRP(-/-) than in WT. CGRP has a preventive action on gastric mucosal injury and a proangiogenic activity to enhance ulcer healing. These results indicate that the CGRP-dependent pathway is a good target for regulating gastric mucosal protection and maintaining gastric mucosal integrity.

75 FR 47310 - Solicitation for Nominations for New Clinical Preventive Health Topics To Be Considered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... preventive services include screening, counseling and preventive medications associated with primary care... secondary prevention topic (screening, counseling or preventive medication). b. Primary care relevance... basis of populations, types of services (screening, counseling, preventive medications) and disease...

Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥40 Years: Data from the National Health and Nutrition Examination Survey, 2011–2012

PubMed Central

Dillon, Charles F.; Eberhardt, Mark S.; Wright, Jacqueline D.; Burt, Vicki L.

2015-01-01

Objective We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. Methods We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥40 years from the National Health and Nutrition Examination Survey, 2011–2012. Results In 2011–2012, one-third of U.S. adults aged ≥40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40–49 years to 54% of those ≥80 years of age, p<0.001). Non-Hispanic white (35%) and black (30%) adults were more likely to take preventive aspirin than non-Hispanic Asian (20%, p<0.001) and Hispanic (22%, p=0.013) adults. Adults with, compared with those without health insurance, and adults with ≥2 doctor visits in the past year, diagnosed diabetes, hypertension, or high cholesterol were twice as likely to take preventive aspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. Conclusion The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID:26556936

An MSI Tumor Specific Frameshift Mutation in a Coding Microsatellite of MSH3 Encodes for HLA-A0201-Restricted CD8+ Cytotoxic T Cell Epitopes

PubMed Central

Garbe, Yvette; Maletzki, Claudia; Linnebacher, Michael

2011-01-01

Background Microsatellite instability (MSI) resulting from inactivation of the DNA mismatch repair system (MMR) characterizes a highly immunological subtype of colorectal carcinomas. Those tumors express multiple frameshift-mutated proteins which present a unique pool of tumor-specific antigens. The DNA MMR protein MSH3 is frequently mutated in MSI+ colorectal tumors, thus making it an attractive candidate for T cell-based immunotherapies. Methodology/Principal Findings FSP-specific CD8+ T cells were generated from a healthy donor using reverse immunology. Those T cells specifically recognized T2 cells sensitized with the respective peptides. Specific recognition and killing of MSI+ colorectal carcinoma cells harbouring the mutated reading frame was observed. The results obtained with T cell bulk cultures could be reproduced with T cell clones obtained from the same cultures. Blocking experiments (using antibodies and cold target inhibition) confirmed peptide as well as HLA-A0201-specificity. Conclusions We identified two novel HLA-A0201-restricted cytotoxic T cell epitopes derived from a (-1) frameshift mutation of a coding A(8) tract within the MSH3 gene. These were 386-FLLALWECSL (FSP18) and 387-LLALWECSL (FSP19) as well as 403-IVSRTLLLV (FSP23) and 402-LIVSRTLLLV (FSP31), respectively. These results suggest that MSH3(-1) represents another promising MSI+-induced target antigen. By identifying two distinct epitopes within MSH3(-1), the sustained immunogenicity of the frameshift mutated sequence was confirmed. Our data therefore encourage further exploitation of MSH3 as a piece for peptide-based vaccines either for therapeutic or –even more important– preventive purposes. PMID:22110587

Reflections on preventive medicine.

PubMed

Miettinen, Olli S

2014-10-01

Having thought much about medicine in my career-long effort to understand it and the research for its advancement, I have come to views rather different form the now-prevailing ones in respect to what preventive medicine is about; what epidemiology is in relation to preventive medicine; what distinguishes preventive medicine in preventive healthcare at large; the relation of preventive medicine to public health; the concept of health promotion; and also the core principles of preventive medicine. All of these views I set forth in this article, for the readers' critical reflection. Copyright © 2014 Elsevier Inc. All rights reserved.

Best practices and performance assessment for preventive maintenance treatments for Virginia pavements.

DOT National Transportation Integrated Search

2015-08-01

Preventive maintenance has the potential to improve network condition by retarding future pavement deterioration. This : report outlines guidelines for implementing a preventive maintenance policy for bituminous pavements. : Preventive maintenance tr...

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

PubMed Central

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

2017-01-01

Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R; Matloub, Hani S; Pritchard, Kirkwood A; Jaradeh, Safwan S; Havlik, Robert

2015-12-01

Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. Copyright © 2015 National Stroke Association. All rights reserved.

Dynamics of keratinocytes in vivo using HO labeling: a sensitive marker of epidermal proliferation state.

PubMed

Hsieh, Elaine A; Chai, Christine M; de Lumen, Benito O; Neese, Richard A; Hellerstein, Marc K

2004-09-01

A heavy water ((2)H(2)O) labeling method recently developed to measure cell proliferation in vivo is applied here to the measurement of murine epidermal cell turnover and to investigate conditions in which keratinocyte proliferation is either inhibited or stimulated. The technique is based on incorporation of (2)H(2)O into the deoxyribose moiety of deoxyribonucleotides in dividing cells. Label incorporation and die-away studies in cells isolated from C57BL/6J mouse epidermis revealed the replacement rate to be 34%-44% per wk (half-life of 1.6-2 wk). The kinetics provided evidence of a non-proliferative subpopulation of cells (10%-15% of the total) within the epidermis. Topical administration of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate for 3 wk increased epidermal cell proliferation by 55% in SENCAR mice. Topical addition of lunasin, an anti-mitotic agent from soy, decreased epidermal cell proliferation modestly though significantly (16% given alone, 9% given with carcinogens). Caloric restriction (by 33% of energy intake) for 4 wk decreased the epidermal cell proliferation rate by 45% in C57BL/6J mice. In summary, epidermal cell proliferation can be measured in vivo using (2)H(2)O labeling in normal, hyper- and hypo-proliferative conditions. Potential applications of this inherently safe method in humans might include studies of psoriasis, wound healing, chemopreventive agents, and caloric intake.

High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial.

PubMed

Jakubowicz, Daniela; Wainstein, Julio; Ahrén, Bo; Bar-Dayan, Yosefa; Landau, Zohar; Rabinovitz, Hadas R; Froy, Oren

2015-05-01

High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-energy dinner and reduced-energy breakfast (Ddiet). In a randomised, open label, crossover design performed in a clinic setting, 18 individuals (aged 30-70 years with BMI 22-35 kg/m(2)) with type 2 diabetes (<10 years duration) treated with metformin and/or diet were given either Bdiet or Ddiet for 7 days. Participants were randomised by a person not involved in the study using a coin flip. Postprandial levels of plasma glucose, insulin, C-peptide and intact and total glucagon-like peptide-1 (iGLP-1 and tGLP-1) were assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ lunch and 858 kJ dinner. The Ddiet comprised 858 kJ breakfast, 2,523 kJ lunch and 2,946 kJ dinner. Twenty-two individuals were randomised and 18 analysed. The AUC for glucose (AUCglucose) throughout the day was 20% lower, whereas AUCinsulin, AUCC-peptide and AUCtGLP-1 were 20% higher for the Bdiet than the Ddiet. Glucose AUC0-180min and its peak were both lower by 24%, whereas insulin AUC0-180min was 11% higher after the Bdiet than the Ddiet. This was accompanied by 30% higher tGLP-1 and 16% higher iGLP-1 levels. Despite the diets being isoenergetic, lunch resulted in lower glucose (by 21-25%) and higher insulin (by 23%) with the Bdiet vs Ddiet. High energy intake at breakfast is associated with significant reduction in overall PPHG in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes. Trial registration ClinicalTrials.gov NCT01977833 Funding No specific funding was received for the study.

Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment

PubMed Central

Suo, Huayi; Zhao, Xin; Qian, Yu; Li, Guijie; Liu, Zhenhu; Xie, Jie; Li, Jian

2014-01-01

The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription–polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity. PMID:25464378

Outcomes Associated With Early Preventive Dental Care Among Medicaid-Enrolled Children in Alabama

PubMed Central

Morrisey, Michael A.; Sen, Bisakha

2017-01-01

Importance There is a recommendation for children to have a dental home by 6 months of age, but there is limited evidence supporting the effectiveness of early preventive dental care or whether primary care providers (PCPs) can deliver it. Objective To investigate the effectiveness of preventive dental care in reducing caries-related treatment visits among Medicaid enrollees. Design, Setting, and Participants High-dimensional propensity scores were used to address selection bias for a retrospective cohort study of children continuously enrolled in coverage from the Alabama Medicaid Agency from birth between 2008 and 2012, adjusting for demographics, access to care, and general health service use. Exposures Children receiving preventive dental care prior to age 2 years from PCPs or dentists vs no preventive dental care. Main Outcome and Measures Two-part models estimated caries-related treatment and expenditures. Results Among 19 658 eligible children, 25.8% (n = 3658) received early preventive dental care, of whom 44% were black, 37.6% were white, and 16.3% were Hispanic. Compared with matched children without early preventive dental care, children with dentist-delivered preventive dental care more frequently had a subsequent caries-related treatment (20.6% vs 11.3%, P < .001), higher rate of visits (0.29 vs 0.15 per child-year, P < .001), and greater dental expenditures ($168 vs $87 per year, P < .001). Dentist-delivered preventive dental care was associated with an increase in the expected number of caries-related treatment visits by 0.14 per child per year (95% CI, 0.11-0.16) and caries-related treatment expenditures by $40.77 per child per year (95% CI, $30.48-$51.07). Primary care provider–delivered preventive dental care did not significantly affect caries-related treatment use or expenditures. Conclusions and Relevance Children with early preventive care visits from dentists were more likely to have subsequent dental care, including caries-related treatment, and greater expenditures than children without preventive dental care. There was no association with subsequent caries-related treatment and preventive dental care from PCPs. We observed no evidence of a benefit of early preventive dental care, regardless of the provider. Additional research beyond administrative data may be necessary to elucidate any benefits of early preventive dental care. PMID:28241184

Preventive practicum training in healthcare organizations. The Meharry model.

PubMed

Levine, R S; St Onge, J; Moriarty, C J; Bailey, S; Logan, T; Zhu, K; Nelson, B K; Hodder, R A; Marino, W

1999-07-01

Practicum training for preventive medicine residents often occurs in agencies whose community is geographically defined and whose governance is closely linked to public election. We were unsure about the financial ability of such departments to support training and are concerned that over-reliance on traditional health departments might not be best for either medically indigent populations or preventive medicine. We, therefore, sought to apply a public health model--based on a strategic partnership between nursing and preventive medicine--to a large health care organization. The result was formation of a mini-health department, suitable for fully accredited preventive medicine practicum training, within the Alvin C. York Veterans Affairs Medical Center, Murfreesboro, TN. This Center serves a defined population of 21,594 patients and about 1600 employees. The theoretical framework for the new department was based on demonstration of a close fit between the competencies expected of preventive medicine physicians by the American College of Preventive Medicine (ACPM) and activities required by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Because of JCAHO requirements, many healthcare organizations already pay for preventive medicine services. By placing preventive medicine training faculty into existing budget slots at our institution, systemwide personnel costs for prevention decreased by about $36,000 per year, even as personnel funding for preventive medicine physicians increased from about $24,000 to $376,000 per year. Moreover, there was dramatic, sustained improvement in 17 indicators of preventive care quality as determined by an external peer review organization. In addition to providing a new venue for training, this model may also improve the quality and reach of preventive services, decreased fixed costs for service delivery, and yield new employment opportunities for preventive medicine physicians.

Delivery of Clinical Preventive Services in Family Medicine Offices

PubMed Central

Crabtree, Benjamin F.; Miller, William L.; Tallia, Alfred F.; Cohen, Deborah J.; DiCicco-Bloom, Barbara; McIlvain, Helen E.; Aita, Virginia A.; Scott, John G.; Gregory, Patrice B.; Stange, Kurt C.; McDaniel, Reuben R.

2005-01-01

BACKGROUND This study aimed to elucidate how clinical preventive services are delivered in family practices and how this information might inform improvement efforts. METHODS We used a comparative case study design to observe clinical preventive service delivery in 18 purposefully selected Midwestern family medicine offices from 1997 to 1999. Medical records, observation of outpatient encounters, and patient exit cards were used to calculate practice-level rates of delivery of clinical preventive services. Field notes from direct observation of clinical encounters and prolonged observation of the practice and transcripts from in-depth interviews of practice staff and physicians were systematically examined to identify approaches to delivering clinical preventive services recommended by the US Preventive Services Task Force. RESULTS Practices developed individualized approaches for delivering clinical preventive services, with no one approach being successful across practices. Clinicians acknowledged a 3-fold mission of providing acute care, managing chronic problems, and prevention, but only some made prevention a priority. The clinical encounter was a central focus for preventive service delivery in all practices. Preventive services delivery rates often appeared to be influenced by competing demands within the clinical encounter (including between different preventive services), having a physician champion who prioritized prevention, and economic concerns. CONCLUSIONS Practice quality improvement efforts that assume there is an optimal approach for delivering clinical preventive services fail to account for practices’ propensity to optimize care processes to meet local contexts. Interventions to enhance clinical preventive service delivery should be tailored to meet the local needs of practices and their patient populations. PMID:16189059

Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.

PubMed

Walford, Geoffrey A; Ma, Yong; Christophi, Costas A; Goldberg, Ronald B; Jarolim, Petr; Horton, Edward; Mather, Kieren J; Barrett-Connor, Elizabeth; Davis, Jaclyn; Florez, Jose C; Wang, Thomas J

2014-05-01

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP). The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887). At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Will OWCP pay for preventive treatment? 10.313... AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines and...

The Implications of Preemptive and Preventive War Doctrines: A Reconsideration

DTIC Science & Technology

2007-07-01

geopolitics, ideology , and personality as combining to produce the fatal brew which resulted in 42 years of nuclear shadowed global menace.26 But...preventive war. 49 1. Preventive war is war, and preventive warfare is warfare. It is not a distinctive genus of war and warfare. The distinguishing

[Genome instability in pulmonary tuberculosis before and after treatment].

PubMed

Dzhokhadze, T A; Buadze, T Zh; Rubanov, K Dzh; Kiriia, N A; Lezhava, T A

2013-11-01

Pulmonary tuberculosis is classified as a disease with a genetic predisposition, and therefore, as with other pathologies related to this group of diseases, by pulmonary tuberculosis, special importance is given to finding those markers that enable early identification of risk groups, such as skrinnig in general population and relatives of patients with tuberculosis, which in turn can provide the basis for preventive measures. One of this markers is the level of genome stability. The aim of this study was a comparative evaluation of the functional parameters of the genome variability in patients with sensitive form of pulmonary tuberculosis before and after treatment, and the possibility of its correction with anti-stress peptide bioregulator - epitalon. The studies were conducted using short-term mitoge -stimulated cell cultures of TB patients, before and after treatment. As an indicator of genome stability has been studied the frequency of structural and numerical chromosome aberrations and fragile sites. It is shown, that in intact cultures from patients with pulmonary tuberculosis, before treatment was significantly higher level of frequency of cells with structural chromosome aberrations, that still retained after the treatment. As for epithalon, it appears that was shown a pronounced protective effect after treatment, on the test of chromosome aberrations, by reducing both overall mean frequency aberrant cells and indicators for all individuals. In the study of fragility of chromosomes in patients with primary tuberculosis was found, that in intact cultures, the proportion of cells with chromosomal fragile sites was higher than in control group of healthy individuals, befor and after treatment. High frequency of chromosome fragility persisted by treatment with peptide bioregulator in both cases - before and after treatment. It is suggested that the identified patterns can be correlated with a high incidence of re- TB.

SES, Heart Failure, and N-terminal Pro-b-type Natriuretic Peptide: The Atherosclerosis Risk in Communities Study.

PubMed

Vart, Priya; Matsushita, Kunihiro; Rawlings, Andreea M; Selvin, Elizabeth; Crews, Deidra C; Ndumele, Chiadi E; Ballantyne, Christie M; Heiss, Gerardo; Kucharska-Newton, Anna; Szklo, Moyses; Coresh, Josef

2018-02-01

Compared with coronary heart disease and stroke, the association between SES and the risk of heart failure is less well understood. In 12,646 participants of the Atherosclerosis Risk in Communities Study cohort free of heart failure history at baseline (1987-1989), the association of income, educational attainment, and area deprivation index with subsequent heart failure-related hospitalization or death was examined while accounting for cardiovascular disease risk factors and healthcare access. Because SES may affect threshold of identifying heart failure and admitting for heart failure management, secondarily the association between SES and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, a marker reflecting cardiac overload, was investigated. Analysis was conducted in 2016. During a median follow-up of 24.3 years, a total of 2,249 participants developed heart failure. In a demographically adjusted model, the lowest-SES group had 2.2- to 2.5-fold higher risk of heart failure compared with the highest SES group for income, education, and area deprivation. With further adjustment for time-varying cardiovascular disease risk factors and healthcare access, these associations were attenuated but remained statistically significant (e.g., hazard ratio=1.92, 95% CI=1.69, 2.19 for the lowest versus highest income), with no racial interaction (p>0.05 for all SES measures). Similarly, compared with high SES, low SES was associated with both higher baseline level of NT-proBNP in a multivariable adjusted model (15% higher, p<0.001) and increase over time (~1% greater per year, p=0.023). SES was associated with clinical heart failure as well as NT-proBNP levels inversely and independently of traditional cardiovascular disease factors and healthcare access. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

78 FR 11611 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... Manufacturing Practice and Hazard Analysis and Risk- Based Preventive Controls for Human Food; Extension of... Analysis and Risk-Based Preventive Controls for Human Food.'' FOR FURTHER INFORMATION CONTACT: Domini Bean... Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food'' with a 120-day comment...

"Macho Men" and Preventive Health Care: Implications for Older Men in Different Social Classes

ERIC Educational Resources Information Center

Springer, Kristen W.; Mouzon, Dawne M.

2011-01-01

The gender paradox in mortality--where men die earlier than women despite having more socioeconomic resources--may be partly explained by men's lower levels of preventive health care. Stereotypical notions of masculinity reduce preventive health care; however, the relationship between masculinity, socioeconomic status (SES), and preventive health…

26 CFR 54.9815-2713T - Coverage of preventive health services (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... the current recommendations of the United States Preventive Services Task Force with respect to the... States Preventive Services Task Force with respect to the individual. The provider bills the plan for an... A or B in the current recommendations of the United States Preventive Services Task Force with...

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Will OWCP pay for preventive treatment? 10..., AS AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines...

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Will OWCP pay for preventive treatment? 10.313... AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines and...

Obstacles to preventive care for individuals with disability: Implications for nurse practitioners.

PubMed

Marrocco, Anna; Krouse, Helene J

2017-05-01

Individuals with disabilities have been identified as a population with a significantly lower usage of preventive services. Nurse practitioners (NPs) provide a key access point in the healthcare delivery system for preventive services for vulnerable populations such as those with disabilities. It is essential to understand existing barriers that prohibit access to effective preventive care for this vulnerable population. Systematic search and review of Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, PubMed, Google Scholar, and government reports and World Health Organizations reports. Twenty-six articles were included in the review. This literature review confirmed previous notions that people with disabilities are receiving much fewer preventive services than the general population. The studies reviewed identified four major barriers that contributed to the lack of preventive care. These barriers included physical environment and system, transportation, provider knowledge and attitude, and financial. Recognition of the obstacles that this subpopulation faces in accessing preventive care services is the first step to effectively remedying this problem. Preventive services have been identified as one of the cornerstones to improving health and quality of life. By understanding the circumstances that restrict those with disabilities from accessing preventive services, NPs can provide meaningful and effective solutions. ©2017 American Association of Nurse Practitioners.

Primary Care Physicians Practicing Preventive Medicine in the Outpatient Setting

PubMed Central

Snipelisky, David; Carter, Kimberly; Sundsted, Karna; Burton, M. Caroline

2016-01-01

Background: Preventive care is an important part of primary care medicine, yet much variation in its practice exists. The aim of this study is to assess physicians’ perspectives of practicing preventive medicine and evaluate which topics are deemed most important. Methods: All primary care medicine providers at two separate academic medical centers (Mayo Clinic, MN and Mayo Clinic, FL) were surveyed via an E-mail questionnaire assessing physicians’ perception of the role of preventive medicine during both acute/routine and yearly visits, physicians’ perception of patients’ response to preventive medicine topics, and which preventive medicine topics are commonly practiced. Results: Of 445 providers meeting inclusion criteria, a total of 183 (41.1%) responded. Providers were more likely to engage patients in preventive medicine during yearly visits more so than acute visits (3.82 vs. 4.72, range 1–5 Likert Scale), yet providers were very likely to partake in such practices during both visits. Providers perceived that patients received the practice of preventive medicine very well (4.13 on 1–5 Likert Scale). No significant difference between provider practice and patient perception was noted between the two sites, although there was some variation based on clinical experience of the provider. Providers were found to most commonly practice topics recommended by the United States Preventive Services Task Force. Conclusions: Our study found a high predisposition to practicing preventive medicine. Providers seem to practice according to published evidence-based medicine recommendations. PMID:26941906

Association Between Number of Preventive Care Guidelines and Preventive Care Utilization by Patients.

PubMed

Taksler, Glen B; Pfoh, Elizabeth R; Stange, Kurt C; Rothberg, Michael B

2018-05-08

The number of preventive care guidelines is rapidly increasing. It is unknown whether the number of guideline-recommended preventive services is associated with utilization. The authors used Poisson regression of 390,778 person-years of electronic medical records data from 2008 to 2015, in 80,773 individuals aged 50-75 years. Analyses considered eligibility for 11 preventive services most closely associated with guidelines: tobacco cessation; control of obesity, hypertension, lipids, or blood glucose; influenza vaccination; and screening for breast, cervical, or colorectal cancers, abdominal aortic aneurysm, or osteoporosis. The outcome was the rate of preventive care utilization over the following year. Results were adjusted for demographics and stratified by the number of disease risk factors (smoking, obesity, hypertension, hyperlipidemia, diabetes). Data were collected in 2016 and analyzed in 2017. Preventive care utilization was lower when the number of guideline-recommended preventive services was higher. The adjusted rate of preventive care utilization decreased from 38.67 per 100 (95% CI=38.16, 39.18) in patients eligible for one guideline-recommended service to 31.59 per 100 (95% CI=31.29, 31.89) in patients eligible for two services and 25.43 per 100 (95% CI=24.68, 26.18) in patients eligible for six or more services (p-trend<0.001). Results were robust to disease risk factors and observed for all but two services (tobacco cessation, obesity reduction). However, for any given number of guideline-recommended services, patients with more disease risk factors had higher utilization rates. The rate of preventive care utilization was lower when the number of guideline-recommended services was higher. Prioritizing recommendations might improve utilization of high-value services. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

PubMed

Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

2012-07-01

A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

Oral health need and access to dental services: evidence from the National Survey of Children's Health, 2007.

PubMed

Bell, Janice F; Huebner, Colleen E; Reed, Sarah C

2012-04-01

This study examines associations between parents' report of their children's oral health and receipt of a dental visit for preventive care. We conducted a cross-sectional analysis of oral health status and receipt of a preventive dental visit among US children and youth, ages 1-17 years, using data from the 2007 National Survey of Children's Health (n = 86,764). Survey-weighted logistic regression was used to estimate associations between perceived oral health status and receipt of a preventive dental health visit in the prior 12 months. Overall, 78 % of children and youth received at least one preventive dental health visit in the prior year. Among the youngest children, lower oral health status was associated with higher odds of receiving a preventive dental visit; among older children, lower oral health status was associated with lower odds of receiving a dental visit for preventive care. Use of preventive dental health care is below national target goals. Younger children in worse oral health are more likely, and older youth less likely, to receive preventive dental care. Public health efforts to educate parents to seek early and ongoing preventive oral health care, rather than services in response to problems, may yield oral health benefits later in childhood and over the life course.

Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future

PubMed Central

Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

2016-01-01

In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination. PMID:26853127

A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing

PubMed Central

Ferrante, Andrea; Gorski, Jack

2012-01-01

The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separates purified peptide/DR1 complexes (pDR1) into two conformers whose ratio is peptide Kd-dependent. In the absence of exchange peptide, DM only releases peptide from the slower migrating conformer. Addition of exchange peptide converts the DM-resistant conformer to the slower migrating conformer, which is DM labile. Thus, exchange peptide generates a conformer of pDR1 which constitutes the intermediate for peptide exchange and the substrate for DM activity. The resolution of the intermediate favors the highest affinity peptide. However, once folded into the DM-resistant conformer, even low affinity peptides can be presented in the absence of free peptide, broadening the repertoire available for presentation. PMID:22545194

78 FR 69604 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... Manufacturing Practice and Hazard Analysis and Risk- Based Preventive Controls for Human Food; Extension of... Hazard Analysis and Risk- Based Preventive Controls for Human Food'' and its information collection... Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food.'' IV. How To...

Amide I SFG Spectral Line Width Probes the Lipid-Peptide and Peptide-Peptide Interactions at Cell Membrane In Situ and in Real Time.

PubMed

Zhang, Baixiong; Tan, Junjun; Li, Chuanzhao; Zhang, Jiahui; Ye, Shuji

2018-06-13

The balance of lipid-peptide and peptide-peptide interactions at cell membrane is essential to a large variety of cellular processes. In this study, we have experimentally demonstrated for the first time that sum frequency generation vibrational spectroscopy can be used to probe the peptide-peptide and lipid-peptide interactions in cell membrane in situ and in real time by determination of the line width of amide I band of protein backbone. Using a "benchmark" model of α-helical WALP23, it is found that the dominated lipid-peptide interaction causes a narrow line width of the amide I band, whereas the peptide-peptide interaction can markedly broaden the line width. When WALP23 molecules insert into the lipid bilayer, a quite narrow line width of the amide I band is observed because of the lipid-peptide interaction. In contrast, when the peptide lies down on the bilayer surface, the line width of amide I band becomes very broad owing to the peptide-peptide interaction. In terms of the real-time change in the line width, the transition from peptide-peptide interaction to lipid-peptide interaction is monitored during the insertion of WALP23 into 1,2-dipalmitoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DPPG) lipid bilayer. The dephasing time of a pure α-helical WALP23 in 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) and DPPG bilayer is determined to be 2.2 and 0.64 ps, respectively. The peptide-peptide interaction can largely accelerate the dephasing time.

Assessing Integration of Clinical and Public Health Skills in Preventive Medicine Residencies: Using Competency Mapping

PubMed Central

Sarigiannis, Amy N.; Boulton, Matthew L.

2012-01-01

Objectives. We evaluated the utility of a competency mapping process for assessing the integration of clinical and public health skills in a newly developed Community Health Center (CHC) rotation at the University of Michigan School of Public Health Preventive Medicine residency. Methods. Learning objectives for the CHC rotation were derived from the Accreditation Council for Graduate Medical Education core clinical preventive medicine competencies. CHC learning objectives were mapped to clinical preventive medicine competencies specific to the specialty of public health and general preventive medicine. Objectives were also mapped to The Council on Linkages Between Academia and Public Health Practice’s tier 2 Core Competencies for Public Health Professionals. Results. CHC learning objectives mapped to all 4 (100%) of the public health and general preventive medicine clinical preventive medicine competencies. CHC population-level learning objectives mapped to 32 (94%) of 34 competencies for public health professionals. Conclusions. Utilizing competency mapping to assess clinical–public health integration in a new CHC rotation proved to be feasible and useful. Clinical preventive medicine learning objectives for a CHC rotation can also address public health competencies. PMID:22690972

The delivery of clinical preventive services: acute care intervention.

PubMed

Hahn, D L

1999-10-01

. Evidence-based clinical preventive services are underutilized. We explored the major factors associated with delivery of these services in a large physician-owned community-based group practice that provided care for both fee-for-service (FFS) and health maintenance organization (HMO) patient populations. We performed a cross-sectional audit of the computerized billing data of all adult outpatients seen at least once by any primary care provider in 1995 (N = 75,621). Delivery of preventive services was stratified by age, sex, visit frequency, insurance status (FFS or HMO), and visit type (acute care only or scheduled preventive visit). Insurance status and visit type were the strongest predictors of clinical preventive service delivery. Patients with FFS coverage received 6% to 13% (absolute difference) fewer of these services than HMO patients. Acute-care-only patients received 9% to 45% fewer services than patients who scheduled preventive visits. The combination of these factors was associated with profound differences. Having insurance to pay for preventive services is an important factor in the delivery of such care. Encouraging all patients to schedule preventive visits has been suggested as a strategy for increasing delivery, but that is not practical in this setting. Assessing the need for preventive services and offering them during acute care visits has equal potential for increasing delivery.

Worker education level is a factor in self-compliance with dust-preventive methods among small-scale agate industrial workers.

PubMed

Aggarwal, Bhagwan D

2013-01-01

High incidences of silicosis are continuing to be reported among the agate workers of small-scale household agate processing units in the Khambhat region of Gujarat (India). The objective of this study was to investigate reasons behind the high prevalence of silicosis, and factors affecting the noncompliance with preventive methods among agate workers. The study was conducted using a questionnaire-based structured interview method among 82 agate workers in Khambhat to assess their awareness level about silicosis and preventive methods, existing morbidity, worker's attitude toward health, and the prevalence of actual use of preventive methods to avoid silica exposure. The majority of the workers (55%) were aware of silicosis and the harmful effects of silica dust exposure (72%) and knew about simple preventive methods to avoid silica dust exposure (80%), but only a minority of the workers (22%) were actually using the simple and available dust-preventive methods. Only 9% of the uneducated workers were using the preventive methods, while usage was higher among educated workers (28%), who had five or more years of schooling, and these workers had fewer health conditions or less morbidity. Gender and job duration had no effect on the usage of dust-preventive methods. The data suggest that noncompliance with use of dust-preventive methods could be the reason behind the higher prevalence of silicosis and health morbidity in agate workers, and that years of schooling plays a significant role in the increased usage and self-compliance with dust-preventive methods among agate workers.

Preventive Orientation of Iraqi Dentists in Baghdad in 2016

PubMed Central

Aledhari, Fatin Abd Alsttar; Gholami, Mahdia; Shamshiri, Ahmad Reza

2017-01-01

Objectives: The aim of the present study was to assess the preventive orientation of Iraqi dentists in terms of their “knowledge” and “attitude” towards caries prevention and to explore their “preventive practice”. Materials and Methods: A cross-sectional study based on a self-administered questionnaire was conducted among 159 dentists who worked in Baghdad during the summer of 2016. The questionnaires obtained information on variables such as knowledge and attitude towards preventive dentistry, preventive practice and demographic variables and were distributed during the official working time. Logistic and multiple regressions served for statistical analyses. Results: From all the respondents, 71% were females and the response rate was 94% (n=150). The mean age was 40.75±9.88 years (range 27–65 years). After checking for completeness, 90 questionnaires remained for data analysis. The most positive attitude towards preventive dental care was related to the question: “whether preventive dentistry is essential for the community” (n=75, 83%). The highest knowledge was reported in response to three questions: “frequency vs. amount of sugar consumption”, “effect of sealant on caries prevention of newly erupted molars” and “effect of dental problems on general health” (n=83, 92.2%). The regression analysis showed a significant association between attendance in the continuing educational courses and preventive practice (P=0.03). Conclusions: To improve preventive dental orientation of Iraqi dentists, dental schools should put more emphasis on the topics about preventive dentistry. This will consequently improve their practice and oral health of the community. PMID:29296109

Practice of preventive dentistry for nursing staff in primary care.

PubMed

Jiménez-Báez, María Valeria; Acuña-Reyes, Raquel; Cigarroa-Martínez, Didier; Ureña-Bogarín, Enrique; Orgaz-Fernández, Jose David

2014-01-01

Determine the domain of preventive dentistry in nursing personnel assigned to a primary care unit. Prospective descriptive study, questionnaire validation, and prevalence study. In the first stage, the questionnaire for the practice of preventive dentistry (CPEP, for the term in Spanish) was validated; consistency and reliability were measured by Cronbach's alpha, Pearson's correlation, factor analysis with intra-class correlation coefficient (ICC). In the second stage, the domain in preventive dental nurses was explored. The overall internal consistency of CPEP is α= 0.66, ICC= 0.64, CI95%: 0.29-0.87 (p >0.01). Twenty-one subjects in the study, average age 43, 81.0% female, average seniority of 12.5 were included. A total of 71.5% showed weak domain, 28.5% regular domain, and there was no questionnaire with good domain result. The older the subjects were, the smaller the domain; female nurses showed greater mastery of preventive dentistry (29%, CI95%: 0.1-15.1) than male nurses. Public health nurses showed greater mastery with respect to other categories (50%, CI95%: 0.56-2.8). The CDEP has enough consistency to explore the domain of preventive dentistry in health-care staff. The domain of preventive dentistry in primary care nursing is poor, required to strengthen to provide education in preventive dentistry to the insured population.

"Macho men" and preventive health care: implications for older men in different social classes.

PubMed

Springer, Kristen W; Mouzon, Dawne M

2011-06-01

The gender paradox in mortality--where men die earlier than women despite having more socioeconomic resources--may be partly explained by men's lower levels of preventive health care. Stereotypical notions of masculinity reduce preventive health care; however, the relationship between masculinity, socioeconomic status (SES), and preventive health care is unknown. Using the Wisconsin Longitudinal Study, the authors conduct a population-based assessment of masculinity beliefs and preventive health care, including whether these relationships vary by SES. The results show that men with strong masculinity beliefs are half as likely as men with more moderate masculinity beliefs to receive preventive care. Furthermore, in contrast to the well-established SES gradient in health, men with strong masculinity beliefs do not benefit from higher education and their probability of obtaining preventive health care decreases as their occupational status, wealth, and/or income increases. Masculinity may be a partial explanation for the paradox of men's lower life expectancy, despite their higher SES.

78 FR 24691 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... Manufacturing Practice and Hazard Analysis and Risk- Based Preventive Controls for Human Food; Extension of... Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food'' that appeared in... Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food'' with a 120-day...

Preventive Health Care Utilization: A Study of Factors Influencing Military Personnel in Their Use of Three Preventive Health Care Factors

DTIC Science & Technology

1978-03-01

0Michael Zubkoff and David Dunlop, " Consumer Behavior in Preventive Health Services," in Consumer Incentives for Health Care, ed. Selma J. Mushkin (New...78 Sorkin, Alan L. Health Economics. Lexington, Mass.: D.C. Heath, 1975. Zubkoff, Michael, and Dunlop, David. " Consumer Behavior in Preventive Health

Correlates of unequal access to preventive care in China: a multilevel analysis of national data from the 2011 China Health and Nutrition Survey.

PubMed

Huang, Chi; Liu, Chao-Jie; Pan, Xiong-Fei; Liu, Xiang; Li, Ning-Xiu

2016-05-12

Preventive care has an essential role in reducing income-related health inequalities. Despite a general consensus of the need of shifting focus from disease treatment to wellness and prevention, little is known about inequalities in access to preventive care in China. Our study aimed to explore the inequalities in preventive care usage and factors that were associated with such inequalities among Chinese adults. Multilevel logistic regression analyses were performed using national data from the 2011 Chinese Health and Nutrition Survey. The study sample comprised 13,483 adults who were covered by Basic Social Medical Insurance (BSMI). We analyzed individual socioeconomic status (marital status, education attainment, annual household income per capita, and medical insurance) and contextual factors for their influence on preventive care usage (region of residence and type of community) after controlling for health needs (age, sex, and health condition). Out of the participants, 6.9 % received preventive care services over the past four weeks and 3.9 % went for a general physical examination prior to the survey. We noted regional disparities in the overall use of preventive care and specific use of general physical examination, with residents from central and northeastern regions less likely to use preventive care including general physical examination than in the more affluent eastern region. Lower levels of education and income were associated with reduced use of preventive care. Subscriptions to less generous social medical insurance programs such as Urban Resident-based Medical Insurance Scheme or New Rural Cooperative Medical Scheme were associated with decreased specific use of general physical examinations, but not overall use of preventive care. Inequalities in preventive care usage were evident in China, and were associated with health needs and socioeconomic characteristics. Current health insurance arrangements may fail to reduce inequalities relating to preventive care. A fair and more coherent policy across all BSMI schemes is needed.

Internet Use and Preventive Health Behaviors Among Couples in Later Life: Evidence from the Health and Retirement Study.

PubMed

Nam, Sangbo; Han, Sae Hwang; Gilligan, Megan

2018-05-22

The aim of this study was to examine the link between internet use and preventive health behaviors. We focused on couples to examine whether there were cross-partner associations between internet use and preventive health behaviors. The data for this study came from the 2010 and 2012 waves of the Health and Retirement Study and the sample consisted of 5,143 pairs of coupled-individuals. Preventive health behaviors included cancer screenings (mammogram and prostate tests), cholesterol tests, and flu shots. Logistic multilevel actor-partner interdependence models were employed to test the study hypotheses. Internet use was associated with a higher likelihood of receiving prostate exams and cholesterol tests for husbands, net of demographic and health characteristics, and insurance status. We found that wives' internet use was associated with a higher likelihood of receiving flu shots and prostate exams for husbands, but husbands' internet use was not associated with wives' preventive health behaviors. Research linking internet use and preventive health behaviors is important because such behaviors are associated not only with health of the older population but also with substantial reductions in health care expenditures. Our findings suggested that internet use of older adults is associated with their own preventive health behaviors, as well as their spouses' preventive health behaviors. Interventions and programs to facilitate older adults' preventive health behaviors should consider couple-based approaches.

High Reinfection Rate after Preventive Chemotherapy for Fishborne Zoonotic Trematodes in Vietnam

PubMed Central

Lier, Tore; Do, Dung Trung; Johansen, Maria Vang; Nguyen, Thi Hop; Dalsgaard, Anders; Asfeldt, Anne Mette

2014-01-01

Background The World Health Organization aims for complete morbidity control of fishborne zoonotic trematodes (FZT) in endemic areas by 2020. The main intervention tool for achieving this goal is regular use of preventive chemotherapy by offering praziquantel to those at risk in endemic areas. The purpose of this study was to investigate the effectiveness of preventive chemotherapy to control FZT in an endemic area in Northern Vietnam. Methodology and principle findings We followed a cohort of 396 people who fulfilled the criteria for receiving preventive chemotherapy. Stool samples were examined by Kato-Katz technique for the presence of trematode eggs before, and two, 16, 29 and 60 weeks after preventive chemotherapy. The prevalence of trematode eggs in stool was 40.2% before, 2.3% two weeks after and increased to a cumulative prevalence of 29.8% sixty weeks after preventive chemotherapy. Conclusions The effectiveness of preventive chemotherapy as a main component in control of FZT is not well documented in most endemic areas. We found a high reinfection rate within the first year after preventive chemotherapy. Since these trematodes are zoonoses, preventive chemotherapy may not have sufficient impact alone on the transmission to have a lasting effect on the prevalence. Animal reservoirs and farm management practices must be targeted to achieve sustainable control of fishborne zoonotic trematode infections, hence control programs should consider a One Health approach. PMID:24945411

Cost effectiveness of the MDOT preventive maintenance program.

DOT National Transportation Integrated Search

2013-04-01

The Michigan Department of Transportations (MDOT) pavement preservation program dates back to 1992. MDOTs pavement preservation strategy is primarily implemented through its capital preventive maintenance (CPM) program, in which preventive main...

Use of caries-preventive agents in children: findings from the dental practice-based research network.

PubMed

Riley, J L; Richman, Joshua S; Rindal, D Brad; Fellows, Jeffrey L; Qvist, Vibeke; Gilbert, Gregg H; Gordan, Valeria V

2010-01-01

Scientific evidence supports the application of caries-preventive agents in children and adolescents, and this knowledge must be applied to the practice of dentistry. There are few multi-region data that allow for comparisons of practice patterns between types of dental practices and geographical regions. The objective of the present study was to characterise the use of specific caries-preventive agents for paediatric patients in a large multi-region sample of practising clinicians. The present study surveyed clinicians from the Dental Practice-based Research Network who perform restorative dentistry in their practices. The survey consisted of a questionnaire that presented a range of questions about caries risk assessment and the use of preventive techniques in children aged 6 to 18 years. Dental sealants (69%) or in-office fluoride (82%) were the most commonly used caries-preventive agents of the caries preventive regimens. The recommendation of at-home caries-preventive agents ranged from 36% to 7%,with the most commonly used agent being non-prescription fluoride rinse. Clinicians who practised in a large group practice model and clinicians who come from the Scandinavian region use caries risk assessment more frequently compared to clinicians who come from regions that had, predominantly, clinicians in private practice. Whether or not clinicians used caries risk assessment with their paediatric patients was poorly correlated with the likelihood of actually using caries-preventive treatments on patients. Although clinicians reported the use of some form of in-office caries-preventive agent, there was considerable variability across practices. These differences could represent a lack of consensus across practising clinicians about the benefits of caries-preventive agents, or a function of differing financial incentives, or patient pools with differing levels of overall caries risk.

Receipt of preventive oral health care by U.S. children: a population-based study of the 2005-2008 medical expenditure panel surveys.

PubMed

Huebner, Colleen E; Bell, Janice F; Reed, Sarah C

2013-11-01

This study provides estimates of the annual use of preventive oral health care by U.S. children ages 6 months-17 years. We estimated the annual use of preventive oral health care with data from the Medical Expenditure Panel Survey for the years 2005 through 2008 (n = 18,218). Additionally, we tested associations between use of preventive oral health care and predisposing factors, enabling factors and health need within three age groups: young children, school-age children and youth. Overall, 21 % of the sample was reported to have received preventive oral health care in the prior year. More school-age children received preventive care than did young children or youth regardless of gender, race/ethnicity, health status, residence, or family size. Among the youngest children, low parental education and lack of health insurance were associated with lower odds of receiving preventive care. School-age children of racial and ethnic minority groups had a higher odds of receiving preventive care than did non-Hispanic Whites. Youth with special health care needs were less likely to receive care than their peers. Within each age group, use of preventive care increased significantly from 2005 to 2008. In the U.S. there has been an increase in use of pediatric preventive dental care. Continued effort is needed to achieve primary prevention. Outreach and education should include all parents and especially parents with low levels of education, parents of children with special health care needs and those without health insurance.

Preventive care utilization: Association with individual- and workgroup-level policy and practice perceptions.

PubMed

Sabbath, Erika L; Sparer, Emily H; Boden, Leslie I; Wagner, Gregory R; Hashimoto, Dean M; Hopcia, Karen; Sorensen, Glorian

2018-06-01

Preventive medical care may reduce downstream medical costs and reduce population burden of disease. However, although social, demographic, and geographic determinants of preventive care have been studied, there is little information about how the workplace affects preventive care utilization. This study examines how four types of organizational policies and practices (OPPs) are associated with individual workers' preventive care utilization. We used data collected in 2012 from 838 hospital patient care workers, grouped in 84 patient care units at two hospitals in Boston. Via survey, we assessed individuals' perceptions of four types of OPPs on their work units. We linked the survey data to a database containing detailed information on medical expenditures. Using multilevel models, we tested whether individual-level perceptions, workgroup-average perceptions, and their combination were associated with individual workers' preventive care utilization (measured by number of preventive care encounters over a two-year period). Adjusting for worker characteristics, higher individual-level perceptions of workplace flexibility were associated with greater preventive care utilization. Higher average unit-level perceptions of people-oriented culture, ergonomic practices, and flexibility were associated with greater preventive care utilization. Overall, we find that workplace policies and practices supporting flexibility, ergonomics, and people-oriented culture are associated with positive preventive care-seeking behavior among workers, with some policies and practices operating at the individual level and some at the group level. Improving the work environment could impact employers' health-related expenditures and improve workers' health-related quality of life. Copyright © 2018 Elsevier Inc. All rights reserved.

Identifying barriers to receiving preventive dental services: expanding access to preventive dental hygiene services through affiliated practice.

PubMed

Gross-Panico, Michelle L; Freeman, Wilbur K

2012-01-01

Minority children and children from lower income families are more likely to experience the burden of oral disease. Since oral disease reduces quality of life, it is a priority to utilize preventive dental services. The research questions ask if affiliated practice increases utilization of preventive dental services by underserved children from birth to 18 years of age, and what the barriers to receiving preventive dental services are and their level of importance. A survey was administered to parents/guardians of patients from birth to 18 years of age who received preventive dental services from Catholic Healthcare West East Valley Children's Dental Clinic, an affiliated practice dental clinic in Chandler, Arizona. Thirty-four surveys were completed: 21 completed in English and 13 completed in Spanish. The data was analyzed to provide descriptive statistics and non-parametrically analyzed using the Friedman's, Kendall's W and Wilcoxon Signed Ranks Tests. The cost of preventive dental services is more important to this population than both convenience of appointment time and distance traveled. As the cost increases for preventive dental services, this population will utilize preventive dental services less frequently. The study indicated that the increase of self-reported utilization of preventive dental services by underserved children, ranging in age from birth to 18 years old, in Arizona affiliated practice dental clinics, was primarily impacted by perceived reduced costs of receiving care. Funding efforts, reimbursement mechanisms and legislative policies should support this dental care delivery model to provide care to underserved children, adults and seniors throughout the U.S.

Health Literacy, Acculturation, and the Use of Preventive Oral Health Care by Somali Refugees Living in Massachusetts

PubMed Central

Hunter Adams, Jo; Penrose, Katherine L.; Cochran, Jennifer; Rybin, Denis; Doros, Gheorghe; Henshaw, Michelle; Paasche-Orlow, Michael

2013-01-01

Background This study investigated the impact of English health literacy and spoken proficiency and acculturation on preventive dental care use among Somali refugees in Massachusetts. Methods 439 adult Somalis in the U.S. ≤ 10 years ago were interviewed. English functional health literacy, dental word recognition, and spoken proficiency were measured using STOFHLA, REALD, and BEST Plus. Logistic regression tested associations of language measures with preventive dental care use. Results Without controlling for acculturation, participants with higher health literacy were 2.0 times more likely to have had preventive care (p=0.02). Subjects with higher word recognition were 1.8 times as likely to have had preventive care (p=0.04). Controlling for acculturation, these were no longer significant, and spoken proficiency was not associated with increased preventive care use. Discussion English health literacy and spoken proficiency were not associated with preventive dental care. Other factors, like acculturation, were more predictive of care use than language skills. PMID:23748902

Individual Differences in Preventive Jealousy Determine Men's Jealousy after Subliminal Exposure to Rivals Wearing High- or Low-Status Clothes.

PubMed

Massar, Karlijn; Buunk, Abraham Bram P

2016-02-01

This study investigated sex differences in jealousy after subliminal exposure to rivals wearing high-status or low-status clothes. It was expected that individual differences in preventive jealousy would moderate the relationship between a rival's characteristics and jealousy. Participants (Men: n = 54, M age = 21.6 yr., SD = 3.5; women: n = 71, M age = 20.7 yr., SD = 1.9) completed a parafoveal subliminal priming paradigm as well as questionnaires about jealousy and preventive jealousy. As predicted, women were not affected by their rival's status, but women high in preventive jealousy reported more jealousy than women low in preventive jealousy. However, whereas men low in preventive jealousy reported equal amounts of jealousy after exposure to a high-status and a low-status rival, surprisingly, and contrary to the expectations, men high in preventive jealousy reported most jealousy after exposure to a low-status rival. To explain these unexpected results, threats to self-esteem were discussed.

Policy Framework for Covering Preventive Services Without Cost Sharing: Saving Lives and Saving Money?

PubMed

Chen, Stephanie C; Pearson, Steven D

2016-08-01

The US Affordable Care Act mandates that private insurers cover a list of preventive services without cost sharing. The list is determined by 4 expert committees that evaluate the overall health effect of preventive services. We analyzed the process by which the expert committees develop their recommendations. Each committee uses different criteria to evaluate preventive services and none of the committees consider cost systematically. We propose that the existing committees adopt consistent evidence review methodologies and expand the scope of preventive services reviewed and that a separate advisory committee be established to integrate economic considerations into the final selection of free preventive services. The comprehensive framework and associated criteria are intended to help policy makers in the future develop a more evidence-based, consistent, and ethically sound approach.

Practice of preventive dentistry for nursing staff in primary care

PubMed Central

Acuña-Reyes, Raquel; Cigarroa-Martínez, Didier; Ureña-Bogarín, Enrique; Orgaz-Fernández, Jose David

2014-01-01

Objectives: Determine the domain of preventive dentistry in nursing personnel assigned to a primary care unit. Methods: Prospective descriptive study, questionnaire validation, and prevalence study. In the first stage, the questionnaire for the practice of preventive dentistry (CPEP, for the term in Spanish) was validated; consistency and reliability were measured by Cronbach's alpha, Pearson's correlation, factor analysis with intra-class correlation coefficient (ICC). In the second stage, the domain in preventive dental nurses was explored. Results: The overall internal consistency of CPEP is α= 0.66, ICC= 0.64, CI95%: 0.29-0.87 (p >0.01). Twenty-one subjects in the study, average age 43, 81.0% female, average seniority of 12.5 were included. A total of 71.5% showed weak domain, 28.5% regular domain, and there was no questionnaire with good domain result. The older the subjects were, the smaller the domain; female nurses showed greater mastery of preventive dentistry (29%, CI95%: 0.1-15.1) than male nurses. Public health nurses showed greater mastery with respect to other categories (50%, CI95%: 0.56-2.8). Conclusions: The CDEP has enough consistency to explore the domain of preventive dentistry in health-care staff. The domain of preventive dentistry in primary care nursing is poor, required to strengthen to provide education in preventive dentistry to the insured population. PMID:25386037

[Directions for future development of preventive medicine in Korea].

PubMed

Kim, Joon Youn

2006-05-01

It is the actual state of the medical society in our country that many graduates of medical schools want to be clinicians, and accordingly Korea's medical situation is relatively too focused on curative medicine. However, this situation is changing due to several factors including a growing number of doctors, inappropriate regulations for medical fees, changes in social status of doctors themselves, and excessive competition between doctors. Furthermore, we expect more advances in medical field of Korea since Korean government started to attach great importance to sciences and produced policies to support sciences, and as a result, more and more interest and effort in the fields of basic research including preventive medicine is being attached especially by young doctors as compared against the past. However, decline of clinical medicine fields doesn't always mean bright future for the field of preventive medicine. True future is possible and meaningful only when we prepare for it by ourselves. In other words, as the promising future is closed to one who spares no effort, we shouldn't fear to oppose unknown challenges and simultaneously need to support colleagues who bear such a positive mind. It is the most important thing for our preventive medicine doctors to evaluate the past and the present of preventive medicine and to foster a prospective mind to prepare for the future of preventive medicine. I set forth my several views according to directions for the development of preventive medicine which we already discussed and publicized in the academic circle of preventive medicine. Those directions are recommen dation of clinical preventive medicine, promotion of preventive medicine specialty, fostering the next generations, improving the quality of genetic epidemiologic study, participation in control of environmental pollution and food safety, contribution to chronic disease control, and preparation to role in medical services for unified Korea.

Disparities in the use of preventive health care among children with disabilities in Taiwan.

PubMed

Tsai, Wen-Chen; Kung, Pei-Tseng; Wang, Jong-Yi

2012-01-01

Children with disabilities face more barriers accessing preventive health services. Prior research has documented disparities in the receipt of these services. However, most are limited to specific types of disability or care. This study investigates disparities in the use of preventive health care among children with disabilities in Taiwan. Three nationwide databases from the Ministry of the Interior, Bureau of Health Promotion, and National Health Research Institutes were linked to gather related information between 2006 and 2008. A total of 8572 children with disabilities aged 1-7 years were included in this study. Multivariate logistic regression analysis was conducted to adjust for covariates. Nationally, only 37.58% of children with disabilities received preventive health care in 2008. Children with severe and very severe disabilities were less likely to use preventive care than those with mild severity. Children with disabilities from the lowest income family were less likely to have preventive care than other income groups. Urbanization was strongly associated with the receipt of preventive health care. However, surprisingly, urban children with disabilities were less likely to receive preventive care than all others. Under universal health insurance coverage, the overall usage of preventive health care is still low among children with disabilities. The study also identified several disparities in their usage. Potential factors affecting the lack of use deserve additional research. Policymakers should target low socioeconomic brackets and foster education about the importance of preventive care. Mobile health services should be continually provided in those areas in need. Capitation reimbursement and other incentives should be considered in improving the utilization among children with disabilities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition

PubMed Central

Müller, Michael; König, Finja; Meyer, Nina; Gattlen, Jasmin; Pieles, Uwe; Peters, Kirsten; Kreikemeyer, Bernd; Mathes, Stephanie; Saxer, Sina

2018-01-01

Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy. PMID:29657766

Effectiveness of preventive medicine education and its determinants among medical students in Malaysia.

PubMed

Anil, Shirin; Zawahir, Mohamed Shukry; Al-Naggar, Redhwan Ahmed

2016-03-01

Preventive medicine has been incorporated in the medical school curriculum, but its effectiveness and the factors that affect it are yet to be widely looked into in the context of Malaysia. We aimed to measure the familiarity with, perception about the importance to learn, and the ability to practice preventive medicine as well as its determinants among the medical students in Malaysia. Thus, a cross sectional study was conducted through an anonymous online survey among 387 randomly selected final year medical students of four large public medical schools in Malaysia from March to September 2014. Of the total sample, 340 (response rate 87.8%) gave a written informed consent and took part in the survey. The familiarity of the sample with preventive medicine was measured in 19 preventive medicine areas, and their perception about the importance of preventive medicine and their ability to practice it were gauged on a Likert scale (low score indicates disagreement and high indicates agreement). Descriptive statistical analysis was performed, followed by logistic regression. The mean age of the respondents was 23.7 (SD 0.77) years, and 61.2% (n = 208) of them were females. Results showed that 22.9% of the sample (n = 78) had a low familiarity with preventive medicine, whereas 76.8% (n = 261) had a high familiarity. The study sample specified that among all the preventive medicine subjects, screening and control as well as smoking cessation and immunization are "extremely important to learn." In univariable analysis, being a female, medical school, family size, and perception about the importance to learn preventive medicine were associated with the ability to practice it. In multivariable analysis, the perception towards the importance to learn preventive medicine was the only significant determinant: aOR (adjusted odds ratio) for those who "agreed" 17.28 (95% CI aOR 4.44-67.26, P < 0.001) and for "strongly agreed" 35.87 (95% CI aOR 8.04-159.87, P < 0.001). Considering these findings, the familiarity of medical students with preventive medicine should be increased. The perception about the importance to learn preventive medicine is a strong determinant for the ability to practice it.

Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers.

PubMed

Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Tabata, Yasuhiko; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

2015-05-01

To improve the anti-tumor activity of EGFR2R-lytic hybrid peptide, we prepared peptide-modified dextran conjugates with the disulfide bonds between thiolated carboxymethyl dextran (CMD-Cys) and cysteine-conjugated peptide (EGFR2R-lytic-Cys). In vitro release studies showed that the peptide was released from the CMD-s-s-peptide conjugate in a concentration-dependent manner in the presence of glutathione (GSH, 2μM-2mM). The CMD-s-s-peptide conjugate exhibited a similar cytotoxic activity with free peptide alone against human pancreatic cancer BxPC-3 cells in vitro. Furthermore, it was shown that the CMD-s-s-peptide conjugates were highly accumulated in tumor tissue in a mouse xenograft model using BxPC-3 cells, and the anti-tumor activity of the conjugate was more effective than that of the free peptide. In addition, the plasma concentrations of peptide were moderately increased and the elimination half-life of the peptide was prolonged after intravenous injection of CMD-s-s-peptide conjugates. These results demonstrated that the conjugate based on thiolated CMD polymer would be potentially useful carriers for the sustained release of the hybrid peptide in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Preventive Migraine Treatment

PubMed Central

Silberstein, Stephen D.

2015-01-01

Purpose of Review: This article reviews the evidence base for the preventive treatment of migraine. Recent Findings: Evidence-based guidelines for the preventive treatment of migraine have recently been published by the American Academy of Neurology (AAN) and the Canadian Headache Society (CHS), providing valuable guidance for clinicians. Strong evidence exists to support the use of metoprolol, timolol, propranolol, divalproex sodium, sodium valproate, and topiramate for migraine prevention, according to the AAN. Based on best available evidence, adverse event profile, and expert consensus, topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, Petasites (butterbur), riboflavin, coenzyme Q10, and magnesium citrate received a strong recommendation for use from the CHS. Summary: Migraine preventive drug treatments are underutilized in clinical practice. Principles of preventive treatment are important to improve compliance, minimize side effects, and improve patient outcomes. Choice of preventive treatment of migraine should be based on the presence of comorbid and coexistent illness, patient preference, reproductive potential and planning, and best available evidence. PMID:26252585

Cancer risk perception and preventive behaviors among grilled meat vendors.

PubMed

Meerith, Penrawee; Harncharoen, Kitiphong; Srisuphanunt, Mayuna; Kaewboonchoo, Orawan

2012-06-01

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that cause cancers in humans. Exposure results from incomplete burning of organic materials. Grilled meat vendors are occupationally exposed to PAHs in smoke from continuously burning charcoal and meat, which may have chance to get cancer. Individual risk perception is a critical antecedent of preventive behavior However relatively little is known about the cancer risk perception and preventive behaviors among grilled meat vendors. The present study aimed to examine cancer risk perception and preventive behaviors and factors associated with preventive behaviors among grilled meat vendors in Bangkok, Thailand. A cross-sectional survey was used in the present study. The subjects consisted of 40 males and 82 females grilled meat vendors who conducted their jobs at Victory Monument, Bang Lumpoo, Pratunam, Jakkawat or Patumwan. They were interviewed regarding cancer risk perception and preventive behaviors. Multiple logistic regression analysis was used to analyze data. Average cancer risk perception score was 23.3 +/- 3.3 out of 32. About 79.5% of the subjects had high risk perception. The prevalence of good preventive behaviors was 86.1%. The three most frequent preventive behaviors among the subjects during grilling meat were using good quality charcoal (65.6%), ventilation fan (41.0%) and wearing long sleeves shirt (36.1%). Only 10.7% always used gloves. Multiple logistic regression analysis showed 2 factors were independently associated with preventive behaviors: educational level and risk perception. The subjects who had higher educational level or risk perception were more likely to develop better behaviors than those who had a lower educational level and perception (p < 0.05). In conclusion, the present study found that the educational background and cancer risk perception were associated with preventive behaviors among grilled meat vendors. To improve the preventive behaviors among grilled meat vendors, interventions focusing on cancer risk perceptions and considering educational background among target group are recommended.

Preventive-care practices among adults with diabetes--Puerto Rico, 2000-2002.

PubMed

2004-11-12

Preventive-care practices among persons with diabetes can prevent or delay complications such as eye disease, kidney disease, or nerve damage that is a precursor to disabling foot disease. However, the level of diabetes-related preventive care is inadequate in the United States, and little has been reported about preventive care in Puerto Rico, where an estimated 10% of adults have diagnosed diabetes. CDC analyzed data from 2000, 2001, and 2002 Behavioral Risk Factor Surveillance System (BRFSS) surveys to assess the percentage of adults with diabetes in Puerto Rico who engaged in five selected preventive-care practices. This report summarizes the results of that analysis, which indicated that, with the exception of hemoglobin A1c testing, the percentages of adults engaging in preventive-care practices were lower than the target percentages set by U.S. national health objectives for 2010.

Association Between Employee Dental Claims, Health Risks, Workplace Productivity, and Preventive Services Compliance.

PubMed

Burton, Wayne N; Chen, Chin-Yu; Li, Xingquan; Schultz, Alyssa B

2017-08-01

This study examined differences in health risks and workplace outcomes among employees who utilized preventive dental services compared with other employees. A retrospective observational study of employees of a large financial services corporation, with data from health risk appraisal questionnaires, medical claims, pharmacy claims, and dental claims. Employees with no dental claims were significantly more likely to have a variety of health risk factors (such as obesity and tobacco use), health conditions (such as diabetes), absenteeism, and lost on-the-job productivity, and were significantly less likely to be compliant with clinical preventive services compared with those with preventive dental claims. Employees with preventive dental claims had fewer health risks and medical conditions and better health and productivity measures. Study employees underutilized free dental care; employers should incorporate preventive dental care awareness into their worksite wellness programs.

Inclusion of Zinc Oxide Nanoparticles into Virus-Like Peptide Nanocapsules Self-Assembled from Viral β-Annulus Peptide

PubMed Central

Fujita, Seiya; Matsuura, Kazunori

2014-01-01

A viral β-annulus peptide connected with a zinc oxide (ZnO)-binding sequence (HCVAHR) at its N-terminal was synthesized, and the inclusion behavior of quantum-sized ZnO nanoparticles into the peptide nanocapsules formed by self-assembly of the peptide in water was investigated. Dynamic light scattering (DLS) measurements showed that ZnO nanoparticles (approximately 10 nm) in the presence of the peptide (0.1 mM) formed assemblies with an average size of 48 ± 24 nm, whereas ZnO nanoparticles in the absence of the peptide formed large aggregates. Transmission electron microscopy (TEM) observations of the ZnO nanoparticles in the presence of the peptide revealed that ZnO nanoparticles were encapsulated into the peptide nanocapsules with a size of approximately 50 nm. Fluorescence spectra of a mixture of the peptide and ZnO nanoparticles suggested that the ZnO surface and the peptide interact. Template synthesis of ZnO nanoparticles with the peptide nanocapsules afforded larger nanoparticles (approximately 40 nm), which are not quantum-sized ZnO. PMID:28344248

Moderating effect of age on the association between future time perspective and preventive coping.

PubMed

Chen, Tao; Liu, Lu-Lu; Cui, Ji-Fang; Chen, Xing-Jie; Shi, Hai-Song; Neumann, David L; Shum, David H K; Wang, Ya; Chan, Raymond C K

2017-09-01

The present study aimed to investigate the moderating effect of age on the relationship between future time perspective (FTP) and future-oriented coping. A total of 1,915 participants aged 9-84 years completed measures of FTP and future-oriented coping. Moderation analyses were conducted to examine whether age played a role in the association between FTP and future-oriented coping (proactive and preventive). Results showed that proactive and preventive coping were negatively correlated with age, and age moderated the association between FTP and preventive coping but not proactive coping. Furthermore, the strength of the positive association between FTP and preventive coping was strongest among the older participants, moderate among the middle-aged participants, and weakest among the younger participants. These results suggest that the association between FTP and preventive coping varies across the lifespan. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

How a North Carolina program boosted preventive oral health services for low-income children.

PubMed

Rozier, R Gary; Stearns, Sally C; Pahel, Bhavna T; Quinonez, Rocio B; Park, Jeongyoung

2010-12-01

Dental caries (tooth decay), the most common chronic disease affecting young children, is exacerbated by limited access to preventive dental services for low-income children. To address this problem, North Carolina implemented a program to reimburse physicians for up to six preventive oral health visits for Medicaid-enrolled children younger than age three. Analysis of physician and dentist Medicaid claims from the period 2000-2006 shows that the program greatly increased preventive oral health services. By 2006 approximately 30 percent of well-child visits for children ages six months up to three years included these services. However, additional strategies are needed to ensure preventive oral health care for more low-income children.

The relationship between perfectionism and engagement in preventive health behaviours: the mediating role of self-concealment.

PubMed

Williams, Charlotte J; Cropley, Mark

2014-10-01

If perfectionists avoid engaging in preventive health behaviours, they may be putting their long-term health and well-being at risk. Correlational analyses based on a sample of 370 university students identified maladaptive perfectionism to be associated with decreased levels of engagement in preventive health behaviours, life satisfaction and well-being and increased levels of self-concealment and psychological distress. Adaptive perfectionism was associated with higher levels of engagement in preventive health behaviours. Self-concealment was identified as a partial mediator in the relationship between maladaptive perfectionism and both engagement in preventive health behaviours and psychological distress. Implications of the findings are discussed. © The Author(s) 2013.

Increasing Receipt of Women's Preventive Services

PubMed Central

Fox, Jared

2015-01-01

Abstract The receipt of clinical preventive services is important for health promotion and prevention of illness, death, and disability for women in the United States. Today, the Affordable Care Act makes a variety of evidence-based preventive services available with no out-of-pocket cost to women with certain health insurance plans. Nevertheless, available service receipt data suggest receipt of the services for all American adults remains suboptimal. This article seeks to raise awareness about the critical gaps in the delivery of preventive services to women and highlight opportunities for women, primary care providers, and public health professionals to increase receipt of clinical preventive services among women. PMID:26447836

Food protein-originating peptides as tastants - Physiological, technological, sensory, and bioinformatic approaches.

PubMed

Iwaniak, Anna; Minkiewicz, Piotr; Darewicz, Małgorzata; Hrynkiewicz, Monika

2016-11-01

Taste is one of the factors based on which the organism makes the selection of what to ingest. It also protects humans from ingesting toxic compounds and is one of the main attributes when thinking about food quality. Five basic taste sensations are recognized by humans: bitter, salty, sour, sweet, and umami. The taste of foods is affected by some molecules of some specific chemical nature. One of them are peptides derived from food proteins. Although they are not the major natural compounds originating from food sources that are responsible for the taste, they are in the area of scientific research due to the specific composition of amino acids which are well-known for their sensory properties. Literature data implicate that sweet, bitter, and umami are the tastes attributable to peptides. Moreover, the bitter peptide tastants are the dominant among the other tastes. Additionally, other biological activities like, e.g., inhibiting enzymes that regulate the body functions and acting as preventive food agents of civilization diseases, are also associated with the taste of peptides. The advance in information technologies has contributed to the elaboration of internet archives (databases) as well as in silico tools for the analysis of biological compounds. It also concerns peptides - namely taste carriers originating from foods. Thus, our paper provides a summary of knowledge about peptides as tastants with special attention paid to the following aspects: a) basis of taste perception, b) taste peptides detected in food protein sequences with special emphasis put on the role of bitter peptides, c) peptides that may enhance/suppress the taste of foods, d) databases as well as bioinformatic approaches suitable to study the taste of peptides, e) taste-taste interactions, f) basis of sensory analysis in the evaluation of the taste of molecules, including peptides, and g) the methodology applied to reduce/eliminate the undesired taste of peptides. The list of taste peptides serving some biological functions is presented in the Supplement file. The information provided includes database resources, whereas peptide sequences are given with InChiKeys, which is aimed at facilitating the Google® search. Our collection of data regarding taste peptides may be supportive for the scientists working with the set of peptide data in the context of structure-function activity of peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of Decision Models in the Development of Evidence-Based Clinical Preventive Services Recommendations: Methods of the U.S. Preventive Services Task Force.

PubMed

Owens, Douglas K; Whitlock, Evelyn P; Henderson, Jillian; Pignone, Michael P; Krist, Alex H; Bibbins-Domingo, Kirsten; Curry, Susan J; Davidson, Karina W; Ebell, Mark; Gillman, Matthew W; Grossman, David C; Kemper, Alex R; Kurth, Ann E; Maciosek, Michael; Siu, Albert L; LeFevre, Michael L

2016-10-04

The U.S. Preventive Services Task Force (USPSTF) develops evidence-based recommendations about preventive care based on comprehensive systematic reviews of the best available evidence. Decision models provide a complementary, quantitative approach to support the USPSTF as it deliberates about the evidence and develops recommendations for clinical and policy use. This article describes the rationale for using modeling, an approach to selecting topics for modeling, and how modeling may inform recommendations about clinical preventive services. Decision modeling is useful when clinical questions remain about how to target an empirically established clinical preventive service at the individual or program level or when complex determinations of magnitude of net benefit, overall or among important subpopulations, are required. Before deciding whether to use decision modeling, the USPSTF assesses whether the benefits and harms of the preventive service have been established empirically, assesses whether there are key issues about applicability or implementation that modeling could address, and then defines the decision problem and key questions to address through modeling. Decision analyses conducted for the USPSTF are expected to follow best practices for modeling. For chosen topics, the USPSTF assesses the strengths and limitations of the systematically reviewed evidence and the modeling analyses and integrates the results of each to make preventive service recommendations.

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

PubMed Central

Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K.; Karimi, Tahereh

2015-01-01

An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73–92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005–0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the total concentration. PMID:25051457

Income-related inequalities in preventive and curative dental care use among working-age Japanese adults in urban areas: a cross-sectional study.

PubMed

Murakami, Keiko; Aida, Jun; Ohkubo, Takayoshi; Hashimoto, Hideki

2014-09-19

Preventive dental care use remains relatively low in Japan, especially among working-age adults. Universal health insurance in Japan covers curative dental care with an out-of-pocket payment limit, though its coverage of preventive dental care is limited. The aim of this study was to test the hypothesis that income inequality in dental care use is found in preventive, but not curative dental care among working-age Japanese adults. A cross-sectional survey was conducted using a computer-assisted, self-administered format for community residents aged 25-50 years. In all, 4357 residents agreed to participate and complete the questionnaire (valid response rate: 31.3%). Preventive dental care use was measured according to whether the participant had visited a dentist or a dental hygienist during the past year for dental scaling or fluoride or orthodontic treatments. Curative dental care use was assessed by dental visits for other reasons. The main explanatory variable was equivalent household income. Logistic regression analyses with linear trend tests were conducted to determine whether there were significant income-related gradients with curative or preventive dental care use. Among the respondents, 40.0% of men and 41.5% of women had used curative dental care in the past year; 24.1% of men and 34.1% of women had used preventive care. We found no significant income-related gradients of curative dental care among either men or women (p = 0.234 and p = 0.270, respectively). Significant income-related gradients of preventive care were observed among both men and women (p < 0.001 and p = 0.003, respectively). Among women, however, income-related differences were no longer significant (p = 0.126) after adjusting for education and other covariates. Compared with men with the lowest income, the highest-income group had a 1.79-fold significantly higher probability for using preventive dental care. The prevalence of preventive dental care use was lower than that of curative care. The results showed income-related inequality in preventive dental care use among men, though there were no significant income-related gradients of curative dental care use among either men or women. Educational attainment had a positive association with preventive dental care use only among women.

Perceived competency towards preventive dentistry among dental graduates: the need for curriculum change

PubMed Central

Arheiam, Arheiam; Bankia, Ibtesam; Ingafou, Mohamed

2015-01-01

Background A previous study has shown that dental practitioners in Benghazi believed that the less prevention-oriented education system is one of the barriers to applying preventive dentistry. Objective To assess attitudes and perceived competence of the dental graduates in Benghazi towards prevention and early management of dental caries. Methods A cross-sectional, questionnaire-based survey was conducted among internship students attending the Department of Community and Preventive Dentistry in Faculty of Dentistry, Benghazi, Libya. The participants were asked to provide demographic information, to respond to statements about their attitudes towards preventive dentistry, and to answer questions regarding their perceived competence in applying preventive dentistry procedures. Results Data from 108 Libyan dental graduates were analysed for this study, of which 64% of them were females and 42.1% of them passed their final year with grade: acceptable. The most acknowledged aspects of preventive dentistry were being useful and essential to the community (95.4 and 90.8%, respectively). The percentage of participants expressing a proficiency in providing oral hygiene instructions was the highest (95.4%). There were differences between study subgroups in their perceived competence of preventive dental practices by gender and academic performance (p≤0.05). Conclusion This study highlighted that the currently implemented undergraduate education programme in Benghazi dental school does not provide dentists with the required attitude and skills to fulfil their role in providing preventive-oriented health services. PMID:25556523

Medicare annual preventive care visits: use increased among fee-for-service patients, but many do not participate.

PubMed

Chung, Sukyung; Lesser, Lenard I; Lauderdale, Diane S; Johns, Nicole E; Palaniappan, Latha P; Luft, Harold S

2015-01-01

Under the Affordable Care Act (ACA), Medicare coverage expanded in 2011 to fully cover annual preventive care visits. We assessed the impact of coverage expansion, using 2007-13 data from primary care patients of Medicare-eligible age at the Palo Alto Medical Foundation (204,388 patient-years), which serves people in four counties near San Francisco, California. We compared trends in preventive visits and recommended preventive services among Medicare fee-for-service and Medicare health maintenance organization (HMO) patients as well as non-Medicare patients ages 65-75 who were covered by private fee-for-service and private HMO plans. Among Medicare fee-for-service patients, the annual use of preventive visits rose from 1.4 percent before the implementation of the ACA to 27.5 percent afterward. This increase was significantly larger than was seen for patients in the other insurance groups. Nevertheless, rates of annual preventive care visit use among Medicare fee-for-service patients remained 10-20 percentage points lower than was the case for people with private coverage (43-44 percent) or those in a Medicare HMO (53 percent). ACA policy changes led to increased preventive service use by Medicare fee-for-service beneficiaries, which suggests that Medicare coverage expansion is an effective way to increase seniors' use of preventive services. Project HOPE—The People-to-People Health Foundation, Inc.

Preventive treatment of migraine.

PubMed

Silberstein, Steven D

2005-01-01

Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.

Caries-preventive self-care for children. Consistent oral health messages to the public?

PubMed

Løken, S Y; Wang, N J; Wigen, T I

2017-05-01

Recommendations regarding caries-preventive self-care for children are provided by several health authorities. To investigate recommendations given to the public regarding children's caries-preventive self-care by Norwegian dentists, dental hygienists, dental nurses and public health nurses. Questionnaires were sent by e-mail and answered by 808 of 1132 persons who provide oral preventive promotion to children in dental services and health centres. The preventive advice was obtained through questions about the preferred preventive methods, fluoride recommendations and sources of knowledge on which the personnel based the advice about caries prevention in children. The responses were analysed using logistic regression. The majority (59-71%) in all professions judged oral hygiene education to be the most important caries-preventive method. Most personnel (84-98%) recommended all children to use fluoride toothpaste, and half of all personnel (53%) recommended fluoride lozenges for 50% or more of children. Multivariate analysis showed that dental nurses recommended lozenges to more children than dentists (OR 2.5, 95% CI 1.7-3.7), while health nurses recommended lozenges to fewer children than dentists (OR 0.5, 95% CI 0.3-0.8). The most important source of knowledge reported by dental personnel was professional education, while health nurses relied on information from dental personnel. Health professions' recommendations regarding caries-preventive self-care for children were mainly similar, although variation existed both between and within professions. Collaboration between professions and awareness of the evidence base for preventive oral care may improve the consistency of information given by health professionals to the public. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HPEPDOCK: a web server for blind peptide-protein docking based on a hierarchical algorithm.

PubMed

Zhou, Pei; Jin, Bowen; Li, Hao; Huang, Sheng-You

2018-05-09

Protein-peptide interactions are crucial in many cellular functions. Therefore, determining the structure of protein-peptide complexes is important for understanding the molecular mechanism of related biological processes and developing peptide drugs. HPEPDOCK is a novel web server for blind protein-peptide docking through a hierarchical algorithm. Instead of running lengthy simulations to refine peptide conformations, HPEPDOCK considers the peptide flexibility through an ensemble of peptide conformations generated by our MODPEP program. For blind global peptide docking, HPEPDOCK obtained a success rate of 33.3% in binding mode prediction on a benchmark of 57 unbound cases when the top 10 models were considered, compared to 21.1% for pepATTRACT server. HPEPDOCK also performed well in docking against homology models and obtained a success rate of 29.8% within top 10 predictions. For local peptide docking, HPEPDOCK achieved a high success rate of 72.6% on a benchmark of 62 unbound cases within top 10 predictions, compared to 45.2% for HADDOCK peptide protocol. Our HPEPDOCK server is computationally efficient and consumed an average of 29.8 mins for a global peptide docking job and 14.2 mins for a local peptide docking job. The HPEPDOCK web server is available at http://huanglab.phys.hust.edu.cn/hpepdock/.

Measures of Knowledge and Attitude Toward Preventive Cardiology.

ERIC Educational Resources Information Center

Allred, Charlene A.; And Others

1985-01-01

The development and validation of an inventory of preventive cardiology at the University of Virginia is described. The inventory contains two instruments designed to measure medical students' preinstructional and postinstructional knowledge of and attitude toward preventive cardiology. (Author/MLW)

Preventive treatment in migraine and the new US guidelines

PubMed Central

Estemalik, E; Tepper, S

2013-01-01

Migraine headaches are among the most common headache disorders seen in various practices. The prevalence of migraine headaches is 18% in women and 6% in men. While millions of Americans suffer from migraine headaches, roughly 3%–13% of identified migraine patients are on preventive therapy, while an estimated 38% actually need a preventive agent. The challenge among physicians is not only when to start a daily preventive agent but which preventive agent to choose. Circumstances warranting prevention have been described in the past, and in 2012, a new set of guidelines with an evidence review on preventive medications was published. A second set of guidelines provided evidence on nonsteroidal anti-inflammatory drugs, herbs, minerals, and vitamins for prevention of episodic migraine. This article describes the updated US guidelines for the prevention of migraines and also outlines the major studies from which these guidelines were derived. PMID:23717045

Adoption of preventive measures during and after the 2009 influenza A (H1N1) virus pandemic peak in Spain.

PubMed

Agüero, Fernando; Adell, Manel Nebot; Pérez Giménez, Anna; López Medina, María José; Garcia Continente, Xavier

2011-09-01

This study describes the preventive measures adopted by the Spanish population towards 2009 influenza A (H1N1) virus and their associated factors. An anonymous computer-assisted telephone interview survey was conducted in Spain in December 2009 and February 2010. Respondents were asked about their perceptions of influenza A (H1N1) virus and the preventive measures adopted. Factors associated with the adoption of preventive measures were assessed by logistic regression analyses. Out of 4892 households approached, 1627 valid responses were obtained (response rate of 33.3%). The most commonly adopted preventive measures were respiratory hygiene and hand washing. Factors independently associated with the adoption of the preventive measures recommended by the Spanish Ministry of Health were female gender, higher educational level, size of municipality of residence >50,000 inhabitants, high perceived susceptibility to infection, high perceived effectiveness of the measures and high perceived usefulness of the information provided by the government. The presence of school-aged children in household was associated with purchasing masks and hand sanitizer. In addition to demographic factors, modifiable factors such as personal beliefs and expectations play a role in the adoption of preventive measures. Copyright © 2011 Elsevier Inc. All rights reserved.

A novel peptide from TCTA protein inhibits proliferation of fibroblast-like synoviocytes of rheumatoid arthritis patients

PubMed Central

Yago, Toru; Kobashigawa, Tsuyoshi; Kawamoto, Manabu; Yamanaka, Hisashi; Kotake, Shigeru

2014-01-01

Background We have demonstrated that a peptide, which we named ‘Peptide A’, derived from the extracellular domain of T-cell leukemia translocation-associated gene (TCTA) protein, inhibited human osteoclastogenesis. Objective In the current study, we examined whether this peptide inhibits the proliferation of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) or not. Material and methods Fibroblast-like synoviocytes obtained from five RA patients were cultured in the absence or presence of 1, 5, 10 µg/ml of peptide. We used 29-mer scrambled peptide as a control. Results The peptide inhibited the proliferation of RA FLS dose-dependently. On the other hand, the scrambled peptide showed no inhibition. Conclusions The peptide inhibits both human osteoclastogenesis and the proliferation of RA FLS. Thus, the peptide may be used for the therapy of both osteoporosis and synovitis of RA patients. This is the first report of the new peptide we discovered, which inhibits both osteoclastogenesis and synovitis. Thus, this new peptide could be a new drug for patients with both osteoporosis and RA. PMID:26155164

Biological activity of Tat (47-58) peptide on human pathogenic fungi.

PubMed

Jung, Hyun Jun; Park, Yoonkyung; Hahm, Kyung-Soo; Lee, Dong Gun

2006-06-23

Tat (47-58) peptide, a positively charged Arginine-rich peptide derived from HIV-1 regulatory protein Tat, is known for a peptidic delivery factor as a cell-penetrating peptide on mammalian cells. In this study, antifungal effect and its mode of action of Tat peptide were investigated on fungal cells. The results indicate that Tat peptide exhibits antifungal activity against pathogenic fungal cells without hemolytic effect on human erythrocytes. To understand the mechanism(s) of Tat peptide, the cellular distribution of the peptide was investigated. Tat peptide internalized in the fungal cells without any damage to cell membrane when examined using an artificial liposome (PC/cholesterol; 10:1, w/w). Moreover, flow cytometry analysis exhibited the uptake of Tat peptide by energy- and salt-independent pathway, and confocal scanning microscopy displayed that this peptide accumulated in the nucleus of fungal cells rapidly without any impediment by time or temperature, which generally influence on the viral infections. After penetration into the nuclear, the peptide affected the process of cell cycle of Candida albicans through the arrest at G1 phase.

14 CFR 91.1425 - CAMP: Maintenance, preventive maintenance, and alteration programs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... RULES Fractional Ownership Operations Program Management § 91.1425 CAMP: Maintenance, preventive maintenance, and alteration programs. Each program manager who maintains program aircraft under a CAMP must... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Maintenance, preventive maintenance...

The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics

PubMed Central

Escano, Jerome; Stauffer, Byron; Brennan, Jacob; Bullock, Monica; Smith, Leif

2014-01-01

Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides. Herein, we further our understanding of the structural differences of mutacin 1140 leader peptide with regard to other class I leader peptides. We have determined that the length of the leader peptide is important for the biosynthesis of mutacin 1140. We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics. PTM enzyme recognition of the leader peptide appears to be evolutionarily distinct from related class I lantibiotics. Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes. PMID:25400246

Physiological effects and therapeutic potential of proinsulin C-peptide

PubMed Central

Maric-Bilkan, Christine; Luppi, Patrizia; Wahren, John

2014-01-01

Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes. PMID:25249503

HLA-DM mediates epitope selection by a "compare-exchange" mechanism when a potential peptide pool is available.

PubMed

Ferrante, Andrea; Anderson, Matthew W; Klug, Candice S; Gorski, Jack

2008-01-01

HLA-DM (DM) mediates exchange of peptides bound to MHC class II (MHCII) during the epitope selection process. Although DM has been shown to have two activities, peptide release and MHC class II refolding, a clear characterization of the mechanism by which DM facilitates peptide exchange has remained elusive. We have previously demonstrated that peptide binding to and dissociation from MHCII in the absence of DM are cooperative processes, likely related to conformational changes in the peptide-MHCII complex. Here we show that DM promotes peptide release by a non-cooperative process, whereas it enhances cooperative folding of the exchange peptide. Through electron paramagnetic resonance (EPR) and fluorescence polarization (FP) we show that DM releases prebound peptide very poorly in the absence of a candidate peptide for the exchange process. The affinity and concentration of the candidate peptide are also important for the release of the prebound peptide. Increased fluorescence energy transfer between the prebound and exchange peptides in the presence of DM is evidence for a tetramolecular complex which resolves in favor of the peptide that has superior folding properties. This study shows that both the peptide releasing activity on loaded MHCII and the facilitating of MHCII binding by a candidate exchange peptide are integral to DM mediated epitope selection. The exchange process is initiated only in the presence of candidate peptides, avoiding possible release of a prebound peptide and loss of a potential epitope. In a tetramolecular transitional complex, the candidate peptides are checked for their ability to replace the pre-bound peptide with a geometry that allows the rebinding of the original peptide. Thus, DM promotes a "compare-exchange" sorting algorithm on an available peptide pool. Such a "third party"-mediated mechanism may be generally applicable for diverse ligand recognition in other biological systems.

Medicaid Primary Care Physician Fees and the Use of Preventive Services among Medicaid Enrollees

PubMed Central

Atherly, Adam; Mortensen, Karoline

2014-01-01

Objective The Patient Protection and Affordable Care Act (ACA) increases Medicaid physician fees for preventive care up to Medicare rates for 2013 and 2014. The purpose of this paper was to model the relationship between Medicaid preventive care payment rates and the use of U.S. Preventive Services Task Force (USPSTF)–recommended preventive care use among Medicaid enrollees. Data Sources/Study Session We used data from the 2003 and 2008 Medical Expenditure Panel Survey (MEPS), a national probability sample of the U.S. civilian, noninstitutionalized population, linked to Kaiser state Medicaid benefits data, including the state Medicaid-to-Medicare physician fee ratio in 2003 and 2008. Study Design Probit models were used to estimate the probability that eligible individuals received one of five USPSF-recommended preventive services. A difference-in-difference model was used to separate out the effect of changes in the Medicaid payment rate and other factors. Data Collection/Extraction Methods Data were linked using state identifiers. Principal Findings Although Medicaid enrollees had a lower rate of use of the five preventive services in univariate analysis, neither Medicaid enrollment nor changes in Medicaid payment rates had statistically significant effects on meeting screening recommendations for the five screenings. The results were robust to a number of different sensitivity tests. Individual and state characteristics were significant. Conclusions Our results suggest that although temporary changes in primary care provider payments for preventive services for Medicaid enrollees may have other desirable effects, they are unlikely to substantially increase the use of these selected USPSTF-recommended preventive care services among Medicaid enrollees. PMID:24628495

42 CFR 440.130 - Diagnostic, screening, preventive, and rehabilitative services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Diagnostic, screening, preventive, and rehabilitative services. 440.130 Section 440.130 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Definitions § 440.130 Diagnostic, screening, preventive, and rehabilitative services. (a) “Diagnostic services...

Effectiveness of a citywide patient immunization navigator program on improving adolescent immunizations and preventive care visit rates.

PubMed

Szilagyi, Peter G; Humiston, Sharon G; Gallivan, Sarah; Albertin, Christina; Sandler, Martha; Blumkin, Aaron

2011-06-01

To assess the impact of a tiered patient immunization navigator intervention (immunization tracking, reminder/recall, and outreach) on improving immunization and preventive care visit rates in urban adolescents. Randomized clinical trial allocating adolescents (aged 11-15 years) to intervention vs standard of care control. Eight primary care practices. Population-based sample of adolescents (N = 7546). Immunization navigators at each practice implemented a tiered protocol: immunization tracking, telephone or mail reminder/recall, and home visits if participants remained unimmunized or behind on preventive care visits. Immunization rates at study end. Secondary outcomes were preventive care visit rates during the previous 12 months and costs. The intervention and control groups were similar at baseline for demographics (mean age, 13.5 years; 63% black, 14% white, and 23% Hispanic adolescents; and 74% receiving Medicaid), immunization rates, and preventive care visit rates. Immunization rates at the end of the study were 44.7% for the intervention group and 32.4% for the control group (adjusted risk ratio, 1.4; 95% confidence interval, 1.3-1.5); preventive care visit rates were 68.0% for the intervention group and 55.2% for the control group (1.2; 1.2-1.3). Findings were similar across practices, sexes, ages, and insurance providers. The number needed to treat for immunizations and preventive care visits was 9. The intervention cost was $3.81 per adolescent per month; the cost per additional adolescent fully vaccinated was $465, and the cost per additional adolescent receiving a preventive care visit was $417. A tiered tracking, reminder/recall, and outreach intervention improved immunization and preventive care visit rates in urban adolescents. clinicaltrials.gov Identifier: NCT00581347.

Access to Preventive Health Care for Cancer Survivors

PubMed Central

Yabroff, K. Robin; Short, Pamela Farley; Machlin, Steven; Dowling, Emily; Rozjabek, Heather; Li, Chunyu; McNeel, Timothy; Ekwueme, Donatus U.; Virgo, Katherine S.

2013-01-01

Background Access to healthcare, particularly effective primary and secondary preventive care, is critical for cancer survivors, in order to minimize the adverse sequelae of cancer and its treatment. Purpose The goal of the study was to evaluate the association between cancer survivorship and access to primary and preventive health care. Methods Cancer survivors (n=4960) and individuals without a cancer history (n=64,431) aged ≥18 years, from the 2008–2010 Medical Expenditure Panel Survey (MEPS), were evaluated. Multiple measures of access and preventive services use were compared. The association between cancer survivorship and access and preventive services was evaluated with multivariate logistic regression models, stratified by age group (18–64 years and ≥65 years), controlling for the effects of age, gender, race/ethnicity, education, marital status, and comorbidities. Data were analyzed in 2013. Results Cancer survivors aged ≥65 years had equivalent or greater access and preventive services use than individuals without a cancer history, in adjusted analyses. However, among those aged 18–64 years with private health insurance, cancer survivors were more likely than other individuals to have a usual source of care and to use preventive services, whereas uninsured or publicly insured cancer survivors were generally less likely to have a usual source of care and to use preventive services than were uninsured or publicly insured adults without a cancer history. Conclusions Although access and preventive care use in cancer survivors is generally equivalent or greater compared to that of other individuals, disparities for uninsured and publicly insured cancer survivors aged 18–64 years suggest that improvements in survivor care are needed. PMID:23953357

Preventive research and interventive research: in favour of to act rather than to react.

PubMed

Erren, T C

2002-08-01

Conventional wisdom knows that "prevention is better than cure". However, in the many cases where we do not understand how to cure or intervent, prevention is not only better but may be the only way to promote public health. As the principal basis for preventive action, this paper advocates to focus more on preventive rather than on interventive research. Preventive research, as defined here, aims to identify a determinant A in the environment which causes an undesirable health effect B in the human body. Preventive research ends when the critical nature of A is convincingly established and ways to avoid A are identified. Interventive research, as defined here, aims to understand and manipulate the chain from A to B within the human body. Examples of real (poliomyelitis, lung cancer, AIDS) and possible scourges (BSE) from the last and this century indicate that preventive research has delivered culprits but that interventive research could not-and likely will not-unravel the whole chain from A to B. Based also on conceptual considerations it is concluded that, while both research approaches are needed, a strategy with more emphasis on preventive research and taking action at an earlier stage may lead to more community success.

Disease prevention policy under Medicare: a historical and political analysis.

PubMed

Schauffler, H H

1993-01-01

I review the history and politics of Medicare disease prevention policy and identify factors associated with the success or failure of legislative initiatives to add preventive services benefits to Medicare. Between 1965 and 1990, 453 bills for Medicare preventive services were introduced in the U.S. Congress, but not until 1980, after 350 bills had failed, was the first preventive service added to the Medicare program. Medicare currently pays for only four of the 44 preventive services recommended for the elderly by the U.S. Preventive Services Task Force (pneumococcal and hepatitis B vaccinations, Pap smears, and mammography). In addition, Congress has funded demonstration programs for the influenza vaccine and comprehensive preventive services. The preventive services added to Medicare reflect the bias of the biomedical model toward screening and immunizations. Counseling services have received the least legislative attention. Factors associated with successful enactment include single-benefit bills, incorporation into budget-deficit reduction legislation, documented evidence of cost-effectiveness, public hearings, sponsorship by chairs of key congressional committees, and persistent congressional leadership. Factors associated with failure include lack of support from Medicare beneficiaries, lack of professional support, impact on total Medicare expenditures, disagreement over or failure to address payment and financing mechanisms, and competing congressional priorities.

Women's Preventive Services Guidelines Affordable Care Act Expands Prevention Coverage for Women's Health and Well-Being

MedlinePlus

... 2012. Type of Preventive Service HHS Guideline for Health Insurance Coverage Frequency Well-woman visits. Well-woman preventive ... established or maintained by an objecting organization, or health insurance coverage offered or arranged by an objecting organization, ...

45 CFR 96.45 - Preventive health and health services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Preventive health and health services. 96.45 Section 96.45 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.45 Preventive health and health services...

45 CFR 96.45 - Preventive health and health services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Preventive health and health services. 96.45 Section 96.45 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.45 Preventive health and health services...

45 CFR 96.45 - Preventive health and health services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Preventive health and health services. 96.45 Section 96.45 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.45 Preventive health and health services...

Investigating preventive-medicine consultations in first-opinion small-animal practice in the United Kingdom using direct observation.

PubMed

Robinson, N J; Brennan, M L; Cobb, M; Dean, R S

2016-02-01

Preventive-medicine consultations account for a large proportion of the veterinary caseload and previous research has suggested these consultations are fundamentally different from those in which the animal is presented for a specific health problem. There has been recent controversy around some aspects of preventive medicine for cats and dogs, and the full health benefits of the preventive-medicine consultation remain unclear. The aim of this study was to compare characteristics of the consultation and the problems discussed during the consultation between preventive-medicine consultations and other types of consultations. Data were gathered during direct observation of small-animal consultations in seven first-opinion practices in the United Kingdom. Data collected included type of clinical examination performed, patient signalment, and details of all problems discussed (including whether the problem was presenting or non-presenting, new or pre-existing, who had raised the problem, body system affected and whether an action was taken). A two-level multivariable logistic-regression model was developed, with canine and feline patients at Level 1 nested within consulting veterinary surgeons at Level 2, and a binary outcome variable of preventive-medicine consultation versus specific health-problem consultation. A total of 1807 patients were presented, of which 690 (38.2%) presented for a preventive-medicine consultation. Dogs were the most frequently presented species (n=1168; 64.6%) followed by cats (n=510; 28.2%), rabbits (n=86; 4.8%) and patients of other species (n=43; 2.4%). The five variables remaining in the multi-level model were whether multiple patients were presented, patient age, clinical examination type, weighing and number of problems discussed. Species, breed, sex, neutering status and practice did not remain in the final model. Many non-presenting problems, including both preventive-medicine problems and specific-health problems, were discussed and acted upon during all types of consultations. Dental and behavioural non-presenting problems were discussed more frequently during preventive-medicine consultations compared with specific health-problem consultations. Preventive-medicine consultations represent an opportunity for veterinary surgeons to discuss other aspects of preventive medicine, and to detect and manage new and ongoing health problems. A greater evidence base is needed to understand whether detecting and managing underlying disease during the preventive-medicine consultation has a positive impact on lifelong patient health and welfare. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Towards making efficient use of household resources for appropriate prevention of malaria: investigating households' ownership, use and expenditures on ITNs and other preventive tools in Southeast Nigeria.

PubMed

Onwujekwe, Obinna; Etiaba, Enyi; Uguru, Nkoli; Uzochukwu, Benjamin; Adjagba, Alex

2014-04-05

Many households own, use and spend money on many malaria preventive tools, some of which are inappropriate and ineffective in preventing malaria. This is despite the promotion of use of effective preventive methods such as Insecticide treated nets (ITNs) and indoor residual house spraying (IRHS). The use of these ineffective methods imposes some economic burden on households with no resultant reduction in the risk of developing malaria. Hence, global and national targets in use of various effective malaria preventive toools are yet to be achieved in Nigeria. This paper presents new evidence on the differential use and expenditures on effective and non-effective malaria preventive methods in Nigeria. Semi-structured interviewer administered pre-tested questionnaire were used to collect data from 500 households from two communities in Enugu state, Nigeria. The two study communities were selected randomly while the households were selected systematically. Information was collected on demography, malaria status of children under 5 within the past month, types of malaria preventive tools used by households and how much was spent on these, the per capita household food expenditure and assets ownership of respondents to determine their socio-economic status. There was high level of ownership of ITNs (73%) and utilization (71.2%), with 40% utilization by children under 5. There were also appreciable high levels of use of other malaria preventive tools such as window and door nets, indoor spray, aerosol spray and cleaning the environment. No significant inequity was found in ownership and utilization of ITNs and in use of other preventive methods across socioeconomic groups. However, households spent a lot of money on other preventive tools and average expenditures were between N0.83-N172 ($0.005-$1.2) The richest households spent the most on window and door nets (P = 0.04). High levels of use and expenditure on ITNs and other malaria preventive tools exist. A programmatic challenge will involve designing ways and means of converting some of the inefficient and inappropriate expenditures on many ineffective malaria preventive tools to proven cost-effective methods such as ITNs and IRHS. This will help to achieve universal coverage with malaria preventive tools.

Biological activity of Tat (47-58) peptide on human pathogenic fungi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Hyun Jun; Park, Yoonkyung; Department of Biotechnology, Chosun University, 375 Seosuk-dong, Kwangju 501-750

2006-06-23

Tat (47-58) peptide, a positively charged Arginine-rich peptide derived from HIV-1 regulatory protein Tat, is known for a peptidic delivery factor as a cell-penetrating peptide on mammalian cells. In this study, antifungal effect and its mode of action of Tat peptide were investigated on fungal cells. The results indicate that Tat peptide exhibits antifungal activity against pathogenic fungal cells without hemolytic effect on human erythrocytes. To understand the mechanism(s) of Tat peptide, the cellular distribution of the peptide was investigated. Tat peptide internalized in the fungal cells without any damage to cell membrane when examined using an artificial liposome (PC/cholesterol;more » 10:1, w/w). Moreover, flow cytometry analysis exhibited the uptake of Tat peptide by energy- and salt-independent pathway, and confocal scanning microscopy displayed that this peptide accumulated in the nucleus of fungal cells rapidly without any impediment by time or temperature, which generally influence on the viral infections. After penetration into the nuclear, the peptide affected the process of cell cycle of Candida albicans through the arrest at G1 phase.« less

Factors associated with free adult preventive health care utilization among physically disabled people in Taiwan: nationwide population-based study.

PubMed

Yen, Suh-May; Kung, Pei-Tseng; Tsai, Wen-Chen

2014-12-05

Few previous studies have specifically addressed the health care utilization situation of the physically disabled. This study aimed to investigate the utilization of free adult preventive health care for physically disabled people and its' affecting factors. The data was obtained from three nationwide databases from 2006 to 2008. This study comprised 329,264 physically disabled people in Taiwan above the age of 40 who had eligible health checks during 2008. We employed descriptive statistics to analyze the use and rate of free preventive health care use by physically disabled adults. Logistic regression analysis was used to explore the factors that affect physically disabled adults' use of free adult preventive health care. 16.37% of the physically disabled adults used free adult preventive health care. Women (17.66%), married (17.16%), a junior high education level (17.89%), and mildly disabled adults (18.77%) had the highest use rate among various participant subgroups. The variables that significantly influenced the use of free adult preventive health care by the physically disabled included gender, age, education, marital status, urbanization of the residence areas, monthly payroll, aboriginal status, catastrophic illnesses status, relevant chronic diseases, and severity of disability. Physically disabled using preventive health care tend to be low. Governments should use the media to reinforce propagation and education of these services to specific, low-utilization groups, and encourage doctors to actively provide preventive health care to communities.

Do female primary care physicians practise preventive care differently from their male colleagues?

PubMed Central

Woodward, C. A.; Hutchison, B. G.; Abelson, J.; Norman, G.

1996-01-01

OBJECTIVE: To assess whether female primary care physicians' reported coverage of patients eligible for certain preventive care strategies differs from male physicians' reported coverage. DESIGN: A mailed survey. SETTING: Primary care practices in southern Ontario. PARTICIPANTS: All primary care physicians who graduated between 1972 and 1988 and practised in a defined geographic area of Ontario were selected from the Canadian Medical Association's physician resource database. Response rate was 50%. MAIN OUTCOME MEASURES: Answers to questions on sociodemographic and practice characteristics, attitudes toward preventive care, and perceptions about preventive care behaviour and practices. RESULTS: In general, reported coverage for Canadian Task Force on the Periodic Health Examination's (CTFPHE) A and B class recommendations was low. However, more female than male physicians reported high coverage of women patients for female-specific preventive care measures (i.e., Pap smears, breast examinations, and mammography) and for blood pressure measurement. Female physicians appeared to question more patients about a greater number of health risks. Often, sex of physician was the most salient factor affecting whether preventive care services thought effective by the CTFPHE were offered. However, when evidence for effectiveness of preventive services was equivocal or lacking, male and female physicians reported similar levels of coverage. CONCLUSION: Female primary care physicians are more likely than their male colleagues to report that their patients eligible for preventive health measures as recommended by the CTFPHE take advantage of these measures. PMID:8969856

Perceived competency towards preventive dentistry among dental graduates: the need for curriculum change.

PubMed

Arheiam, Arheiam; Bankia, Ibtesam; Ingafou, Mohamed

2015-01-01

A previous study has shown that dental practitioners in Benghazi believed that the less prevention-oriented education system is one of the barriers to applying preventive dentistry. To assess attitudes and perceived competence of the dental graduates in Benghazi towards prevention and early management of dental caries. A cross-sectional, questionnaire-based survey was conducted among internship students attending the Department of Community and Preventive Dentistry in Faculty of Dentistry, Benghazi, Libya. The participants were asked to provide demographic information, to respond to statements about their attitudes towards preventive dentistry, and to answer questions regarding their perceived competence in applying preventive dentistry procedures. Data from 108 Libyan dental graduates were analysed for this study, of which 64% of them were females and 42.1% of them passed their final year with grade: acceptable. The most acknowledged aspects of preventive dentistry were being useful and essential to the community (95.4 and 90.8%, respectively). The percentage of participants expressing a proficiency in providing oral hygiene instructions was the highest (95.4%). There were differences between study subgroups in their perceived competence of preventive dental practices by gender and academic performance (p≤0.05). This study highlighted that the currently implemented undergraduate education programme in Benghazi dental school does not provide dentists with the required attitude and skills to fulfil their role in providing preventive-oriented health services.

Exploration of the Medicinal Peptide Space.

PubMed

Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

2016-01-01

The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

PREVENTIVE MAINTENANCE. HONEYWELL PLANNING GUIDE.

ERIC Educational Resources Information Center

Honeywell, Inc., Minneapolis, Minn.

THIS HONEYWELL PAMPHLET DISCUSSES SOME ASPECTS OF PREVENTIVE MAINTENANCE OF AUTOMATIC CONTROLS, HEATING, VENTILATING, AND AIR CONDITIONING, AND COMPARES IN-PLANT WITH CONTRACT SERVICE, CONCLUDING THAT CONTRACT SERVICE IS PREFERABLE AND DESCRIBING A NUMBER OF MAINTENANCE PLANS WHICH THEY FURNISH. PREVENTIVE MAINTENANCE PROVIDES--(1) MORE EFFICIENT…

Receipt of Preventive Services After Oregon's Randomized Medicaid Experiment.

PubMed

Marino, Miguel; Bailey, Steffani R; Gold, Rachel; Hoopes, Megan J; O'Malley, Jean P; Huguet, Nathalie; Heintzman, John; Gallia, Charles; McConnell, K John; DeVoe, Jennifer E

2016-02-01

It is predicted that gaining health insurance via the Affordable Care Act will result in increased rates of preventive health services receipt in the U.S., primarily based on self-reported findings from previous health insurance expansion studies. This study examined the long-term (36-month) impact of Oregon's 2008 randomized Medicaid expansion ("Oregon Experiment") on receipt of 12 preventive care services in community health centers using electronic health record data. Demographic data from adult (aged 19-64 years) Oregon Experiment participants were probabilistically matched to electronic health record data from 49 Oregon community health centers within the OCHIN community health information network (N=10,643). Intent-to-treat analyses compared receipt of preventive services over a 36-month (2008-2011) period among those randomly assigned to apply for Medicaid versus not assigned, and instrumental variable analyses estimated the effect of actually gaining Medicaid coverage on preventive services receipt (data collected in 2012-2014; analysis performed in 2014-2015). Intent-to-treat analyses revealed statistically significant differences between patients randomly assigned to apply for Medicaid (versus not assigned) for 8 of 12 assessed preventive services. In intent-to-treat analyses, Medicaid coverage significantly increased the odds of receipt of most preventive services (ORs ranging from 1.04 [95% CI=1.02, 1.06] for smoking assessment to 1.27 [95% CI=1.02, 1.57] for mammography). Rates of preventive services receipt will likely increase as community health center patients gain insurance through Affordable Care Act expansions. Continued effort is needed to increase health insurance coverage in an effort to decrease health disparities in vulnerable populations. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Knowledge of and Attitudes Toward Evidence-Based Guidelines for and Against Clinical Preventive Services: Results from a National Survey.

PubMed

Lantz, Paula M; Evans, W Douglas; Mead, Holly; Alvarez, Carmen; Stewart, Lisa

2016-03-01

Both the underuse and overuse of clinical preventive services relative to evidence-based guidelines are a public health concern. Informed consumers are an important foundation of many components of the Affordable Care Act, including coverage mandates for proven clinical preventive services recommended by the US Preventive Services Task Force. Across sociodemographic groups, however, knowledge of and positive attitudes toward evidence-based guidelines for preventive care are extremely low. Given the demonstrated low levels of consumers' knowledge of and trust in guidelines, coupled with their strong preference for involvement in preventive care decisions, better education and decision-making support for evidence-based preventive services are greatly needed. Both the underuse and overuse of clinical preventive services are a serious public health problem. The goal of our study was to produce population-based national data that could assist in the design of communication strategies to increase knowledge of and positive attitudes toward evidence-based guidelines for clinical preventive services (including the US Preventive Services Task Force, USPSTF) and to reduce uncertainty among patients when guidelines change or are controversial. In late 2013 we implemented an Internet-based survey of a nationally representative sample of 2,529 adults via KnowledgePanel, a probability-based survey panel of approximately 60,000 adults, statistically representative of the US noninstitutionalized population. African Americans, Hispanics, and those with less than a high school education were oversampled. We then conducted descriptive statistics and multivariable logistic regression analysis to identify the prevalence of and sociodemographic characteristics associated with key knowledge and attitudinal variables. While 36.4% of adults reported knowing that the Affordable Care Act requires insurance companies to cover proven preventive services without cost sharing, only 7.7% had heard of the USPSTF. Approximately 1 in 3 (32.6%) reported trusting that a government task force would make fair guidelines for preventive services, and 38.2% believed that the government uses guidelines to ration health care. Most of the respondents endorsed the notion that research/scientific evidence and expert medical opinion are important for the creation of guidelines and that clinicians should follow guidelines based on evidence. But when presented with patient vignettes in which a physician made a guideline-based recommendation against a cancer-screening test, less than 10% believed that this recommendation alone, without further dialogue and/or the patient's own research, was sufficient to make such a decision. Given these demonstrated low levels of knowledge and mistrust regarding guidelines, coupled with a strong preference for shared decision making, better consumer education and decision supports for evidence-based guidelines for clinical preventive services are greatly needed. © 2016 Milbank Memorial Fund.

Prevention and synergistic control of Ph(+) ALL by a DNA vaccine and 6-mercaptopurine.

PubMed

Köchling, Joachim; Rott, Yvonne; Arndt, Stefanie; Marschke, Christina; Schmidt, Manuel; Wittig, Burghardt; Kalies, Katrin; Westermann, Jürgen; Henze, Günter

2012-09-07

Although the outcome of patients with acute lymphoblastic leukemia (ALL) has been improved continuously by chemotherapy and tyrosine kinase inhibitors, prognosis of patients with Philadelphia chromosome positive (Ph(+)) ALL still remains poor. Since further intensification of chemotherapy is limited by toxic side effects and patients with high risk of transplant-related mortality are not eligible for allogeneic stem cell transplantation new treatment strategies are urgently needed for the prevention of Ph(+) ALL relapse. There is increasing evidence that the immune system plays an essential role for the eradication or immunologic control of remaining leukemia cells. We developed several DNA-based vaccines encoding a BCR-ABL(p185) specific peptide and GM-CSF, and CD40-L, IL-27 or IL-12 and evaluated the preventive and therapeutic efficacy against a lethal challenge of syngeneic Ph(+) ALL in Balb/c mice. In vivo cell depletion assays and cytokine expression studies were performed and the efficacy of the DNA vaccine was compared with 6-mercaptopurine (6-MP) alone and the combination of the DNA vaccine and 6-MP. Preventive immunization with the vaccine BCR-ABL/GM-CSF/IL-12 and the TLR-9 agonist dSLIM induced an innate and adaptive immune response mediated by NK-cells, CD4(+) T-cells and CD8(+) T-cells leading to a survival rate of 80%. Therapeutic vaccination resulted in a significantly longer leukemia-free survival (40.7 days vs. 20.4 days) and a higher survival rate (56% vs. 10%) compared to chemotherapy with 6-MP. Remarkably, in combination with the vaccine 6-MP acted synergistically and led to 100% survival. These results demonstrate that minimal residual disease of Ph(+) ALL can be significantly better controlled by a combined treatment approach of immunotherapy and chemotherapy. This provides a rationale for improving maintenance therapy in order to reduce the relapse rate in patients with Ph(+) ALL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention.

PubMed

Xie, Jennifer Y; De Felice, Milena; Kopruszinski, Caroline M; Eyde, Nathan; LaVigne, Justin; Remeniuk, Bethany; Hernandez, Pablo; Yue, Xu; Goshima, Naomi; Ossipov, Michael; King, Tamara; Streicher, John M; Navratilova, Edita; Dodick, David; Rosen, Hugh; Roberts, Ed; Porreca, Frank

2017-07-01

Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine. Nor-binaltorphimine (nor-BNI), a long-acting KOR antagonist or CYM51317, a novel short-acting KOR antagonist, were given systemically either during sumatriptan priming or immediately before environmental stress challenge. The effects of KOR blockade in the amygdala on stress-induced allodynia was determined by administration of nor-BNI into the right or left central nucleus of the amygdala (CeA). Results KOR blockade prevented both stress-induced allodynia and increased plasma CGRP. Stress increased dynorphin content and phosphorylated KOR in both the left and right CeA in sumatriptan-primed rats. However, KOR blockade only in the right CeA prevented stress-induced cephalic allodynia as well as extracephalic allodynia, measured in either the right or left hindpaws. U69,593, a KOR agonist, given into the right, but not the left, CeA, produced allodynia selectively in sumatriptan-primed rats. Both stress and U69,593-induced allodynia were prevented by right CeA U0126, a mitogen-activated protein kinase inhibitor, presumably acting downstream of KOR. Conclusions Our data reveal a novel lateralized KOR circuit that mediated stress-induced cutaneous allodynia and increased plasma CGRP in an injury-free model of functional cephalic pain with features of migraine and medication overuse headache. Selective, small molecule, orally available, and reversible KOR antagonists are currently in development and may represent a novel class of preventive therapeutics for migraine.

Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.

PubMed

Kato, Ryuji; Kaga, Chiaki; Kunimatsu, Mitoshi; Kobayashi, Takeshi; Honda, Hiroyuki

2006-06-01

Peptide array, the designable peptide library covalently synthesized on cellulose support, was applied to assay peptide-cell interaction, between solid-bound peptides and anchorage-dependant cells, to study objective peptide design. As a model case, cell-adhesive peptides that could enhance cell growth as tissue engineering scaffold material, was studied. On the peptide array, the relative cell-adhesion ratio of NIH/3T3 cells was 2.5-fold higher on the RGDS (Arg-Gly-Asp-Ser) peptide spot as compared to the spot with no peptide, thus indicating integrin-mediated peptide-cell interaction. Such strong cell adhesion mediated by the RGDS peptide was easily disrupted by single residue substitution on the peptide array, thus indicating that the sequence recognition accuracy of cells was strictly conserved in our optimized scheme. The observed cellular morphological extension with active actin stress-fiber on the RGD motif-containing peptide supported our strategy that peptide array-based interaction assay of solid-bound peptide and anchorage-dependant cells (PIASPAC) could provide quantitative data on biological peptide-cell interaction. The analysis of 180 peptides obtained from fibronectin type III domain (no. 1447-1629) yielded 18 novel cell-adhesive peptides without the RGD motif. Taken together with the novel candidates, representative rules of ineffective amino acid usage were obtained from non-effective candidate sequences for the effective designing of cell-adhesive peptides. On comparing the amino acid usage of the top 20 and last 20 peptides from the 180 peptides, the following four brief design rules were indicated: (i) Arg or Lys of positively charged amino acids (except His) could enhance cell adhesion, (ii) small hydrophilic amino acids are favored in cell-adhesion peptides, (iii) negatively charged amino acids and small amino acids (except Gly) could reduce cell adhesion, and (iv) Cys and Met could be excluded from the sequence combination since they have less influence on the peptide design. Such rules that are indicative of the nature of the functional peptide sequence can be obtained only by the mass comparison analysis of PIASPAC using peptide array. By following such indicative rules, numerous amino acid combinations can be effectively screened for further examination of novel peptide design.

[Dental caries prevention in infants in Cameroon. Status of the place of oro-dental preventive treatments given to children in Cameroon].

PubMed

Bouhom, V; Parfait, S; Lagaye, E; Nancy, J

2007-06-01

This research main purpose is to determine the different preventive measures applied to children at the dentist's office in Cameroon; and to identify the priorities to be developed in the strategies and access to preventive cares for the whole population in general and for children in particular. The authors present the result of a survey conducted on the dentists established in Cameroon. The survey evaluates the specific preventive dental decay strategies applied to children.

Suicidality among College and University Students: Contributing Factors and Preventive Response.

ERIC Educational Resources Information Center

Jones, Joan Wickham

This paper surveys and evaluates the research since 1975 on college and university student suicidality in the United States. It focuses on factors which contribute to suicidality, preventive responses to suicide and how well the preventive responses address the contributing factors. Contributing factors examined include various feeling states…

14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Operation after maintenance, preventive...

29 CFR 2590.715-2713 - Coverage of preventive health services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Coverage of preventive health services. 2590.715-2713... ADMINISTRATION, DEPARTMENT OF LABOR GROUP HEALTH PLANS RULES AND REGULATIONS FOR GROUP HEALTH PLANS Other Requirements § 2590.715-2713 Coverage of preventive health services. (a) Services—(1) In general. Beginning at...

Bromine isotopic signature facilitates de novo sequencing of peptides in free-radical-initiated peptide sequencing (FRIPS) mass spectrometry.

PubMed

Nam, Jungjoo; Kwon, Hyuksu; Jang, Inae; Jeon, Aeran; Moon, Jingyu; Lee, Sun Young; Kang, Dukjin; Han, Sang Yun; Moon, Bongjin; Oh, Han Bin

2015-02-01

We recently showed that free-radical-initiated peptide sequencing mass spectrometry (FRIPS MS) assisted by the remarkable thermochemical stability of (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) is another attractive radical-driven peptide fragmentation MS tool. Facile homolytic cleavage of the bond between the benzylic carbon and the oxygen of the TEMPO moiety in o-TEMPO-Bz-C(O)-peptide and the high reactivity of the benzylic radical species generated in •Bz-C(O)-peptide are key elements leading to extensive radical-driven peptide backbone fragmentation. In the present study, we demonstrate that the incorporation of bromine into the benzene ring, i.e. o-TEMPO-Bz(Br)-C(O)-peptide, allows unambiguous distinction of the N-terminal peptide fragments from the C-terminal fragments through the unique bromine doublet isotopic signature. Furthermore, bromine substitution does not alter the overall radical-driven peptide backbone dissociation pathways of o-TEMPO-Bz-C(O)-peptide. From a practical perspective, the presence of the bromine isotopic signature in the N-terminal peptide fragments in TEMPO-assisted FRIPS MS represents a useful and cost-effective opportunity for de novo peptide sequencing. Copyright © 2015 John Wiley & Sons, Ltd.

Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants

PubMed Central

Sgarbossa, Antonella; Giacomazza, Daniela; di Carlo, Marta

2015-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular amyloid-beta peptide (Aβ) and intracellular neurofibrillar tangles, associated with loss of neurons in the brain and consequent learning and memory deficits. Aβ is the major component of the senile plaques and is believed to play a central role in the development and progress of AD both in oligomer and fibril forms. Inhibition of the formation of Aβ fibrils as well as the destabilization of preformed Aβ in the Central Nervous System (CNS) would be an attractive therapeutic target for the treatment of AD. Moreover, a large number of studies indicate that oxidative stress and mitochondrial dysfunction may play an important role in AD and their suppression or reduction via antioxidant use could be a promising preventive or therapeutic intervention for AD patients. Many antioxidant compounds have been demonstrated to protect the brain from Aβ neurotoxicity. Ferulic acid (FA) is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger. Here we present the role of FA as inhibitor or disaggregating agent of amyloid structures as well as its effects on biological models. PMID:26184304

Estimation of metabolic factors related to insulin resistance and metabolic syndrome in young people.

PubMed

Płaczkowska, Sylwia; Pawlik-Sobecka, Lilla; Kokot, Izabela; Piwowar, Agnieszka

2018-05-09

Civilizational developments occurring during recent decades have resulted in an increased incidence of a variety of metabolic disorders related to insulin resistance in younger people. The determination of decision limits for insulin resistance indices, especially among young people, is a significant challenge in clinical practice. The aim of this study was the estimation of metabolic factors related to their relationship to insulin resistance and metabolic syndrome (MS) features in young, apparently healthy people. Moreover, we evaluated the optimal decision limits for patients with MS identification for HOMA1-IR, HOMA2-IR, HOMA2 obtained from C-peptide concentrations. 349 apparently healthy people aged 18-31 (260 women and 89 men), were enrolled in this study. The present analysis of metabolic, anthropometric and clinical parameters observed them in clusters covering the criteria of MS recognition, but MS in this group was only partially related to insulin resistance. The HOMA1-IR decision limit estimation is likely to became be useful in the prognostication of metabolic disturbances in young, apparently healthy people. A measure of insulin resistance that can provide a reliable early prediction of MS is likely to provide an opportunity for instigating preventive measures of significant clinical utility.

Increased introduction, advertising, and sales of preventive drugs during 1986-2002 in Sweden.

PubMed

Nilsson, J Lars G; Melander, Arne

2006-01-01

The objective of this study was to survey how introduction of new drugs and promotional activities influence drug sales in Sweden. All drugs on the Swedish market were categorized as curative, symptom-alleviating, substitutive, or preventive. The number of new drugs introduced, drug sales in volume and value, and the number of drug advertisements appearing in the major Swedish medical journal during 1986-2002 were determined for each of the 4 drug categories. Between 1986 and 1998, the relative shares of the 4 drug categories were relatively constant. From 1998 to 2002, the share of new preventive drugs increased from 24% to 30%, their share of advertisements increased from 20% to 35%, and their sales value increased from 25% to 30%. During the same period, the shares of other drugs decreased correspondingly. Pharmaceutical companies have shifted their attention to the introduction, advertising, and sales of preventive drugs in an attempt to exploit preventive medicine. This might lead to waste of resources when expensive preventive drugs are used by numerous patients over many years, as the benefit of preventive drugs for the individual patient cannot be judged easily.

Anti-dengue virus serotype 2 activity and mode of action of a novel peptide.

PubMed

Chew, M-F; Tham, H-W; Rajik, M; Sharifah, S H

2015-10-01

To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry). Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug. © 2015 The Society for Applied Microbiology.

Assessment of the management factors that influence the development of preventive care in the New South Wales public dental service.

PubMed

Masoe, Angela V; Blinkhorn, Anthony S; Taylor, Jane; Blinkhorn, Fiona A

2015-01-01

Oral diseases, particularly dental caries, remain one of the most common chronic health problems for adolescents, and are a major public health concern. Public dental services in New South Wales, Australia offer free clinical care and preventive advice to all adolescents under 18 years of age, particularly those from disadvantaged backgrounds. This care is provided by dental therapists and oral health therapists (therapists). It is incumbent upon clinical directors (CDs) and health service managers (HSMs) to ensure that the appropriate clinical preventive care is offered by clinicians to all their patients. The aims of this study were to 1) explore CDs' and HSMs' perceptions of the factors that could support the delivery of preventive care to adolescents, and to 2) record the strategies they have utilized to help therapists provide preventive care to adolescents. In-depth, semistructured interviews were undertaken with 19 CDs and HSMs from across NSW local health districts. A framework matrix was used to systematically code data and enable key themes to be identified for analysis. The 19 CDs and HSMs reported that fiscal accountability and meeting performance targets impacted on the levels and types of preventive care provided by therapists. Participants suggested that professional clinical structures for continuous quality improvement should be implemented and monitored, and that an adequate workforce mix and more resources for preventive dental care activities would enhance therapists' ability to provide appropriate levels of preventive care. CDs and HSMs stated that capitalizing on the strengths of visiting pediatric dental specialists and working with local health district clinical leaders would be a practical way to improve models of preventive oral health care for adolescents. The main issue raised in this study is that preventive dentistry per se lacks strong support from the central funding agency, and that increasing prevention activities is not a simple task of changing regulations or increasing professional education.

Social impact bonds and their application to preventive health.

PubMed

Fitzgerald, John L

2013-05-01

Although preventive health in Australia has been acknowledged as central to national health and wellbeing, efforts to reform the delivery of preventive health have to date produced limited results. The financing of preventive health at a national level is based on outcome- or performance-based funding mechanisms; however, delivery of interventions and activities at a state level have not been subjected to outcome-based funding processes. A new financing tool being applied in the area of social services (social impact bonds) has emerged as a possible model for application in the prevention arena. This paper explores key issues in the consideration of this funding model in the prevention arena. When preventive health is conceptualised as a merit good, the role of government is clarified and outcome measures fully articulated, social impact bonds may be a viable funding option to supplement core public health activities. WHAT IS KNOWN ABOUT THE TOPIC? The complexities of outcome monitoring in preventive health are well understood.Likewise, the problem of linking funding to outcomes from preventive health practice has also been debated at length in health policy. However, not much is known about the application of social impact bonds into the preventive health arena.WHAT DOES THIS PAPER ADD? This paper discusses the limitations and opportunities facing the application of the social impact bond financing model in the preventive health arena. This has not been undertaken previously.WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Social impact bonds have received significant recent attention from federal and state government treasury departments as potential financing tools for government. Health policy practitioners are watching this space very closely to see the outcomes of a New South Wales trial. Health promotion practitioners and primary care practitioners who deliver preventive services will need to keep abreast of this issue as it will have significant impact on their practice if states and territories introduce outcome-based funding processes.

Related factors and use of free preventive health services among adults with intellectual disabilities in Taiwan

PubMed Central

2014-01-01

Background This study aimed to investigate the utilization of preventive health services in the adults with intellectual disabilities from the nationwide database. Methods The research method of this study is secondary data analysis. The data was obtained from three nationwide databases from 2006 to 2008. This study employed descriptive statistics to analyze the use and rate of preventive health services by intellectual disabled adults. Chi-square test was used to determine the relationship between the utilization of preventive health services and these variables. Multivariate logistic regression analysis was used to explore the factors that affect intellectual disabled adults’ use of preventive health services. Results Our findings indicated 16.65% of people with intellectual disabilities aged over 40 years used the preventive health services. Females were more frequent users than males (18.27% vs. 15.21%, p <0.001). The utilization rate decreased with increasing severity of intellectual disabilities. The utilization was lowest (13.83%) for those with very severe disability, whereas that was the highest (19.38%) for those with mild severity. The factors significantly influencing utilization of the services included gender, age, and marital status, urbanization of resident areas, monthly payroll, low-income household status, catastrophic illnesses status and relevant chronic diseases and severity of disability. Conclusions Although Taiwan’s Health Promotion Administration (HPA) has provided free preventive health services for more than 15 years, people with intellectual disabilities using preventive health care tend to be low. Demographics, economic conditions, health status, relevant chronic diseases, environmental factor, and severity of disability are the main factors influencing the use of preventive healthcare. According to the present findings, it is recommended that the government should increase the reimbursement of the medical staff performing health examinations for the persons with intellectual disabilities. It is also suggested to conduct media publicity and education to the public and the nursing facilities for the utilization of adult preventive health services. PMID:24923548

Related factors and use of free preventive health services among adults with intellectual disabilities in Taiwan.

PubMed

Yen, Suh-May; Kung, Pei-Tseng; Chiu, Li-Ting; Tsai, Wen-Chen

2014-06-12

This study aimed to investigate the utilization of preventive health services in the adults with intellectual disabilities from the nationwide database. The research method of this study is secondary data analysis. The data was obtained from three nationwide databases from 2006 to 2008. This study employed descriptive statistics to analyze the use and rate of preventive health services by intellectual disabled adults. Chi-square test was used to determine the relationship between the utilization of preventive health services and these variables. Multivariate logistic regression analysis was used to explore the factors that affect intellectual disabled adults' use of preventive health services. Our findings indicated 16.65% of people with intellectual disabilities aged over 40 years used the preventive health services. Females were more frequent users than males (18.27% vs. 15.21%, p <0.001). The utilization rate decreased with increasing severity of intellectual disabilities. The utilization was lowest (13.83%) for those with very severe disability, whereas that was the highest (19.38%) for those with mild severity. The factors significantly influencing utilization of the services included gender, age, and marital status, urbanization of resident areas, monthly payroll, low-income household status, catastrophic illnesses status and relevant chronic diseases and severity of disability. Although Taiwan's Health Promotion Administration (HPA) has provided free preventive health services for more than 15 years, people with intellectual disabilities using preventive health care tend to be low. Demographics, economic conditions, health status, relevant chronic diseases, environmental factor, and severity of disability are the main factors influencing the use of preventive healthcare. According to the present findings, it is recommended that the government should increase the reimbursement of the medical staff performing health examinations for the persons with intellectual disabilities. It is also suggested to conduct media publicity and education to the public and the nursing facilities for the utilization of adult preventive health services.

Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease.

PubMed

McClean, Paula L; Hölscher, Christian

2014-01-01

Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD). It has been shown that insulin signalling is desensitised in the brains of AD patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and long-lasting analogues such as liraglutide (Victoza(®)) are on the market as type 2 diabetes treatments. We have previously shown that liraglutide improved cognitive function, reduced amyloid plaque deposition, inflammation, overall APP and oligomer levels and enhanced LTP when injected peripherally for two months in 7 month old APPswe/PS1ΔE9 (APP/PS1) mice. This showed that liraglutide has preventive effects at the early stage of AD development. The current study investigated whether Liraglutide would have restorative effects in late-stage Alzheimer's disease in mice. Accordingly, 14-month-old APP/PS1 and littermate control mice were injected with Liraglutide (25 nmol/kg bw) ip. for 2 months. Spatial memory was improved by Liraglutide-treatment in APP/PS1 mice compared with APP/PS1 saline-treated mice. Overall plaque load was reduced by 33%, and inflammation reduced by 30%, while neuronal progenitor cell count in the dentate gyrus was increased by 50%. LTP was significantly enhanced in APP/PS1 liraglutide-treated mice compared with APP/PS1 saline mice, corroborated with increased synapse numbers in hippocampus and cortex. Total brain APP and beta-amyloid oligomer levels were reduced in Liraglutide-treated APP/PS1 mice while IDE levels were increased. These results demonstrate that Liraglutide not only has preventive properties, but also can reverse some of the key pathological hallmarks of AD. Liraglutide is now being tested in clinical trials in AD patients. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program.

PubMed

Blumenfeld, Andrew; Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Turkel, Catherine C; Binder, William J

2010-10-01

Chronic migraine (CM) is a prevalent and disabling neurological disorder. Few prophylactic treatments for CM have been investigated. OnabotulinumtoxinA, which inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, has been evaluated in randomized, placebo-controlled studies for the preventive treatment of a variety of headache disorders, including CM. These studies have yielded insight into appropriate patient selection, injection sites, dosages, and technique. Initial approaches used a set of fixed sites for the pericranial injections. However, the treatment approach evolved to include other sites that corresponded to the location of pain and tenderness in the individual patient in addition to the fixed sites. The Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection paradigm uses both fixed and follow-the-pain sites, with additional specific follow-the-pain sites considered depending on individual symptoms. The PREEMPT paradigm for injecting onabotulinumtoxinA has been shown to be safe, well-tolerated, and effective in well-designed, controlled clinical trials and is the evidence-based approach recommended to optimize clinical outcomes for patients with CM. © 2010 American Headache Society.

Promoting Good Mental Health from Primary to Early Secondary Grades--Preventive Interventions in Schools.

ERIC Educational Resources Information Center

Jason, Leonard A.; Ferone, Louise

1980-01-01

The paper describes a four-year research effort aimed at developing preventive educational interventions for children with behavior problems in inner city schools. The implications of switching the emphasis from early secondary to primary preventive programs are discussed. (Author)

The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics.

PubMed

Escano, Jerome; Stauffer, Byron; Brennan, Jacob; Bullock, Monica; Smith, Leif

2014-12-01

Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides. Herein, we further our understanding of the structural differences of mutacin 1140 leader peptide with regard to other class I leader peptides. We have determined that the length of the leader peptide is important for the biosynthesis of mutacin 1140. We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics. PTM enzyme recognition of the leader peptide appears to be evolutionarily distinct from related class I lantibiotics. Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Simulations of a Membrane-Anchored Peptide: Structure, Dynamics, and Influence on Bilayer Properties

PubMed Central

Jensen, Morten Ø.; Mouritsen, Ole G.; Peters, Günther H.

2004-01-01

A three-dimensional structure of a model decapeptide is obtained by performing molecular dynamics simulations of the peptide in explicit water. Interactions between an N-myristoylated form of the folded peptide anchored to dipalmitoylphosphatidylcholine fluid phase lipid membranes are studied at different applied surface tensions by molecular dynamics simulations. The lipid membrane environment influences the conformational space explored by the peptide. The overall secondary structure of the anchored peptide is found to deviate at times from its structure in aqueous solution through reversible conformational transitions. The peptide is, despite the anchor, highly mobile at the membrane surface with the peptide motion along the bilayer normal being integrated into the collective modes of the membrane. Peptide anchoring moderately alters the lateral compressibility of the bilayer by changing the equilibrium area of the membrane. Although membrane anchoring moderately affects the elastic properties of the bilayer, the model peptide studied here exhibits conformational flexibility and our results therefore suggest that peptide acylation is a feasible way to reinforce peptide-membrane interactions whereby, e.g., the lifetime of receptor-ligand interactions can be prolonged. PMID:15189854

14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Operation after maintenance, preventive...

14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Operation after maintenance, preventive...

The Cost and Effectiveness of School-Based Preventive Dental Care.

ERIC Educational Resources Information Center

Klein, Stephen P.; And Others

The National Preventive Dentistry Demonstration Program assessed the cost and effectiveness of various types and combinations of school-based preventive dental care procedures. The program involved 20,052 first, second, and fifth graders from five fluoridated and five non-fluoridated communities. These children were examined at baseline and…

Use of Preventive Services by Men Enrolled in Medicare+Choice Plans

PubMed Central

Morales, Leo S.; Rogowski, Jeannette; Freedman, Vicki A.; Wickstrom, Steven L.; Adams, John L.; Escarce, José J.

2004-01-01

Objectives. We examined the effect of demographic and socioeconomic factors on use of preventive services (prostate-specific antigen testing, colorectal cancer screening, and influenza vaccination) among elderly men enrolled in 2 Medicare+Choice health plans. Methods. Data were derived from administrative files and a survey of 1915 male enrollees. We used multivariate logistic regression to assess the effects of enrollee characteristics on preventive service use. Results. Age, marital status, educational attainment, and household wealth were associated with receipt of one or more preventive services. However, the effects of these variables were substantially attenuated relative to earlier studies of Medicare. Conclusions. Some Medicare HMOs have been successful in attenuating racial and socioeconomic disparities in the use of preventive services by older men. PMID:15117703

Preventive maintenance. 'Problem recognition style' can be used to segment the market and promote healthier lifestyles.

PubMed

Jayanti, R K

1997-01-01

Problem recognition styles--desired state types (DSTs) and actual state types (ASTs)--have an effect on preventive health care decision making. Segmenting the market along these lines can help marketers position products and services to educate and attract people who will not see a doctor unless there is something wrong with them. Both groups expect the same benefits from preventive health care actions, but ASTs fail to act on those expectations. Therefore, marketing strategy touting the benefits of preventive health care might be futile. Educational promotional campaigns aimed at both DSTs and ASTs also are wasteful because DSTs already possess much health knowledge, lead wellness-oriented lifestyles, and practice preventive health behaviors.

Analysis of the (Trimethylsilyl)propionic Acid-β(12-28) Peptide Binding Equilibrium with NMR Spectroscopy.

PubMed

Jayawickrama, D A; Larive, C K

1999-06-01

The binding of a small molecule, (trimethylsilyl)propionic acid (TSP), to a 17-residue peptide, β(12-28), is examined using (1)H NMR spectroscopy. β(12-28) (VHHQKLVFFAEDVGSNK) is a central fragment of the 40-42-residue Alzheimer's-associated Aβ peptide. This peptide has been previously shown to form soluble aggregates in low-pH aqueous solution. The TSP resonance is broadened appreciably in solutions containing relatively high concentrations (∼2 mM) of the peptide. The changes in TSP line width measured by titration of a peptide solution with TSP indicate a 1:1 binding stoichiometry. If the concentrations of both the peptide and TSP are reduced by 1 order of magnitude, the resonances of both species are sharp, suggesting that TSP binds predominately to the aggregated peptide. Nuclear Overhauser effect experiments indicate that the TSP interacts predominately with the side chains of the aliphatic peptide residues Leu(17) and Val(18). Pulsed-field gradient NMR measurements of TSP and peptide diffusion coefficients provide a more quantitative picture of the TSP-peptide binding equilibrium. The measured diffusion coefficients were used to calculate the fractions of the free and bound TSP. These results substantiate the conclusion that the stoichiometry of the TSP-peptide binding equilibrium is essentially 1:1 and further indicate anticooperative behavior in solutions containing an excess of TSP resulting in a dissociation of the peptide aggregates.

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

PubMed Central

Wei, C M; Kim, C H; Miller, V M; Burnett, J C

1993-01-01

This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

A brief, peer-led HIV prevention program for college students in Bangkok, Thailand.

PubMed

Thato, Ratsiri; Penrose, Joyce

2013-02-01

To test the effectiveness of a brief theory-based HIV prevention program led by peers among college students. A quasi-experimental research using a pretest-posttest nonequivalent control group design with 2-mo follow-up. A university in Bangkok. For peer leaders, 70 undergrad students taking health sexuality course were invited to participate in the study. Then, a convenience sample of undergraduate students was recruited through peer leaders, 226 for experimental group and 209 for control group. Information, motivation, behavioral skills, and AIDS/STIs preventive behaviors. The study revealed that a Brief, Peer-Led HIV Prevention Program significantly increased knowledge of preventive behaviors (β = 2.67, P < .000), motivated participants to have a better attitude toward preventive behaviors (β = -5.26, P < .000), better subjective norms (β = -1.54, P < .000), and greater intentions to practice preventive behavior (β = -1.38, P < .000). The program also significantly decreased perceived difficulty of AIDS/STIs preventive behaviors (β = 2.38, P < .000) and increased perceived effectiveness at AIDS/STIs preventive behavior (β = -3.03, P < .000). However, it did not significantly increase AIDS/STIs preventive behaviors (β = 2.13, P > .05). Findings of this study provide initial evidence as to how theoretical variables were operated to effectively increase knowledge, change motivation, and behavioral skills of AIDS/STIs preventive behavior among Thai college students. More research is needed to further test the effectiveness of the program on AIDS/STIs preventive behaviors among college students. Copyright © 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The association between medical students' lifestyles and their attitudes towards preventive counseling in different countries.

PubMed

Yu, Yan; Yang, Yuxuan; Li, Zhifang; Zhou, Bo; Zhao, Yi; Yuan, Shen; Zhang, Ruijuan; Sebranek, Matthew; Veerman, Lennert; Li, Mu; Gong, Enying; Chen, Shu; Ma, Wenjie; Huang, Liping; Cho, KaWing; Leeder, Stephen; Yan, Lijing

2015-11-14

Preventive counselling is an effective approach to reducing the prevalence of non-communicable diseases. Studies have shown that there is a positive association between healthy behaviors of Colombian medical students and favorable attitudes towards preventive counselling. However, there is limited research that explores this relationship in different countries. The current study aimed to determine how the health behaviors of medical students from China, U.S., and Australia, are associated with attitudes towards preventive counseling. Students from five Chinese medical schools, Duke University in the U.S., and the University of Queensland in Australia, completed a 32-item, self-reported online survey. The survey was used to examine the prevalence of healthy behaviors and their association with attitudes towards preventive counseling. The target sample size was 150 students from each grade, or 450 students in total from different medical universities. Logistic regression analyses were used to assess the association between health behaviors and attitudes towards preventive counseling, stratified by grade and adjusted by gender. A positive association was found between healthy behaviors and attitudes towards preventive counseling for all medical students. There are significant differences among medical students' self-reported health behaviors and their attitudes towards preventive counselling from three different countries (P < 0.05). Chinese medical students were more positive in stress control (OR > 1) and more passive in limiting their smoking and alcohol behaviors compared to medical students in Duke University. However, compared to medical students in University of Queensland, five Chinese medical students were more passive in stress control (OR < 1). Based on the finding that healthy behaviors are positively related to favorable attitudes towards preventative counselling, medical students should adopt targeted courses and training in preventive counseling and develop healthy lifestyles.

Child- and state-level characteristics associated with preventive dental care access among U.S. children 5-17 years of age.

PubMed

Lin, Mei; Sappenfield, William; Hernandez, Leticia; Clark, Cheryl; Liu, Jihong; Collins, Jennifer; Carle, Adam C

2012-12-01

The objectives of this study is to identify factors associated with lack of preventive dental care among U.S. children and state-level factors that explain variation in preventive dental care access across states. We performed bivariate analyses and multilevel regression analyses among 68,350 children aged 5-17 years using the 2007 National Survey of Children's Health data and relevant state-level data. Odds ratios (ORs) for child- and state-level variables were calculated to estimate associations with preventive dental care. We calculated interval odds ratios (IOR), median odds ratios (MOR), and intraclass correlation coefficients (ICC) to quantify variation in preventive dental care across states. Lack of preventive dental care was associated with various child-level factors. For state-level factors, a higher odds of lack of preventive dental care was associated with a higher percentage of Medicaid-enrolled children not receiving dental services (OR = 1.30, 95 % confidence interval (CI): 1.15-1.47); higher percentage of children uninsured (OR = 1.48, 95 % CI: 1.29-1.69); lower dentist-to-population ratio (OR = 1.36, 95 % CI: 1.03-1.80); and lower percentage of dentists submitting Medicaid/State Children's Health Insurance Program claims (OR = 1.04, 95 % CI: 1.01-1.06). IORs for the first three state-level factors did not contain one, indicating that these state-level characteristics were important in understanding variation across states. Lack of preventive dental care varied by state (MOR = 1.40). The state-level variation (ICC = 3.66 %) accounted for a small percentage of child- and state-level variation combined. Child- and state-level characteristics were associated with preventive dental care access among U.S. children aged 5-17 years. State-level factors contribute to variation in dental care access across states and need to be considered in state-level planning.

Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

PubMed

Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

2016-10-10

Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Peptide hormones and lipopeptides: from self‐assembly to therapeutic applications

PubMed Central

Hutchinson, J. A.; Burholt, S.

2017-01-01

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self‐assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agents. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28127868

45 CFR 96.45 - Preventive health and health services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Preventive health and health services. 96.45 Section 96.45 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.45 Preventive health and health services...

Preventive Maintenance. FMO: Fundamentals of Machine Operation. Third Edition.

ERIC Educational Resources Information Center

Hathaway, Louis

This text is intended to provide students with basic information on conducting preventive maintenance on agricultural machinery. The following topics are covered in the individual chapters: the importance of preventive maintenance and recommended service intervals; engine intake and exhaust systems (air cleaners, turbochargers, intake and exhaust…

Passive smoking: directions for health education among Malaysian college students.

PubMed

Kurtz, M E; Johnson, S M; Ross-Lee, B

1992-01-01

This study investigated knowledge, attitudes, and preventive efforts of Malaysian college students regarding health risks associated with passive smoking, as well as possible directions for intervention and health education programs. Students responded anonymously to a structured written questionnaire. Statistical analyses were conducted to examine (1) differences in knowledge, attitudes, and preventive efforts between smokers and nonsmokers and between men and women; (2) the relationship between smoking by parents, siblings, and friends, and students' knowledge, attitudes, and preventive efforts; and (3) relationships between knowledge, attitudes, and preventive efforts. Peer groups and siblings had a substantial influence on students' attitudes toward passive smoking and their preventive efforts when exposed to passive smoke. A regression analysis revealed a statistically significant linear dependence of preventive efforts on knowledge and attitudes, with the attitude component playing the dominant role. This research suggests that educational efforts on passive smoking, directed toward young college students in developing countries such as Malaysia, should concentrate heavily on changing attitudes and reducing the effects of peer group and sibling influences.

45 CFR 96.45 - Preventive health and health services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Preventive health and health services. 96.45 Section 96.45 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.45 Preventive health and health services...

Human proinsulin C-peptide from a precursor overexpressed in Pichia pastoris.

PubMed

Huang, Yang-Bin; Li, Jiang; Gao, Xin; Sun, Jiu-Ru; Lu, Yi; Feng, Tao; Fei, Jian; Cui, Da-Fu; Xia, Qi-Chang; Ren, Jun; Zhang, You-Shang

2006-08-01

In this article we report the production of human proinsulin C-peptide with 31 amino acid residues from a precursor overexpressed in Pichia pastoris. A C-peptide precursor expression plasmid containing nine C-peptide genes in tandem was constructed and used to transform P. pastoris. Transformants with a high copy number of the C-peptide precursor gene integrated into the chromosome of P. pastoris were selected. In high-density fermentation in a 300 liter fermentor using a simple culture medium composed mainly of salt and methanol, the C-peptide precursor was overexpressed to a level of 2.28 g per liter. A simple procedure was established to purify the expression product from the culture medium. The purified C-peptide precursor was converted into C-peptide by trypsin and carboxypeptidase B joint digestion. The yield of C-peptide with a purity of 96% was 730 mg per liter of culture. The purified C-peptide was characterized by mass spectrometry, N- and C-terminal amino acid sequencing, and sodium dodecylsulfate-polyacrylamide gel electrophoresis.

Biological assay using T cell response for Cry-consensus peptide designed for the peptide-based immunotherapy of Japanese cedar pollinosis.

PubMed

Kozutsumi, Daisuke; Tsunematsu, Masako; Yamaji, Taketo; Kino, Kohsuke

2007-01-01

Cry-consensus peptide is a linearly linked peptide of T-cell epitopes for the management of Japanese cedar (JC) pollinosis and is expected to become a new drug for immunotherapy. However, the mechanism of T-cell epitopes in allergic diseases is not well understood, and thus, a simple in vitro procedure for evaluation of its biological activity is desired. Peripheral blood mononuclear cells (PBMC) were isolated from 27 JC pollinosis patients and 10 healthy subjects, and cultured in vitro for 4 days in the presence of Cry-consensus peptide and (3)H-thymidine. The relationship between growth stimulation (stimulation index; SI) and antigen-specific IgE levels in serum was also investigated in JC pollinosis patients. Moreover, to confirm the importance of the primary sequence in Cry-consensus peptide, heat-treated Cry-consensus peptide and a mixture of the amino acids of which Cry-consensus peptide is composed, and their (3)H-thymidine uptake was compared with Cry-consensus peptide. Finally, whether Cry-consensus peptide stimulates PBMCs from healthy subjects was investigated. The mean SI of JC patients showed a good correlation with Cry-consensus peptide concentration in the culture medium; however, the SI was independent of the anti-Cry j 1 IgE level. Heat-denatured Cry-consensus peptide retained a PBMC proliferation stimulatory effect comparable to the original Cry-consensus peptide, while the mixture of amino acids constituting Cry-consensus peptide did not stimulate PBMC proliferation. PBMCs from healthy subjects did not respond to Cry-consensus peptide at all. These data indicate that the PBMC response of patients suffering from JC pollinosis to Cry-consensus peptide is specific for the sequence of T cell epitopes thereof and may be useful for the evaluation of the efficacy of Cry-consensus peptide in vivo.

Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

NASA Astrophysics Data System (ADS)

Lin, Wen Jen; Chien, Wei Hsuan

2015-09-01

The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly( d,l-lactide- co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

Cost of Treatment Procedures in the National Preventive Dentistry Demonstration Program.

ERIC Educational Resources Information Center

Foch, Craig B.; And Others

The National Preventive Dentistry Demonstration Program (NPDDP) delivered five different regimens of school based preventive dental care to groups of children in 10 American cities between 1977 and 1981. All clinical techniques employed had previously been demonstrated to be both safe and effective in clinical trials. The purpose of the NPDDP was…

Patient Stratification for Preventive Care in Dentistry

PubMed Central

Giannobile, W.V.; Braun, T.M.; Caplis, A.K.; Doucette-Stamm, L.; Duff, G.W.; Kornman, K.S.

2013-01-01

Prevention reduces tooth loss, but little evidence supports biannual preventive care for all adults. We used risk-based approaches to test tooth loss association with 1 vs. 2 annual preventive visits in high-risk (HiR) and low-risk (LoR) patients. Insurance claims for 16 years for 5,117 adults were evaluated retrospectively for tooth extraction events. Patients were classified as HiR for progressive periodontitis if they had ≥ 1 of the risk factors (RFs) smoking, diabetes, interleukin-1 genotype; or as LoR if no RFs. LoR event rates were 13.8% and 16.4% for 2 or 1 annual preventive visits (absolute risk reduction, 2.6%; 95%CI, 0.5% to 5.8%; p = .092). HiR event rates were 16.9% and 22.1% for 2 and 1 preventive visits (absolute risk reduction, 5.2%; 95%CI, 1.8% to 8.4%; p = .002). Increasing RFs increased events (p < .001). Oral health care costs were not increased by any single RF, regardless of prevention frequency (p > .41), but multiple RFs increased costs vs. no (p < .001) or 1 RF (p = .001). For LoR individuals, the association between preventive dental visits and tooth loss was not significantly different whether the frequency was once or twice annually. A personalized medicine approach combining gene biomarkers with conventional risk factors to stratify populations may be useful in resource allocation for preventive dentistry (ClinicalTrials.gov, NCT01584479). PMID:23752171

The Alzheimer's Amyloid-Degrading Peptidase, Neprilysin: Can We Control It?

PubMed Central

Nalivaeva, N. N.; Belyaev, N. D.; Zhuravin, I. A.; Turner, A. J.

2012-01-01

The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid β-peptide (Aβ) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aβ levels are regulated by a dynamic equilibrium between Aβ release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aβ clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance. PMID:22900228

Superior Antifouling Performance of a Zwitterionic Peptide Compared to an Amphiphilic, Non-Ionic Peptide.

PubMed

Ye, Huijun; Wang, Libing; Huang, Renliang; Su, Rongxin; Liu, Boshi; Qi, Wei; He, Zhimin

2015-10-14

The aim of this study was to explore the influence of amphiphilic and zwitterionic structures on the resistance of protein adsorption to peptide self-assembled monolayers (SAMs) and gain insight into the associated antifouling mechanism. Two kinds of cysteine-terminated heptapeptides were studied. One peptide had alternating hydrophobic and hydrophilic residues with an amphiphilic sequence of CYSYSYS. The other peptide (CRERERE) was zwitterionic. Both peptides were covalently attached onto gold substrates via gold-thiol bond formation. Surface plasmon resonance analysis results showed that both peptide SAMs had ultralow or low protein adsorption amounts of 1.97-11.78 ng/cm2 in the presence of single proteins. The zwitterionic peptide showed relatively higher antifouling ability with single proteins and natural complex protein media. We performed molecular dynamics simulations to understand their respective antifouling behaviors. The results indicated that strong surface hydration of peptide SAMs contributes to fouling resistance by impeding interactions with proteins. Compared to the CYSYSYS peptide, more water molecules were predicted to form hydrogen-bonding interactions with the zwitterionic CRERERE peptide, which is in agreement with the antifouling test results. These findings reveal a clear relation between peptide structures and resistance to protein adsorption, facilitating the development of novel peptide-containing antifouling materials.

[Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

PubMed

Akazawa, S; Harada, A; Futatsuki, K

1984-07-01

It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

Evidence of effectiveness of preventive dental care in reducing dental treatment use and related expenditures.

PubMed

Pourat, Nadereh; Choi, Moonkyung Kate; Chen, Xiao

2018-02-06

Preventive dental health services are intended to reduce the likelihood of development of tooth decay and the need for more intensive treatment overtime. The evidence on the effectiveness of preventive dental care in reducing treatment services and expenditures is lagging for adults, particularly those with lower incomes and chronic conditions. We assessed the impact of preventive dental services on dental treatment service use and expenditures overall and by category of service. We calculated the annual numbers of preventive (periodic diagnostic and prophylactic procedures) and treatment (restorative, surgery, prosthodontic, endodontic, and periodontic) services per beneficiary using Medicaid enrollment and claims data for beneficiaries with three categories of conditions (diabetes, heart disease, and respiratory disease) from 10 largest California counties. We used Cragg hurdle exponential regression models controlling for past service use, demographics, length of enrollment, and county. We found that using preventive services in 2005-2007 was associated with higher likelihood and number of treatment dental services used, but associated with lower treatment expenditures in 2008. The reduction in expenditures was noted only in restorative, prosthodontics, and periodontic services. The findings provide much needed evidence of the contribution of preventive dental care in maintaining oral health of low-income adults with chronic conditions and potential for savings to the Medicaid program. Providing lower cost preventive dental care to the individuals with chronic conditions would achieve better oral health and lower treatment expenditures. © 2018 American Association of Public Health Dentistry.

[Preventive activities in primary health care: identifying the agreement among evidence-based guidelines].

PubMed

Gosalbes Soler, V; Márquez Calderón, S; Maiques Galán, A; Latour Pérez, J; Bernal Delgado, E; Puig Barberá, J; Arranz Lázaro, M

2000-01-01

The purpose of this article is to identify the agreement among evidence-based guidelines about recommendations on preventive activities in low risk adults. For which we identified, from the 1996 US Task Force on Preventive Services Guide those preventives activities classified like A or B (recommendation in favour of provision) and like D or E (recommendation against provision), excepting those D and E recommendations based on descriptives studies or expert opinions. Both preventive activities aimed at pregnant women and children and those which are not applicable to our context were excluded. Selected preventive services were compared with the range of age, sex and periodicity in which agreement with the recommendations of American College of Physicians and Canadian Task Force on Preventive Services existed. We found the following agreements. Screening activities. In favour: screening for hypercholesterolemia, hypertension, breast cancer, colorectal cancer, uterine cervix cancer, rubella, visual and hearing impairment and problem drinking. Against: cancer of prostate, lung, bladder and thyroid, and asymptomatic bacteriuria. Counseling activities. In favour: smoking, motor-vehicles injuries, alcohol consumption, unintended pregnancy. Immunizations and quimioprophylaxis. In favour: Vaccines for influenza, tetanus-diphtheria, hepatitis B and measles-mumps-rubella. Postexposure prophylaxis to hepatitis A, hepatitis B, meningococcal, rabies and tetanus. We see then, that a high degree in agreement among the main guidelines exists; about the preventive activities to perform in Primary Health Services, nevertheless we observed low fulfillment of certain preventive activities in Primary Health Services, different barriers for the accomplishment from these activities were described.

Perceived barriers to and facilitators of the implementation of priority clinical preventive services guidelines.

PubMed

Ayres, Cynthia G; Griffith, Hurdis M

2007-03-01

To obtain feedback from contracted health plan (HP) clinicians responsible for implementing preventive services regarding an established set of priority guidelines identified by a coalition of medical directors and to identify barriers to and facilitators of the implementation of these priority guidelines in clinician practice. Qualitative design using a focus group approach. Three focus group meetings among contracted HP clinicians were conducted in New Jersey in 3 geographic regions (northern, central, and southern New Jersey). Clinicians directly involved in delivering preventive services to pediatric, adult, and geriatric patients participated. Barriers to guideline implementation were identified by the clinicians regarding payment and cost, time, legal issues, inconsistency among HP tools, tracking, a lack of internalization, and the patient-clinician relationship. In addition, facilitators of guideline implementation, including HP support, patient materials, clinician awareness, and tool consistency, were identified. Clinicians' perceived barriers to guideline implementation are in themselves a barrier to the delivery of preventive care services. If clinicians perceive barriers to implementing priority recommendations, they may be unlikely to make the conscious effort to deliver preventive care. There needs to be better dialogue between HPs and contracted clinicians to minimize the perceptions of barriers and to increase clinician awareness of and sensitivity to preventive care for priority implementation. To improve the delivery of preventive services in clinician practice, competing HPs must communicate in a single voice with contracted clinicians in the area of preventive care.

Teacher and Principal Survey Results in the National Preventive Dentistry Demonstration Program.

ERIC Educational Resources Information Center

Klein, Stephen P.; And Others

The National Preventive Dentistry Demonstration Program was conducted to assess the costs and benefits of combinations of school-based preventive dental care procedures. The program involved almost 30,000 elementary school children from 10 sites across the country. Classroom procedures, such as weekly fluoride mouthrinse, were administered or…

29 CFR 2590.715-2713 - Coverage of preventive health services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Coverage of preventive health services. 2590.715-2713... ADMINISTRATION, DEPARTMENT OF LABOR GROUP HEALTH PLANS RULES AND REGULATIONS FOR GROUP HEALTH PLANS Other Requirements § 2590.715-2713 Coverage of preventive health services. (a) Services—(1) In general. Beginning at...

Preventive Law for School Administrators.

ERIC Educational Resources Information Center

Hawkins, Harold L.

This chapter focuses on the need for a revised relationship between schools and the courts through the concept of preventive law. The chapter reviews court cases and presents an overview of conflict resolution models and strategies for reducing litigation. Preventive law assumes that greater use of its strategies affords a lesser need for conflict…

14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Operation after maintenance, preventive...

14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Operation after maintenance, preventive...

78 FR 2996 - Meeting of the Community Preventive Services Task Force (Task Force)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Meeting of the Community Preventive Services Task Force (Task Force) AGENCY: Centers for Disease Control and Prevention... for Disease Control and Prevention (CDC) announces the next meeting of the Community Preventive...

75 FR 32186 - Task Force on Community Preventive Services

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

... by space available. Purpose: The mission of the Task Force is to develop and publish the Guide to... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Task Force on Community Preventive Services Name: Task Force on Community Preventive Services meeting. Times and Dates: 8...

Impact of a Preventive Cardiology Curriculum on Knowledge and Attitudes of First-Year Medical Students.

ERIC Educational Resources Information Center

Veitia, Marie C.; And Others

1993-01-01

A study of 54 first-year Marshall University (West Virginia) medical students found that a preventive cardiology curriculum improved both knowledge of and attitudes about preventive cardiology in general and on all 4 subscales (epidemiological evidence, risk factor characteristics, pathophysiology, primary interventions). (Author/MSE)

Receipt of Preventive Services After Oregon’s Randomized Medicaid Experiment

PubMed Central

Marino, Miguel; Bailey, Steffani R.; Gold, Rachel; Hoopes, Megan J.; O’Malley, Jean P.; Huguet, Nathalie; Heintzman, John; Gallia, Charles; McConnell, K. John; DeVoe, Jennifer E.

2015-01-01

Introduction It is predicted that gaining health insurance via the Affordable Care Act will result in increased rates of preventive health services receipt in the U.S, primarily based on self-reported findings from previous health insurance expansion studies. This study examined the long-term (36-month) impact of Oregon’s 2008 randomized Medicaid expansion (“Oregon Experiment”) on receipt of 12 preventive care services in community health centers using electronic health record data. Methods Demographic data from adult (aged 19–64 years) Oregon Experiment participants were probabilistically matched to electronic health record data from 49 Oregon community health centers within the OCHIN community health information network (N=10,643). Intent-to-treat analyses compared receipt of preventive services over a 36-month (2008–2011) period among those randomly assigned to apply for Medicaid versus not assigned, and instrumental variable analyses estimated the effect of actually gaining Medicaid coverage on preventive services receipt (data collected in 2012–2014; analysis performed in 2014–2015). Results Intent-to-treat analyses revealed statistically significant differences between patients randomly assigned to apply for Medicaid (versus not assigned) for eight of 12 assessed preventive services. In intent-to-treat[MM1] analyses, Medicaid coverage significantly increased the odds of receipt of most preventive services (ORs ranging from 1.04 [95% CI=1.02, 1.06] for smoking assessment to 1.27 [95% CI=1.02, 1.57] for mammography). Conclusions Rates of preventive services receipt will likely increase as community health center patients gain insurance through Affordable Care Act expansions. Continued effort is needed to increase health insurance coverage in an effort to decrease health disparities in vulnerable populations. PMID:26497264

WHY DO YOU NEED TO USE A CARIES RISK ASSESSMENT PROTOCOL TO PROVIDE AN EFFECTIVE CARIES PREVENTIVE REGIME?

PubMed

Afuakwah, Charles; Welbury, Richard

2015-11-01

Clinical guidelines recommend an individual is given a caries risk status based on analysis of defined clinical and social criteria before implementing a tailored preventive plan. Improve documentation of caries risk assessment (CRA) in a general dental practice setting, using a systems-based approach to quality improvement methods. Investigate the impact of quality improvement efforts on subsequent design and delivery of preventive care. Identify barriers to delivery of CRA and provision of preventive care. Data for patients aged 0-16 years was collected over two cycles using standard audit methodology. The first cycle was a retrospective analysis (n = 400) using random sampling. The second cycle a prospective analysis (n = 513) using consecutive sampling over a 15-week period. Five staff meetings with feedback occurred between cycles. In cycle one, no specific CRA system was identified. CRA status was not stated widely, risk factors were not analysed and there was variation with respect to the prescription and delivery of preventive strategies. These discrepancies were demonstrable for all four participating dentists and at all ages. In cycle two, 100% recorded CRA. All risk factors were analysed and individual caries risk was correctly annotated. There was 100% compliance with the protocol for preventive plans. The use of CRA improved documentation of caries risk status. This has improved subsequent prescription of age specific evidence-based preventive care appropriate to the risk status of that individual. Barriers were identified to the delivery of CRA and the provision of comprehensive preventive care by the dentists and other healthcare professionals.

A Preventive Health Care and Safety Curriculum for an Industry.

ERIC Educational Resources Information Center

Mooney, Kathleen R.

The preventive health care curriculum described in this paper was designed for the employees of Autotech Automatic Test Equipment Division in Los Angeles, California. First, the paper describes Autotech, and its health insurance and on-site health facilities. Next, a rationale is provided for offering employees classes on preventive medicine and…

Press Responsibility for Health News: Beyond Precision and Toward Prevention.

ERIC Educational Resources Information Center

Burd, Gene

In addition to investigative and interpretative reporting, journalists might adopt a new approach to the news--preventive journalism. Preventive journalism would concentrate on news and information that could be used to prevent crises and conditions upon which the mass media thrive. In one area, public health, preventive journalism could be used…

Parenting after Divorce: Evaluation of Preventive Programs for Divorcing Families.

ERIC Educational Resources Information Center

Warren, Nancy J.; And Others

Preventive educational programs are potentially useful in reducing the effects of divorce on children and families. Parenting After Divorce is an ongoing study designed to evaluate preventive programs. Divorcing families with children aged 7-12 are identified from court records and contacted to participate. Families are randomly assigned to one of…

Few Americans Receive All High-Priority, Appropriate Clinical Preventive Services.

PubMed

Borsky, Amanda; Zhan, Chunliu; Miller, Therese; Ngo-Metzger, Quyen; Bierman, Arlene S; Meyers, David

2018-06-01

As of 2015, only 8 percent of US adults ages thirty-five and older had received all of the high-priority, appropriate clinical preventive services recommended for them. Nearly 5 percent of adults did not receive any such services. Further delivery system-level efforts are needed to increase the use of preventive services.

Managed care, consumerism, preventive medicine: does a causal connection exist?

PubMed

Rizzo, John A; Xie, Yang

2006-07-01

Managed care plans, and HMOs in particular, have long touted that their emphasis is on preventive care, to avoid expensive illness later in life. However, few articles in the contemporary literature adequately address this claim. The available evidence seems to support that HMOs do, in fact, provide greater access to preventive services, but the limitations of this research are substantial. This article discusses the scientific evidence on the relationships between managed care arrangements and the implications for preventive care in the current era, emphasizing consumer choices and less-restrictive plan structures.

Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study

PubMed Central

Caru, Maxime; Kern, Laurence; Bousquet, Marc; Curnier, Daniel

2018-01-01

AIM To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs). METHODS A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors (i.e., abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking). RESULTS It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression. CONCLUSION This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce a protection for some risk factors, despite having a CVD. PMID:29707165

Higher Education and Health Investments: Does More Schooling Affect Preventive Health Care Use?◆

PubMed Central

Fletcher, Jason M.; Frisvold, David E.

2012-01-01

While it is well-known that individuals with higher levels of education consume more preventive medical care, there are several potential explanations for this stylized fact. These explanations include causal and non-causal mechanisms, and distinguishing among explanations is relevant for accessing the importance of educational spillovers on lifetime health outcomes as well as uncovering the determinants of preventive care. In this paper, we use regression analysis, sibling fixed effects, and matching estimators to examine the impact of education on preventive care. In particular, we use a cohort of 10,000 Wisconsin high school graduates that has been followed for nearly 50 years and find evidence that attending college is associated with an increase in the likelihood of using several types of preventive care by approximately five to fifteen percent for college attendees in the early 1960s. We also find that greater education may influence preventive care partly through occupational channels and access to care. These findings suggest that increases in education have the potential to spillover on long-term health choices. PMID:22368727

CART PEPTIDE IN THE NUCLEUS ACCUMBENS REGULATES PSYCHOSTIMULANTS: CORRELATIONS BETWEEN PSYCHOSTIMULANT AND CART PEPTIDE EFFECTS

PubMed Central

JOB, MARTIN O.; KUHAR, MICHAEL J.

2017-01-01

In this study, we reexamined the effect of CART peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis. PMID:28215744

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly

NASA Astrophysics Data System (ADS)

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-01

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation. Electronic supplementary information (ESI) available: Additional figures (Tables S1-S3 and Fig. S1-S6). See DOI: 10.1039/c6nr01072e

CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

NASA Astrophysics Data System (ADS)

Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

2016-03-01

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06335c

A doctor of the highest caliber treats an illness before it happens.

PubMed

Zhan, Mei

2009-01-01

"A doctor of the highest caliber treats an illness before it happens," a seemingly antiquated doctrine in traditional Chinese medicine, is enjoying surging popularity among practitioners in urban China and the United States today. In this essay, I examine how the meanings and contours of traditional Chinese medicine have shifted in recent decades as it is molded into a "preventive medicine" through translocal encounters. From the 1960s and the early 1970s, the emphasis China's socialist health care placed on preventive health among the rural poor shaped the practice of Chinese herbal medicine and especially acupuncture. This version of preventive medicine was also exported to the Third World, which China strove to champion. Since the end of the Cold War and especially during the 1990s, as China strives to "get on track with the world" (specifically, affluent nation-states, especially in North America and the European Union), traditional Chinese medicine has been rapidly commodified and reinvented as a new kind of preventive medicine tailored for cosmopolitan, middle-class lifestyles. The emergence of this radically new preventive medicine resuscitates certain stories of antiquity and continuity, emphasizing that traditional Chinese medicine has always been "preventive" while obliterating recent memories of the proletariat world and its preventive medicine.

Patient stratification for preventive care in dentistry.

PubMed

Giannobile, W V; Braun, T M; Caplis, A K; Doucette-Stamm, L; Duff, G W; Kornman, K S

2013-08-01

Prevention reduces tooth loss, but little evidence supports biannual preventive care for all adults. We used risk-based approaches to test tooth loss association with 1 vs. 2 annual preventive visits in high-risk (HiR) and low-risk (LoR) patients. Insurance claims for 16 years for 5,117 adults were evaluated retrospectively for tooth extraction events. Patients were classified as HiR for progressive periodontitis if they had ≥ 1 of the risk factors (RFs) smoking, diabetes, interleukin-1 genotype; or as LoR if no RFs. LoR event rates were 13.8% and 16.4% for 2 or 1 annual preventive visits (absolute risk reduction, 2.6%; 95%CI, 0.5% to 5.8%; p = .092). HiR event rates were 16.9% and 22.1% for 2 and 1 preventive visits (absolute risk reduction, 5.2%; 95%CI, 1.8% to 8.4%; p = .002). Increasing RFs increased events (p < .001). Oral health care costs were not increased by any single RF, regardless of prevention frequency (p > .41), but multiple RFs increased costs vs. no (p < .001) or 1 RF (p = .001). For LoR individuals, the association between preventive dental visits and tooth loss was not significantly different whether the frequency was once or twice annually. A personalized medicine approach combining gene biomarkers with conventional risk factors to stratify populations may be useful in resource allocation for preventive dentistry (ClinicalTrials.gov, NCT01584479).

Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

PubMed

Desai, Meghna; Gutman, Julie; L'lanziva, Anne; Otieno, Kephas; Juma, Elizabeth; Kariuki, Simon; Ouma, Peter; Were, Vincent; Laserson, Kayla; Katana, Abraham; Williamson, John; ter Kuile, Feiko O

2015-12-19

Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine. We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941. Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group. At current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine. The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Use of Preventive Services by the Elderly. Paper 2.

ERIC Educational Resources Information Center

Gluck, Michael E.; And Others

This study examined the implications of potential Medicare coverage for the use of preventive services by analyzing current use and and the determinants of that use by the elderly. Trends in available data suggested that the use of preventive services varies widely according to the type of service and that the rates of use of specific services…

Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

PubMed

Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

2017-08-01

The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

Migraine preventive therapy: selection of appropriate patients and general principles of management.

PubMed

D'Amico, Domenico; Lanteri-Minet, Michel

2006-08-01

The goal of this review is to communicate the rationale and the possible benefits of migraine preventive treatments to clinicians and patients, and to address the many problematic issues created by missed diagnosis or misdiagnoses and inadequate migraine management. Successful implementation of migraine preventive treatment requires appropriate patient selection based on several factors, including the frequency of migraine attacks (> or =2-3 attacks/month), the level of disability incurred and the frequency of acute medication usage. Unfortunately, several epidemiologic surveys indicate that preventive therapies are significantly underutilized, which supports the need for greater dialog concerning migraine prevention between consumers and physicians. Effective migraine preventive therapy should reduce the frequency, duration, and severity of migraine, and also improve function, reduce disability, and possibly reduce the risk of worsening the headache syndrome, through acute medication overuse.

Protective effect of C-peptide on experimentally induced diabetic nephropathy and the possible link between C-peptide and nitric oxide.

PubMed

Elbassuoni, Eman A; Aziz, Neven M; El-Tahawy, Nashwa F

2018-06-01

Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by N G -nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.

Strategies for generating peptide radical cations via ion/ion reactions.

PubMed

Gilbert, Joshua D; Fisher, Christine M; Bu, Jiexun; Prentice, Boone M; Redwine, James G; McLuckey, Scott A

2015-02-01

Several approaches for the generation of peptide radical cations using ion/ion reactions coupled with either collision induced dissociation (CID) or ultraviolet photo dissociation (UVPD) are described here. Ion/ion reactions are used to generate electrostatic or covalent complexes comprised of a peptide and a radical reagent. The radical site of the reagent can be generated multiple ways. Reagents containing a carbon-iodine (C-I) bond are subjected to UVPD with 266-nm photons, which selectively cleaves the C-I bond homolytically. Alternatively, reagents containing azo functionalities are collisionally activated to yield radical sites on either side of the azo group. Both of these methods generate an initial radical site on the reagent, which then abstracts a hydrogen from the peptide while the peptide and reagent are held together by either electrostatic interactions or a covalent linkage. These methods are demonstrated via ion/ion reactions between the model peptide RARARAA (doubly protonated) and various distonic anionic radical reagents. The radical site abstracts a hydrogen atom from the peptide, while the charge site abstracts a proton. The net result is the conversion of a doubly protonated peptide to a peptide radical cation. The peptide radical cations have been fragmented via CID and the resulting product ion mass spectra are compared to the control CID spectrum of the singly protonated, even-electron species. This work is then extended to bradykinin, a more broadly studied peptide, for comparison with other radical peptide generation methods. The work presented here provides novel methods for generating peptide radical cations in the gas phase through ion/ion reaction complexes that do not require modification of the peptide in solution or generation of non-covalent complexes in the electrospray process. Copyright © 2015 John Wiley & Sons, Ltd.

Ligand-regulated peptide aptamers.

PubMed

Miller, Russell A

2009-01-01

The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

Peptide reranking with protein-peptide correspondence and precursor peak intensity information.

PubMed

Yang, Chao; He, Zengyou; Yang, Can; Yu, Weichuan

2012-01-01

Searching tandem mass spectra against a protein database has been a mainstream method for peptide identification. Improving peptide identification results by ranking true Peptide-Spectrum Matches (PSMs) over their false counterparts leads to the development of various reranking algorithms. In peptide reranking, discriminative information is essential to distinguish true PSMs from false PSMs. Generally, most peptide reranking methods obtain discriminative information directly from database search scores or by training machine learning models. Information in the protein database and MS1 spectra (i.e., single stage MS spectra) is ignored. In this paper, we propose to use information in the protein database and MS1 spectra to rerank peptide identification results. To quantitatively analyze their effects to peptide reranking results, three peptide reranking methods are proposed: PPMRanker, PPIRanker, and MIRanker. PPMRanker only uses Protein-Peptide Map (PPM) information from the protein database, PPIRanker only uses Precursor Peak Intensity (PPI) information, and MIRanker employs both PPM information and PPI information. According to our experiments on a standard protein mixture data set, a human data set and a mouse data set, PPMRanker and MIRanker achieve better peptide reranking results than PetideProphet, PeptideProphet+NSP (number of sibling peptides) and a score regularization method SRPI. The source codes of PPMRanker, PPIRanker, and MIRanker, and all supplementary documents are available at our website: http://bioinformatics.ust.hk/pepreranking/. Alternatively, these documents can also be downloaded from: http://sourceforge.net/projects/pepreranking/.

Novel electrochemical biosensor based on cationic peptide modified hemin/G-quadruples enhanced peroxidase-like activity.

PubMed

Yu, Qian; Wu, Yongmei; Liu, Zi; Lei, Sheng; Li, Gaiping; Ye, Baoxian

2018-06-01

This work designed an artificial substrate peptide to synthesize peptide-hemin/G-quadruplex (peptide-DNAzyme) conjugates. In addition to enhancing catalytic activity of hemin/G-quadruplex, the peptide could also be induced and cleaved by prostate specific antigen (PSA). It was the first report on peptide-DNAzyme conjugates in application of the peptide biosensor. The polyethyleneimine-reduced graphene oxide@hollow platinum nanotubes (PEI-rGO@PtNTs) nanocomposites were cast on the glassy carbon electrode in order to form the interface of biocompatibility and huge surface area for bioprobes immobilization. In absence of PSA, the peptide-DNAzyme conjugates retained intact on the surface of the electrode to produce a strong response signal. But in presence of PSA, the peptide-DNAzyme conjugates were destroyed to release electron mediators, resulting in dramatical decrease of the electrochemicl signal. Therefore, the method had high sensitivity and super selectivity with the limit of detection calculated as 2.0 fg/mL. Furthermore, the strategy would be promising to apply for other proteases by transforming the synthetic peptide module of target. Copyright © 2018 Elsevier B.V. All rights reserved.

[Practice and experience in early clinical education of dental students in preventive dentistry].

PubMed

Tao, Dan-ying; Shu, Chen-bin; Pan, Ying; Feng, Xi-ping

2013-02-01

To help dental students acquaint the medical environment, doctor-patient communication and relationship, early clinic education was arranged in our college of stomatology. The interesting topics were chosen to enhance the learning enthusiasm of the students in the teaching practice of preventive dentistry. Students were encouraged to practice the skill of doctor-patient communication. To obtain the satisfactory teaching effect and aim, it was important to pay attention to the aspects in the groups and clinical practice. Early clinic education in preventive dentistry help the students understand the specialty of preventive dentistry.

Tools for the Job: The POMR in Preventive Medicine

PubMed Central

Dixon-Warren, Brian

1977-01-01

There is increasing interest in practical preventive care in the family doctor's office. The concepts underlying the problem oriented medical record (POMR) include the principles of preventive medicine, and it is thus an excellent vehicle for implementation. However, the classical POMR model must be modified to the context of family practice, and priorities defined by each practice. This article describes how elements of the POMR can be used in planning preventive care. An appraisal of one's own practice is a valuable part of the planning; follow up can assess patient compliance and the effectiveness of the program. PMID:21304858

The Cost and Effectiveness of School-Based Preventive Dental Care.

ERIC Educational Resources Information Center

Klein, Stephen P.; And Others

1985-01-01

The cost and effectiveness of various types and combinations of school-based preventive dental care procedures were assessed in the National Preventive Dentistry Demonstration Program, a four-year study involving more than 20,000 students, from ten schools nationwide. Communal water fluoridation was reaffirmed as the most cost-effective means of…

Detection of trans–cis flips and peptide-plane flips in protein structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Touw, Wouter G., E-mail: wouter.touw@radboudumc.nl; Joosten, Robbie P.; Vriend, Gert, E-mail: wouter.touw@radboudumc.nl

A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely availablemore » and the method is available from a web server, a web-service interface and through WHAT-CHECK.« less

Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum

PubMed Central

Lee, Sungwook; Park, Boyoun; Kang, Kwonyoon

2009-01-01

In contrast to the fairly well-characterized mechanism of assembly of MHC class I-peptide complexes, the disassembly mechanism by which peptide-loaded MHC class I molecules are released from the peptide-loading complex and exit the endoplasmic reticulum (ER) is poorly understood. Optimal peptide binding by MHC class I molecules is assumed to be sufficient for triggering exit of peptide-filled MHC class I molecules from the ER. We now show that protein disulfide isomerase (PDI) controls MHC class I disassembly by regulating dissociation of the tapasin-ERp57 disulfide conjugate. PDI acts as a peptide-dependent molecular switch; in the peptide-bound state, it binds to tapasin and ERp57 and induces dissociation of the tapasin-ERp57 conjugate. In the peptide-free state, PDI is incompetent to bind to tapasin or ERp57 and fails to dissociate the tapasin-ERp57 conjugates, resulting in ER retention of MHC class I molecules. Thus, our results indicate that even after optimal peptide loading, MHC class I disassembly does not occur by default but, rather, is a regulated process involving PDI-mediated interactions within the peptide-loading complex. PMID:19477919

General practitioners' use of caries-preventive agents in adult patients versus pediatric patients: findings from the dental practice-based research network.

PubMed

Riley, Joseph L; Gordan, Valeria V; Rindal, D Brad; Fellows, Jeffrey L; Williams, O Dale; Ritchie, Lloyd K; Gilbert, Gregg H

2010-06-01

In this study, the authors tested the frequency of dentists' recommendations for and use of caries-preventive agents for children as compared with adults. The authors surveyed 467 general dentists in the Dental Practice-Based Research Network who practice within the United States and treat both pediatric and adult patients. They asked dentists to identify the percentage of their patients for whom they had administered or recommended dental sealants, in-office and at-home fluoride, chlorhexidine rinse and xylitol gum. Dentists were less likely to provide adult patients than pediatric patients with in-office caries-preventive agents. However, the rate at which they recommended at-home preventive regimens for the two groups of patients was similar. Dentists with a conservative approach to caries treatment were the most likely to use and recommend the use of caries-preventive agents at similar rates in adults as in children. In addition, dentists in practices with a greater number of patients who had dental insurance were significantly more likely to provide in-office fluoride or sealants to adult patients than to pediatric patients. General dentists use in-office caries-preventive agents more commonly with their pediatric patients than with their adult patients. General dentists should consider providing additional in-office caries-preventive agents for their adult patients who are at increased risk of experiencing dental caries.

Effects of analogues of hydra peptide morphogen on DNA synthesis in the myocardium of newborn albino rats.

PubMed

Sazonova, E N; Yakovenko, I G; Kryzhanovskaya, S Yu; Budylev, A A; Timoshin, S S

2012-01-01

DNA-synthetic activity of myocardial cells was studied by (3)H-thymidine autoradiography in newborn albino rats after intraperitoneal injection of hydra peptide morphogen and its analogues. Administration of hydra peptide morphogen stimulated proliferative activity in the myocardium. Short analogues of hydra peptide morphogen, 6C and 3C peptides, produced a similar effect. Administration of arginine-containing analogue of hydra peptide morphogen significantly reduced the number of DNA-synthesizing nuclei in the ventricular myocardium of newborn albino rats. The role of the structure of the peptide molecule in the realization of the morphogenetic effects of hydra peptide morphogen is discussed.

Large-Scale Interaction Profiling of Protein Domains Through Proteomic Peptide-Phage Display Using Custom Peptidomes.

PubMed

Seo, Moon-Hyeong; Nim, Satra; Jeon, Jouhyun; Kim, Philip M

2017-01-01

Protein-protein interactions are essential to cellular functions and signaling pathways. We recently combined bioinformatics and custom oligonucleotide arrays to construct custom-made peptide-phage libraries for screening peptide-protein interactions, an approach we call proteomic peptide-phage display (ProP-PD). In this chapter, we describe protocols for phage display for the identification of natural peptide binders for a given protein. We finally describe deep sequencing for the analysis of the proteomic peptide-phage display.

78 FR 48636 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110... Manufacturing Practice and Hazard Analysis and Risk- Based Preventive Controls for Human Food; Extension of...-Based Preventive Controls for Human Food,'' that appeared in the Federal Register of January 16, 2013...

A Cost Analysis Plan for the National Preventive Dentistry Demonstration Program.

ERIC Educational Resources Information Center

Foch, Craig B.

The National Preventive Dentistry Demonstration Project (NPDDP) delivers school-based preventive dental care to approximately 14,000 children in ten United States cities. The program, begun in 1976, is to be conducted over a six and one-half year period. The costing definitions and allocation rules to be used in the project are the principal…

Pathways Explaining the Reduction of Adult Criminal Behaviour by a Randomized Preventive Intervention for Disruptive Kindergarten Children

ERIC Educational Resources Information Center

Vitaro, Frank; Barker, Edward D.; Brendgen, Mara; Tremblay, Richard E.

2012-01-01

Objective: This study aimed to identify the pathways through which a preventive intervention targeting young low-SES disruptive boys could result in lower crime involvement during adulthood. Method: The preventive intervention was implemented when the children were between 7 and 9 years and included three components (i.e. social skills, parental…

Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

Cancer.gov

Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their

Health Belief Factors and Dispositional Optimism as Predictors of STD and HIV Preventive Behavior

ERIC Educational Resources Information Center

Zak-Place, Jennifer; Stern, Marilyn

2004-01-01

Identifying factors predictive of youth's engaging in preventive behaviors related to sexually transmitted diseases (STDs) and HIV remains a prominent public health concern. The utility of the Health Belief Model (HBM) continues to be suggested in identifying preventive behaviors. This study sought to examine the full HBM, including self-efficacy,…

[On the economical issues of prevention].

PubMed

Zakorkina, N A

2007-01-01

It is revealed that the implementation level of the preventive activities impact the economic losses related to morbidity. One ruble invested into the preventive actions reduces the economical losses up to 392 rubles. Thus, the methodological approach to the evaluation of the preventive measures targeted to the morbidity of the adolescents are to be based on the economical profitability.

A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly.

PubMed

Li, Yong; Li, Wang; He, Kai-Yu; Li, Pei; Huang, Yan; Nie, Zhou; Yao, Shou-Zhuo

2016-04-28

In natural biological systems, proteins exploit various functional peptide motifs to exert target response and activity switch, providing a functional and logic basis for complex cellular activities. Building biomimetic peptide-based bio-logic systems is highly intriguing but remains relatively unexplored due to limited logic recognition elements and complex signal outputs. In this proof-of-principle work, we attempted to address these problems by utilizing multi-functional peptide probes and the peptide-mediated nanoparticle assembly system. Here, the rationally designed peptide probes function as the dual-target responsive element specifically responsive to metal ions and enzymes as well as the mediator regulating the assembly of gold nanoparticles (AuNPs). Taking advantage of Zn2+ ions and chymotrypsin as the model inputs of metal ions and enzymes, respectively, we constructed the peptide logic system computed by the multi-functional peptide probes and outputted by the readable colour change of AuNPs. In this way, the representative binary basic logic gates (AND, OR, INHIBIT, NAND, IMPLICATION) have been achieved by delicately coding the peptide sequence, demonstrating the versatility of our logic system. Additionally, we demonstrated that the three-input combinational logic gate (INHIBIT-OR) could also be successfully integrated and applied as a multi-tasking biosensor for colorimetric detection of dual targets. This nanoparticle-based peptide logic system presents a valid strategy to illustrate peptide information processing and provides a practical platform for executing peptide computing or peptide-related multiplexing sensing, implying that the controllable nanomaterial assembly is a promising and potent methodology for the advancement of biomimetic bio-logic computation.

Investigating the Counteracting Effect of Trehalose on Urea-Induced Protein Denaturation Using Molecular Dynamics Simulation.

PubMed

Paul, Subrata; Paul, Sandip

2015-08-27

Molecular dynamics simulations are performed to investigate the counteracting effect of trehalose against urea-induced denaturation of S-peptide analogue. The calculations of Cα root-mean-square deviation, radius of gyration, and solvent-accessible surface area reveal that the peptide loses its native structure in aqueous 8 M urea solution at 310 K and that this unfolding process is prevented in the presence of trehalose. Interestingly, the native structure of the peptide in ternary mixed urea/trehalose solution is similar to that in the pure water system. The estimation of helical percentage of peptide residues as well as peptide-peptide intramolecular hydrogen bond number for different systems also support the above findings. Decomposition of protein-urea total interaction energy into electrostatic and van der Waals contributions shows that the presence of trehalose molecules makes the latter contribution unfavorable without affecting the former. These observations are further supported by preferential interaction calculations. Furthermore, the hydrogen bond analyses show that with the addition of urea molecules to the peptide-water system, the formation of peptide-urea hydrogen bonds takes place at the expense of peptide-water hydrogen bonds. In ternary mixed osmolytes system, because of formation of a considerable amount of peptide-trehalose hydrogen bonds, some urea molecules are excluded from the peptide surface. This essentially reduces the interaction between peptide and urea molecules, and because of this, we notice a reduction in the number of peptide-urea hydrogen bonds. Interestingly, the total number of peptide-solution species hydrogen bonds in the pure water system is very similar to that for the mixed osmolytes system. From these observations we infer that in the ternary solution, peptide-solution species hydrogen bonds are shared by water, urea, and trehalose molecules. The presence of trehalose in the mixed osmolyte system causes a significant reduction in the translational dynamics of water molecules. We discuss these results to understand the molecular explanation of trehalose's counteracting ability on urea-induced protein denaturation.

Evaluation of dermal wound healing activity of synthetic peptide SVVYGLR.

PubMed

Uchinaka, Ayako; Kawaguchi, Naomasa; Ban, Tsuyoshi; Hamada, Yoshinosuke; Mori, Seiji; Maeno, Yoshitaka; Sawa, Yoshiki; Nagata, Kohzo; Yamamoto, Hirofumi

2017-09-23

SVVYGLR peptide (SV peptide) is a 7-amino-acid sequence with angiogenic properties that is derived from osteopontin in the extracellular matrix and promotes differentiation of fibroblasts to myofibroblast-like cells and the production of collagen type Ⅲ by cardiac fibroblasts. However, the effects of SV peptide on dermal cells and tissue are unknown. In this study, we evaluated the effects of this peptide in a rat model of dermal wound healing. The synthetic SV peptide was added to dermal fibroblasts or keratinocytes, and their cellular motility was evaluated. In an in vivo wound healing exeriment, male rats aged 8 weeks were randomly assigned to the SV peptide treatment, non-treated control, or phosphate-buffered saline (PBS) groups. Wound healing was assessed by its repair rate and histological features. Scratch assay and cell migration assays using the Chemotaxicell method showed that SV peptide significantly promoted the cell migration in both fibroblasts and keratinocytes. In contrast the proliferation potency of these cells was not affected by SV peptide. In the rat model, wound healing progressed faster in the SV peptide-treated group than in the control and PBS groups. The histopathological analyses showed that the SV peptide treatment stimulated the migration of fibroblasts to the wound area and increased the number of myofibroblasts. Immunohistochemical staining showed a marked increase of von Willebland factor-positive neomicrovessels in the SV peptide-treated group. In conclusion, SV peptide has a beneficial function to promote wound healing by stimulating granulation via stimulating angiogenesis, cell migration, and the myofibroblastic differentiation of fibroblasts. Copyright © 2017 Elsevier Inc. All rights reserved.

A Randomized Trial of the Effect of Centralized Reminder/Recall on Immunizations and Preventive Care Visits for Adolescents

PubMed Central

Szilagyi, Peter G.; Albertin, Christina; Humiston, Sharon G.; Rand, Cynthia M.; Schaffer, Stanley; Brill, Howard; Stankaitis, Joseph; Yo, Byung-Kwang; Blumkin, Aaron; Stokley, Shannon

2015-01-01

Objective To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. Methods We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11–17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4, 115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. Results Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P < .01 vs control), 17% for telephone (P < .05), and 13% for control groups. The proportion of adolescents with a preventive visit (within 12 months) was: mailed (65%; P <.01), telephone (63%; P <.05), and controls (59%). The number needed to treat for an additional fully vaccinated adolescent was 14 for mailed and 25 for telephone reminders; for an additional preventive visit, it was 17 and 29. The intervention cost $18.78 (mailed) or $16.68 (phone) per adolescent per year to deliver. The cost per additional adolescent fully vaccinated was $463.99 for mailed and $714.98 for telephone; the cost per additional adolescent receiving a preventive visit was $324.75 and $487.03. Conclusions Managed care-based mail or telephone reminder/recall improved adolescent immunizations and preventive visits, with modest costs and modest impact. PMID:23510607

Examining public knowledge and preferences for adult preventive services coverage.

PubMed

Williams, Jessica A R; Ortiz, Selena E

2017-01-01

To examine (1) what individuals know about the existing adult preventive service coverage provisions of the Affordable Care Act (ACA), and (2) which preventive services individuals think should be covered without cost sharing. An online panel from Survey Monkey was used to obtain a sample of 2,990 adults age 18 and older in March 2015, analyzed 2015-2017. A 17-item survey instrument was designed and used to evaluate respondents' knowledge of the adult preventive services provision of the ACA. Additionally, we asked whether various preventive services should be covered. The data include age, sex, race/ethnicity, and educational attainment as well as measures of political ideology, previous insurance status, the number of chronic conditions, and usual source of care. Respondents correctly answered 38.6% of the questions about existing coverage under the ACA, while on average respondents thought 12.1 of 15 preventive services should be covered (SD 3.5). Respondents were more knowledgeable about coverage for routine screenings, such as blood pressure (63.4% correct) than potentially stigmatizing screenings, such as for alcohol misuse (28.8% correct). Blood pressure screening received the highest support of coverage (89.8%) while coverage of gym memberships received the lowest support (59.4%). Individuals with conservative ideologies thought fewer services on average should be covered, but the difference was small-around one service less than those with liberal ideologies. Overwhelmingly, individuals think that most preventive services should be covered without cost sharing. Despite several years of coverage for preventive services, there is still confusion and lack of knowledge about which services are covered.

Insulin C-peptide test

MedlinePlus

C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

CD28 homodimer interface mimetic peptide acts as a preventive and therapeutic agent in models of severe bacterial sepsis and gram-negative bacterial peritonitis.

PubMed

Ramachandran, Girish; Kaempfer, Raymond; Chung, Chun-Shiang; Shirvan, Anat; Chahin, Abdullah B; Palardy, John E; Parejo, Nicolas A; Chen, Yaping; Whitford, Melissa; Arad, Gila; Hillman, Dalia; Shemesh, Ronen; Blackwelder, William; Ayala, Alfred; Cross, Alan S; Opal, Steven M

2015-03-15

Severe gram-negative bacterial infections and sepsis are major causes of morbidity and mortality. Dysregulated, excessive proinflammatory cytokine expression contributes to the pathogenesis of sepsis. A CD28 mimetic peptide (AB103; previously known as p2TA) that attenuates CD28 signaling and T-helper type 1 cytokine responses was tested for its ability to increase survival in models of polymicrobial infection and gram-negative sepsis. Mice received AB103, followed by an injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS); underwent induction E. coli 018:K1 peritonitis induction, followed by treatment with AB103; or underwent cecal ligation and puncture (CLP), followed by treatment with AB103. The effects of AB103 on factors associated with and the lethality of challenge infections were analyzed. AB103 strongly attenuated induction of tumor necrosis factor α and interleukin 6 (IL-6) by LPS in human peripheral blood mononuclear cells. Receipt of AB103 following intraperitoneal injection of LPS resulted in survival among 73% of CD1 mice (11 of 15), compared with 20% of controls (3 of 15). Suboptimal doses of antibiotic alone protected 20% of mice (1 of 5) from E. coli peritonitis, whereas 100% (15 of 15) survived when AB103 was added 4 hours following infection. Survival among mice treated with AB103 12 hours after CLP was 100% (8 of 8), compared with 17% among untreated mice (1 of 6). In addition, receipt of AB103 12 hours after CLP attenuated inflammatory cytokine responses and neutrophil influx into tissues and promoted bacterial clearance. Receipt of AB103 24 hours after CLP still protected 63% of mice (5 of 8). Single-dose AB103 reduces mortality in experimental models of polymicrobial and gram-negative bacterial infection and sepsis, warranting further studies of this agent in clinical trials. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Impact of a Patient Incentive Program on Receipt of Preventive Care

PubMed Central

Mehrotra, Ateev; An, Ruopeng; Patel, Deepak N.; Sturm, Roland

2014-01-01

Objectives Patient financial incentives are being promoted as a mechanism to increase receipt of preventive care, encourage healthy behavior, and improve chronic disease management. However, few empirical evaluations have assessed such incentive programs. Study Design In South Africa, a private health plan has introduced a voluntary incentive program which costs enrollees approximately $20 per month. In the program, enrollees earn points when they receive preventive care. These points translate into discounts on retail goods such as airline tickets, movie tickets, or cell phones. Methods We compared the change in 8 preventive care services over the years 2005–11 between those who entered the incentive program and those that did not. We used multivariate regression models with individual random effects to try to address selection bias. Results Of the 4,186,047 unique individuals enrolled in the health plan, 65.5% (2,742,268) voluntarily enrolled in the incentive program. Joining the incentive program was associated with a statistically higher odds of receiving all 8 preventive care services. The odds ratio and estimated percentage point increase for receipt of cholesterol testing was 2.70 (8.9%), glucose testing 1.51 (4.7%), glaucoma screening 1.34 (3.9%), dental exam 1.64 (6.3%), HIV test 3.47 (2.6%), prostate specific antigen testing 1.39 (5.6%), Papanicolaou screening 2.17 (7.0%), and mammogram 1.90 (3.1%) (p<0.001 for all eight services). However, preventive care rates among those in the incentive program was still low. Conclusions Voluntary participation in a patient incentive program was associated with a significantly higher likelihood of receiving preventive care, though receipt of preventive care among those in the program was still lower than ideal. PMID:25180436

Preventive Services Use among African American and Latino Adult Caregivers in South Los Angeles

PubMed Central

Mendez-Luck, Carolyn A.; Walker, Kara Odom; Luck, Jeff

2016-01-01

Background The burden of informal caregiving is significant and well-documented, yet the evidence is mixed as to whether being a caregiver presents an additional barrier to receiving recommended preventive care. Objectives To determine whether (1) caregivers compared to non-caregivers were less likely to receive preventive health services; and (2) higher intensity caregivers were less likely to receive preventive health services than lower intensity caregivers. Research Design, Subjects, and Measures Data were from a telephone survey of Latino and African American adults 50 years or older in South Los Angeles (n=702). Outcomes were flu vaccination, pneumococcal vaccination, and colorectal cancer screening. Logistic regression models adjusted for predisposing, enabling, and need factors according to the Andersen Model of Access to Health Care for Low-Income Populations. Results Caregiver type (e.g., adult child, non-related) was associated with varying odds of receiving a preventive service. Caregivers had lower odds than non-caregivers of receiving preventive services although odds of receiving a flu vaccination improved slightly for caregivers of persons with memory loss compared to other caregivers. More weekly caregiving hours was associated with higher odds of receiving flu vaccination (AOR 1.1, 95% CI=1.0, 1.1) or colorectal cancer screening (AOR 1.1, 95% CI=1.0, 1.1). Caregivers and non-caregivers age 65 and older or with chronic conditions were more likely to receive vaccinations. Conclusions Preventive service use was influenced by characteristics of the caregiving situation. An opportunity may exist to leverage care recipients’ ongoing contact with health care providers to increase caregivers’ own access to preventive services. PMID:27414461

Examining public knowledge and preferences for adult preventive services coverage

PubMed Central

Ortiz, Selena E.

2017-01-01

Introduction To examine (1) what individuals know about the existing adult preventive service coverage provisions of the Affordable Care Act (ACA), and (2) which preventive services individuals think should be covered without cost sharing. Methods An online panel from Survey Monkey was used to obtain a sample of 2,990 adults age 18 and older in March 2015, analyzed 2015–2017. A 17-item survey instrument was designed and used to evaluate respondents’ knowledge of the adult preventive services provision of the ACA. Additionally, we asked whether various preventive services should be covered. The data include age, sex, race/ethnicity, and educational attainment as well as measures of political ideology, previous insurance status, the number of chronic conditions, and usual source of care. Results Respondents correctly answered 38.6% of the questions about existing coverage under the ACA, while on average respondents thought 12.1 of 15 preventive services should be covered (SD 3.5). Respondents were more knowledgeable about coverage for routine screenings, such as blood pressure (63.4% correct) than potentially stigmatizing screenings, such as for alcohol misuse (28.8% correct). Blood pressure screening received the highest support of coverage (89.8%) while coverage of gym memberships received the lowest support (59.4%). Individuals with conservative ideologies thought fewer services on average should be covered, but the difference was small—around one service less than those with liberal ideologies. Conclusions Overwhelmingly, individuals think that most preventive services should be covered without cost sharing. Despite several years of coverage for preventive services, there is still confusion and lack of knowledge about which services are covered. PMID:29261757

Estimating Demand for and Supply of Pediatric Preventive Dental Care for Children and Identifying Dental Care Shortage Areas, Georgia, 2015.

PubMed

Cao, Shanshan; Gentili, Monica; Griffin, Paul M; Griffin, Susan O; Harati, Pravara; Johnson, Ben; Serban, Nicoleta; Tomar, Scott

Demand for dental care is expected to outpace supply through 2025. The objectives of this study were to determine the extent of pediatric dental care shortages in Georgia and to develop a general method for estimation that can be applied to other states. We estimated supply and demand for pediatric preventive dental care for the 159 counties in Georgia in 2015. We compared pediatric preventive dental care shortage areas (where demand exceeded twice the supply) designated by our methods with dental health professional shortage areas designated by the Health Resources & Services Administration. We estimated caries risk from a multivariate analysis of National Health and Nutrition Examination Survey data and national census data. We estimated county-level demand based on the time needed to perform preventive dental care services and the proportion of time that dentists spend on pediatric preventive dental care services from the Medical Expenditure Panel Survey. Pediatric preventive dental care supply exceeded demand in Georgia in 75 counties: the average annual county-level pediatric preventive dental care demand was 16 866 hours, and the supply was 32 969 hours. We identified 41 counties as pediatric dental care shortage areas, 14 of which had not been designated by the Health Resources & Services Administration. Age- and service-specific information on dental care shortage areas could result in more efficient provider staffing and geographic targeting.

CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.

PubMed

Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

2016-04-14

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.

Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic differentiation of C2C12 cells.

PubMed

Hadavi, Mahvash; Hasannia, Sadegh; Faghihi, Shahab; Mashayekhi, Farhad; Homazadeh, Homayoun; Mostofi, Seyed Behrooz

2018-01-26

Zein nanoparticles as a carrier system for BMP6-derived peptide were prepared by liquid-liquid phase separation procedure and characterized with SEM, DLS, FTIR and thermogravimetric methods. After peptide encapsulation, nanoparticle size increased from 236.3 ± 92.2 nm to 379.4 ± 116.8 nm. The encapsulation efficiency of peptide was 72.6% and the release of peptide from Zein nanoparticles was partly sustained in trypsin containing phosphate buffered saline (pH 7.4) for up to 14 days. Peptide-loaded nanoparticles showed similar cell viability compared with blank ones. ALP activity of C2C12 cells treated with peptide-loaded nanoparticles (500 µg/mL) was evaluated 7, 14, 21 and 28 days after culture. In peptide-loaded nanoparticles, ALP activity was significantly higher (p < .05) compared with other groups at day 14. Alizarin Red S staining showed, C2C12 cells behind peptide-loaded nanoparticles had significantly (p < .05) higher calcium deposition at day 21. The results of RT-qPCR show that the BMP-6 peptide activated expression of RUNX2 as a transcription factor. In turn, RUNX2 regulates SPP1 and BGLAP gene expression, as osteogenic marker genes. The results confirm that the peptide-loaded Zein nanoparticles, as osteoinductive material, may be used to repair small area of bone defects, with low load bearing.

Evaluation of preventive technologies in Germany: case studies of mammography, prostate cancer screening, and fetal ultrasound.

PubMed

Perleth, M; Busse, R; Gibis, B; Brand, A

2001-01-01

In this article, three preventive strategies-mammography screening for breast cancer, PSA screening for prostate cancer, and routine ultrasound in normal pregnancy-are discussed in the context of German health care. Epidemiologic data and German studies evaluating different aspects of these preventive measures were identified and analyzed. Only a few studies could be identified that investigate these preventive measures. Despite sufficient evidence, in part derived from a German study, there is not yet a mammography screening program. In contrast, ultrasound in pregnancy is offered routinely, although there are controversies regarding the benefit of this practice. PSA screening is not offered as part of the screening program for prostate cancer. However, PSA tests as well as mammographies are done in large numbers in German ambulatory care-a practice that could be considered wild or opportunistic screening. These case studies show that preventive programs and practices in Germany are not sufficiently based on sound evidence. The paucity of evaluation activities related to prevention in Germany is probably due to the low threshold to introduce new preventive programs into the German healthcare system in the past.

Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study.

PubMed

Caru, Maxime; Kern, Laurence; Bousquet, Marc; Curnier, Daniel

2018-04-26

To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs). A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors ( i.e ., abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking). It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression. This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce a protection for some risk factors, despite having a CVD.

Application of preventive medicine resources in the health insurance system.

PubMed

Oliveira, Karla Regina Dias de; Liberal, Márcia Mello Costa de; Zucchi, Paola

2015-01-01

To identify the financial resources and investments provided for preventive medicine programs by health insurance companies of all kinds. Data were collected from 30 large health insurance companies, with over 100 thousand individuals recorded, and registered at the Agência Nacional de Saúde Suplementar. It was possible to identify the percentage of participants of the programs in relation to the total number of beneficiaries of the health insurance companies, the prevention and promotion actions held in preventive medicine programs, the inclusion criteria for the programs, as well as the evaluation of human resources and organizational structure of the preventive medicine programs. Most of the respondents (46.7%) invested more than US$ 50,000.00 in preventive medicine program, while 26.7% invested more than US$ 500,000.00. The remaining, about 20%, invested less than US$ 50,000.00, and 3.3% did not report the value applied.

Avian Influenza Risk Perception and Preventive Behavior among Traditional Market Workers and Shoppers in Taiwan: Practical Implications for Prevention

PubMed Central

Liu, Ming-Der

2011-01-01

Background Avian influenza (AI) can be highly pathogenic and fatal. Preventive behavior such as handwashing and wearing face masks has been recommended. However, little is known about what psychosocial factors might influence people's decision to adopt such preventive behavior. This study aims to explore risk perception and other factors associated with handwashing and wearing face masks to prevent AI. Methodology/Principal Findings An interviewer-administered survey was conducted among 352 traditional market workers and shoppers in Taiwan between December 2009 and January 2010. Factors associated with the recommended AI preventive behavior (i.e., when in a traditional market, wearing a face mask and also washing hands after any contact with poultry) included: having correct knowledge about the fatality rate of AI (adjusted odds ratio [AOR] = 4.18), knowing of severe cases of AI (AOR = 2.13), being informed of local AI outbreaks (AOR = 2.24), living in northeastern Taiwan (AOR = 6.01), having a senior high-school education (AOR = 3.33), and having a university or higher education (AOR = 6.86). Gender interactive effect was also found among participants with a senior high-school education, with males being less likely to engage in the recommended AI preventive behavior than their female counterparts (AOR = 0.34). Conclusions/Significance Specific information concerning AI risk perception was associated with the recommended AI preventive behavior. In particular, having correct knowledge about the fatality rate of AI and being informed of severe cases and local outbreaks of AI were linked to increased AI preventive behavior. These findings underscore the importance of transparency in dealing with epidemic information. These results also have practical implications for prevention and policy-making to more effectively promote the recommended AI preventive behavior in the public. PMID:21912667

Dental Homes for Children With Autism: A Longitudinal Analysis of Iowa Medicaid's I-Smile Program.

PubMed

Chi, Donald L; Momany, Elizabeth T; Mancl, Lloyd A; Lindgren, Scott D; Zinner, Samuel H; Steinman, Kyle J

2016-05-01

Medicaid-enrolled children with autism spectrum disorder (ASD) encounter significant barriers to dental care. Iowa's I-Smile Program was implemented in 2006 to improve dental use for all children in Medicaid. This study compared dental home and preventive dental utilization rates for Medicaid-enrolled children by ASD status and within three time periods (pre-implementation, initial implementation, maturation) and determined I-Smile's longitudinal influence on ASD-related dental use disparities. Data from 2002-2011 were analyzed for newly Medicaid-enrolled children aged 3-17 years (N=30,059); identified each child's ASD status; and assessed whether the child had a dental home or utilized preventive dental care. Log-linear regression models were used to generate rate ratios. Analyses were conducted in 2015. In 2003-2011, 9.8% of children with ASD had dental homes compared with 8% of children without ASD; 36.3% of children with ASD utilized preventive care compared to 45.7% of children without ASD. There were no significant differences in dental home rates by ASD status during pre-implementation, initial implementation, or maturation. There were no significant differences in preventive dental utilization by ASD status during pre-implementation or initial implementation, but children with ASD were significantly less likely to utilize preventive care during maturation (rate ratio=0.79, p<0.001). Longitudinal trends in dental home and preventive dental utilization rates were not significant (p=0.54 and p=0.71, respectively). Among newly Medicaid-enrolled children in Iowa's I-Smile Program, those with ASDs were not less likely than those without ASD to have dental homes but were significantly less likely to utilize preventive dental care. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Caregiver Burdens and Preventive Dental Care for Children with Autism Spectrum Disorder, Developmental Disability and/or Mental Health Conditions: National Survey of CSHCN, 2009-2010.

PubMed

Wiener, R Constance; Vohra, Rini; Sambamoorthi, Usha; Madhavan, S Suresh

2016-12-01

Objective The purpose of this study is to examine the burdens of caregivers on perception of the need and receipt of preventive dental care for a subset of children with special health care needs-children with Autism Spectrum disorder, developmental disability and/or mental health conditions (CASD/DD/MHC). Methods The authors used the 2009-2010 National Survey of CSHCN. The survey included questions addressing preventive dental care and caregivers' financial, employment, and time-related burdens. The associations of these burdens on perceptions and receipt of preventive dental care use were analyzed with bivariate Chi square analyses and multinomial logistic regressions for CASD/DD/MHC (N = 16,323). Results Overall, 16.3 % of CASD/DD/MHC had an unmet preventive dental care need. There were 40.0 % of caregivers who reported financial burden, 20.3 % who reported employment burden, and 10.8 % who reported time burden. A higher percentage of caregivers with financial burden, employment burden, and time-related burden reported that their CASD/DD/MHC did not receive needed preventive dental care (14.1, 16.5, 17.7 % respectively) compared to caregivers without financial, employment, or time burdens (9.0, 9.6 %, 11.0 % respectively). Caregivers with financial burden (adjusted multinomial odds ratio, 1.38 [95 % CI 1.02, 1.86] and employment burden (adjusted multinomial odds ratio, 1.45 [95 % CI 1.02, 2.06] were more likely to report that their child did not receive preventive dental care despite perceived need compared to caregivers without financial or employment burdens. Conclusions for practice Unmet needs for preventive dental care were associated with employment and financial burdens of the caregivers of CASD/DD/MHC.

A randomized trial of the effect of centralized reminder/recall on immunizations and preventive care visits for adolescents.

PubMed

Szilagyi, Peter G; Albertin, Christina; Humiston, Sharon G; Rand, Cynthia M; Schaffer, Stanley; Brill, Howard; Stankaitis, Joseph; Yoo, Byung-Kwang; Blumkin, Aaron; Stokley, Shannon

2013-01-01

To assess the impact of a managed care-based patient reminder/recall system on immunization rates and preventive care visits among low-income adolescents. We conducted a randomized controlled trial between December 2009 and December 2010 that assigned adolescents aged 11-17 years to one of three groups: mailed letter, telephone reminders, or control. Publicly insured youths (n = 4115) were identified in 37 participating primary care practices. The main outcome measures were immunization rates for routine vaccines (meningococcus, pertussis, HPV) and preventive visit rates at study end. Intervention and control groups were similar at baseline for demographics, immunization rates, and preventive visits. Among adolescents who were behind at the start, immunization rates at study end increased by 21% for mailed (P < .01 vs control), 17% for telephone (P < .05), and 13% for control groups. The proportion of adolescents with a preventive visit (within 12 months) was: mailed (65%; P < .01), telephone (63%; P < .05), and controls (59%). The number needed to treat for an additional fully vaccinated adolescent was 14 for mailed and 25 for telephone reminders; for an additional preventive visit, it was 17 and 29. The intervention cost $18.78 (mailed) or $16.68 (phone) per adolescent per year to deliver. The cost per additional adolescent fully vaccinated was $463.99 for mailed and $714.98 for telephone; the cost per additional adolescent receiving a preventive visit was $324.75 and $487.03. Managed care-based mail or telephone reminder/recall improved adolescent immunizations and preventive visits, with modest costs and modest impact. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Developing a typology of African Americans with limited literacy based on preventive health practice orientation: implications for colorectal cancer screening strategies.

PubMed

Gordon, Thomas F; Bass, Sarah Bauerle; Ruzek, Sheryl B; Wolak, Caitlin; Rovito, Michael J; Ruggieri, Dominique G; Ward, Stephanie; Paranjape, Anuradha; Greener, Judith

2014-01-01

Preventive health messages are often tailored to reach broad sociodemographic groups. However, within groups, there may be considerable variation in perceptions of preventive health practices, such as colorectal cancer screening. Segmentation analysis provides a tool for crafting messages that are tailored more closely to the mental models of targeted individuals or subgroups. This study used cluster analysis, a psychosocial marketing segmentation technique, to develop a typology of colorectal cancer screening orientation among 102 African American clinic patients between the ages of 50 and 74 years with limited literacy. Patients were from a general internal medicine clinic in a large urban teaching hospital, a subpopulation known to have high rates of colorectal cancer and low rates of screening. Preventive screening orientation variables included the patients' responses to questions involving personal attitudes and preferences toward preventive screening and general prevention practices. A k-means cluster analysis yielded three clusters of patients on the basis of their screening orientation: ready screeners (50.0%), cautious screeners (30.4%), and fearful avoiders (19.6%). The resulting typology clearly defines important subgroups on the basis of their preventive health practice perceptions. The authors propose that the development of a validated typology of patients on the basis of their preventive health perceptions could be applicable to a variety of health concerns. Such a typology would serve to standardize how populations are characterized and would provide a more accurate view of their preventive health-related attitudes, values, concerns, preferences, and behaviors. Used with standardized assessment tools, it would provide an empirical basis for tailoring health messages and improving medical communication.

Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

PubMed

Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

2018-06-01

The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP

PubMed Central

Lisy, Ondrej; Huntley, Brenda K.; McCormick, Daniel J.; Kurlansky, Paul A.; Burnett, John C.

2008-01-01

Objectives Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Background Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Methods Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Results Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. Conclusions The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides. PMID:18582636

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna

Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrilsmore » formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.« less

Identification and accurate quantification of structurally related peptide impurities in synthetic human C-peptide by liquid chromatography-high resolution mass spectrometry.

PubMed

Li, Ming; Josephs, Ralf D; Daireaux, Adeline; Choteau, Tiphaine; Westwood, Steven; Wielgosz, Robert I; Li, Hongmei

2018-06-04

Peptides are an increasingly important group of biomarkers and pharmaceuticals. The accurate purity characterization of peptide calibrators is critical for the development of reference measurement systems for laboratory medicine and quality control of pharmaceuticals. The peptides used for these purposes are increasingly produced through peptide synthesis. Various approaches (for example mass balance, amino acid analysis, qNMR, and nitrogen determination) can be applied to accurately value assign the purity of peptide calibrators. However, all purity assessment approaches require a correction for structurally related peptide impurities in order to avoid biases. Liquid chromatography coupled to high resolution mass spectrometry (LC-hrMS) has become the key technique for the identification and accurate quantification of structurally related peptide impurities in intact peptide calibrator materials. In this study, LC-hrMS-based methods were developed and validated in-house for the identification and quantification of structurally related peptide impurities in a synthetic human C-peptide (hCP) material, which served as a study material for an international comparison looking at the competencies of laboratories to perform peptide purity mass fraction assignments. More than 65 impurities were identified, confirmed, and accurately quantified by using LC-hrMS. The total mass fraction of all structurally related peptide impurities in the hCP study material was estimated to be 83.3 mg/g with an associated expanded uncertainty of 3.0 mg/g (k = 2). The calibration hierarchy concept used for the quantification of individual impurities is described in detail. Graphical abstract ᅟ.

Adsorption of insulin peptide on charged single-walled carbon nanotubes: significant role of ordered water molecules.

PubMed

Shen, Jia-Wei; Wu, Tao; Wang, Qi; Kang, Yu; Chen, Xin

2009-06-02

Ordered hydration shells: The more ordered hydration shells outside the charged CNT surfaces prevent more compact adsorption of the peptide in the charged CNT systems [picture: see text], but peptide binding strengths on the charged CNT surfaces are stronger due to the electrostatic interaction.Studies of adsorption dynamics and stability for peptides/proteins on single-walled carbon nanotubes (SWNTs) are of great importance for a better understanding of the properties and nature of nanotube-based biosystems. Herein, the dynamics and mechanism of the adsorption of the insulin chain B peptide on different charged SWNTs are investigated by explicit solvent molecular dynamics simulations. The results show that all types of surfaces effectively attract the model peptide. Water molecules play a significant role in peptide adsorption on the surfaces of charged carbon nanotubes (CNTs). Compared to peptide adsorption on neutral CNT surfaces, the more ordered hydration shells outside the tube prevent more compact adsorption of the peptide in charged CNT systems. This shield effect leads to a smaller conformational change and van der Waals interaction between the peptide and surfaces, but peptide binding strengths on charged CNT surfaces are stronger than those on the neutral CNT surface due to the strong electrostatic interaction. The result of these simulations implies the possibility of improving the binding strength of peptides/proteins on CNT surfaces, as well as keeping the integrity of the peptide/protein conformation in peptide/protein-CNT complexes by charging the CNTs.

78 FR 24693 - Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... Analysis and Risk-Based Preventive Controls for Human Food'' (the proposed preventive controls rule) and... Farm.'' The purpose of the draft RA is to provide a science-based risk analysis of those activity/food... Food, Drug, and Cosmetic Act for hazard analysis and risk-based preventive controls (the proposed...

Determining Factors for Utilization of Preventive Health Services among Adults with Disabilities in Taiwan

ERIC Educational Resources Information Center

Kung, Pei-Tseng; Tsai, Wen-Chen; Li, Ya-Hsin

2012-01-01

Taiwan has provided free health checks for adults since 1995. However, very little previous research has explored the use of preventive health services by physically and mentally disabled adults. The present study aimed to understand this use of preventive health services and the factors that influence it. Research participants included disabled…

Disparities in the Use of Preventive Health Care among Children with Disabilities in Taiwan

ERIC Educational Resources Information Center

Tsai, Wen-Chen; Kung, Pei-Tseng; Wang, Jong-Yi

2012-01-01

Children with disabilities face more barriers accessing preventive health services. Prior research has documented disparities in the receipt of these services. However, most are limited to specific types of disability or care. This study investigates disparities in the use of preventive health care among children with disabilities in Taiwan. Three…

Academic Relationships and Teaching Resources. Fogarty International Center Series on the Teaching of Preventive Medicine, Volume 6.

ERIC Educational Resources Information Center

Clark, Duncan W., Ed.

The monograph is one of the Fogarty International Center Series on the Teaching of Preventive Medicine, undertaken to: (1) review and evaluate the state of the art of prevention and control of human diseases; (2) identify deficiences in knowledge requiring further research (including analysis of financial resources, preventive techniques, and…

Application of preventive medicine resources in the health insurance system

PubMed Central

de Oliveira, Karla Regina Dias; Liberal, Márcia Mello Costa De; Zucchi, Paola

2015-01-01

ABSTRACT Objective To identify the financial resources and investments provided for preventive medicine programs by health insurance companies of all kinds. Methods Data were collected from 30 large health insurance companies, with over 100 thousand individuals recorded, and registered at the Agência Nacional de Saúde Suplementar. Results It was possible to identify the percentage of participants of the programs in relation to the total number of beneficiaries of the health insurance companies, the prevention and promotion actions held in preventive medicine programs, the inclusion criteria for the programs, as well as the evaluation of human resources and organizational structure of the preventive medicine programs. Conclusion Most of the respondents (46.7%) invested more than US$ 50,000.00 in preventive medicine program, while 26.7% invested more than US$ 500,000.00. The remaining, about 20%, invested less than US$ 50,000.00, and 3.3% did not report the value applied. PMID:26761558

Determinants of preventive oral health behaviour among senior dental students in Nigeria.

PubMed

Folayan, Morenike O; Khami, Mohammad R; Folaranmi, Nkiru; Popoola, Bamidele O; Sofola, Oyinkan O; Ligali, Taofeek O; Esan, Ayodeji O; Orenuga, Omolola O

2013-06-18

To study the association between oral health behaviour of senior dental students in Nigeria and their gender, age, knowledge of preventive care, and attitudes towards preventive dentistry. Questionnaires were administered to 179 senior dental students in the six dental schools in Nigeria. The questionnaire obtained information on age, gender, oral self-care, knowledge of preventive dental care and attitudes towards preventive dentistry. Attending a dental clinic for check-up by a dentist or a classmate within the last year was defined as preventive care use. Students who performed oral self-care and attended dental clinic for check-ups were noted to have complied with recommended oral self-care. Chi-square test and binary logistic regression models were used for statistical analyses. More male respondents agreed that the use of fluoride toothpaste was more important than the tooth brushing technique for caries prevention (P < 0.001). While the use of dental floss was very low (7.3%), more females were more likely to report using dental floss (p=0.03). Older students were also more likely to comply with recommended oral self-care (p<0.001). In binary regression models, respondents who were younger (p=0.04) and those with higher knowledge of preventive dental care (p=0.008) were more likely to consume sugary snacks less than once a day. Gender differences in the awareness of the superiority of using fluoridated toothpaste over brushing in caries prevention; and in the use of dental floss were observed. While older students were more likely to comply with recommended oral self-care measures, younger students with good knowledge of preventive dental care were more likely to consume sugary snacks less than once a day.

Determining Hospital Ship (T-AH) Staffing Requirements for Humanitarian Assistance Missions

DTIC Science & Technology

2007-10-16

12 Table 3. Number of Biomedical Equipment Repairs Performed at Each Site.............................. 12 Table 4. Preventive ...pediatric, dental, and optometry services, repaired medical equipment, taught preventive and general health classes at local schools, and conducted...of glasses to the people of Nias. Preventive medicine (PM) teams and USPHS personnel traveled across the island testing drinking water, spraying for

Interactions Between Peptide and Preservatives: Effects on Peptide Self-Interactions and Antimicrobial Efficiency In Aqueous Multi-Dose Formulations.

PubMed

Heljo, P; Ross, A; Zarraga, I E; Pappenberger, A; Mahler, H-C

2015-10-01

Antimicrobial preservatives are known to interact with proteins and potentially affect their stability in aqueous solutions. In this systematic study, the interactions of a model peptide with three commonly used preservatives, benzyl alcohol, phenol and m-cresol, were evaluated. The impact on peptide oligomerization was studied using GC-MALS, SEC-MALS and DLS, antimicrobial efficiency of different formulations were studied using the Ph. Eur. antimicrobial efficacy test, and the molecular adsorption of preservative molecules on reversible peptide oligomers was monitored using NMR. The hydrodynamic radius and molar mass of the peptide oligomers was shown to clearly increase in the presence of m-cresol but less significantly with phenol and benzyl alcohol. The increase in size was most likely caused by peptide self-interactions becoming more attractive, leading to reversible oligomerization. On the other hand, increasing the concentration of peptide in multi-dose formulations led to reduced molecular mobility and decreased antimicrobial efficacy of all preservatives. Peptide-preservative interactions not only affect peptide self-interactions, but also antimicrobial efficiency of the preservatives and are thus of significant relevance. Adsorption of preservatives on oligomeric states of peptides is proposed as a mechanism to explain this reduced antimicrobial efficacy.

Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

NASA Astrophysics Data System (ADS)

Feng, Mei; Bell, David R.; Zhou, Ruhong

2017-12-01

The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

Effects of 8-mer acidic peptide concentration on the morphology and photoluminescence of synthesized ZnO nanomaterials

NASA Astrophysics Data System (ADS)

Moon, Chung Hee; Tousi, Marzieh; Cheeney, Joseph; Ngo-Duc, Tam-Triet; Zuo, Zheng; Liu, Jianlin; Haberer, Elaine D.

2015-11-01

An 8-mer ZnO-binding peptide, VPGAAEHT, was identified using a M13 pVIII phage display library and employed as an additive during aqueous-based ZnO synthesis at 65 °C. Unlike most other well-studied ZnO-binding sequences which are strongly basic (pI > pH 7), the 8-mer peptide was overall acidic (pI < pH 7) in character, including only a single basic residue. The selected peptide strongly influenced ZnO nanostructure formation. Morphology and optical emission properties were found to be dependent on the concentration of peptide additive. Using lower peptide concentrations (<0.1 mM), single crystal hexagonal rods and platelets were produced, and using higher peptide concentrations (≥0.1 mM), polycrystalline layered platelets, yarn-like structures, and microspheres were assembled. Photoluminescence analysis revealed a characteristic ZnO band-edge peak, as well as sub-bandgap emission peaks. Defect-related green emission, typically associated with surface-related oxygen and zinc vacancies, was significantly reduced by the peptide additive, while blue emission, attributable to oxygen and zinc interstitials, emerged with increased peptide concentrations. Peptide-directed synthesis of ZnO materials may be useful for gas sensing and photocatalytic applications in which properly engineered morphology and defect levels have demonstrated enhanced performance.

Antagonistic effect of disulfide-rich peptide aptamers selected by cDNA display on interleukin-6-dependent cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemoto, Naoto, E-mail: nemoto@fms.saitama-u.ac.jp; Innovation Center for Startups, National Institute of Advanced Industrial Science and Technology, 2-2-2 Marunouchi, Chiyoda-ku, Tokyo 100-0005; Janusys Corporation, 508, Saitama Industrial Technology Center, Skip City, 3-12-18 Kami-Aoki, Kawaguchi, Saitama 333-0844

2012-04-27

Highlights: Black-Right-Pointing-Pointer Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. Black-Right-Pointing-Pointer Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. Black-Right-Pointing-Pointer Inhibitory effect of peptide depends on number and pattern of its disulfide bonds. -- Abstract: Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library bymore » in vitro peptide selection using the evolutionary molecular engineering method 'cDNA display'. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.« less

99m Tc-HYNIC-(Ser)3 -J18 peptide: A radiotracer for non-small-cell lung cancer targeting.

PubMed

Shaghaghi, Zahra; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-02-14

Radiolabeled peptide could be a useful tool for the diagnosis of non-small-cell lung cancer (NSCLC). In this study, HYNIC-(Ser) 3 -J18 peptide was labeled with 99m Tc using EDDA/tricine as coligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular-specific binding and tumor targeting in A-549 cells and tumor-bearing mice, respectively. The high radiochemical purity was obtained and this radiolabeled peptide exhibited high stability in buffer and serum. The radiolabeled peptide showed high affinity for the A-549 cells with a dissociation constant value (K D ) of 4.4 ± 0.8 nm. The tumor-muscles ratios were 2.7 and 4.4 at 1 and 2 hr after injection of 99m Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 in tumor-bearing mice. The tumor uptake was decreased after preinjection with non-labeled peptide for this radiolabeled peptide in blocking experiment. The results of this study showed the 99m Tc-(EDDA/tricine)-(Ser) 3 -HYNIC-J18 peptide might be a promising radiolabeled peptide for NSCLC targeting. © 2018 John Wiley & Sons A/S.

Preventing invasive breast cancer using endocrine therapy.

PubMed

Thorat, Mangesh A; Cuzick, Jack

2017-08-01

Developments in breast cancer treatment have resulted in reduction in breast cancer mortality in the developed world. However incidence continues to rise and greater use of preventive interventions including the use of therapeutic agents is needed to control this burden. High quality evidence from 9 major trials involving more than 83000 participants shows that selective oestrogen receptor modulators (SERMs) reduce breast cancer incidence by 38%. Combined results from 2 large trials with 8424 participants show that aromatase inhibitors (AIs) reduce breast cancer incidence by 53%. These benefits are restricted to prevention of ER positive breast cancers. Restricting preventive therapy to high-risk women improves the benefit-harm balance and many guidelines now encourage healthcare professionals to discuss preventive therapy in these women. Further research is needed to improve our risk-prediction models for the identification of high risk women for preventive therapy with greater accuracy and to develop surrogate biomarkers of response. Long-term follow-up of the IBIS-I trial has provided valuable insights into the durability of benefits from preventive therapy, and underscores the need for such follow up to fully evaluate other agents. Full utilisation of preventive therapy also requires greater knowledge and awareness among both doctors and patients about benefits, harms and risk factors. Healthcare professionals should routinely discuss preventive therapy with women at high-risk of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

An update on the potential role of C-peptide in diabetes and osteoporosis.

PubMed

Pujia, Arturo; Gazzaruso, Carmine; Montalcini, Tiziana

2017-12-01

C-peptide secretion is deficient or absent in type 1 diabetes mellitus. It is well accepted that insulin replacement therapy cannot prevent the development of long-term diabetes-related complications, which can often be disabling or even life-threatening. Several cross-sectional investigations have suggested that residual C-peptide production in patients with type 1 diabetes mellitus would help prevent a number of complications. In animal models of diabetes and in patients with type 1 diabetes mellitus, C-peptide replacement improves renal function, skin and skeletal muscle blood flow, nerve conduction, glucose utilization, and other diabetes-related complications. Recent investigations suggest a new beneficial effect of C-peptide, which to date has never been studied. It is known that osteoporosis is the most prevalent short-term complication in type 1 diabetes mellitus. This review will highlight new insights into the pathophysiology and future therapeutic modalities for osteoporosis in individuals with diabetes. This review provides a concise summary of old and new insights into the role of C-peptide in diabetes-related complications. The data suggest that C-peptide is a bioactive peptide, acting independently of insulin, which binds to a G-protein-coupled membrane binding site in different cell types. By triggering Ca 2+ -dependent intracellular signaling pathways, both Na + , K + -ATPase and endothelial nitric oxide synthase are activated. C-peptide may act on osteoblast cells by ERK 1/2 pathway activation, modulate collagen biosynthesis and RANKL expression. Furthermore, C-peptide-deficient postmenopausal women, not affected by diabetes, have a lower bone mineral density than those with normal C-peptide levels. Taken together these studies encourage further investigations to elucidate the role of C-peptide in preventing bone loss in type 1 diabetes mellitus and in those individuals with C-peptide deficiency and osteoporosis.

The dominant interaction between peptide and urea is electrostatic in nature: a molecular dynamics simulation study.

PubMed

Tobi, Dror; Elber, Ron; Thirumalai, Devarajan

2003-03-01

The conformational equilibrium of a blocked valine peptide in water and aqueous urea solution is studied using molecular dynamics simulations. Pair correlation functions indicate enhanced concentration of urea near the peptide. Stronger hydrogen bonding of urea-peptide compared to water-peptide is observed with preference for helical conformation. The potential of mean force, computed using umbrella sampling, shows only small differences between urea and water solvation that are difficult to quantify. The changes in solvent structure around the peptide are explained by favorable electrostatic interactions (hydrogen bonds) of urea with the peptide backbone. There is no evidence for significant changes in hydrophobic interactions in the two conformations of the peptide in urea solution. Our simulations suggest that urea denatures proteins by preferentially forming hydrogen bonds to the peptide backbone, reducing the barrier for exposing protein residues to the solvent, and reaching the unfolded state. Copyright 2003 Wiley Periodicals, Inc. Biopolymers: 359-369, 2003

Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency.

PubMed

Yin, Haifang; Boisguerin, Prisca; Moulton, Hong M; Betts, Corinne; Seow, Yiqi; Boutilier, Jordan; Wang, Qingsong; Walsh, Anthony; Lebleu, Bernard; Wood, Matthew Ja

2013-09-24

We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO) and control peptide 3 (B-3-PMO and 3-B-PMO) were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO), further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO) was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG), indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.Molecular Therapy-Nucleic Acids (2013) 2, e124; doi:10.1038/mtna.2013.51; published online 24 September 2013.

Production of human antimicrobial peptide LL-37 in Escherichia coli using a thioredoxin-SUMO dual fusion system.

PubMed

Li, Yifeng

2013-02-01

LL-37 is a human antimicrobial peptide that has been shown to possess multiple functions in host defense. In this report, the peptide was expressed as a fusion with a thioredoxin-SUMO dual-tag. Upon SUMO protease mediated cleavage at the SUMO/peptide junction, LL-37 with its native N-terminus was generated. The released peptide was separated from the dual-tag and cleavage enzyme by size-exclusion chromatography. Mass spectrometry analysis proves that the recombinant peptide has a molecular weight as theoretically expected for its native form. The produced peptide displayed antimicrobial activity against Escherichia coli K-12. On average, 2.4 mg peptide was obtained from one liter of bacterial culture. Thus, the described approach provides an effective alternative for producing active recombinant LL-37 with its natural amino acid sequence in E. coli. Copyright © 2012 Elsevier Inc. All rights reserved.

Lipid raft-like liposomes used for targeted delivery of a chimeric entry-inhibitor peptide with anti-HIV-1 activity.

PubMed

Gómara, María José; Pérez-Pomeda, Ignacio; Gatell, José María; Sánchez-Merino, Victor; Yuste, Eloisa; Haro, Isabel

2017-02-01

The work reports the design and synthesis of a chimeric peptide that is composed of the peptide sequences of two entry inhibitors which target different sites of HIV-1 gp41. The chimeric peptide offers the advantage of targeting two gp41 regions simultaneously: the fusion peptide and the loop both of which are membrane active and participate in the membrane fusion process. We therefore use lipid raft-like liposomes as a tool to specifically direct the chimeric inhibitor peptide to the membrane domains where the HIV-1 envelope protein is located. Moreover, the liposomes that mimic the viral membrane composition protect the chimeric peptide against proteolytic digestion thereby increasing the stability of the peptide. The described liposome preparations are suitable nanosystems for managing hydrophobic entry-inhibitor peptides as putative therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP.

PubMed

Lisy, Ondrej; Huntley, Brenda K; McCormick, Daniel J; Kurlansky, Paul A; Burnett, John C

2008-07-01

Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico.

PubMed

Gonzalez-Mejia, M Elba; Porchia, Leonardo M; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

2016-05-01

Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.

Do We Need to Understand the Technology to Get to the Science? A Systematic Review of the Concept of Computer Literacy in Preventive Health Programs

ERIC Educational Resources Information Center

Dominick, Gregory M.; Friedman, Daniela B.; Hoffman-Goetz, Laurie

2009-01-01

Objective: To systematically review definitions and descriptions of computer literacy as related to preventive health education programs. Method: A systematic review of the concept of computer literacy as related to preventive health education was conducted. Empirical studies published between 1994 and 2007 on prevention education programs with a…

Association between knowledge of caries preventive practices, preventive oral health habits of parents and children and caries experience in children resident in sub-urban Nigeria.

PubMed

Folayan, Morenike O; Kolawole, Kikelomo A; Oyedele, Titus; Chukwumah, Nneka M; Chukumah, Nneka M; Onyejaka, Nneka; Agbaje, Hakeem; Oziegbe, Elizabeth O; Oshomoji, Olusegun V; Osho, Olusegun V

2014-12-16

The objectives of this study were to assess the association between children and parents' knowledge of caries preventive practices, the parents' caries preventive oral health behaviours and children's caries preventive oral health behaviour and caries experience. Three hundred and twenty four participants aged 8-12 years, 308 fathers and 318 mothers were recruited through a household survey conducted in Suburban Nigeria. A questionnaire was administered to generate information on fathers, mothers and children's knowledge of caries prevention measures and their oral health behaviour. Clinical examination was conducted on the children to determine their dmft/DMFT. Analysis was conducted to determine the predictors of the children's good oral health behaviour. The mothers' oral health behaviours were significant predictors of the children's oral health behaviours. Children who had good knowledge of caries prevention measures had significant increased odds of brushing their teeth twice daily or more. The children's caries prevalence was 13.9%, the mean dmft was 0.2 and the mean DMFT was 0.09. None of the dependent variables could predict the presence of caries in children. The study highlights the effect of maternal oral health behaviour on the oral health behaviour of children aged 8 years to 12 years in suburban Nigeria. A pilot study is needed to evaluate how enhanced maternal preventive oral health practices can improve the oral health preventive practices of children.

Impact of communication on preventive services among deaf American Sign Language users.

PubMed

McKee, Michael M; Barnett, Steve L; Block, Robert C; Pearson, Thomas A

2011-07-01

Deaf American Sign Language (ASL) users face communication and language barriers that limit healthcare communication with their providers. Prior research has not examined preventive services with ASL-skilled clinicians. The goal of this study was to determine whether provider language concordance is associated with improved receipt of preventive services among deaf respondents. This cross-sectional study included 89 deaf respondents aged 50-75 years from the Deaf Health Survey (2008), a Behavioral Risk Factor Surveillance System survey adapted for use with deaf ASL users. Association between the respondent's communication method with the provider (i.e., categorized as either concordant-doctor signs or discordant-other) and preventive services use was assessed using logistic regression adjusting for race, gender, income, health status, health insurance, and education. Analyses were conducted in 2010. Deaf respondents who reported having a concordant provider were more likely to report a greater number of preventive services (OR=3.42, 95% CI=1.31, 8.93, p=0.0122) when compared to deaf respondents who reported having a discordant provider even after adjusting for race, gender, income, health status, health insurance, and education. In unadjusted analyses, deaf respondents who reported having a concordant provider were more likely to receive an influenza vaccination in the past year (OR=4.55, p=0.016) when compared to respondents who had a discordant provider. Language-concordant patient-provider communication is associated with higher appropriate use of preventive services by deaf ASL users. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Cyanine-based probe\\tag-peptide pair fluorescence protein imaging and fluorescence protein imaging methods

DOEpatents

Mayer-Cumblidge, M. Uljana; Cao, Haishi

2013-01-15

A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Preventive actions taken by workers after workers' health surveillance: a controlled trial.

PubMed

Boschman, J S; Van der Molen, H F; Frings-Dresen, M H W; Sluiter, J K

2013-12-01

To evaluate construction workers' preventive actions and occupational physician's (OPs) recommendations after a job-specific workers' health surveillance (WHS) compared with the currently used generic WHS. After the WHS, the OPs' written recommendations were captured. At the 3-month follow-up, the workers were asked about the preventive actions they had undertaken. A generalized linear mixed model was used to compare proportions of workers. At follow-up, the proportion of workers who reported taking preventive actions was significantly higher in the intervention group (80%, 44/55) than in the control group (67%, 80 of 121), (P = 0.04). In the intervention group, the OPs provided a higher proportion of workers with written recommendations (82%, 63 of 77, vs 57%, 69 of 121; P = 0.03). The job-specific WHS aided OPs in providing workers with recommendations and workers in undertaking (job-specific) preventive actions.

Assessing Knowledge and Perceptions Related to Preventive Methods and Treatment of Malaria in the Local Endemic Area of Trujillo, Honduras.

PubMed

Campodonico, Joanna; Sevilla-Martir, Javier; Arrizabalaga, Gustavo; Kochhar, Komal

2015-01-01

Malaria in Honduras is endemic and accounts for 40% of the total cases in Central America. Our goal was to assess knowledge of preventive methods and current treatment of malaria among the affected community of Trujillo, Honduras. A cross-sectional survey was administered to 71 individuals. Most respondents had a good understanding about common malaria symptoms but not about the complications associated with severe cases. More important, we found that less than 20% of the respondents recognized indoor residual sprays and insecticide-treated nets as effective preventive measures, which are the most efficient preventive methods. Our study highlights the perceptions the people of Trujillo have about malaria. From our observations, we put forward recommendations to implement a comprehensive campaign to educate the Trujillo population about malaria preventive methods and to recruit local and international efforts to distribute insecticide-treated nets.

Determinants of preventive oral health behaviour among senior dental students in Nigeria

PubMed Central

2013-01-01

Background To study the association between oral health behaviour of senior dental students in Nigeria and their gender, age, knowledge of preventive care, and attitudes towards preventive dentistry. Methods Questionnaires were administered to 179 senior dental students in the six dental schools in Nigeria. The questionnaire obtained information on age, gender, oral self-care, knowledge of preventive dental care and attitudes towards preventive dentistry. Attending a dental clinic for check-up by a dentist or a classmate within the last year was defined as preventive care use. Students who performed oral self-care and attended dental clinic for check-ups were noted to have complied with recommended oral self-care. Chi-square test and binary logistic regression models were used for statistical analyses. Results More male respondents agreed that the use of fluoride toothpaste was more important than the tooth brushing technique for caries prevention (P < 0.001). While the use of dental floss was very low (7.3%), more females were more likely to report using dental floss (p=0.03). Older students were also more likely to comply with recommended oral self-care (p<0.001). In binary regression models, respondents who were younger (p=0.04) and those with higher knowledge of preventive dental care (p=0.008) were more likely to consume sugary snacks less than once a day. Conclusion Gender differences in the awareness of the superiority of using fluoridated toothpaste over brushing in caries prevention; and in the use of dental floss were observed. While older students were more likely to comply with recommended oral self-care measures, younger students with good knowledge of preventive dental care were more likely to consume sugary snacks less than once a day. PMID:23777298

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Dippel, Diederik W J; Dijkgraaf, Marcel G W; van der Poll, Tom; Prins, Jan M; Vermeij, Frederique H; Roos, Yvo B W E M; Brouwer, Matthijs C; Zwinderman, Aeilko H; van de Beek, Diederik; Nederkoorn, Paul J

2014-10-01

Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Caregiver Burdens and Preventive Dental Care for Children with Autism Spectrum disorder, developmental disability and/or mental health conditions: National Survey of CSHCN, 2009–10

PubMed Central

Vohra, Rini; Sambamoorthi, Usha; Madhavan, S. Suresh

2016-01-01

Objective The purpose of this study is to examine the burdens of caregivers on one perception of the need and receipt of preventive dental care for a subset of children with special health care needs—children with Autism Spectrum disorder, developmental disability and/or mental health conditions (CASD/DD/MHC). Methods The authors used the 2009–2010 National Survey of CSHCN. The survey included questions addressing preventive dental care and caregivers’ financial, employment, and time-related burdens. The associations of these burdens on perceptions and receipt of preventive dental care use were analyzed with bivariate Chi square analyses and multinomial logistic regressions for CASD/DD/MHC (N=16,323). Results Overall, 16.3% of CASD/DD/MHC had an unmet preventive dental care need. There were 40.0% of caregivers who reported financial burden, 20.3% who reported employment burden, and 10.8% who reported time burden. A higher percentage of caregivers with financial burden, employment burden, and time-related burden reported that their CASD/DD/MHC did not receive needed preventive dental care (14.1 %, 16.5%, 17.7% respectively) compared to caregivers without financial, employment, or time burdens (9.0%, 9.6%, 11.0% respectively). Caregivers with financial burden (adjusted multinomial odds ratio, 1.38 [95%CI: 1.02, 1.86]) and employment burden (adjusted multinomial odds ratio, 1.45 [95%CI: 1.02, 2.06]) were more likely to report that their child did not receive preventive dental care despite perceived need compared to caregivers without financial or employment burdens. Conclusions for practice Unmet needs for preventive dental care were associated with employment and financial burdens of the caregivers of CASD/DD/MHC. PMID:27465058

Bimodal imprint chips for peptide screening: integration of high-throughput sequencing by MS and affinity analyses by surface plasmon resonance imaging.

PubMed

Wang, Weizhi; Li, Menglin; Wei, Zewen; Wang, Zihua; Bu, Xiangli; Lai, Wenjia; Yang, Shu; Gong, He; Zheng, Hui; Wang, Yuqiao; Liu, Ying; Li, Qin; Fang, Qiaojun; Hu, Zhiyuan

2014-04-15

Peptide probes and drugs have widespread applications in disease diagnostics and therapy. The demand for peptides ligands with high affinity and high specificity toward various targets has surged in the biomedical field in recent years. The traditional peptide screening procedure involves selection, sequencing, and characterization steps, and each step is manual and tedious. Herein, we developed a bimodal imprint microarray system to embrace the whole peptide screening process. Silver-sputtered silicon chip fabricated with microwell array can trap and pattern the candidate peptide beads in a one-well-one-bead manner. Peptides on beads were photocleaved in situ. A portion of the peptide in each well was transferred to a gold-coated chip to print the peptide array for high-throughput affinity analyses by surface plasmon resonance imaging (SPRi), and the peptide left in the silver-sputtered chip was ready for in situ single bead sequencing by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Using the bimodal imprint chip system, affinity peptides toward AHA were efficiently screened out from the 7 × 10(4) peptide library. The method provides a solution for high efficiency peptide screening.

Phosphorylation-dependent mineral-type specificity for apatite-binding peptide sequences.

PubMed

Addison, William N; Miller, Sharon J; Ramaswamy, Janani; Mansouri, Ahmad; Kohn, David H; McKee, Marc D

2010-12-01

Apatite-binding peptides discovered by phage display provide an alternative design method for creating functional biomaterials for bone and tooth tissue repair. A limitation of this approach is the absence of display peptide phosphorylation--a post-translational modification important to mineral-binding proteins. To refine the material specificity of a recently identified apatite-binding peptide, and to determine critical design parameters (net charge, charge distribution, amino acid sequence and composition) controlling peptide affinity for mineral, we investigated the effects of phosphorylation and sequence scrambling on peptide adsorption to four different apatites (bone-like mineral, and three types of apatite containing initially 0, 5.6 and 10.5% carbonate). Phosphorylation of the VTKHLNQISQSY peptide (VTK peptide) led to a 10-fold increase in peptide adsorption (compared to nonphosphorylated peptide) to bone-like mineral, and a 2-fold increase in adsorption to the carbonated apatite, but there was no effect of phosphorylation on peptide affinity to pure hydroxyapatite (without carbonate). Sequence scrambling of the nonphosphorylated VTK peptide enhanced its specificity for the bone-like mineral, but scrambled phosphorylated VTK peptide (pVTK) did not significantly alter mineral-binding suggesting that despite the importance of sequence order and/or charge distribution to mineral-binding, the enhanced binding after phosphorylation exceeds any further enhancement by altered sequence order. Osteoblast culture mineralization was dose-dependently inhibited by pVTK and to a significantly lesser extent by scrambled pVTK, while the nonphosphorylated and scrambled forms had no effect, indicating that inhibition of osteoblast mineralization is dependent on both peptide sequence and charge. Computational modeling of peptide-mineral interactions indicated a favorable change in binding energy upon phosphorylation that was unaffected by scrambling. In conclusion, phosphorylation of serine residues increases peptide specificity for bone-like mineral, whose adsorption is determined primarily by sequence composition and net charge as opposed to sequence order. However, sequence order in addition to net charge modulates the mineralization of osteoblast cultures. The ability of such peptides to inhibit mineralization has potential utility in the management of pathologic calcification. Copyright © 2010 Elsevier Ltd. All rights reserved.

Dynamics of Protonated Peptide Ion Collisions with Organic Surfaces: Consonance of Simulation and Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratihar, Subha; Barnes, George L.; Laskin, Julia

In this Perspective mass spectrometry experiments and chemical dynamics simulations are described which have explored the atomistic dynamics of protonated peptide ions, peptide-H+, colliding with organic surfaces. These studies have investigated surface-induced dissociation (SID) for which peptide-H+ fragments upon collision with the surface, peptide-H+ physisorption on the surface, soft landing (SL), and peptide-H+ reaction with the surface, reactive landing (RL). The simulations include QM+MM and QM/MM direct dynamics. For collisions with self-assembled monolayer (SAM) surfaces there is quite good agreement between experiment and simulation in the efficiency of energy transfer to the peptide-H+ ion’s internal degrees of freedom. Both themore » experiments and simulations show two mechanisms for peptide-H+ fragmentation, i.e. shattering and statistical, RRKM dynamics. Mechanisms for SL are probed in simulations of collisions of protonated dialanine with a perfluorinated SAM surface. RL has been studied experimentally for a number of peptide-H+ + surface systems, and qualitative agreement between simulation and experiment is found for two similar systems.« less

Preventive Care for the Elderly

PubMed Central

Mallery, Laurie; Rockwood, Kenneth

1992-01-01

The practice of preventive medicine in the elderly population needs to be revitalized. A review of the existing literature of preventive medicine for recommendations for the elderly uncovers two problems: most screening studies have had few elderly subjects, and the focus has been mainly on early disease detection and prevention of mortality. Prevention of morbidity and of functional impairment should receive more emphasis. PMID:21221297

Responses of proenkephalin Peptide F to aerobic exercise stress in the plasma and white blood cell biocompartments.

PubMed

Kraemer, William J; Fragala, Maren S; van Henegouwen, Wendy R H Beijersbergen; Gordon, Scott E; Bush, Jill A; Volek, Jeff S; Triplett, N Travis; Dunn-Lewis, Courtenay; Comstock, Brett A; Szivak, Tunde K; Flanagan, Shawn D; Hooper, David R; Luk, Hui-Ying; Mastro, Andrea M

2013-04-01

Proenkephalin Peptide F [107-140] is an enkephalin-containing peptide found predominantly within the adrenal medulla, co-packaged with epinephrine within the chromaffin granules. In vivo studies indicate that Peptide F has classic opioid analgesia effects; in vitro studies suggest potential immune cell interactions. In this investigation we examined patterns of Peptide F concentrations in different bio-compartments of the blood at rest and following sub-maximal cycle exercise to determine if Peptide F interacts with the white blood cell (WBC) bio-compartment during aerobic exercise. Eight physically active men (n=8) performed sub-maximal (80-85% V˙O2peak) cycle ergometer exercise for 30 min. Plasma Peptide F and WBC Peptide F immunoreactivity were examined pre-exercise, mid-exercise and immediately post-, 5-min post-, 15-min post-, 30-min post- and 60-min post-exercise and at similar time-points during a control condition (30 min rest). Peptide F concentrations significantly (p<0.05) increased at 5 and 60 min post-exercise, compared to pre-exercise concentrations. No significant increases in Peptide F concentrations in the WBC fraction were observed during or after exercise. However, a significant decrease was observed at 30 min post-exercise. An ultradian pattern of Peptide F distribution was apparent during rest. Furthermore, concentrations of T cells, B cells, NK cells, and total WBCs demonstrated significant changes in response to aerobic exercise. Data indicated that Peptide F was bound in significant molar concentrations in the WBC fraction and that this biocompartment may be one of the tissue targets for binding interactions. These data indicate that Peptide F is involved with immune cell modulation in the white blood circulatory biocompartment of blood. Copyright © 2013. Published by Elsevier Inc.

The Role of C-Peptide as Marker of Cardiometabolic Risk in Women With Polycystic Ovary Syndrome: A Controlled Study

PubMed Central

de Medeiros, Sebastiao Freitas; Angelo, Laura Camila Antunes; de Medeiros, Matheus Antonio Souto; Banhara, Camila Regis; Barbosa, Bruna Barcelo; Yamamoto, Marcia Marly Winck

2018-01-01

Background The aim of this study was to examine the role of C-peptide as a biological marker of cardiometabolic risk in polycystic ovary syndrome (PCOS). Methods This case-control study enrolled 385 PCOS patients and 240 normal cycling women. Anthropometric and clinical variables were taken at first visit. Fasting C-peptide, glucose, lipids, and hormone measurements were performed. Simple and multiple correlations between C-peptide and other variables associated with dysmetabolism and cardiovascular disease were examined. Results C-peptide was well correlated with several anthropometric, metabolic, and endocrine parameters. In PCOS patients, stepwise multiple regression including C-peptide as the criterion variable and other predictors of cardiovascular disease risk provided a significant model in which the fasting C-peptide/glucose ratio, glucose, body weight, and free estrogen index (FEI) were retained (adjusted R2 = 0.988, F = 7.161, P = 0.008). Conclusion C-peptide levels alone or combined with C-peptide/glucose ratio, glucose, body weight, and FEI provided a significant model to identify PCOS patients with higher risk of future cardiometabolic diseases. PMID:29416587

A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Chaoyang; Zhang, Pengju; Jiang, Anli

C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover,more » C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.« less

T7 lytic phage-displayed peptide libraries exhibit less sequence bias than M13 filamentous phage-displayed peptide libraries.

PubMed

Krumpe, Lauren R H; Atkinson, Andrew J; Smythers, Gary W; Kandel, Andrea; Schumacher, Kathryn M; McMahon, James B; Makowski, Lee; Mori, Toshiyuki

2006-08-01

We investigated whether the T7 system of phage display could produce peptide libraries of greater diversity than the M13 system of phage display due to the differing processes of lytic and filamentous phage morphogenesis. Using a bioinformatics-assisted computational approach, collections of random peptide sequences obtained from a T7 12-mer library (X(12)) and a T7 7-mer disulfide-constrained library (CX(7)C) were analyzed and compared with peptide populations obtained from New England BioLabs' M13 Ph.D.-12 and Ph.D.-C7C libraries. Based on this analysis, peptide libraries constructed with the T7 system have fewer amino acid biases, increased peptide diversity, and more normal distributions of peptide net charge and hydropathy than the M13 libraries. The greater diversity of T7-displayed libraries provides a potential resource of novel binding peptides for new as well as previously studied molecular targets. To demonstrate their utility, several of the T7-displayed peptide libraries were screened for streptavidin- and neutravidin-binding phage. Novel binding motifs were identified for each protein.

Discovery of an artificial peptide agonist to the fibroblast growth factor receptor 1c/βKlotho complex from random peptide T7 phage display.

PubMed

Sakamoto, Kotaro; Kawata, Yayoi; Masuda, Yasushi; Umemoto, Tadashi; Ito, Takashi; Asami, Taiji; Takekawa, Shiro; Ohtaki, Tetsuya; Inooka, Hiroshi

2016-11-04

Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually. After subsequent peptide dimerization using a short polyethyleneglycol (PEG) linker, the dimeric F91-8A07 peptide showed higher potent agonist activity than that of FGF21 in cultured primary human adipocytes. Moreover, the dimeric peptide led to an expression of the early growth response protein-1 (Egr-1) mRNA in vivo, which is a target gene of FGFR1c. To the best of our knowledge, this is the first report of a FGFR1c/KLB complex-selective artificial peptide agonist. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A designed beta-hairpin forming peptide undergoes a consecutive stepwise process for self-assembly into nanofibrils.

PubMed

Wang, Chong; Sha, Yinlin

2010-04-01

We used a de novo designed, beta-hairpin forming T1 peptide as a model to investigate the kinetics of peptide fibrogenesis by a combination of light scattering (LS), circular dichroism (CD), fluorescence, and atomic force microscopy (AFM). The results demonstrate that the T1 fibrogenesis undergoes a consecutive stepwise process, with a high degree of cooperation, presenting sigmoidal time-courses of the peptide aggregation, the subsequent conformational conversion of the backbone, and the peptide sidechains' rearrangement. We suggest that the conformational conversion was initiated after the peptide aggregates reach a dimensional size threshold, which could be a key step in the formation of beta-structural nuclei that catalyze the subsequent reactions. Furthermore, besides triggering the peptide aggregation, the interactions between the peptide sidechains predominately facilitate the regular alignment of the peptide molecules and the formation of a well-defined suprastructure. This work provides an insight of the hierarchical self-assembly of beta-hairpin forming peptides. It is helpful for designing beta-structural peptides for self-assembly into nanowires, which would have potential applications in the construction of nano-materials.

Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses.

PubMed

Moon, Ho-Jin; Nikapitiya, Chamilani; Lee, Hyun-Cheol; Park, Min-Eun; Kim, Jae-Hoon; Kim, Tae-Hwan; Yoon, Ji-Eun; Cho, Won-Kyung; Ma, Jin Yeul; Kim, Chul-Joong; Jung, Jae U; Lee, Jong-Soo

2017-07-07

The antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission. Moreover, TAT-Kα2 peptide protected the mice, that were challenged with lethal doses of highly pathogenic influenza A H5N1 or H1N1 viruses. Mechanistically, we found that TAT-Kα2 peptide destabilized the viral membranes, depending on their lipid composition of the viral envelop. In addition to IAV, the Kα2 peptide inhibited infections with enveloped viruses, such as Vesicular Stomatitis Virus (VSV) and Respiratory Syncytial Virus (RSV), without cytotoxicity. These results suggest that TAT-Kα2 peptide is a potential antiviral agent for controlling emerging or re-emerging enveloped viruses, particularly diverse subtypes of IAVs.

Preventive Biomechanics: A Paradigm Shift With a Translational Approach to Injury Prevention.

PubMed

Hewett, Timothy E; Bates, Nathaniel A

2017-09-01

Preventive medicine techniques have alleviated billions of dollars' worth of the economic burden in the medical care system through the implementation of vaccinations and screenings before the onset of disease symptoms. Knowledge of biomechanical tendencies has progressed rapidly over the past 20 years such that clinicians can identify, in healthy athletes, the underlying mechanisms that lead to catastrophic injuries such as anterior cruciate ligament (ACL) ruptures. As such, preventive medicine concepts can be applied to noncontact musculoskeletal injuries to reduce the economic burden of sports medicine treatments and enhance the long-term health of athletes. To illustrate the practical medical benefits that could be gained from preventive biomechanics applied to the ACL as well as the need and feasibility for the broad implementation of these principles. Literature review. The recent literature pertinent to the screening and prevention of musculoskeletal injuries was reviewed and compiled into a clinical commentary on the current state and applicability of preventive biomechanics. Investigators have identified neuromuscular training protocols that screen for and correct the underlying biomechanical deficits that lead to ACL injuries. The literature shows that when athletes comply with these prescribed training protocols, the incidence of injuries is significantly reduced within that population. Such preventive biomechanics practices employ basic training methods that would be familiar to athletic coaches and have the potential to save billions of dollars in cost in sports medicine. The widespread implementation of preventive biomechanics concepts could profoundly affect the field of sports medicine with a minimum of initial investment.

Delivery of preventive care: the national Canadian Family Physician Cancer and Chronic Disease Prevention Survey.

PubMed

Katz, Alan; Lambert-Lanning, Anita; Miller, Anthony; Kaminsky, Barbara; Enns, Jennifer

2012-01-01

To determine family physicians' practice of, knowledge about, and attitudes toward delivering preventive care during periodic health examinations (PHEs). A stratified sample of 5013 members of the College of Family Physicians of Canada were randomly selected to receive a questionnaire by mail. Descriptive analysis was performed on a national data set of 1010 respondents. Canada. A sample of family physicians from each Canadian province. Physicians were asked questions about whether they addressed aspects of preventive care, such as tobacco smoking, nutrition, physical activity, alcohol intake, and sun exposure with patients during PHEs. The questions were designed to gauge attitudes and identify barriers to the provision of preventive care. Most respondents (87% to 89%) indicated that they were comfortable counseling their patients about issues such as nutrition, physical activity, and alcohol consumption; however, many of these respondents did not refer their patients to specialists or provide them with additional resources to educate patients about the health risks of their conditions. While tobacco smoking risks and cessation were addressed by most family physicians (79%) during PHEs, other topics, such as sun exposure, were often overlooked. The results of this survey indicate that while many family physicians follow the evidence-based guidelines for preventive care, current levels of preventive care in the primary care setting are below national standards. It is critical that Canadians receive optimal preventive care to improve the outlook of the chronic disease burden on the health care system.

Governance of malaria prevention: How decision-makers' and pregnant women's sensemaking contribute to unintended consequences.

PubMed

Danhoundo, Georges; Wiktorowicz, Mary E; Yaya, Sanni

2017-03-01

Although malaria in pregnancy predisposes women to increased perinatal mortality and morbidity, complex issues underlie its persistence. To develop a better understanding of the factors affecting women's access to Intermittent Preventive Treatment in Benin, we used the theoretical lens of "sensemaking" to clarify policymakers', health professionals', and women's perspectives concerning preventive policies and barriers to access. Several assumptions were found to underlie Benin's malaria preventive policy that contribute to the unintended effect of deterring pregnant women in poverty from accessing preventive treatment. Health system dysfunctions including drug shortages and deficiencies in health care professionalism exacerbate the unintended effect.

Activation of multiple mitogen-activated protein kinases by recombinant calcitonin gene-related peptide receptor.

PubMed

Parameswaran, N; Disa, J; Spielman, W S; Brooks, D P; Nambi, P; Aiyar, N

2000-02-18

Calcitonin gene-related peptide is a 37-amino-acid neuropeptide and a potent vasodilator. Although calcitonin gene-related peptide has been shown to have a number of effects in a variety of systems, the mechanisms of action and the intracellular signaling pathways, especially the regulation of mitogen-activated protien kinase (MAPK) pathway, is not known. In the present study we investigated the role of calcitonin gene-related peptide in the regulation of MAPKs in human embryonic kidney (HEK) 293 cells stably transfected with a recombinant porcine calcitonin gene-related peptide-1 receptor. Calcitonin gene-related peptide caused a significant dose-dependent increase in cAMP response and the effect was inhibited by calcitonin gene-related peptide(8-37), the calcitonin gene-related peptide-receptor antagonist. Calcitonin gene-related peptide also caused a time- and concentration-dependent increase in extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (P38 MAPK) activities, with apparently no significant change in cjun-N-terminal kinase (JNK) activity. Forskolin, a direct activator of adenylyl cyclase also stimulated ERK and P38 activities in these cells suggesting the invovement of cAMP in this process. Calcitonin gene-related peptide-stimulated ERK and P38 MAPK activities were inhibited significantly by calcitonin gene-related peptide receptor antagonist, calcitonin gene-related peptide-(8-37) suggesting the involvement of calcitonin gene-related peptide-1 receptor. Preincubation of the cells with the cAMP-dependent protein kinase inhibitor, H89 [¿N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride¿] inhibited calcitonin gene-related peptide-mediated activation of ERK and p38 kinases. On the other hand, preincubation of the cells with wortmannin ¿[1S-(1alpha,6balpha,9abeta,11alpha, 11bbeta)]-11-(acetyloxy)-1,6b,7,8,9a,10,11, 11b-octahydro-1-(methoxymethyl)-9a,11b-dimethyl-3H-furo[4,3, 2-de]indeno[4,5-h]-2-benzopyran-3,6,9-trione¿, a PI3-kinase inhibitor, attenuated only calcitonin gene-related peptide-induced ERK and not P38 MAPK activation. Thus, these data suggest that activation of ERK by calcitonin gene-related peptide involves a H89-sensitive protein kinase A and a wortmannin-sensitive PI3-kinase while activation of p38 MAPK by calcitonin gene-related peptide involves only the H89 sensitive pathway and is independent of PI3 kinase. This also suggests that although both ERK and P38 can be activated by protein kinase A, the distal signaling components to protein kinase A in the activation of these two kinases (ERK and P38) are different.

Nanoliposome is a Promising Carrier of Protein and Peptide Biomolecule for the Treatment of Cancer.

PubMed

Kumar Giri, Tapan; Giri, Ayan; Kumar Barman, Tapan; Maity, Subhasis

2016-01-01

Nano-liposomes are the newly developed delivery systems for cancer therapy that are finding a position particularly suitable as peptide and protein carriers. These are three-layered self-assembled structures with nanoparticulate carrier systems. The overall pharmacological properties of commonly used protein and peptide in cancer therapy can be improved by the incorporation of protein and peptide into the nano-liposome. The surface modifications can be made liposomes to make compatible with targeting ligands has made these nanocarriers for targeted delivery. This review discusses the method of preparation and characterization of liposome based protein peptide delivery for the treatment of cancer. This review also explores latest work intended for targeted treatment of cancer by nano-liposomal protein and peptide delivery system. This type of delivery is targeting protein and peptide to tumor site by avoiding the reticuloendothelial system. Methods of nano-liposome delivery containing protein and peptide are also highlighted.

[Protective effect of garlic oil given at different time against acute liver injury induced by CCl4].

PubMed

Zhang, Gui-li; Zeng, Tao; Wang, Qing-shan; Zhao, Xiu-lan; Song, Fu-yong; Xie, Ke-qin

2010-03-01

To observe and compare the protective effect of garlic oil against carbon tetrachloride (CCL)-induced acute liver injury. The experiments include 4 preventive groups and 2 therapeutic groups. In every preventive and therapeutic group, the mice were randomized into 6 groups with 15 each, including one negative control group, one solvent control group, one CCl4 model group and 3 garlic oil groups (25, 50, and 100 mg/kg body weight). Before given a single gavage of CCl4 (80 mg/kg), the mice were pretreated with garlic oil by gavage in preventive group 1 (30 days, once daily), preventive group 2 (5 days, once daily), preventive group 3 (ahead of 2 h, once), preventive group 4 (immediately, once) or the vehicle (corn oil, 10 ml/kg) in solvent control group. In therapeutic groups, the mice were gavaged garlic oil 2 h (once, in therapeutic 1) or for 5 days (once daily, in therapeutic 2) after administration CCl. After 24 h of the last administration, blood was collected and centrifuged at 2500 r/min at 4 degrees C for 10 min, and serum was removed to measure ALT and AST activities. The liver was dissected, weighed to calculate the liver coefficient (relative liver weight). At the same time, the liver samples were studied by histological examinations. Compared with negative group, the liver coefficient and the activities of ALT and AST in serum of model group were increased remarkably (P < 0.01). Compared with CCl model group, the liver coefficient and the activities of ALT and AST in serum were decreased significantly (P < 0.01) by garlic oil dose-dependently in each preventive group. Simultaneously, histological assessment showed that garlic oil effectively alleviated hepatocyte injuries induced by CCl4. Comparing the preventive effects of garlic oil in every group, it was better in preventive group 3 than others. However, all indexes and histological examinations in therapeutic group 1 did not show the difference with those of CCl4 model group. In therapeutic group 2, all indexes recovered after 5 d of CCl4 administration. Garlic oil can prevent acute liver injury induced by CCl4 and the effect is better in ahead of 2 h group than others.

The American College of Preventive Medicine Policy Recommendations on Reducing and Preventing Firearm-Related Injuries and Deaths.

PubMed

Strong, Bethany L; Ballard, Sarah-Blythe; Braund, Wendy

2016-12-01

The American College of Preventive Medicine Policy Committee makes policy guidelines and recommendations on preventive medicine and public health topics for public health decision makers. After a review of the current evidence available in 2016, the College is providing a consensus-based set of policy recommendations designed to reduce firearm-related morbidity and mortality in the U.S. These guidelines address seven general areas pertaining to the public health threat posed by firearms: gun sales and background checks, assault weapons and high-capacity weapons, mental health, research funding, gun storage laws, and physician counseling. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

PaFlexPepDock: parallel ab-initio docking of peptides onto their receptors with full flexibility based on Rosetta.

PubMed

Li, Haiou; Lu, Liyao; Chen, Rong; Quan, Lijun; Xia, Xiaoyan; Lü, Qiang

2014-01-01

Structural information related to protein-peptide complexes can be very useful for novel drug discovery and design. The computational docking of protein and peptide can supplement the structural information available on protein-peptide interactions explored by experimental ways. Protein-peptide docking of this paper can be described as three processes that occur in parallel: ab-initio peptide folding, peptide docking with its receptor, and refinement of some flexible areas of the receptor as the peptide is approaching. Several existing methods have been used to sample the degrees of freedom in the three processes, which are usually triggered in an organized sequential scheme. In this paper, we proposed a parallel approach that combines all the three processes during the docking of a folding peptide with a flexible receptor. This approach mimics the actual protein-peptide docking process in parallel way, and is expected to deliver better performance than sequential approaches. We used 22 unbound protein-peptide docking examples to evaluate our method. Our analysis of the results showed that the explicit refinement of the flexible areas of the receptor facilitated more accurate modeling of the interfaces of the complexes, while combining all of the moves in parallel helped the constructing of energy funnels for predictions.

Elucidation of peptide-directed palladium surface structure for biologically tunable nanocatalysts.

PubMed

Bedford, Nicholas M; Ramezani-Dakhel, Hadi; Slocik, Joseph M; Briggs, Beverly D; Ren, Yang; Frenkel, Anatoly I; Petkov, Valeri; Heinz, Hendrik; Naik, Rajesh R; Knecht, Marc R

2015-05-26

Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, which was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then elucidated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences.

Elucidation of Peptide-Directed Palladium Surface Structure for Biologically Tunable Nanocatalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bedford, Nicholas M.; Ramezani-Dakhel, Hadi; Slocik, Joseph M.

Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, whichmore » was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then eluddated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences« less

Cancer-preventive activities of tocopherols and tocotrienols.

PubMed

Ju, Jihyeung; Picinich, Sonia C; Yang, Zhihong; Zhao, Yang; Suh, Nanjoo; Kong, Ah-Ng; Yang, Chung S

2010-04-01

The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.

Comparing and decomposing differences in preventive and hospital care: USA versus Taiwan.

PubMed

Hsiou, Tiffany R; Pylypchuk, Yuriy

2012-07-01

As the USA expands health insurance coverage, comparing utilization of healthcare services with countries like Taiwan that already have universal coverage can highlight problematic areas of each system. The universal coverage plan of Taiwan is the newest among developed countries, and it is known for readily providing access to care at low costs. However, Taiwan experiences problems on the supply side, such as inadequate compensation for providers, especially in the area of preventive care. We compare the use of preventive, hospital, and emergency care between the USA and Taiwan. The rate of preventive care use is much higher in the USA than in Taiwan, whereas the use of hospital and emergency care is about the same. Results of our decomposition analysis suggest that higher levels of education and income, along with inferior health status in the USA, are significant factors, each explaining between 7% and 15% of the gap in preventive care use. Our analysis suggests that, in addition to universal coverage, proper remuneration schemes, education levels, and cultural attitudes towards health care are important factors that influence the use of preventive care. Copyright © 2011 John Wiley & Sons, Ltd.

N-Sulfanylethylaminooxybutyramide (SEAoxy): A Crypto-Thioester Compatible with Fmoc Solid-Phase Peptide Synthesis.

PubMed

Tsuda, Shugo; Mochizuki, Masayoshi; Sakamoto, Ken; Denda, Masaya; Nishio, Hideki; Otaka, Akira; Yoshiya, Taku

2016-11-18

An N-sulfanylethylaminooxybutyramide (SEAoxy) has been developed as a novel thioester equivalent for native chemical ligation. SEAoxy peptide was straightforwardly synthesized by conventional Fmoc solid-phase peptide synthesis without a problem. Moreover, SEAoxy peptide could be directly applied to native chemical ligation owing to the intramolecular N-to-S acyl shift that releases the peptide-thioester in situ. This methodology was successfully applied to the synthesis of two bioactive peptides.

Molecular dynamics study of a nanotube-binding amphiphilic helical peptide at different water/hydrophobic interfaces.

PubMed

Chiu, Chi-Cheng; Dieckmann, Gregg R; Nielsen, Steven O

2008-12-25

Many potential applications of single-walled carbon nanotubes (SWNTs) require that they be isolated from one another. This may be accomplished through covalent or noncovalent SWNT functionalization. The noncovalent approach preserves the intrinsic electrical, optical, and mechanical properties of SWNTs and can be achieved by dispersing SWNTs in aqueous solution using surfactants, polymers, or biomacromolecules like DNA or polypeptides. The designed amphiphilic helical peptide nano-1, which contains hydrophobic valine and aromatic phenylalanine residues for interaction with SWNTs and glutamic acid and lysine residues for water solubility, has been shown to debundle and disperse SWNTs, although the details of the peptide-SWNT interactions await elucidation. Here we use fully atomistic molecular dynamics simulations to investigate the nano-1 peptide at three different water/hydrophobic interfaces: water/oil, water/graphite, and water/SWNT. The amphiphilic nature of the peptide is characterized by its secondary structure, peptide-water hydrogen bonding, and peptide-hydrophobic surface van der Waals energy. We show that nano-1 has reduced amphiphilic character at the water/oil interface because the peptide helix penetrates into the hydrophobic phase. The peptide alpha-helix cannot match its hydrophobic face to the rigid planar graphite surface without partially unfolding. In contrast, nano-1 can curve on the SWNT surface in an alpha-helical conformation to simultaneously maximize its hydrophobic contacts with the SWNT and its hydrogen bonds with water. The molecular insight into the peptide conformation at the various hydrophobic surfaces provides guidelines for future peptide design.

Protein nanopore-based, single-molecule exploration of copper binding to an antimicrobial-derived, histidine-containing chimera peptide.

PubMed

Mereuta, Loredana; Schiopu, Irina; Asandei, Alina; Park, Yoonkyung; Hahm, Kyung-Soo; Luchian, Tudor

2012-12-11

Metal ions binding exert a crucial influence upon the aggregation properties and stability of peptides, and the propensity of folding in various substates. Herein, we demonstrate the use of the α-HL protein as a powerful nanoscopic tool to probe Cu(2+)-triggered physicochemical changes of a 20 aminoacids long, antimicrobial-derived chimera peptide with a His residue as metal-binding site, and simultaneously dissect the kinetics of the free- and Cu(2+)-bound peptide interaction to the α-HL pore. Combining single-molecule electrophysiology on reconstituted lipid membranes and fluorescence spectroscopy, we show that the association rate constant between the α-HL pore and a Cu(2+)-free peptide is higher than that of a Cu(2+)-complexed peptide. We posit that mainly due to conformational changes induced by the bound Cu(2+) on the peptide, the resulting complex encounters a higher energy barrier toward its association with the protein pore, stemming most likely from an extra entropy cost needed to fit the Cu(2+)-complexed peptide within the α-HL lumen region. The lower dissociation rate constant of the Cu(2+)-complexed peptide from α-HL pore, as compared to that of Cu(2+)-free peptide, supports the existence of a deeper free energy well for the protein interaction with a Cu(2+)-complexed peptide, which may be indicative of specific Cu(2+)-mediated contributions to the binding of the Cu(2+)-complexed peptide within the pore lumen.

Anticancer and cancer preventive properties of marine polysaccharides: some results and prospects.

PubMed

Fedorov, Sergey N; Ermakova, Svetlana P; Zvyagintseva, Tatyana N; Stonik, Valentin A

2013-12-02

Many marine-derived polysaccharides and their analogues have been reported as showing anticancer and cancer preventive properties. These compounds demonstrate interesting activities and special modes of action, differing from each other in both structure and toxicity profile. Herein, literature data concerning anticancer and cancer preventive marine polysaccharides are reviewed. The structural diversity, the biological activities, and the molecular mechanisms of their action are discussed.

A preventive groupwork intervention with new immigrants to Israel.

PubMed

Roskin, M

1986-03-01

The act of immigration brings with it numerous major life changes and requires considerable social readjustment. Immigrants are, however, seldom offered specific training in how to effectively interact in a new culture. This paper describes an initial preventive groupwork effort to help English-speaking immigrants living in an Israeli absorption center to adjust successfully to life in a new culture. Suggestions for future preventive interventions with immigrants are considered.

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

PubMed Central

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2016-01-01

Objective Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Methods Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6–8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) were orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Results Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. Conclusion E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. PMID:26315492

Cholesterol-directed nanoparticle assemblies based on single amino acid peptide mutations activate cellular uptake and decrease tumor volume† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02616a Click here for additional data file.

PubMed Central

Li, Shang; Zou, Rongfeng; Tu, Yaoquan

2017-01-01

Peptide drugs have been difficult to translate into effective therapies due to their low in vivo stability. Here, we report a strategy to develop peptide-based therapeutic nanoparticles by screening a peptide library differing by single-site amino acid mutations of lysine-modified cholesterol. Certain cholesterol-modified peptides are found to promote and stabilize peptide α-helix formation, resulting in selectively cell-permeable peptides. One cholesterol-modified peptide self-assembles into stable nanoparticles with considerable α-helix propensity stabilized by intermolecular van der Waals interactions between inter-peptide cholesterol molecules, and shows 68.3% stability after incubation with serum for 16 h. The nanoparticles in turn interact with cell membrane cholesterols that are disproportionately present in cancer cell membranes, inducing lipid raft-mediated endocytosis and cancer cell death. Our results introduce a strategy to identify peptide nanoparticles that can effectively reduce tumor volumes when administered to in in vivo mice models. Our results also provide a simple platform for developing peptide-based anticancer drugs. PMID:29163910

Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge

PubMed Central

Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

2010-01-01

The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-γin vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV. PMID:20331473

Functional selection of a type IV pili-binding peptide that specifically inhibits Salmonella Typhi adhesion to/invasion of human monocytic cells.

PubMed

Wu, Hong-Yan; Zhang, Xiao-Lian; Pan, Qin; Wu, Jianguo

2005-11-01

Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.

Preventive dental health care experiences of preschool-age children with special health care needs

PubMed Central

Huebner, Colleen E.; Chi, Donald L.; Masterson, Erin; Milgrom, Peter

2014-01-01

Purpose This study examined the preventive dental health care experiences of young children with special needs and determined the feasibility of conducting clinical dental examinations at a community-based early intervention services center. Methods Study methods included 90 parent interviews and dental examinations of their preschool-age children. Results Thirteen percent of the children received optimal preventive care, defined as twice daily tooth brushing with fluoridated toothpaste and two preventive dental visits in the prior 12 months; 37 percent experienced care that fell short in both areas. Optimal care was more common among children of parents who reported tooth brushing was not a struggle and those with a personal dentist. Parents' opinion of the study experience was generally positive. Conclusions Few children with special needs receive effective preventive care early, when primary prevention could be achieved. Barriers to optimal care could be readily addressed by the dental community in coordination with early intervention providers. PMID:25082666

The chromatography-free release, isolation and purification of recombinant peptide for fibril self-assembly.

PubMed

Hartmann, B M; Kaar, W; Yoo, I K; Lua, L H L; Falconer, R J; Middelberg, A P J

2009-12-01

One of the major expenses associated with recombinant peptide production is the use of chromatography in the isolation and purification stages of a bioprocess. Here we report a chromatography-free isolation and purification process for recombinant peptide expressed in Escherichia coli (E. coli). Initial peptide release is by homogenization and then by enzymatic cleavage of the peptide-containing fusion protein, directly in the E. coli homogenate. Release is followed by selective solvent precipitation (SSP) to isolate and purify the peptide away from larger cell contaminants. Specifically, we expressed in E. coli the self-assembling beta-sheet forming peptide P(11)-2 in fusion to thioredoxin. Homogenate was heat treated (55 degrees C, 15 min) and then incubated with tobacco etch virus protease (TEVp) to release P(11)-2 having a native N-terminus. SSP with ethanol at room temperature then removed contaminating proteins in an integrated isolation-purification step; it proved necessary to add 250 mM NaCl to homogenate to prevent P(11)-2 from partitioning to the precipitate. This process structure gave recombinant P(11)-2 peptide at 97% polypeptide purity and 40% overall yield, without a single chromatography step. Following buffer-exchange of the 97% pure product by bind-elute chromatography into defined chemical conditions, the resulting peptide was shown to be functionally active and able to form self-assembled fibrils. To the best of our knowledge, this manuscript reports the first published process for chromatography-free recombinant peptide release, isolation and purification. The process proved able to deliver functional recombinant peptide at high purity and potentially low cost, opening cost-sensitive materials applications for peptide-based materials.

Peptide modified nanofibrous scaffold promotes human mesenchymal stem cell proliferation and long-term passaging.

PubMed

Mobasseri, Rezvan; Tian, Lingling; Soleimani, Masoud; Ramakrishna, Seeram; Naderi-Manesh, Hossein

2018-03-01

Long-term culture, passage and proliferation of human mesenchymal stem cells (hMSCs) cause loss of their stemness properties including self-renewal and multipotency. By optimizing the MSCs environment in vitro, maintaining the stemness state and better controlling the cell fate might be possible. We have recently reported the significant effects of bioactive Tat protein-derived peptide named R-peptide on hMSC adhesion, morphology and proliferation, which has demonstrated R-peptide enhanced MSC early adhesion and proliferation in comparison to other bioactive molecules including RGD peptide, fibronectin and collagen. In this study, R-peptide was used to evaluate stemness properties of MSCs after long-term passaging. R-peptide conjugated poly caprolactone (PCL) nanofibrous scaffold and unmodified nanofibrous scaffold were used to study the impact of R-peptide modified PCL nanofibers and PCL nanofibers on cell behavior. The results showed early formation of focal adhesion (FA) complex on R-peptide modified scaffolds at 30min after cell seeding. The rate of cell proliferation was significantly increased due to presence of R-peptide, and the MSCs marker analyses using flow cytometry and immunocytochemistry staining proved the ability of R-peptide to maintain mesenchymal stem cell properties (high proliferation, expression of multipotent markers and differentiation capacity) even after long-term passage culturing. Accordingly, our (The) results concluded that bioactive R-peptide in combination with nanofibrous scaffold can mimic the native ECM comprising micro/nano architecture and biochemical molecules in a best way. The designed scaffold can link extracellular matrix (ECM) to nucleus via formation of FA and organization of cytoskeleton, causing fast and strong attachment of MSCs and allowing integrin-mediated signaling to start. Copyright © 2017 Elsevier B.V. All rights reserved.

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model.

PubMed

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2015-10-01

Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) was orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20 μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Preventive oral health intervention for pediatricians.

PubMed

2008-12-01

This policy is a compilation of current concepts and scientific evidence required to understand and implement practice-based preventive oral health programs designed to improve oral health outcomes for all children and especially children at significant risk of dental decay. In addition, it reviews cariology and caries risk assessment and defines, through available evidence, appropriate recommendations for preventive oral health intervention by primary care pediatric practitioners.

A cardioactive peptide from the southern armyworm, Spodoptera eridania.

PubMed

Furuya, K; Hackett, M; Cirelli, M A; Schegg, K M; Wang, H; Shabanowitz, J; Hunt, D F; Schooley, D A

1999-01-01

A cardioactive peptide was isolated from extracts of whole heads of the southern armyworm, Spodoptera eridania. This peptide has the sequence ENFAVGCTPGYQRTADGRCKPTF (Mr = 2516.8), determined from both Edman sequencing and tandem mass spectrometry in combination with off-line micropreparative capillary liquid chromatography. This peptide, termed Spoer-CAP23, has excitatory effects on a semi-isolated heart from larval Manduca sexta, causing an inotropic effect at low concentrations of peptide and chronotropic and inotropic effects at high doses. The threshold concentration for stimulatory effects of the synthetic peptide on the semi-isolated heart was about 1 nM, suggesting a physiological role as a neuropeptide.

Availability of Maintained Systems

DTIC Science & Technology

1983-03-01

o -4 >1 w Administrative0 and Logistic Time 0 -4W 0 E-44 4q Operating Time ( > .1 Preventive Maintenance | 04 SOperating Time t Ready Time Operatinf...point in time. It excludes ready time, preventive-maintenance downtime, logistic time, and waiting or administrative downtime. It may be expressed as: A...satisfactorily at a given point in time. It excludes logistic tim-3 and waiting or administrative downtime. It includes active preventive and

Peptide functionalized gold nanoparticles: the influence of pH on binding efficiency

NASA Astrophysics Data System (ADS)

Harrison, Emma; Hamilton, Jeremy W. J.; Macias-Montero, Manuel; Dixon, Dorian

2017-07-01

We report herein on the synthesis of mixed monolayer gold nanoparticles (AuNPs) capped with both polyethylene glycol (PEG) and one of three peptides. Either a receptor-mediated endocytosis peptide, an endosomal escape pathway (H5WYG) peptide or the Nrp-1 targeting RGD peptide (CRGDK) labeled with FITC. All three peptides have a thiol containing cysteine residue which can be used to bind the peptides to the AuNPs. In order to investigate the influence of pH on peptide attachment, PEGylated AuNPs were centrifuged, the supernatant removed, and the nanoparticles were then re-suspended in a range of pH buffer solutions above, below and at the respective isoelectric points of the peptides before co-functionalization. Peptide attachment was investigated using dynamic light scattering, Ultra-violet visible spectroscopy (UV/Vis), FTIR and photo luminescence spectroscopy. UV/Vis analysis coupled with protein assay results and photoluminescence of the FITC tagged RGD peptide concluded that a pH of ∼8 optimized the cysteine binding and stability, irrespective of the peptide used.

Stabilization of coiled-coil peptide domains by introduction of trifluoroleucine.

PubMed

Tang, Y; Ghirlanda, G; Vaidehi, N; Kua, J; Mainz, D T; Goddard III, W A; DeGrado, W F; Tirrell, D A

2001-03-06

Substitution of leucine residues by 5,5,5-trifluoroleucine at the d-positions of the leucine zipper peptide GCN4-p1d increases the thermal stability of the coiled-coil structure. The midpoint thermal unfolding temperature of the fluorinated peptide is elevated by 13 degrees C at 30 microM peptide concentration. The modified peptide is more resistant to chaotropic denaturants, and the free energy of folding of the fluorinated peptide is 0.5-1.2 kcal/mol larger than that of the hydrogenated form. A similarly fluorinated form of the DNA-binding peptide GCN4-bZip binds to target DNA sequences with affinity and specificity identical to those of the hydrogenated form, while demonstrating enhanced thermal stability. Molecular dynamics simulation on the fluorinated GCN4-p1d peptide using the Surface Generalized Born implicit solvation model revealed that the coiled-coil binding energy is 55% more favorable upon fluorination. These results suggest that fluorination of hydrophobic substructures in peptides and proteins may provide new means of increasing protein stability, enhancing protein assembly, and strengthening receptor-ligand interactions.

Interactions of S-peptide analogue in aqueous urea and trimethylamine-N-oxide solutions: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Sarma, Rahul; Paul, Sandip

2013-07-01

The ability of the osmolyte, trimethylamine-N-oxide (TMAO), to protect proteins from deleterious effect of urea, another commonly available osmolyte, is well-established. However, the molecular mechanism of this counteraction is not understood yet. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here molecular dynamics simulation results of a 15-residue model peptide in two different conformations: helix and extended. For both conformations, simulations are carried out in pure water as well as in binary and ternary aqueous solutions of urea and TMAO. Analysis of solvation characteristics reveals direct interactions of urea and TMAO with peptide residues. However, the number of TMAO molecules that enter in the first solvation shell of the peptide is significantly lower than that of urea, and, unlike water and urea, TMAO shows its inability to form hydrogen bond with backbone oxygen and negatively charged sidechains. Preferential accumulation of urea near the peptide surface and preferential exclusion of TMAO from the peptide surface are observed. Inclusion of osmolytes in the peptide solvation shell leads to dehydration of the peptide in binary and ternary solutions of urea and TMAO. Solvation of peptide residues are investigated more closely by calculating the number of hydrogen bonds between the peptide and solution species. It is found that number of hydrogen bonds formed by the peptide with solution species increases in binary urea solution (relative to pure water) and this relative enhancement in hydrogen bond number reduces upon addition of TMAO. Our simulation results also suggest that, in the ternary solution, the peptide solvation layer is better mixed in terms of water and urea as compared to binary urea solution. Implications of the results for counteraction mechanism of TMAO are discussed.

Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy.

PubMed

Vasconcelos, Luís; Lehto, Tõnis; Madani, Fatemeh; Radoi, Vlad; Hällbrink, Mattias; Vukojević, Vladana; Langel, Ülo

2018-02-01

Peptides able to translocate cell membranes while carrying macromolecular cargo, as cell-penetrating peptides (CPPs), can contribute to the field of drug delivery by enabling the transport of otherwise membrane impermeable molecules. Formation of non-covalent complexes between amphipathic peptides and oligonucleotides is driven by electrostatic and hydrophobic interactions. Here we investigate and quantify the coexistence of distinct molecular species in multiple equilibria, namely peptide monomer, peptide self-aggregates and peptide/oligonucleotide complexes. As a model for the complexes, we used a stearylated peptide from the PepFect family, PF14 and siRNA. PF14 has a cationic part and a lipid part, resembling some characteristics of cationic lipids. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) were used to detect distinct molecular entities in solution and at the plasma membrane of live cells. For that, we labeled the peptide with carboxyrhodamine 6G and the siRNA with Cyanine 5. We were able to detect fluorescent entities with diffusional properties characteristic of the peptide monomer as well as of peptide aggregates and peptide/oligonucleotide complexes. Strategies to avoid peptide adsorption to solid surfaces and self-aggregation were developed and allowed successful FCS measurements in solution and at the plasma membrane. The ratio between the detected molecular species was found to vary with pH, peptide concentration and the proximity to the plasma membrane. The present results suggest that the diverse cellular uptake mechanisms, often reported for amphipathic CPPs, might result from the synergistic effect of peptide monomers, self-aggregates and cargo complexes, distributed unevenly at the plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

The Importance of Efficacy: Using the Extended Parallel Process Model to Examine Factors Related to Preschool-Age Children Enrolled in Medicaid Receiving Preventive Dental Visits

ERIC Educational Resources Information Center

Askelson, Natoshia M.; Chi, Donald L.; Momany, Elizabeth T.; Kuthy, Raymond A.; Carter, Knute D.; Field, Kathryn; Damiano, Peter C.

2015-01-01

Early preventive dental visits are vital to the oral health of children. Yet many children, especially preschool-age children enrolled in Medicaid, do not receive early visits. This study attempts to uncover factors that can be used to encourage parents to seek preventive dental care for preschool-age children enrolled in Medicaid. The extended…

An Examination of the Concept of Social Integration as Related to Preventive Medical Care in Poverty Families in Rural and Urban Areas.

ERIC Educational Resources Information Center

Slesinger, Doris P.

Based on an in-depth study of 125 mothers of young infants in both urban and rural areas of Wisconsin, this study analyzed the utilization of preventive medical services for the infant. The hypothesis that "mothers who are more socially integrated will be more likely to use preventive medical services than those who are less integrated,…

Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide.

PubMed

Morris, Christopher J; Smith, Mathew W; Griffiths, Peter C; McKeown, Neil B; Gumbleton, Mark

2011-04-10

With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LTP-1) displaying the disulphide-constrained 7-mer peptide sequence, C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LTP-1 peptide-phage clone and the corresponding free synthetic LTP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LTP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p<0.05) to the cumulative transport of less than 0.004% for control phage-clone groups. To characterise phage-independent activity of LTP-1 peptide, the LTP-1 peptide was conjugated to a 53kDa anionic PAMAM dendrimer. Compared to respective peptide-dendrimer control conjugates, the LTP-1-PAMAM conjugate displayed a two-fold (bioavailability up to 31%) greater extent of absorption in the IPRL. The LTP-1 peptide-mediated enhancement of transport, when LTP-1 was either attached to the phage clone or conjugated to dendrimer, was sequence-dependent and could be competitively inhibited by co-instillation of excess synthetic free LTP-1 peptide. The specific nature of the target receptor or mechanism involved in LTP-1 lung transport remains unclear although the enhanced transport is enabled through a mechanism that is non-disruptive with respect to the pulmonary transport of hydrophilic permeability probes. This study shows proof-of principle that array technologies can be effectively exploited to identify peptides mediating enhanced transmucosal delivery of macromolecule therapeutics across an intact organ. Copyright © 2010 Elsevier B.V. All rights reserved.

A Peptide Filtering Relation Quantifies MHC Class I Peptide Optimization

PubMed Central

Goldstein, Leonard D.; Howarth, Mark; Cardelli, Luca; Emmott, Stephen; Elliott, Tim; Werner, Joern M.

2011-01-01

Major Histocompatibility Complex (MHC) class I molecules enable cytotoxic T lymphocytes to destroy virus-infected or cancerous cells, thereby preventing disease progression. MHC class I molecules provide a snapshot of the contents of a cell by binding to protein fragments arising from intracellular protein turnover and presenting these fragments at the cell surface. Competing fragments (peptides) are selected for cell-surface presentation on the basis of their ability to form a stable complex with MHC class I, by a process known as peptide optimization. A better understanding of the optimization process is important for our understanding of immunodominance, the predominance of some T lymphocyte specificities over others, which can determine the efficacy of an immune response, the danger of immune evasion, and the success of vaccination strategies. In this paper we present a dynamical systems model of peptide optimization by MHC class I. We incorporate the chaperone molecule tapasin, which has been shown to enhance peptide optimization to different extents for different MHC class I alleles. Using a combination of published and novel experimental data to parameterize the model, we arrive at a relation of peptide filtering, which quantifies peptide optimization as a function of peptide supply and peptide unbinding rates. From this relation, we find that tapasin enhances peptide unbinding to improve peptide optimization without significantly delaying the transit of MHC to the cell surface, and differences in peptide optimization across MHC class I alleles can be explained by allele-specific differences in peptide binding. Importantly, our filtering relation may be used to dynamically predict the cell surface abundance of any number of competing peptides by MHC class I alleles, providing a quantitative basis to investigate viral infection or disease at the cellular level. We exemplify this by simulating optimization of the distribution of peptides derived from Human Immunodeficiency Virus Gag-Pol polyprotein. PMID:22022238

Two-level QSAR network (2L-QSAR) for peptide inhibitor design based on amino acid properties and sequence positions.

PubMed

Du, Q S; Ma, Y; Xie, N Z; Huang, R B

2014-01-01

In the design of peptide inhibitors the huge possible variety of the peptide sequences is of high concern. In collaboration with the fast accumulation of the peptide experimental data and database, a statistical method is suggested for peptide inhibitor design. In the two-level peptide prediction network (2L-QSAR) one level is the physicochemical properties of amino acids and the other level is the peptide sequence position. The activity contributions of amino acids are the functions of physicochemical properties and the sequence positions. In the prediction equation two weight coefficient sets {ak} and {bl} are assigned to the physicochemical properties and to the sequence positions, respectively. After the two coefficient sets are optimized based on the experimental data of known peptide inhibitors using the iterative double least square (IDLS) procedure, the coefficients are used to evaluate the bioactivities of new designed peptide inhibitors. The two-level prediction network can be applied to the peptide inhibitor design that may aim for different target proteins, or different positions of a protein. A notable advantage of the two-level statistical algorithm is that there is no need for host protein structural information. It may also provide useful insight into the amino acid properties and the roles of sequence positions.

Designing peptide inhibitor of insulin receptor to induce diabetes mellitus type 2 in animal model Mus musculus.

PubMed

Permatasari, Galuh W; Utomo, Didik H; Widodo

2016-10-01

A designing peptide as agent for inducing diabetes mellitus type 2 (T2DM) in an animal model is challenging. The computational approach provides a sophisticated tool to design a functional peptide that may block the insulin receptor activity. The peptide that able to inhibit the binding between insulin and insulin receptor is a warrant for inducing T2DM. Therefore, we designed a potential peptide inhibitor of insulin receptor as an agent to generate T2DM animal model by bioinformatics approach. The peptide has been developed based on the structure of insulin receptor binding site of insulin and then modified it to obtain the best properties of half life, hydrophobicity, antigenicity, and stability binding into insulin receptor. The results showed that the modified peptide has characteristics 100h half-life, high-affinity -95.1±20, and high stability 28.17 in complex with the insulin receptor. Moreover, the modified peptide has molecular weight 4420.8g/Mol and has no antigenic regions. Based on the molecular dynamic simulation, the complex of modified peptide-insulin receptor is more stable than the commercial insulin receptor blocker. This study suggested that the modified peptide has the promising performance to block the insulin receptor activity that potentially induce diabetes mellitus type 2 in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ground and Excited-Electronic-State Dissociations of Hydrogen-Rich and Hydrogen-Deficient Tyrosine Peptide Cation Radicals

NASA Astrophysics Data System (ADS)

Viglino, Emilie; Lai, Cheuk Kuen; Mu, Xiaoyan; Chu, Ivan K.; Tureček, František

2016-09-01

We report a comprehensive study of collision-induced dissociation (CID) and near-UV photodissociation (UVPD) of a series of tyrosine-containing peptide cation radicals of the hydrogen-rich and hydrogen-deficient types. Stable, long-lived, hydrogen-rich peptide cation radicals, such as [AAAYR + 2H]+● and several of its sequence and homology variants, were generated by electron transfer dissociation (ETD) of peptide-crown-ether complexes, and their CID-MS3 dissociations were found to be dramatically different from those upon ETD of the respective peptide dications. All of the hydrogen-rich peptide cation radicals contained major (77%-94%) fractions of species having radical chromophores created by ETD that underwent photodissociation at 355 nm. Analysis of the CID and UVPD spectra pointed to arginine guanidinium radicals as the major components of the hydrogen-rich peptide cation radical population. Hydrogen-deficient peptide cation radicals were generated by intramolecular electron transfer in CuII(2,2 ':6 ',2 ″-terpyridine) complexes and shown to contain chromophores absorbing at 355 nm and undergoing photodissociation. The CID and UVPD spectra showed major differences in fragmentation for [AAAYR]+● that diminished as the Tyr residue was moved along the peptide chain. UVPD was found to be superior to CID in localizing Cα-radical positions in peptide cation radical intermediates.

Expression of the cationic antimicrobial peptide lactoferricin fused with the anionic peptide in Escherichia coli.

PubMed

Kim, Ha-Kun; Chun, Dae-Sik; Kim, Joon-Sik; Yun, Cheol-Ho; Lee, Ju-Hoon; Hong, Soon-Kwang; Kang, Dae-Kyung

2006-09-01

Direct expression of lactoferricin, an antimicrobial peptide, is lethal to Escherichia coli. For the efficient production of lactoferricin in E. coli, we developed an expression system in which the gene for the lysine- and arginine-rich cationic lactoferricin was fused to an anionic peptide gene to neutralize the basic property of lactoferricin, and successfully overexpressed the concatemeric fusion gene in E. coli. The lactoferricin gene was linked to a modified magainin intervening sequence gene by a recombinational polymerase chain reaction, thus producing an acidic peptide-lactoferricin fusion gene. The monomeric acidic peptide-lactoferricin fusion gene was multimerized and expressed in E. coli BL21(DE3) upon induction with isopropyl-beta-D-thiogalactopyranoside. The expression levels of the fusion peptide reached the maximum at the tetramer, while further increases in the copy number of the fusion gene substantially reduced the peptide expression level. The fusion peptides were isolated and cleaved to generate the separate lactoferricin and acidic peptide. About 60 mg of pure recombinant lactoferricin was obtained from 1 L of E. coli culture. The purified recombinant lactoferricin was found to have a molecular weight similar to that of chemically synthesized lactoferricin. The recombinant lactoferricin showed antimicrobial activity and disrupted bacterial membrane permeability, as the native lactoferricin peptide does.

Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.

PubMed

Yan, Jin; He, Wangxiao; Yan, Siqi; Niu, Fan; Liu, Tianya; Ma, Bohan; Shao, Yongping; Yan, Yuwei; Yang, Guang; Lu, Wuyuan; Du, Yaping; Lei, Bo; Ma, Peter X

2018-02-27

Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.

Use of preventive dental care among medicaid-enrolled, school-aged US children in immigrant and nonimmigrant families: trends in Pennsylvania From 2005 through 2010.

PubMed

Yun, Katherine; Chesnokova, Arina; Shults, Justine; Pinto, Andres; Rubin, David M

2014-12-01

We describe trends in receipt of preventive dental care among Medicaid-enrolled children in Pennsylvania between 2005 and 2010, comparing the US children of immigrants with their co-ethnic peers in nonimmigrant families. We analyzed Pennsylvania Medicaid claims, birth records, and census data for children born in Pennsylvania and enrolled in Medicaid for 10 or more months during any of the calendar years assessed. Receipt of preventive dental care was more likely among Latino children in immigrant families than among their peers in nonimmigrant families; also, it was more likely among White children in immigrant families than among their peers in nonimmigrant families. Rates of preventive dental care use among African American and Asian children in immigrant and nonimmigrant families were comparable. From 2005 to 2010, the percentage of Latino children in nonimmigrant families who received preventive dental care increased from 33% to 61%. Changes in other groups were significant but less dramatic. Receipt of preventive dental care has increased among Medicaid-enrolled children in Pennsylvania, with marked gains among Latino children. Within each racial/ethnic group, the children of immigrants were either more likely than or equally likely as children in nonimmigrant families to receive care.

Clinician-Reported Barriers to Implementing Breast Cancer Chemoprevention in the UK: A Qualitative Investigation.

PubMed

Smith, Samuel G; Side, Lucy; Meisel, Susanne F; Horne, Rob; Cuzick, Jack; Wardle, Jane

2016-01-01

The use of tamoxifen and raloxifene as preventive therapy for women at increased risk of breast cancer was approved by the National Institute for Health and Care Excellence (NICE) in 2013. We undertook a qualitative investigation to investigate the factors affecting the implementation of preventive therapy within the UK. We recruited general practitioners (GPs) (n = 10) and clinicians working in family history or clinical genetics settings (FHCG clinicians) (n = 15) to participate in semi-structured interviews. Data were coded thematically within the Consolidated Framework for Implementation Research. FHCG clinicians focussed on the perceived lack of benefit of preventive therapy and difficulties interpreting the NICE guidelines. FHCG clinicians felt poorly informed about preventive therapy, and this discouraged patient discussions on the topic. GPs were unfamiliar with the concept of preventive therapy, and were not aware that they may be asked to prescribe it for high-risk women. GPs were reluctant to initiate therapy because it is not licensed, but were willing to continue a prescription if it had been started in secondary or tertiary care. Barriers to implementing preventive therapy within routine clinical practice are common and could be addressed by engaging all stakeholders during the development of policy documents. © 2016 The Author(s) Published by S. Karger AG, Basel.

Awareness of healthcare workers regarding preventive measures of communicable diseases among Hajj pilgrims at the entry point in Western Saudi Arabia.

PubMed

Al-Ghamdi, Adel S; Kabbash, Ibrahim A

2011-11-01

To determine the level of knowledge of healthcare workers (HCWs) towards preventive measures for communicable diseases among pilgrims, and to highlight the difficulties faced by HCWs in implementing preventive measures at entry point. A cross-sectional study was conducted at King Abdulaziz International Airport Hajj Terminals in Jeddah, Kingdom of Saudi Arabia during Hajj season from October to November 2009 including 325 healthcare workers (HCWs). Data were collected using a self-administered questionnaire. Difficulties reported by HCWs were refusal of vaccine, or chemoprophylaxis by some pilgrims, language barriers, and difficulties in organizing pilgrims. The different items related to meningococcal meningitis were answered correctly by most HCWs except for preventive measures applied to infants and children. Less than one half were aware of the period of validity for Yellow Fever vaccine certificate and measures to be taken for unvaccinated pilgrims. Only 32.9% were aware of preventive measures that should be applied against influenza A (H1N1). Physicians, those reading guidelines, and those with high experience a showed significantly better level of knowledge than other categories. The HCWs have difficulties in some preventive measures, especially among non-physicians, those with less years of experience, and those who did not read the written guidelines, which highlighted the importance of training courses before Hajj season.

Competencies for population-based clinical managers. A survey of managed care medical directors.

PubMed

Halbert, R J; Bokor, A; Castrence-Nazareno, R; Parkinson, M D; Lewis, C E

1998-07-01

The evolution of American health care into integrated systems of delivery and finance requires a specialized set of population-based skills for physicians. The field of preventive medicine represents one source of this expertise. Specific competencies for the emerging area of managerial medicine have not been well delineated. Using concept documents from the Residency Review Committee for Preventive Medicine and the American Board of Preventive Medicine, a list of proposed competencies for managerial medicine was identified. Surveys were mailed to medical directors of all members of the American Association of Health Plans and to a random sample of diplomates of the American Board of Preventive Medicine. Respondents were asked to rate the importance of these competencies for a population-oriented clinician manager. Areas rated highly by medical directors included health services research (including outcome research), quality assurance and improvement, health risk assessment and reduction, programmatic skills, and clinical preventive skills. Responses from preventive medicine specialists were similar, but placed lower emphasis on these skills. Despite its limited response rate, this survey may be useful in the implementation of specialty training in managerial medicine. Residency training programs may choose to emphasize specific content area that reflect the priorities expressed by physicians actively involved in management.

Endoscopic detection of murine colonic dysplasia using a novel fluorescence-labeled peptide

NASA Astrophysics Data System (ADS)

Miller, Sharon J.; Joshi, Bishnu P.; Gaustad, Adam; Fearon, Eric R.; Wang, Thomas D.

2011-03-01

Current endoscopic screening does not detect all pre-malignant (dysplastic) colorectal mucosa, thus requiring the development of more sensitive, targeted techniques to improve detection. The presented work utilizes phage display to identify a novel peptide binder to colorectal dysplasia in a CPC;Apc mouse model. A wide-field, small animal endoscope capable of fluorescence excitation (450-475 nm) identified polyps via white light and also collected fluorescence images (510 nm barrier filter) of peptide binding. The peptide bound ~2-fold greater to the colonic adenomas when compared to the control peptide. We have imaged fluorescence-labeled peptide binding in vivo that is specific towards distal colonic adenomas.

Peptide Logic Circuits Based on Chemoenzymatic Ligation for Programmable Cell Apoptosis.

PubMed

Li, Yong; Sun, Sujuan; Fan, Lin; Hu, Shanfang; Huang, Yan; Zhang, Ke; Nie, Zhou; Yao, Shouzhou

2017-11-20

A novel and versatile peptide-based bio-logic system capable of regulating cell function is developed using sortase A (SrtA), a peptide ligation enzyme, as a generic processor. By modular peptide design, we demonstrate that mammalian cells apoptosis can be programmed by peptide-based logic operations, including binary and combination gates (AND, INHIBIT, OR, and AND-INHIBIT), and a complex sequential logic circuit (multi-input keypad lock). Moreover, a proof-of-concept peptide regulatory circuit was developed to analyze the expression profile of cell-secreted protein biomarkers and trigger cancer-cell-specific apoptosis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural Insight into Recognition of Plant Peptide Hormones by Receptors.

PubMed

Zhang, Heqiao; Han, Zhifu; Song, Wen; Chai, Jijie

2016-11-07

Secreted signaling peptides or peptide hormones play crucial roles in plant growth and development through coordination of cell-cell communication. Perception of peptide hormones in plants generally relies on membrane-localized receptor kinases (RKs). Progress has recently been made in structural elucidation of interactions between posttranslationally modified peptide hormones and RKs. The structural studies suggest conserved receptor binding and activation mechanisms of this type of peptide hormones involving their conserved C-termini. Here, we review these structural data and discuss how the conserved mechanisms can be used to match peptide-RK pairs. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Improving the cost-effectiveness of a healthcare system for depressive disorders by implementing telemedicine: a health economic modeling study.

PubMed

Lokkerbol, Joran; Adema, Dirk; Cuijpers, Pim; Reynolds, Charles F; Schulz, Richard; Weehuizen, Rifka; Smit, Filip

2014-03-01

Depressive disorders are significant causes of disease burden and are associated with substantial economic costs. It is therefore important to design a healthcare system that can effectively manage depression at sustainable costs. This article computes the benefit-to-cost ratio of the current Dutch healthcare system for depression, and investigates whether offering more online preventive interventions improves the cost-effectiveness overall. A health economic (Markov) model was used to synthesize clinical and economic evidence and to compute population-level costs and effects of interventions. The model compared a base case scenario without preventive telemedicine and alternative scenarios with preventive telemedicine. The central outcome was the benefit-to-cost ratio, also known as return-on-investment (ROI). In terms of ROI, a healthcare system with preventive telemedicine for depressive disorders offers better value for money than a healthcare system without Internet-based prevention. Overall, the ROI increases from €1.45 ($1.72) in the base case scenario to €1.76 ($2.09) in the alternative scenario in which preventive telemedicine is offered. In a scenario in which the costs of offering preventive telemedicine are balanced by reducing the expenditures for curative interventions, ROI increases to €1.77 ($2.10), while keeping the healthcare budget constant. For a healthcare system for depressive disorders to remain economically sustainable, its cost-benefit ratio needs to be improved. Offering preventive telemedicine at a large scale is likely to introduce such an improvement. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Cyanine-based probe\\tag-peptide pair for fluorescence protein imaging and fluorescence protein imaging methods

DOEpatents

Mayer-Cumblidge, M Uljana [Richland, WA; Cao, Haishi [Richland, WA

2010-08-17

A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Chemical methods for peptide and protein production.

PubMed

Chandrudu, Saranya; Simerska, Pavla; Toth, Istvan

2013-04-12

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

Will sacubitril-valsartan diminish the clinical utility of B-type natriuretic peptide testing in acute cardiac care?

PubMed

Mair, Johannes; Lindahl, Bertil; Giannitsis, Evangelos; Huber, Kurt; Thygesen, Kristian; Plebani, Mario; Möckel, Martin; Müller, Christian; Jaffe, Allan S

2017-06-01

Since the approval of sacubitril-valsartan for the treatment of chronic heart failure with reduced ejection fraction, a commonly raised suspicion is that a wider clinical use of this new drug may diminish the clinical utility of B-type natriuretic peptide testing as sacubitril may interfere with B-type natriuretic peptide clearance. In this education paper we critically assess this hypothesis based on the pathophysiology of the natriuretic peptide system and the limited published data on the effects of neprilysin inhibition on natriuretic peptide plasma concentrations in humans. As the main clinical application of B-type natriuretic peptide testing in acute cardiac care is and will be the rapid rule-out of suspected acute heart failure there is no significant impairment to be expected for B-type natriuretic peptide testing in the acute setting. However, monitoring of chronic heart failure patients on sacubitril-valsartan treatment with B-type natriuretic peptide testing may be impaired. In contrast to N-terminal-proBNP, the current concept that the lower the B-type natriuretic peptide result in chronic heart failure patients, the better the prognosis during treatment monitoring, may no longer be true.

Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

PubMed

Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

2010-08-01

The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-gammain vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

Active immunizations with peptide-DC vaccines and passive transfer with antibodies protect neutropenic mice against disseminated candidiasis.

PubMed

Xin, Hong

2016-01-04

We previously report that peptide-pulsed dendritic cell (DC) vaccination, which targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in immunocompetent mice. Passive transfer of immune sera from the peptide immunized mice or peptide-related monoclonal antibodies demonstrated that protection was medicated by peptide-specific antibodies. In this study the efficacy of active and passive immunization against disseminated candidiasis was tested in mice with cyclophosphamide-induced neutropenia. Peptide-DC vaccines were given to mice prior to induction of neutropenia. We show active immunization with either Fba or Met6 peptide-DC vaccine significantly improved the survival and reduced the fungal burden of disseminated candidiasis in those immunocompromised mice. Importantly, we show that administration of two protective monoclonal antibodies also protect neutropenic mice against the disease, implying possibility of developing a successful passive immunotherapy strategy to treat the disease and protect against disseminated candidiasis. The results of this study are crucial as they address the fundamental questions as to whether the synthetic peptide vaccine induced immunity protects the host during a neutropenic episode. We anticipate that this peptide-vaccine study will serve as the foundation of future investigations into new peptide vaccines comprised of cell surface peptides from other medically important Candida species, as well as other fungi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Factors affecting compliance with preventive treatment for tuberculosis at Mistassini Lake, Quebec, Canada.

PubMed

Rideout, M; Menzies, R

1994-02-01

Non-compliance is the most important cause of failure of anti-tuberculous therapy throughout the world. In 1990 and 1991, an outbreak of tuberculosis occurred on the Mistassini Cree territory in Northern Quebec, Canada, and a number of cases of active tuberculosis occurred among known tuberculin-positive contacts who were non-compliant with preventive therapy. To better understand the factors affecting compliance with preventive treatment, a review of patients prescribed preventive treatment over the past 10 y was conducted. A freely-translated, interviewer-administered questionnaire was used to measure personal/lifestyle factors and knowledge/attitudes about tuberculosis. Clinic dossiers were reviewed to assess compliance. One hundred and two (102) subjects prescribed preventive treatment between 1981 and 1991 were interviewed, of whom 33.7% were judged to have been compliant. The most significant factor associated with compliance with preventive therapy was year of therapy. Between 1981 and 1985, 78% completed treatment, compared to less than 20% since 1986 (p < .0001). The major factor identified as associated with this sudden change was a shift in responsibility for tuberculosis treatment follow-up from native community health workers to non-native nurses in 1985/86. We conclude that tuberculosis control programs must be tailored to take into account the importance of cultural factors in promoting compliance with therapy.

[Prevention of stress in the workplace].

PubMed

Vaccani, R

2009-01-01

The chronological/logical path goes from the base distinction that classify the stressing phenomena between the two categories, eu-stress and dis-stress. It is underlined the subjective characteristic of stressing processes, the statement that what might be eu-stress for someone can be dis-stress for others. The organizational setting can be considered as a privileged preventive intervention area. Therefore it is suggested this categorization for the stress organizational causes: Causes connected to the organizational system (Incoherencies or structural understaffing, procedural incoherencies); Causes connected to the wrong alignment of competencies; Causes connected to the wrong alignment of aptitudes; Causes connected to the social dynamics of abuse of power. The categories to differentiate the stress organizational causes are proposed to give a useful glossary to design various preventive actions: Preventive actions on the organizational setting; Preventive actions through education; Preventive actions about role redesign; Preventive actions aimed at sustaining ethical social cohabitation. Finally, it is assessed that the approach to organizational stress requires an holistic, multi disciplinary perspective analysis, able to connect the ethic and qualitative characteristic of the markets (closed and open markets) to the organizational setting, to the subject peculiar character at work and its impact with working roles, to the social dynamics derived from hierarchical roles, to the organizational moods, to the individual perceptions, to the clinical paths.

Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

PubMed

Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

2016-01-01

This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing.

PubMed

Morozov, Giora I; Zhao, Huaying; Mage, Michael G; Boyd, Lisa F; Jiang, Jiansheng; Dolan, Michael A; Venna, Ramesh; Norcross, Michael A; McMurtrey, Curtis P; Hildebrand, William; Schuck, Peter; Natarajan, Kannan; Margulies, David H

2016-02-23

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.

Increase in dermcidin-derived peptides in sweat of patients with atopic eczema caused by a humorous video.

PubMed

Kimata, Hajime

2007-01-01

Dermcidin (DCD)-derived peptide is an antimicrobial peptide produced by the sweat glands. However, the levels of DCD-derived peptide in sweat were decreased in patients with atopic eczema (AE). The effect of viewing a humorous video on the levels of DCD-derived peptide was studied. Twenty patients with AE viewed an 87-min humorous video (Modern Times, featuring Charlie Chaplin). Just before and immediately after viewing, sweat was collected, and the levels of DCD-derived peptide and total protein in sweat were measured. Viewing a humorous video increased the levels of DCD-derived peptide without affecting the levels of total protein in sweat. Viewing a humorous video increased DCD-derived peptide in sweat of patients with AE, and thus, it may be helpful in the treatment of skin infection of AE.

Active Immunizations with Peptide-DC Vaccines and Passive Transfer with Antibodies Protect Neutropenic Mice against Disseminated Candidiasis

PubMed Central

Xin, Hong

2015-01-01

We previously report that peptide-pulsed dendritic cell (DC) vaccination, which targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in immunocompetent mice. Passive transfer of immune sera from the peptide immunized mice or peptide-related monoclonal antibodies demonstrated that protection was medicated by peptide-specific antibodies. In this study the efficacy of active and passive immunization against disseminated candidiasis was tested in mice with cyclophosphamide-induced neutropenia. Peptide-DC vaccines were given to mice prior to induction of neutropenia. We show active immunization with either Fba or Met6 peptide-DC vaccine significantly improved the survival and reduced the fungal burden of disseminated candidiasis in those immunocompromised mice. Importantly, we show that administration of two protective monoclonal antibodies also protect neutropenic mice against the disease, implying possibility of developing a successful passive immunotherapy strategy to treat the disease and protect against disseminated candidiasis. The results of this study are crucial as they address the fundamental questions as to whether the synthetic peptide vaccine induced immunity protects the host during a neutropenic episode. We anticipate that this peptide-vaccine study will serve as the foundation of future investigations into new peptide vaccines comprised of cell surface peptides from other medically important Candida species, as well as other fungi. PMID:26620842

LC-MS-based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitization potential.

PubMed

Natsch, Andreas; Gfeller, Hans

2008-12-01

A key step in the skin sensitization process is the formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. Based on this mechanistic understanding, there is a renewed interest in in vitro assays to determine the reactivity of chemicals toward peptides in order to predict their sensitization potential. A standardized peptide reactivity assay yielded a promising predictivity. This published assay is based on high-performance liquid chromatography with ultraviolet detection to quantify peptide depletion after incubation with test chemicals. We had observed that peptide depletion may be due to either adduct formation or peptide oxidation. Here we report a modified assay based on both liquid chromatography-mass spectrometry (LC-MS) analysis and detection of free thiol groups. This approach allows simultaneous determination of (1) peptide depletion, (2) peptide oxidation (dimerization), (3) adduct formation, and (4) thiol reactivity and thus generates a more detailed characterization of the reactivity of a molecule. Highly reactive molecules are further discriminated with a kinetic measure. The assay was validated on 80 chemicals. Peptide depletion could accurately be quantified both with LC-MS detection and depletion of thiol groups. The majority of the moderate/strong/extreme sensitizers formed detectable peptide adducts, but many sensitizers were also able to catalyze peptide oxidation. Whereas adduct formation was only observed for sensitizers, this oxidation reaction was also observed for two nonsensitizing fragrance aldehydes, indicating that peptide depletion might not always be regarded as sufficient evidence for rating a chemical as a sensitizer. Thus, this modified assay gives a more informed view of the peptide reactivity of chemicals to better predict their sensitization potential.

Changes in beta cell function during the proximate post-diagnosis period in persons with type 1 diabetes.

PubMed

DiMeglio, Linda A; Cheng, Peiyao; Beck, Roy W; Kollman, Craig; Ruedy, Katrina J; Slover, Robert; Aye, Tandy; Weinzimer, Stuart A; Bremer, Andrew A; Buckingham, Bruce

2016-06-01

Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time. Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled. Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations. C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-tumor effects of a novel chimeric peptide on S180 and H22 xenografts bearing nude mice.

PubMed

Wu, Dongdong; Gao, Yanfeng; Chen, Lixiang; Qi, Yuanming; Kang, Qiaozhen; Wang, Haili; Zhu, Linyu; Ye, Yong; Zhai, Mingxia

2010-05-01

In recent years, many endogenous peptides have been identified by screening combinatory phage display peptide library, which play important roles in the process of angiogenesis. A heptapeptide, ATWLPPR, binds specifically to NRP-1 and selectively inhibits VEGF165 binding to VEGFR-2. Another heptapeptide, NLLMAAS, blocks both Ang-1 and Ang-2 binding to Tie-2 in a dose-dependent manner. In the present study, we aimed to connect ATWLPPR (V1) with NLLMAAS (V2) via a flexible linker, Ala-Ala, to reconstruct a novel peptide ATWLPPRAANLLMAAS (V3). We firstly investigated the anti-tumor and anti-angiogenic effects of peptide V3 on sarcoma S180 and hepatoma H22 bearing BALB/c nude mice. Mice were continuously subcutaneously administrated with normal saline, V1 (320microg/kg/d), V2 (320microg/kg/d), V1+V2 (320microg/kg/d), and V3 (160, 320 and 480microg/kg/d), for 7 days. Treatment with peptide V3 could significantly reduce the tumor weight and volume. Pathological examination showed that the tumors treated with peptide V3 had a larger region of necrosis than that of peptide V1, V2, and V1+V2 at the same dose. A significant decrease of microvessel density (MVD) in a dose-dependent manner was observed in each group of peptide V3. The results of pathological examination on normal tissue, lung, heart, liver, spleen, kidney and white blood cells showed that peptide V3 might have no significant toxicity. In conclusion, our results demonstrated that peptide V3 could be more effective on inhibiting tumor growth and angiogenesis than that of V1, V2, and V1+V2. Peptide V3 could be considered as a novel chimeric peptide with potent anti-tumor activity. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Analysis of protein glycation products by MALDI-TOF/MS.

PubMed

Kislinger, Thomas; Humeny, Andreas; Peich, Carlo C; Becker, Cord-Michael; Pischetsrieder, Monika

2005-06-01

Matrix-assisted laser desorption ionization-mass spectrometry with time-of-flight detection (MALDI-TOF/MS) is a promising tool to analyze advanced glycation end product (AGE)-modified proteins. The combination of soft ionization (MALDI) with time-of-flight mass detection allows analysis of peptides and proteins of a molecular mass up to 300 kDa with minimal sample workup. Because the direct structural analysis of intact AGE proteins is not possible due to the formation of broad and poorly resolved peaks, peptide mapping was introduced into the analysis of AGE proteins by MALDI-TOF/MS, allowing site-specific analysis of defined AGEs. When methylglyoxal-modified lysozyme was subjected to MALDI-TOF/MS peptide mapping, methylimidazolone and argpyrimidine attached to the arginine residue and carboxyethyl (CEL) bound to the lysine were detected on peptide(aa1-7) (KVFGRCE). In contrast, only one methylimidazolone was found on peptide(aa8-35) (LAAAMKRHGLDNYRGYSLGNWVCAAKFE) and peptide(aa120-129) (VQAWIRGCRL), respectively. The analysis of AGE protein, which had been incubated with glucose, revealed the presence of an Amadori product and a carboxymethyl residue (CML) on peptide(aa1-7) and peptide(aa8-35), as well as an imidazolone A on peptide(aa120-129). Furthermore, the early Maillard reaction of lysozyme, which had been glycated by seven different sugars, was monitored by MALDI-TOF/MS peptide mapping. Finally, this approach was successfully applied for site- and product-specific relative quantification of AGEs. For example, kinetics of CML and Amadori product formation on peptide(aa1-7), as well as imidazolone A formation on peptide(aa120-129), were determined.

Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes.

PubMed

Asmar, Meena; Højberg, Patricia V; Deacon, Carolyn F; Hare, Kristine; Holst, Jens J; Madsbad, Sten

2010-02-25

This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P<0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P=0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P<0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in beta-cell function characterizing T2DM. Copyright 2010 Elsevier B.V. All rights reserved.

Preventive induction of labor for non-urgent indications at term and maternal and neonatal outcomes.

PubMed

Zhang, Lin; Zhang, Hao; Zhang, Jun; Zhang, Jin Wen; Ye, Jiang Feng; Branch, D Ware

2016-04-21

Induction of labor (IOL) is a common practice in many parts of the world. However, the benefits and risks of preventive IOL for the mother and baby have yet to be critically assessed. This study is to investigate the effects of preventive IOL for non-urgent indications at term on maternal and neonatal outcomes. In this study, we applied a propensity score model to mimic a randomized clinical trial. Maternal and neonatal outcomes were compared between women with preventive IOL at 37-39 weeks of gestation and women with ongoing pregnancy (expectant management). The subjects were from the Consortium on Safe Labor, a study of over 200,000 births from 19 hospitals across the US from 2002 to 2008. Both nulliparous and multiparous women induced preventively for non-urgent indications at 37-38 weeks' gestation had lower rates of cesarean delivery compared to those delivered at later gestational weeks. However, preventive IOL was associated with increased risks of adverse neonatal outcomes (adjusted odds ratio [aOR] = 1.68, 95% confidence interval [CI], 0.97-2.92 for nulliparas; aOR = 2.22, 1.32-3.74 for multiparas) and admission to NICU (aOR = 1.48, 0.99-2.20 for nulliparas; aOR = 2.08, 1.47-2.96 for multiparas) at 37 weeks' gestation. A longer maternal hospital stay was found among all women with preventive IOL. Preventive IOL for non-urgent indications may be associated with a decreased risk of cesarean delivery at early term but increased risks of adverse neonatal outcomes at 37 weeks. It also results in a longer hospital stay than expectant management.

Clustering of unhealthy lifestyle behaviors is associated with a low adherence to recommended preventive practices among COPD patients in Spain.

PubMed

de Miguel-Díez, Javier; Jiménez-García, Rodrigo; Hernández-Barrera, Valentín; Maestu, Luis Puente; Aparicio, Irene Jarana; Ramos, Alicia Oliva; López de Andrés, Ana; Carrasco-Garrido, Pilar

2014-08-01

To analyze clustering of unhealthy lifestyle behavior and its relationship with non-adherence to recommended clinical preventive care services among Spanish COPD patients. Cross-sectional study including 2,575 COPD subjects from the 2006 Spanish National Health Survey (NHS) and 2009 European Health Survey for Spain (EHISS). Subjects were asked about the following recommended preventive practices: uptake of blood pressure (BP) measurement, lipid profile, influenza vaccination and dental examination. Lifestyle behaviors included: smoking status, physical activity, alcohol consumption and obesity. Logistic regression models were built to assess the association between clustering of unhealthy lifestyle and the uptake of preventive activities. Blood pressure measurement in the previous 6 months and a blood lipid test in the last year had not been taken by 11.74% and 23.26% of the subjects, respectively, in 2006 NHS and by 11.16% and 16.33% of the subjects, respectively, in EHISS 2009. Then, 36.36% percent had not been vaccinated and 70.61% had not received dental examination in 2006 NHS and these percentages decreased to 27.33% and 66.22%, respectively, in 2009 EHISS. A higher number of unhealthy lifestyle behaviors increased the probability of not being vaccinated and not having a dental examination. Clustering of unhealthy lifestyle behaviors is linearly associated with a greater number of preventive measures unfulfilled. Compliance with healthy lifestyles and adherence to recommended clinical preventive services is under desirable levels among Spanish COPD patients. Patients with lifestyles considered as "worse" are those who also have lower uptake of recommended preventive activities.

Impedimetric detection of pathogenic Gram-positive bacteria using an antimicrobial peptide from class IIa bacteriocins.

PubMed

Etayash, Hashem; Jiang, Keren; Thundat, Thomas; Kaur, Kamaljit

2014-02-04

Real-time, label-free detection of Gram-positive bacteria with high selectivity and sensitivity is demonstrated using an interdigitated impedimetric array functionalized with naturally produced antimicrobial peptide from class IIa bacteriocins. The antimicrobial peptide, leucocin A, was chemically synthesized and covalently immobilized on interdigitated gold microelectrodes via the interaction between the C-terminal carboxylic acid of the peptide and free amines of a preattached thiolated linker. Exposing the peptide sensor to various concentrations of Gram-positive bacteria generated reproducible impedance spectra that detected peptide-bacteria interactions at a concentration of 1 cell/μL. The peptide sensor also selectively detected Listeria monocytogenes from other Gram-positive strains at a concentration of 10(3) cfu mL(-1). The study highlights that short peptide ligands from bacteriocin class offer high selectivity in bacterial detection and can be used in developing a robust, portable biosensor device to efficiently detect pathogenic Gram-positive bacteria in food samples.

Development of bisphenol A-removing recombinant Escherichia coli by monomeric and dimeric surface display of bisphenol A-binding peptide.

PubMed

Maruthamuthu, Murali Kannan; Hong, Jiyeon; Arulsamy, Kulandaisamy; Somasundaram, Sivachandiran; Hong, SoonHo; Choe, Woo-Seok; Yoo, Ik-Keun

2018-04-01

Peptide-displaying Escherichia coli cells were investigated for use in adsorptive removal of bisphenol A (BPA) both in Luria-Bertani medium including BPA or ATM thermal paper eluted wastewater. Two recombinant strains were constructed with monomeric and dimeric repeats of the 7-mer BPA-binding peptide (KSLENSY), respectively. Greater than threefold increased adsorption of BPA [230.4 µmol BPA per g dry cell weight (DCW)] was found in dimeric peptide-displaying cells compared to monomeric strains (63.4 µmol per g DCW) in 15 ppm BPA solution. The selective removal of BPA from a mixture of BPA analogs (bisphenol F and bisphenol S) was verified in both monomeric and dimeric peptide-displaying cells. The binding chemistry of BPA with the peptide was assumed, based on molecular docking analysis, to be the interaction of BPA with serine and asparagine residues within the 7-mer peptide sequence. The peptide-displaying cells also functioned efficiently in thermal paper eluted wastewater containing 14.5 ppm BPA.

The development and utility of a novel scale that quantifies the glycemic progression toward type 1 diabetes over 6 months.

PubMed

Sosenko, Jay M; Skyler, Jay S; Beam, Craig A; Boulware, David; Mahon, Jeffrey L; Krischer, Jeffrey P; Greenbaum, Carla J; Rafkin, Lisa E; Matheson, Della; Herold, Kevan C; Palmer, Jerry P

2015-05-01

We developed a scale to serve as a potential end point for 6-month glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive relatives of individuals with T1D. The PS6M was developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the TrialNet Pathway to Prevention Study (PTP). It is the difference between 6-month glucose sum values (30-120 min oral glucose tolerance test values) and values predicted for nonprogressors. The PS6M predicted T1D in the PTP (P < 0.001). The area under the receiver operating chacteristic curve was greater (P < 0.001) for the PS6M than for the baseline-to-6-month difference. PS6M values were higher in those with two or more autoantibodies, 30-0 min C-peptide values <2.00 ng/mL, or DPT-1 Risk Scores >7.00 (P < 0.001 for all). The PS6M is an indicator of short-term glycemic progression to T1D that could be a useful tool for assessing preventive treatments and biomarkers. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Improved breast cancer cell-specific intracellular drug delivery and therapeutic efficacy by coupling decoration with cell penetrating peptide and SP90 peptide.

PubMed

Fan, Li-Qiang; Du, Guo-Xiu; Li, Peng-Fei; Li, Ming-Wei; Sun, Yao; Zhao, Li-Ming

2016-12-01

Lack of satisfactory specificity towards tumor cells and poor intracellular delivery efficacy are the major drawbacks with conventional cancer chemotherapy. Conjugated anticancer drugs to targeting moieties e.g. to peptides with the ability to recognize cancer cells and to cell penetrating peptide can improve these characteristics, respectively. Combining a tumor homing peptide with an appropriate cell-penetrating peptide can enhance the tumor-selective internalization efficacy of the carrying cargo molecules. In the present study, the breast cancer homing ability of SP90 peptide and the synergistic effect of SP90 with a cell-penetrating peptide(C peptide) were evaluated. SP90 and chimeric peptide SP90-C specifically targeted cargo molecule into breast cancer cells, especially triple negative MDA-MB-231 cell, in a dose- and time-dependent manner, but not normal breast cells and other cancer cells, while C peptide alone had no cell-selectivity. SP90-C increased the intracellular delivery efficiency by 12-fold or 10-fold compared to SP90 or C peptide alone, respectively. SP90 and SP90-C conjugation increased the anti-proliferative and apoptosis-inducing activity of HIV-1 Vpr, a potential novel anticancer protein drug, to breast cancer cell but not normal breast cell by arresting cells in G2/M phase. With excellent breast cancer cell-selective penetrating efficacy, SP90-C appears as a promising candidate vector for targeted anti-cancer drug delivery. SP90-VPR-C is a potential novel breast cancer-targeted anticancer agent for its high anti-tumor activity and low toxicity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

PubMed Central

2012-01-01

Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2) to bind to N-type voltage-activated calcium channels (CaV2.2) [Brittain et al. Nature Medicine 17:822–829 (2011)]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K) that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion) observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP) release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of action on the target. PMID:22828369

Randomized trial of preventive angioplasty in myocardial infarction.

PubMed

Wald, David S; Morris, Joan K; Wald, Nicholas J; Chase, Alexander J; Edwards, Richard J; Hughes, Liam O; Berry, Colin; Oldroyd, Keith G

2013-09-19

In acute ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to treat the artery responsible for the infarct (infarct, or culprit, artery) improves prognosis. The value of PCI in noninfarct coronary arteries with major stenoses (preventive PCI) is unknown. From 2008 through 2013, at five centers in the United Kingdom, we enrolled 465 patients with acute STEMI (including 3 patients with left bundle-branch block) who were undergoing infarct-artery PCI and randomly assigned them to either preventive PCI (234 patients) or no preventive PCI (231 patients). Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia. The primary outcome was a composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina. An intention-to-treat analysis was used. By January 2013, the results were considered conclusive by the data and safety monitoring committee, which recommended that the trial be stopped early. During a mean follow-up of 23 months, the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI (infarct-artery-only PCI), which translated into rates of 9 events per 100 patients and 23 per 100, respectively (hazard ratio in the preventive-PCI group, 0.35; 95% confidence interval [CI], 0.21 to 0.58; P<0.001). Hazard ratios for the three components of the primary outcome were 0.34 (95% CI, 0.11 to 1.08) for death from cardiac causes, 0.32 (95% CI, 0.13 to 0.75) for nonfatal myocardial infarction, and 0.35 (95% CI, 0.18 to 0.69) for refractory angina. In patients with STEMI and multivessel coronary artery disease undergoing infarct-artery PCI, preventive PCI in noninfarct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events, as compared with PCI limited to the infarct artery. (Funded by Barts and the London Charity; PRAMI Current Controlled Trials number, ISRCTN73028481.).

Evaluating Ga-68 Peptide Conjugates for Targeting VPAC Receptors: Stability and Pharmacokinetics.

PubMed

Kumar, Pardeep; Tripathi, Sushil K; Chen, C P; Wickstrom, Eric; Thakur, Mathew L

2018-05-25

In recent years, considerable progress has been made in the use of gallium-68 labeled receptor-specific peptides for imaging oncologic diseases. The objective was to examine the stability and pharmacokinetics of [ 68 Ga]NODAGA and DOTA-peptide conjugate targeting VPAC [combined for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP)] receptors on tumor cells. A VPAC receptor-specific peptide was chosen as a model peptide and conjugated to NODAGA and DOTA via solid-phase synthesis. The conjugates were characterized by HPLC and MALDI-TOF. Following Ga-68 chelation, the radiochemical purity of Ga-68 labeled peptide conjugate was determined by radio-HPLC. The stability was tested against transmetallation using 100 nM Fe 3+ /Zn 2+ /Ca 2+ ionic solution and against transchelation using 200 μM DTPA solution. The ex vivo and in vivo stability of the Ga-68 labeled peptide conjugate was tested in mouse plasma and urine. Receptor specificity was determined ex vivo by cell binding assays using human breast cancer BT474 cells. Positron emission tomography (PET)/X-ray computed tomography (CT) imaging, tissue distribution, and blocking studies were performed in mice bearing BT474 xenografts. The chemical and radiochemical purity was greater than 95 % and both conjugates were stable against transchelation and transmetallation. Ex vivo stability at 60 min showed that the NODAGA-peptide-bound Ga-68 reduced to 42.1 ± 3.7 % (in plasma) and 37.4 ± 2.9 % (in urine), whereas the DOTA-peptide-bound Ga-68 was reduced to 1.2 ± 0.3 % (in plasma) and 4.2 ± 0.4 % (in urine) at 60 min. Similarly, the in vivo stability for [ 68 Ga]NODAGA-peptide was decreased to 2.1 ± 0.2 % (in plasma) and 2.2 ± 0.4 % (in urine). For [ 68 Ga]DOTA-peptide, it was decreased to 1.4 ± 0.3 % (in plasma) and 1.2 ± 0.4 % (in urine) at 60 min. The specific BT474 cell binding was 53.9 ± 0.8 % for [ 68 Ga]NODAGA-peptide, 25.8 ± 1.4 % for [ 68 Ga]-DOTA-peptide, and 18.8 ± 2.5 % for [ 68 Ga]GaCl 3 at 60 min. Inveon microPET/CT imaging at 1 h post-injection showed significantly (p < 0.05) higher tumor to muscle (T/M) ratio for [ 68 Ga]NODAGA-peptide (3.4 ± 0.3) as compared to [ 68 Ga]DOTA-peptide (1.8 ± 0.6). For [ 68 Ga]GaCl 3 and blocked mice, their ratios were 1.5 ± 0.6 and 1.5 ± 0.3 respectively. The tissue distributions data were similar to the PET imaging data. NODAGA is superior to DOTA in terms of radiolabeling kinetics. The method of radiolabeling was reproducible and yielded higher specific activity. Although both agents have relatively low in vivo stability, PET/CT imaging studies delineated BC tumors with [ 68 Ga]NODAGA-peptide, but not with [ 68 Ga]DOTA-peptide.

Post-translational modifications in secreted peptide hormones in plants.

PubMed

Matsubayashi, Yoshikatsu

2011-01-01

More than a dozen secreted peptides are now recognized as important hormones that coordinate and specify cellular functions in plants. Recent evidence has shown that secreted peptide hormones often undergo post-translational modification and proteolytic processing, which are critical for their function. Such 'small post-translationally modified peptide hormones' constitute one of the largest groups of peptide hormones in plants. This short review highlights recent progress in research on post-translationally modified peptide hormones, with particular emphasis on their structural characteristics and modification mechanisms.

Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

PubMed Central

Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A.; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T.; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

2015-01-01

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

Which risk factors are more associated with ischemic rather than hemorrhagic stroke in black Africans?

PubMed

Owolabi, Mayowa O; Agunloye, Atinuke M

2013-10-01

To comprehensively examine the relationship of vascular risk factors to stroke type in native black Africans. We explored 34 candidate demographic, clinical, and laboratory variables in 282 consecutive adult stroke patients with brain imaging. Ischemic stroke (IS) was found in 61.7% (174). Gender, alcohol, cigarette, homocysteine, C-reactive peptide, anthropometry, and carotid parameters were not significantly associated with stroke type (p>0.05). Patients with IS had relatively lower BP, were significantly older, and more frequently had diabetes mellitus, cardiac disease, or previous transient ischemic attack than patients with hemorrhagic stroke (HS). However, in multivariate regression model predicting 69% of stroke type correctly, age≥62 years (OR: 4.0, 95% CI: 2.0-7.9), previous TIA (OR: 4.3, 95% CI: 1.2-15.7) and systolic BP≥140 mmHg (OR: 0.4, 95% CI: 0.2-0.9) were the only independent significant predictors of IS. With increasing proportion of the population over 61 years and better BP control, the proportion of IS is expected to rise in black African countries currently undergoing epidemiological transition (changing lifestyle/disease pattern). Therefore, relevant components of the stroke intervention quadrangle (stroke surveillance, acute care, preventive and rehabilitation services) should be tailored toward this need. Copyright © 2013 Elsevier B.V. All rights reserved.

Preventive dental health care experiences of preschool-age children with special health care needs.

PubMed

Huebner, Colleen E; Chi, Donald L; Masterson, Erin; Milgrom, Peter

2015-01-01

This study examined the preventive dental health care experiences of young children with special needs and determined the feasibility of conducting clinical dental examinations at a community-based early intervention services center. Study methods included 90 parent interviews and dental examinations of their preschool-age children. Thirteen percent of the children received optimal preventive care, defined as twice daily tooth brushing with fluoridated toothpaste and two preventive dental visits in the prior 12 months; 37% experienced care that fell short in both areas. Optimal care was more common among children of parents who reported tooth brushing was not a struggle and those with a personal dentist. Parents' opinion of the study experience was generally positive. Few children with special needs receive effective preventive care early, when primary prevention could be achieved. Barriers to optimal care could be readily addressed by the dental community in coordination with early intervention providers. © 2014 Special Care Dentistry Association and Wiley Periodicals, Inc.

Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ16-22 and Sup357-13 in AOT reverse micelles

NASA Astrophysics Data System (ADS)

Martinez, Anna Victoria; Małolepsza, Edyta; Rivera, Eva; Lu, Qing; Straub, John E.

2014-12-01

Knowledge of how intermolecular interactions of amyloid-forming proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein linked to spongiform encephalopathies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sub-sequence, Aβ16-22, and the GNNQQNY subsequence, Sup357-13. In this study, molecular dynamics simulations were used to examine these peptide fragments encapsulated in reverse micelles (RMs) in order to identify the fundamental principles that govern how sequence and solution environment influence peptide aggregation. Aβ16-22 and Sup357-13 are observed to organize into anti-parallel and parallel β-sheet arrangements. Confinement in the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles is shown to stabilize extended peptide conformations and enhance peptide aggregation. Substantial fluctuations in the reverse micelle shape are observed, in agreement with earlier studies. Shape fluctuations are found to facilitate peptide solvation through interactions between the peptide and AOT surfactant, including direct interaction between non-polar peptide residues and the aliphatic surfactant tails. Computed amide I IR spectra are compared with experimental spectra and found to reflect changes in the peptide structures induced by confinement in the RM environment. Furthermore, examination of the rotational anisotropy decay of water in the RM demonstrates that the water dynamics are sensitive to the presence of peptide as well as the peptide sequence. Overall, our results demonstrate that the RM is a complex confining environment where substantial direct interaction between the surfactant and peptides plays an important role in determining the resulting ensemble of peptide conformations. By extension the results suggest that similarly complex sequence-dependent interactions may determine conformational ensembles of amyloid-forming peptides in a cellular environment.

PS80 interferes with the antiallergic effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, at very low concentration through modulation of Th1/Th2 balance.

PubMed

Kozutsumi, Daisuke; Tsunematsu, Masako; Yamaji, Taketo; Murakami, Rika; Yokoyama, Minehiko; Kino, Kohsuke

2006-07-01

Polysorbate 80 (PS80 or Tween-80) is often used as an additive to promote the rapid solubilization of pharmaceuticals in aqueous solutions. We investigated whether coinjection of a minimal amount of PS80 had a modulatory effect on the immunotherapeutic effects of Cry (Cryptomeria)-consensus peptide, a novel peptide developed for the therapeutic management of Japanese cedar pollinosis, using a Cry j 1-sensitized mouse model with experimental allergic rhinitis. Subcutaneous challenge with Cry-consensus peptide plus 50 microg/ml of PS80 did not affect the antigen-specific proliferation of splenocytes, but decreased the potency of Cry-consensus peptide to inhibit antigen-specific interleukin (IL)-5 production by the cells significantly in comparison with challenge with Cry-consensus peptide alone. However, there was no significant difference between the effect of Cry-consensus peptide administration on interferon (IFN)-gamma production in the presence and absence of PS80, indicating that PS80 interfered with the T helper 1 (Th1)-dominant T helper balance induced by Cry-consensus peptide challenge. Moreover, the increase in the level of antigen-specific immunoglobulin G2a (IgG2a) induced by Cry-consensus peptide challenge was inhibited slightly but unambiguously by PS80 coinjection. These in vitro experiments indicated that PS80 induces Th2-type differentiation of T helper cells through preferential inhibition of IFN-gamma expression relative to IL-5 expression in splenocytes in a concentration-dependent manner. In naïve mice, sensitization by Cry-consensus peptide with PS80 induced antigen-specific IL-5 production more potently than sensitization by Cry-consensus peptide alone, and when PS80 was added to bone marrow-derived dendritic cells, the endocytosis of fluorescence-labelled Cry-consensus peptide was dramatically inhibited in a concentration-dependent manner. Therefore, we conclude that PS80 has an immunomodulatory effect on the antigen-specific response resulting in a shift towards Th2 predominance with respect to the antigen recognition stage. Taken together, our findings suggest that PS80 might decrease the efficacy of Cry-consensus peptide through modulation of the efficiency of antigen endocytosis and/or of the direction of successive T helper cell differentiation.

Mutagenesis of NosM Leader Peptide Reveals Important Elements in Nosiheptide Biosynthesis

PubMed Central

Jin, Liang; Wu, Xuri; Xue, Yanjiu; Jin, Yue; Wang, Shuzhen

2016-01-01

ABSTRACT Nosiheptide, a typical member of the ribosomally synthesized and posttranslationally modified peptides (RiPPs), exhibits potent activity against multidrug-resistant Gram-positive bacterial pathogens. The precursor peptide of nosiheptide (NosM) is comprised of a leader peptide with 37 amino acids and a core peptide containing 13 amino acids. To pinpoint elements in the leader peptide that are essential for nosiheptide biosynthesis, a collection of mutants with unique sequence features, including N- and C-terminal motifs, peptide length, and specific sites in the leader peptide, was generated by mutagenesis in vivo. The effects of various mutants on nosiheptide biosynthesis were evaluated. In addition to the necessity of a conserved motif LEIS box, native length and the N-terminal 12 amino acid residues were indispensable, and single-site substitutions of these 12 amino acid residues resulted in changes ranging from a greater-than-5-fold decrease to a 2-fold increase of nosiheptide production, depending on the sites and substituted residues. Moreover, although the C-terminal motif is not conservative, significant effects of this portion on nosiheptide production were also evident. Taken together, the present results further highlight the importance of the leader peptide in nosiheptide biosynthesis, and provide new insights into the diversity and specificity of leader peptides in the biosynthesis of various RiPPs. IMPORTANCE As a representative thiopeptide, nosiheptide exhibits excellent antibacterial activity. Although the biosynthetic gene cluster and several modification steps have been revealed, the presence and roles of the leader peptide within the precursor peptide of the nosiheptide gene cluster remain elusive. Thus, identification of specific elements in the leader peptide can significantly facilitate the genetic manipulation of the gene cluster for increasing nosiheptide production or generating diverse analogues. Given the complexity of the biosynthetic process, the instability of the leader peptide, and the unavailability of intermediates, cocrystallization of intermediates, leader peptide, and modification enzymes is currently not feasible. Therefore, a mutagenesis approach was used to construct a series of leader peptide mutants to uncover a number of crucial and characteristic elements affecting nosiheptide biosynthesis, which moves a considerable distance toward a thorough understanding of the biosynthetic machinery for thiopeptides. PMID:27913416

The Effect of Free Adult Preventive Care Services on Subsequent Utilization of Inpatient Services in Taiwan.

PubMed

Tian, Wei-Hua

2016-07-01

The objective of this article is to investigate the relationship between the utilization of free adult preventive care services and subsequent utilization of inpatient services among elderly people under the National Health Insurance program in Taiwan. The study used secondary data from the 2005 Taiwan National Health Interview Survey and claim data from the 2006 Taiwan National Health Insurance Research Database for the elderly aged 65 or over. A bivariate probit model was used to avoid the possible endogeneity in individuals' utilization of free adult preventive care and inpatient services. This study finds that, when individuals had utilized the preventive care services in 2005, the probability that they utilized inpatient services in 2006 was significantly reduced by 13.89%. The findings of this study may provide a good reference for policy makers to guide the efficient allocation of medical resources through the continuous promotion of free adult preventive care services under the National Health Insurance program. © Australian Council for Educational Research 2016.

Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach.

PubMed

Andreatta, Massimo; Lund, Ole; Nielsen, Morten

2013-01-01

Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides. The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities in peptide data by performing two essential tasks simultaneously: alignment and clustering of peptide data. We apply the method to de-convolute binding motifs in a panel of peptide datasets with different degrees of complexity spanning from the simplest case of pre-aligned fixed-length peptides to cases of unaligned peptide datasets of variable length. Example applications described in this article include mixtures of binders to different MHC class I and class II alleles, distinct classes of ligands for SH3 domains and sub-specificities of the HLA-A*02:01 molecule. The Gibbs clustering method is available online as a web server at http://www.cbs.dtu.dk/services/GibbsCluster.

Synthesis of peptide thioacids at neutral pH using bis(2-sulfanylethyl)amido peptide precursors.

PubMed

Pira, Silvain L; Boll, Emmanuelle; Melnyk, Oleg

2013-10-18

Reaction of bis(2-sulfanylethyl)amido (SEA) peptides with triisopropylsilylthiol in water at neutral pH yields peptide thiocarboxylates. An alkylthioester derived from β-alanine was used to trap the released bis(2-sulfanylethyl)amine and displace the equilibrium toward the peptide thiocarboxylate.

Manual Solid-Phase Peptide Synthesis of Metallocene-Peptide Bioconjugates

ERIC Educational Resources Information Center

Kirin, Srecko I.; Noor, Fozia; Metzler-Nolte, Nils; Mier, Walter

2007-01-01

A simple and relatively inexpensive procedure for preparing a biologically active peptide using solid phase peptide synthesis (SPPS) is described. Fourth-year undergraduate students have gained firsthand experience from the solid-phase synthesis techniques and they have become familiar with modern analytical techniques based on the particular…

Peptide synthesis on glass substrate using acoustic droplet ejector.

PubMed

Youngki Choe; Shih-Jui Chen; Eun Sok Kim

2014-03-01

This paper describes the synthesis of a 9-mers-long peptide ladder structure of glycine on a modified glass surface using a nanoliter droplet ejector. To synthesize peptide on a glass substrate, SPOT peptide synthesis protocol was followed with a nozzleless acoustic droplet ejector being used to eject about 300 droplets of preactivated amino acid solution to dispense 60 nL of the solution per mer. The coupling efficiency of each mer was measured with FITC fluorescent tag to be 96%, resulting in net 70% efficiency for the whole 9-mer-long peptide of glycine. Usage of a nanoliter droplet ejector for SPOT peptide synthesis increases the density of protein array on a chip.

Peptide-Like Molecules (PLMs): A Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents

PubMed Central

Wipf, Peter; Xiao, Jingbo; Stephenson, Corey R. J.

2010-01-01

Peptides are natural ligands and substrates for receptors and enzymes and exhibit broad physiological effects. However, their use as therapeutic agents often suffers from poor bioavailability and insufficient membrane permeability. The success of peptide mimicry hinges on the ability of bioisosteres, in particular peptide bond replacements, to adopt suitable secondary structures relevant to peptide strands and position functional groups in equivalent space. This perspective highlights past and ongoing studies in our group that involve new methods development as well as specific synthetic library preparations and applications in chemical biology, with the goal to enhance the use of alkene and cyclopropane peptide bond isosteres. PMID:20725595

Smoking, health behavior, and value priorities.

PubMed

Kristiansen, C M

1985-01-01

In a postal survey, 113 respondents completed the Rokeach terminal value survey with the additional value, health, and questions regarding their preventive health behavior. Analyses showed that lighter nonsmokers displayed better preventive behavior than heavier smokers. Lighter nonsmokers also reported valuing health more than heavier smokers reported, and were oriented toward safety and inner-directedness compared with heavier smokers who were oriented toward satisfaction and outer-directedness. The preventive behavior of lighter nonsmokers increased with the value of social goals while the preventive behavior of heavier smokers was related to personal goals. These results are considered in the context of previous research which suggested that smokers and nonsmokers may have different value priorities. The implications of these findings for health education are discussed.

Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site

PubMed Central

Naranda, Tatjana; Wong, Kenneth; Kaufman, R. Ilene; Goldstein, Avram; Olsson, Lennart

1999-01-01

Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin. PMID:10377456

Design, Synthesis and Affinity Properties of Biologically Active Peptide and Protein Conjugates of Cotton Cellulose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards, J. V.; Goheen, Steven C.

The formation of peptide and protein conjugates of cellulose on cotton fabrics provides promising leads for the development of wound healing, antibacterial, and decontaminating textiles. An approach to the design, synthesis, and analysis of bioconjugates containing cellulose peptide and protein conjugates includes: 1) computer graphic modeling for a rationally designed structure; 2) attachment of the peptide or protein to cotton cellulose through a linker amino acid, and 3) characterization of the resulting bioconjugate. Computer graphic simulation of protein and peptide cellulose conjugates gives a rationally designed biopolymer to target synthetic modifications to the cotton cellulose. Techniques for preparing these typesmore » of conjugates involve both sequential assembly of the peptide on the fabric and direct crosslinking of the peptide or protein as cellulose bound esters or carboxymethylcellulose amides.« less

Discovery of a polystyrene binding peptide isolated from phage display library and its application in peptide immobilization.

PubMed

Qiang, Xu; Sun, Keyong; Xing, Lijun; Xu, Yifeng; Wang, Hong; Zhou, Zhengpin; Zhang, Juan; Zhang, Fang; Caliskan, Bilgen; Wang, Min; Qiu, Zheng

2017-06-01

Phage peptide display is a powerful technique for discovery of various target-specific ligands. However, target-unrelated peptides can often be obtained and cause ambiguous results. Peptide PB-TUP has been isolated repeatedly in our laboratory on different targets and we conducted a research on PB-TUP phage to investigate their binding properties and rate of propagation. ELISA and phage recovery assay demonstrated that PB-TUP phage had a significant superior affinity to polystyrene solid surface compared with control phage clones. In this study, some incidental bindings are excluded like blocking agents and non-specific binding of secondary antibodies. Propagation rate assays of the selected phage clones showed that the growth rate of PB-TUP phage was not superior to the control phages. Furthermore, the binding of PB-TUB to polystyrene was concentration dependent and varied with solution pH. Molecular modeling revealed that stable structures of α-helix and β-turn may contribute to the binding of PB-TUP to polystyrene plate. The PB-TUP sequence was fused to the N-terminus of peptide P2 and the fusion peptide significantly increased the binding affinity to polystyrene. The fusion peptide also enhanced the cell adhesion ability of peptide P2 with human umbilical vein endothelial cell (HUVEC). The addition of the polystyrene binding peptide provided a convenient method for peptide immobilization.

Analysis of Intrinsic Peptide Detectability via Integrated Label-Free and SRM-Based Absolute Quantitative Proteomics.

PubMed

Jarnuczak, Andrew F; Lee, Dave C H; Lawless, Craig; Holman, Stephen W; Eyers, Claire E; Hubbard, Simon J

2016-09-02

Quantitative mass spectrometry-based proteomics of complex biological samples remains challenging in part due to the variability and charge competition arising during electrospray ionization (ESI) of peptides and the subsequent transfer and detection of ions. These issues preclude direct quantification from signal intensity alone in the absence of a standard. A deeper understanding of the governing principles of peptide ionization and exploitation of the inherent ionization and detection parameters of individual peptides is thus of great value. Here, using the yeast proteome as a model system, we establish the concept of peptide F-factor as a measure of detectability, closely related to ionization efficiency. F-factor is calculated by normalizing peptide precursor ion intensity by absolute abundance of the parent protein. We investigated F-factor characteristics in different shotgun proteomics experiments, including across multiple ESI-based LC-MS platforms. We show that F-factors mirror previously observed physicochemical predictors as peptide detectability but demonstrate a nonlinear relationship between hydrophobicity and peptide detectability. Similarly, we use F-factors to show how peptide ion coelution adversely affects detectability and ionization. We suggest that F-factors have great utility for understanding peptide detectability and gas-phase ion chemistry in complex peptide mixtures, selection of surrogate peptides in targeted MS studies, and for calibration of peptide ion signal in label-free workflows. Data are available via ProteomeXchange with identifier PXD003472.

Risk of developing tuberculosis disease among persons diagnosed with latent tuberculosis infection in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; Cobelens, Frank; van den Hof, Susan

2016-11-01

Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands. Copyright ©ERS 2016.

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

DOE PAGES

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.; ...

2016-02-11

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8 + T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities ofmore » TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.« less

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

DOE PAGES

Kong, Rui; Xu, Kai; Zhou, Tongqing; ...

2016-05-13

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. In this paper, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showedmore » that the N-terminal portion of the fusion peptide can be solvent-exposed. Finally, these results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.« less

Cloning and heterologous expression of the antibiotic peptide (ABP) genes from Rhizopus oligosporus NBRC 8631.

PubMed

Yamada, Osamu; Sakamoto, Kazutoshi; Tominaga, Mihoko; Nakayama, Tasuku; Koseki, Takuya; Fujita, Akiko; Akita, Osamu

2005-03-01

We carried out protein sequencing of purified Antibiotic Peptide (ABP), and cloned two genes encoding this peptide as abp1 and abp2, from Rhizopus oligosporus NBRC 8631. Both genes contain an almost identical 231-bp segment, with only 3 nucleotide substitutions, encoding a 77 amino acid peptide. The abp gene product comprises a 28 amino acid signal sequence and a 49 amino acid mature peptide. Northern blot analysis showed that at least one of the abp genes is transcribed in R. oligosporus NBRC 8631. A truncated form of abp1 encoding only the mature peptide was fused with the alpha-factor signal peptide and engineered for expression in Pichia pastoris SMD1168H. Culture broth of the recombinant Pichia displayed ABP activity against Bacillus subtilis NBRC 3335 after induction of heterologous gene expression. This result indicates that mature ABP formed the active structure without the aid of other factors from R. oligosporus, and was secreted.

Predelivery uterine arteries embolization in patients with placental implant anomalies: a cost-effective procedure.

PubMed

Niola, Raffaella; Giurazza, Francesco; Torbica, Aleksandra; Schena, Emiliano; Silvestre, Mattia; Maglione, Franco

2017-01-01

Postpartum hemorrhages occur in 5 % of all deliveries. Open surgery and endovascular embolization techniques are the options commonly applied to face this life-threatening scenario. A cost analysis has been performed to compare the standard embolization endovascular approach, performed postpartum in emergency settlement, with a novel proposed preventive embolization approach, and performed in election in selected high-risk patients before the delivery. Two groups have been compared: 46 patients (non-preventive group) and 67 patients (preventive group). The computation of the detailed costs derived from the real costs supported by the hospital, based on the regional tariff in the period considered. The total expense for the 46 patients of the non-preventive group was 640.551,84€ (13.925,04€/patient); all of them received transfusions and 43.4 % underwent to hysterectomy; the total expense for the 67 patients of the preventive group was 509.720,59€ (7.607,77€/ patient); 36 % required transfusions and 26 % underwent to hysterectomy. Overall, in the preventive group, there is a mean saving of 45 %, it else 6.317€/patient. In this sample, predelivery uterine artery embolization has proved to be a cost-effective procedure, reducing the length of the hospital stay and the number of transfers to the intensive care unit, in pregnants with placental implant anomalies.

Dentists' opinion and knowledge about preventive dental care in Saudi Arabia: a nationwide cross-sectional study.

PubMed

Togoo, Rafi Ahmed; Al-Rafee, Mohammed A; Kandyala, Reena; Luqam, Master; Al-Bulowey, Mohammed A

2012-05-01

The aim of this study was to determine the dentists' opinions on causes for high prevalence of dental caries in the country and to assess their level of knowledge about preventive dental care. A questionnaire based national crosssectional survey among 500 dentists was conducted under the auspices of Directorate of Dentistry, Ministry of Health. The data was analyzed using SPSS software version 11.0 and descriptive statistics were obtained. The response rate was 87.8% (n = 439). 83% of dentists identified poor oral hygiene as the major reason for high prevalence of caries, only 39% of patients reportedly brushed teeth at least once a day, oral prophylaxis (83%) is the most common preventive practice followed, social factors (62.5%) are the most challenging barriers in preventive dental programs, 71.3% always give chair side dental health education, school based programs (66.6%) are most effective tools for dental health education. Majority of dentists in Saudi Arabia are adequately informed and motivated toward preventive dental care but they are in need of further support from policy makers to enhance preventive dental programs in the Kingdom. Oral hygiene should be improved in the country by reaching out to the entire community through extensive and continued education programs.

Use of Preventive Dental Care Among Medicaid-Enrolled, School-Aged US Children in Immigrant and Nonimmigrant Families: Trends in Pennsylvania From 2005 Through 2010

PubMed Central

Chesnokova, Arina; Shults, Justine; Pinto, Andres; Rubin, David M.

2014-01-01

Objectives. We describe trends in receipt of preventive dental care among Medicaid-enrolled children in Pennsylvania between 2005 and 2010, comparing the US children of immigrants with their co-ethnic peers in nonimmigrant families. Methods. We analyzed Pennsylvania Medicaid claims, birth records, and census data for children born in Pennsylvania and enrolled in Medicaid for 10 or more months during any of the calendar years assessed. Results. Receipt of preventive dental care was more likely among Latino children in immigrant families than among their peers in nonimmigrant families; also, it was more likely among White children in immigrant families than among their peers in nonimmigrant families. Rates of preventive dental care use among African American and Asian children in immigrant and nonimmigrant families were comparable. From 2005 to 2010, the percentage of Latino children in nonimmigrant families who received preventive dental care increased from 33% to 61%. Changes in other groups were significant but less dramatic. Conclusions. Receipt of preventive dental care has increased among Medicaid-enrolled children in Pennsylvania, with marked gains among Latino children. Within each racial/ethnic group, the children of immigrants were either more likely than or equally likely as children in nonimmigrant families to receive care. PMID:25322290

Prevention. How much harm? How much benefit? 3. Physical, psychological and social harm.

PubMed Central

Marshall, K G

1996-01-01

Harm caused by preventive programs may be physical, psychological, social or, if informed consent has not been obtained, ethical. Adverse effects of preventive screening programs may occur at any of the three levels of the "screening cascade", the screening procedure itself, the investigation of abnormal results of screening tests or the treatment of detected abnormalities or diseases. The greatest harm occurs at the second and third levels. Examples of procedures that may cause physical harm are venipuncture, mammography, colonoscopy, breast biopsy, transrectal ultrasonography, prostate biopsy, weight-reducing and cholesterol-lowering diets and radical prostatectomy. The psychological and social harm of preventive programs involves anticipated discomfort or perception of adverse effects of preventive interventions; unpleasant interactions with health care workers, time required for preventive programs, excessive overall awareness of health, anxiety over the results of a screening test implications of a positive screening test, consequences of being labelled as "sick" or "at risk," psychopathologic effects induced directly by preventive programs and, in the case of a false-negative test result, false assurance of disease-free status. Since the positive predictive value of screening tests in the general population is always low, most abnormal test results are "false-positive," these engender a great deal of psychological discuss among patients. PMID:8800074

Monitoring latent tuberculosis infection diagnosis and management in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; de Vries, Gerard; Cobelens, Frank; van den Hof, Susan

2016-05-01

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events.In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation.Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events.Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40-60%. Copyright ©ERS 2016.

Topical Administration of Somatostatin Prevents Retinal Neurodegeneration in Experimental Diabetes

PubMed Central

Hernández, Cristina; García-Ramírez, Marta; Corraliza, Lidia; Fernández-Carneado, Jimena; Farrera-Sinfreu, Josep; Ponsati, Berta; González-Rodríguez, Águeda; Valverde, Ángela M.; Simó, Rafael

2013-01-01

Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration. For this purpose, rats with streptozotocin-induced diabetes mellitus (STZ-DM) were treated with either SST eye drops or vehicle for 15 days. Nondiabetic rats treated with vehicle served as a control group. Functional abnormalities were assessed by electroretinography (ERG), and neurodegeneration was assessed by measuring glial activation and the apoptotic rate. In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. Intraretinal concentrations of glutamate and its main transporter glutamate/aspartate transporter (GLAST) were also determined. Treatment with SST eye drops prevented ERG abnormalities, glial activation, apoptosis, and the misbalance between proapoptotic and survival signaling detected in STZ-DM rats. In addition, SST eye drops inhibited glutamate accumulation in the retina and GLAST downregulation induced by diabetes mellitus. We conclude that topical administration of SST has a potent effect in preventing retinal neurodegeneration induced by diabetes mellitus. In addition, our findings open up a new preventive pharmacological strategy targeted to early stages of DR. PMID:23474487

Role of gastrin-releasing peptide in pepsinogen secretion from the isolated perfused rat stomach.

PubMed

Skak-Nielsen, T; Holst, J J; Christensen, J D; Fjalland, B

1988-10-01

We studied the effects of the neuropeptide gastrin-releasing peptide on pepsinogen secretion using an isolated perfused rat stomach with intact vagal innervation. Following electrical stimulation of the vagus nerves, the pepsin output to the luminal effluent increased from 94 +/- 7 to 182 +/- 24 units pepsin/min and the release of immunoreactive gastrin-releasing peptide to the venous effluent increased from 0.059 +/- 0.014 to 0.138 +/- 0.028 pmol/min. Infusion of gastrin-releasing peptide at 10(-8) M significantly increased pepsin output (from 87 +/- 17 to 129 +/- 22 units pepsin/min) and simultaneous infusion of gastrin-releasing peptide and carbachol at 10(-8) and 10(-6) M, respectively, resulted in an increase to almost 4 times the basal values. Atropine reduced but did not abolish the pepsin response to vagal stimulation and to infusion of gastrin-releasing peptide. Our results suggest that gastrin-releasing peptide participates in the vagal control of pepsinogen secretion.

Dynamics at a Peptide-TiO2 Anatase (101) Interface.

PubMed

Polimeni, Marco; Petridis, Loukas; Smith, Jeremy C; Arcangeli, Caterina

2017-09-28

The interface between biological matter and inorganic materials is a widely investigated research topic due to possible applications in biomedicine and nanotechnology. In this context, the molecular level adsorption mechanism that drives specific recognition between small peptide sequences and inorganic surfaces represents an important topic likely to provide much information useful for designing bioderived materials. Here, we investigate the dynamics at the interface between a Ti-binding peptide sequence (AMRKLPDAPGMHC) and a TiO 2 anatase surface by using molecular dynamics (MD) simulations. In the simulations the adsorption mechanism is characterized by diffusion of the peptide from the bulk water phase toward the TiO 2 surface, followed by the anchoring of the peptide to the surface. The anchoring is mediated by the interfacial water layers by means of the charged groups of the side chains of the peptide. The peptide samples anchored and dissociated states from the surface and its conformation is not affected by the surface when anchored.

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

PubMed

Jiang, Ying; Gao, Ge; Fang, Gang; Gustafson, Eric L; Laverty, Maureen; Yin, Yanbin; Zhang, Yong; Luo, Jingchu; Greene, Jonathan R; Bayne, Marvin L; Hedrick, Joseph A; Murgolo, Nicholas J

2003-05-01

PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

Characterization of three peptides derived from prosomatostatin [prosomatostatin-(1-63)-, -(65-76)- and -(79-92)-peptides] in a human pancreatic tumour.

PubMed

Conlon, J M; Eriksson, B; Grimelius, L; Oberg, K; Thim, L

1987-11-15

By using only reverse-phase h.p.l.c., three fragments of prosomatostatin were isolated from an extract of a human pancreatic neuroendocrine tumour that produced somatostatin, vasoactive intestinal polypeptide and gastrin-releasing peptide. The amino acid composition of the peptides indicated that they represented prosomatostatin-(1-63)-peptide, prosomatostain-(65-76)-peptide and prosomatostatin-(79-92)-peptide (somatostatin-14). The identity of prosomatostatin-(1-63)-peptide was confirmed by characterization of the products of digestion with Armillaria mellea (honey fungus) proteinase. Partial micro-sequencing of prosomatostatin-(1-63)-peptide showed that the Gly24-Ala25 bond of preprosomatostatin was the site of cleavage of the signal peptide. Thus human prosomatostatin is a protein of 92 amino acid residues that is proteolytically cleaved in a pancreatic tumour at the site of a dibasic-residue (arginine-lysine) processing site and at a single-monobasic-residue (arginine) processing site.

Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.

Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of keymore » binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.« less

Biomimetic and Aggregation-Driven Crystallization Route for Room-Temperature Material Synthesis: Growth of β-Ga2O3 Nanoparticles Using Peptide Assemblies as Nanoreactors

PubMed Central

Lee, Sang-Yup; Gao, Xueyun; Matsui, Hiroshi

2008-01-01

The room temperature synthesis of β-Ga2O3 nanocrystal was examined by coupling two biomimetic crystallization techniques, the enzymatic peptide nano-assembly templating and the aggregation-driven crystallization. The catalytic template of peptide assembly nucleated and mineralized primary β-Ga2O3 crystals, and then fused them to grow single-crystalline and monodisperse nanoparticles in the cavity of the peptide assembly at room temperature. In this work, the peptide assembly was exploited as a nano-reactor with an enzymatic functionality catalyzing the hydrolysis of gallium precursors. In addition, the characteristic ring-structure of peptide assembly is expected to provide an efficient dehydration pathway and the crystallization control over the surface tension, which are advantageous for the β-Ga2O3 crystal growth. This multifunctional peptide assembly could be applied for syntheses of a variety of nanomaterials that are kinetically difficult to grow at room temperature. PMID:17302413

Magnetic field effect on the structural properties of a peptide model: Molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Housaindokht, Mohammad Reza; Moosavi, Fatemeh

2018-06-01

The effect of magnetization on the properties of a system containing a peptide model is studied by molecular dynamics simulation at a range of 298-318 K. Two mole fractions of 0.001 and 0.002 of peptide were simulated and the variation of hydrogen bond number, orientational ordering parameter, gyration radius, mean square displacement, as well as radial distribution function, were under consideration. The results show that applying magnetic field will increase the number of hydrogen bonds between water molecules by clustering them and decreases the interaction of water and peptide. This reduction may cause more available free space and enhance the movement of the peptide. As a result, the diffusion coefficient of the peptide becomes greater and its conformation changes. Orientational ordering parameter besides radius of gyration demonstrates that peptide is expanded by static magnetic field and its orientational ordering parameter is affected.

A Signal Peptide Derived from hsp60 Binds HLA-E and Interferes with CD94/NKG2A Recognition

PubMed Central

Michaëlsson, Jakob; Teixeira de Matos, Cristina; Achour, Adnane; Lanier, Lewis L.; Kärre, Klas; Söderström, Kalle

2002-01-01

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule which presents a restricted set of nonameric peptides, derived mainly from the signal sequence of other MHC class I molecules. It interacts with CD94/NKG2 receptors expressed on the surface of natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also presents a peptide derived from the leader sequence of human heat shock protein 60 (hsp60). This peptide gains access to HLA-E intracellularly, resulting in up-regulated HLA-E/hsp60 signal peptide cell-surface levels on stressed cells. Notably, HLA-E molecules in complex with the hsp60 signal peptide are no longer recognized by CD94/NKG2A inhibitory receptors. Thus, during cellular stress an increased proportion of HLA-E molecules may bind the nonprotective hsp60 signal peptide, leading to a reduced capacity to inhibit a major NK cell population. Such stress induced peptide interference would gradually uncouple CD94/NKG2A inhibitory recognition and provide a mechanism for NK cells to detect stressed cells in a peptide-dependent manner. PMID:12461076

Facile and selective covalent grafting of an RGD-peptide to electrospun scaffolds improves HUVEC adhesion.

PubMed

Dettin, Monica; Zamuner, Annj; Roso, Martina; Iucci, Giovanna; Samouillan, Valerie; Danesin, Roberta; Modesti, Michele; Conconi, Maria Teresa

2015-10-01

The development of a biomimetic surface able to promote endothelialization is fundamental in the search for blood vessel substitutes that prevent the formation of thrombi or hyperplasia. This study aims at investigating the effect of functionalization of poly-ε-caprolactone or poly(L-lactic acid-co-ɛ-caprolactone) electrospun scaffolds with a photoreactive adhesive peptide. The designed peptide sequence contains four Gly-Arg-Gly-Asp-Ser-Pro motifs per chain and a p-azido-Phe residue at each terminus. Different peptide densities on the scaffold surface were obtained by simply modifying the peptide concentration used in pretreatment of the scaffold before UV irradiation. Scaffolds of poly-ε-caprolactone embedded with adhesive peptides were produced to assess the importance of peptide covalent grafting. Our results show that the scaffolds functionalized with photoreactive peptides enhance adhesion at 24 h with a dose-dependent effect and control the proliferation of human umbilical vein endothelial cells, whereas the inclusion of adhesive peptide in the electrospun matrices by embedding does not give satisfactory results. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Influence of Dimerization of Lipopeptide Laur-Orn-Orn-Cys-NH2 and an N-terminal Peptide of Human Lactoferricin on Biological Activity.

PubMed

Kamysz, Elżbieta; Sikorska, Emilia; Dawgul, Małgorzata; Tyszkowski, Rafał; Kamysz, Wojciech

Lactoferrin (LF) is a naturally occurring antimicrobial peptide that is cleaved by pepsin to lactoferricin (LFcin). LFcin has an enhanced antimicrobial activity as compared to that of LF. Recently several hetero- and homodimeric antimicrobial peptides stabilized by a single disulfide bond linking linear polypeptide chains have been discovered. We have demonstrated that the S-S bond heterodimerization of lipopeptide Laur-Orn-Orn-Cys-NH 2 (peptide III) and the synthetic N -terminal peptide of human lactoferricin (peptide I) yields a dimer (peptide V), which is almost as microbiologically active as the more active monomer and at the same time it is much less toxic. Furthermore, it has been found that the S-S bond homodimerization of both peptide I and peptide III did not affect antimicrobial and haemolytic activity of the compounds. The homo- and heterodimerization of peptides I and III resulted in either reduction or loss of antifungal activity. This work suggests that heterodimerization of antimicrobial lipopeptides via intermolecular disulfide bond might be a powerful modification deserving consideration in the design of antimicrobial peptides.

Peptide library synthesis on spectrally encoded beads for multiplexed protein/peptide bioassays

NASA Astrophysics Data System (ADS)

Nguyen, Huy Q.; Brower, Kara; Harink, Björn; Baxter, Brian; Thorn, Kurt S.; Fordyce, Polly M.

2017-02-01

Protein-peptide interactions are essential for cellular responses. Despite their importance, these interactions remain largely uncharacterized due to experimental challenges associated with their measurement. Current techniques (e.g. surface plasmon resonance, fluorescence polarization, and isothermal calorimetry) either require large amounts of purified material or direct fluorescent labeling, making high-throughput measurements laborious and expensive. In this report, we present a new technology for measuring antibody-peptide interactions in vitro that leverages spectrally encoded beads for biological multiplexing. Specific peptide sequences are synthesized directly on encoded beads with a 1:1 relationship between peptide sequence and embedded code, thereby making it possible to track many peptide sequences throughout the course of an experiment within a single small volume. We demonstrate the potential of these bead-bound peptide libraries by: (1) creating a set of 46 peptides composed of 3 commonly used epitope tags (myc, FLAG, and HA) and single amino-acid scanning mutants; (2) incubating with a mixture of fluorescently-labeled antimyc, anti-FLAG, and anti-HA antibodies; and (3) imaging these bead-bound libraries to simultaneously identify the embedded spectral code (and thus the sequence of the associated peptide) and quantify the amount of each antibody bound. To our knowledge, these data demonstrate the first customized peptide library synthesized directly on spectrally encoded beads. While the implementation of the technology provided here is a high-affinity antibody/protein interaction with a small code space, we believe this platform can be broadly applicable to any range of peptide screening applications, with the capability to multiplex into libraries of hundreds to thousands of peptides in a single assay.

Modeling alternative binding registers of a minimal immunogenic peptide on two class II major histocompatibility complex (MHC II) molecules predicts polarized T-cell receptor (TCR) contact positions.

PubMed

Murray, J S; Fois, S D S; Schountz, T; Ford, S R; Tawde, M D; Brown, J C; Siahaan, T J

2002-03-01

Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

PubMed Central

Mangion, Kenneth; Carrick, David; Hennigan, Barry W; Payne, Alexander R; McClure, John; Mason, Maureen; Das, Rajiv; Wilson, Rebecca; Edwards, Richard J; Petrie, Mark C; McEntegart, Margaret; Eteiba, Hany; Oldroyd, Keith G; Berry, Colin

2016-01-01

Objective We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar. PMID:27504003

Updated Priorities Among Effective Clinical Preventive Services

PubMed Central

Maciosek, Michael V.; LaFrance, Amy B.; Dehmer, Steven P.; McGree, Dana A.; Flottemesch, Thomas J.; Xu, Zack; Solberg, Leif I.

2017-01-01

PURPOSE The Patient Protection and Affordable Care Act’s provisions for first-dollar coverage of evidence-based preventive services have reduced an important barrier to receipt of preventive care. Safety-net providers, however, still serve a substantial uninsured population, and clinician and patient time remain limited in all primary care settings. As a consequence, decision makers continue to set priorities to help focus their efforts. This report updates estimates of relative health impact and cost-effectiveness for evidence-based preventive services. METHODS We assessed the potential impact of 28 evidence-based clinical preventive services in terms of their cost-effectiveness and clinically preventable burden, as measured by quality-adjusted life years (QALYs) saved. Each service received 1 to 5 points on each of the 2 measures—cost-effectiveness and clinically preventable burden—for a total score ranging from 2 to 10. New microsimulation models were used to provide updated estimates of 12 of these services. Priorities for improving delivery rates were established by comparing the ranking with what is known of current delivery rates nationally. RESULTS The 3 highest-ranking services, each with a total score of 10, are immunizing children, counseling to prevent tobacco initiation among youth, and tobacco-use screening and brief intervention to encourage cessation among adults. Greatest population health improvement could be obtained from increasing utilization of clinical preventive services that address tobacco use, obesity-related behaviors, and alcohol misuse, as well as colorectal cancer screening and influenza vaccinations. CONCLUSIONS This study identifies high-priority preventive services and should help decision makers select which services to emphasize in quality-improvement initiatives. PMID:28376457

Preventive care and recall intervals. Targeting of services in child dental care in Norway.

PubMed

Wang, N J; Aspelund, G Ø

2010-03-01

Skewed caries distribution has made interesting the use of a high risk strategy in child dental services. The purpose of this study was to describe the preventive dental care given and the recall intervals used for children and adolescents in a low caries risk population, and to study how the time spent for preventive care and the length of intervals were associated with characteristics of the children and factors related to care delivery. Time spent for and type of preventive care, recall intervals, oral health and health behaviour of children and adolescents three to 18 years of age (n = 576) and the preventive services delivered were registered at routine dental examinations in the public dental services. The time used for preventive dental care was on average 22% of the total time used in a course of treatment (7.3 of 33.4 minutes). Less than 15% of the variation in time spent for prevention was explained by oral health, oral health behaviours and other characteristics of the children and the service delivery. The mean (SD) recall intervals were 15.4 (4.6) months and 55% of the children were given intervals equal to or longer than 18 months. Approximately 30% of the variation in the length of the recall intervals was explained by characteristics of the child and the service delivery. The time used for preventive dental care of children in a low risk population was standardized, while the recall intervals to a certain extent were individualized according to dental health and dental health behaviour.

Physician and patient gender concordance and the delivery of comprehensive clinical preventive services.

PubMed

Flocke, Susan A; Gilchrist, Valerie

2005-05-01

Understanding the role of patient- and physician-gender on delivery of preventive services has important implications for identifying strategies to increase preventive service delivery. We attempt to overcome methodological limitations of previous studies in examining the association of the patient-physician gender interaction on the delivery of preventive screening, counseling, and immunization services. In this cross-sectional study, research nurses directly observed 3256 consecutive adult patient visits to 138 family physicians. Delivery of gender neutral US Preventive Services Task Force (USPSTF) recommended screening, health behavior counseling, and immunization services was assessed by direct observation and medical record review. Multilevel regression analyses were used to test the interaction effect of physician and patient gender with preventive service delivery, controlling for patient age, insurance type, number of office visits in the past 2 years and physician age. The interaction effect of physician and patient gender was not significantly associated with delivery of gender neutral screening, counseling, or immunizations. Patients of female physicians were more up-to-date on counseling services (P < 0.01) and immunizations (P < 0.05) than patients of male physicians. Male patients, independent of physician gender, were more up-to-date on counseling and immunizations (P < 0.01). Physician-patient gender concordance is not associated with delivery of more preventive services. Rather, female physicians provide more counseling and immunization services to all of their patients. Previous research showing higher rates of gender-specific screening achieved by women physicians may have been an indication of an overall greater prevention orientation among women physicians rather than a specific benefit of gender concordance.

National Survey of Preventive Health Services in US Emergency Departments

PubMed Central

Delgado, M. Kit; Acosta, Colleen D.; Ginde, Adit A.; Wang, N. Ewen; Strehlow, Matthew C.; Khandwala, Yash S.; Camargo, Carlos A.

2012-01-01

Study objective We describe the availability of preventive health services in US emergency departments (EDs), as well as ED directors’ preferred service and perceptions of barriers to offering preventive services. Methods Using the 2007 National Emergency Department Inventory (NEDI)–USA, we randomly sampled 350 (7%) of 4,874 EDs. We surveyed directors of these EDs to determine the availability of (1) screening and referral programs for alcohol, tobacco, geriatric falls, intimate partner violence, HIV, diabetes, and hypertension; (2) vaccination programs for influenza and pneumococcus; and (3) linkage programs to primary care and health insurance. ED directors were asked to select the service they would most like to implement and to rate 5 potential barriers to offering preventive services. Results Two hundred seventy-seven EDs (80%) responded across 46 states. Availability of services ranged from 66% for intimate partner violence screening to 19% for HIV screening. ED directors wanted to implement primary care linkage most (17%) and HIV screening least (2%). ED directors “agreed/strongly agreed” that the following are barriers to ED preventive care: cost (74%), increased patient length of stay (64%), lack of follow-up (60%), resource shifting leading to worse patient outcomes (53%), and philosophical opposition (27%). Conclusion Most US EDs offer preventive services, but availability and ED director preference for type of service vary greatly. The majority of EDs do not routinely offer Centers for Disease Control and Prevention–recommended HIV screening. Most ED directors are not philosophically opposed to offering preventive services but are concerned with added costs, effects on ED operations, and potential lack of follow-up. PMID:20889237

Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial.

PubMed

Dodick, David W; Silberstein, Stephen D; Bigal, Marcelo E; Yeung, Paul P; Goadsby, Peter J; Blankenbiller, Tricia; Grozinski-Wolff, Melissa; Yang, Ronghua; Ma, Yuju; Aycardi, Ernesto

2018-05-15

Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine. To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose. Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12. Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded. Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8). The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose. Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2). Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy. clinicaltrials.gov Identifier: NCT02629861.

Peptide Assembly-Driven Metal-Organic Framework (MOF) Motors for Micro Electric Generator

PubMed Central

Ikezoe, Yasuhiro; Fang, Justin; Wasik, Tomasz L.; Uemura, Takashi; Zheng, Yongtai; Kitagawa, Susumu

2014-01-01

Peptide-MOF motors, whose motions are driven by anisotropic surface gradients created via peptide self-assembly around nanopores of MOFs, can rotate microscopic rotors and magnet fast enough to generate electric power of 0.1 µW. To make the peptide-MOF generator recyclable, a new MOF is applied as a host motor engine, which has a more rigid framework with higher H2O affinity so that peptide release occurs more efficiently via guest exchange without the destruction of MOF. PMID:25418936

Exploring peptide hormones in plants: identification of four peptide hormone-receptor pairs and two post-translational modification enzymes.

PubMed

Matsubayashi, Yoshikatsu

2018-01-01

The identification of hormones and their receptors in multicellular organisms is one of the most exciting research areas and has lead to breakthroughs in understanding how their growth and development are regulated. In particular, peptide hormones offer advantages as cell-to-cell signals in that they can be synthesized rapidly and have the greatest diversity in their structure and function. Peptides often undergo post-translational modifications and proteolytic processing to generate small oligopeptide hormones. In plants, such small post-translationally modified peptides constitute the largest group of peptide hormones. We initially explored this type of peptide hormone using bioassay-guided fractionation and later by in silico gene screening coupled with biochemical peptide detection, which led to the identification of four types of novel peptide hormones in plants. We also identified specific receptors for these peptides and transferases required for their post-translational modification. This review summarizes how we discovered these peptide hormone-receptor pairs and post-translational modification enzymes, and how these molecules function in plant growth, development and environmental adaptation.

Exploring peptide hormones in plants: identification of four peptide hormone-receptor pairs and two post-translational modification enzymes

PubMed Central

MATSUBAYASHI, Yoshikatsu

2018-01-01

The identification of hormones and their receptors in multicellular organisms is one of the most exciting research areas and has lead to breakthroughs in understanding how their growth and development are regulated. In particular, peptide hormones offer advantages as cell-to-cell signals in that they can be synthesized rapidly and have the greatest diversity in their structure and function. Peptides often undergo post-translational modifications and proteolytic processing to generate small oligopeptide hormones. In plants, such small post-translationally modified peptides constitute the largest group of peptide hormones. We initially explored this type of peptide hormone using bioassay-guided fractionation and later by in silico gene screening coupled with biochemical peptide detection, which led to the identification of four types of novel peptide hormones in plants. We also identified specific receptors for these peptides and transferases required for their post-translational modification. This review summarizes how we discovered these peptide hormone–receptor pairs and post-translational modification enzymes, and how these molecules function in plant growth, development and environmental adaptation. PMID:29434080

Using peptide array to identify binding motifs and interaction networks for modular domains.

PubMed

Li, Shawn S-C; Wu, Chenggang

2009-01-01

Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

Elucidation of the binding preferences of peptide recognition modules: SH3 and PDZ domains.

PubMed

Teyra, Joan; Sidhu, Sachdev S; Kim, Philip M

2012-08-14

Peptide-binding domains play a critical role in regulation of cellular processes by mediating protein interactions involved in signalling. In recent years, the development of large-scale technologies has enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. These efforts have provided significant insights into the binding specificities of these modular domains. Many research groups have taken advantage of this unprecedented volume of specificity data and have developed a variety of new algorithms for the prediction of binding specificities of peptide-binding domains and for the prediction of their natural binding targets. This knowledge has also been applied to the design of synthetic peptide-binding domains in order to rewire protein-protein interaction networks. Here, we describe how these experimental technologies have impacted on our understanding of peptide-binding domain specificities and on the elucidation of their natural ligands. We discuss SH3 and PDZ domains as well characterized examples, and we explore the feasibility of expanding high-throughput experiments to other peptide-binding domains. Copyright © 2012. Published by Elsevier B.V.

TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

PubMed Central

Neerincx, Andreas; Hermann, Clemens; Antrobus, Robin; van Hateren, Andy; Cao, Huan; Trautwein, Nico; Stevanović, Stefan; Elliott, Tim; Deane, Janet E; Boyle, Louise H

2017-01-01

Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether any other co-factors associate with TAPBPR, which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on MHC class I molecules, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex. DOI: http://dx.doi.org/10.7554/eLife.23049.001 PMID:28425917

Conformational analysis of a synthetic fish kisspeptin 1 peptide in membrane mimicking environments

PubMed Central

Shahi, Neetu; Singh, Atul Kumar; Khangembam, Victoria Chanu; Singh, Arvind Kumar; Kumar, Satish

2017-01-01

Kisspeptin 1 is a neuropeptide hormone of the RFamide family, which act as an upstream regulator of brain-pituitary-gonad (BPG) axis in most vertebrates including teleosts. In the present study, a 16 amino acid long putative mature bioactive peptide (kiss 1) from preprokisspeptin 1 of golden mahseer, Tor putitora (Hamilton, 1822), was synthesized and characterized using an integrated (experimental and in silico) approach. The far-UV circular dichroism (CD) spectrum of this peptide was evaluated both in aqueous and membrane mimicking solvents (TFE, HFIP and Dioxane). The results indicate that kiss 1 peptide adopted helical, turn and β conformations in membrane like environments. The near-UV CD spectroscopy was also carried out to examine the tertiary packing around aromatic residues of kiss 1 peptide and the peptide-membrane complex. The kiss 1 peptide exhibited little signal in water, but a prominent negative band was observed at around 275 nm when membrane mimetic solution was added. The observed ordered conformations of kiss 1 peptide in the different solvents indicated its potential biological activity which could enhance the secretion of gonadotropin-releasing hormone (GnRH) at BPG axis. The conformational information generated from the present study reinforces the application prospects of bioactive synthetic peptide analogs of kisspeptin 1 in improving the reproductive performances of important cultivable fish species. PMID:28977030

Role of gastrin-releasing peptides in breast cancer metastasis.

PubMed

Ni, Chunsheng; Zhao, Xiulan; Sun, Tao; Liu, Yanrong; Gu, Qiang; Sun, Baocun

2012-12-01

The gastrin-releasing peptide, which is an unfolded protein response regulator and functions as a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, is a regulatory human peptide that elicits gastrin release and regulates gastric acid secretion and enteric motor function. It has been shown to exhibit mitogenic activity in small cell lung cancer and plays a role in a lot of other human cancers including tumors in colon, stomach, pancreas, breast, and prostate. This study investigated the gastrin-releasing peptide expression in breast cancer to demonstrate the role of this biomarker in breast cancer metastasis. Gastrin-releasing peptide was analyzed in breast cancer tissue microarray specimens, including 200 primary breast cancer specimens and the corresponding lymph nodes from the same patients, through immunohistochemistry. The effect of gastrin-releasing peptide on the invasion ability of MCF-7 cells was evaluated using transwell assays. Gastrin-releasing peptide was highly expressed in breast cancer patients with lymph node metastasis. Besides, among the patients with lymph node metastasis, the ones with higher expression of gastrin-releasing peptide had shorter survival time. Overexpression of gastrin-releasing peptide significantly enhanced cell invasiveness. Conversely, a knockdown of gastrin-releasing peptide through the short hairpin RNA approach remarkably reduced MCF-7 cell invasion. Gastrin-releasing peptide expression may be associated with lymph node metastasis and may be used as an indicator of undesirable prognosis in patients with breast cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

How much of virus-specific CD8 T cell reactivity is detected with a peptide pool when compared to individual peptides?

PubMed

Zhang, Wenji; Moldovan, Ioana; Targoni, Oleg S; Subbramanian, Ramu A; Lehmann, Paul V

2012-10-29

Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool), we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is needed for the activation threshold of the CD8 T cells. The presence of such T cells with very high functional avidity for the viral antigens can explain why the effect of peptide competition is relatively minor within the CEF-pool.

AnchorDock for Blind Flexible Docking of Peptides to Proteins.

PubMed

Slutzki, Michal; Ben-Shimon, Avraham; Niv, Masha Y

2017-01-01

Due to increasing interest in peptides as signaling modulators and drug candidates, several methods for peptide docking to their target proteins are under active development. The "blind" docking problem, where the peptide-binding site on the protein surface is unknown, presents one of the current challenges in the field. AnchorDock protocol was developed by Ben-Shimon and Niv to address this challenge.This protocol narrows the docking search to the most relevant parts of the conformational space. This is achieved by pre-folding the free peptide and by computationally detecting anchoring spots on the surface of the unbound protein. Multiple flexible simulated annealing molecular dynamics (SAMD) simulations are subsequently carried out, starting from pre-folded peptide conformations, constrained to the various precomputed anchoring spots.Here, AnchorDock is demonstrated using two known protein-peptide complexes. A PDZ-peptide complex provides a relatively easy case due to the relatively small size of the protein, and a typical peptide conformation and binding region; a more challenging example is a complex between USP7 N-term and a p53-derived peptide, where the protein is larger, and the peptide conformation and a binding site are generally assumed to be unknown. AnchorDock returned native-like solutions ranked first and third for the PDZ and USP7 complexes, respectively. We describe the procedure step by step and discuss possible modifications where applicable.

Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes.

PubMed

Hernández, Cristina; García-Ramírez, Marta; Corraliza, Lidia; Fernández-Carneado, Jimena; Farrera-Sinfreu, Josep; Ponsati, Berta; González-Rodríguez, Agueda; Valverde, Angela M; Simó, Rafael

2013-07-01

Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration. For this purpose, rats with streptozotocin-induced diabetes mellitus (STZ-DM) were treated with either SST eye drops or vehicle for 15 days. Nondiabetic rats treated with vehicle served as a control group. Functional abnormalities were assessed by electroretinography (ERG), and neurodegeneration was assessed by measuring glial activation and the apoptotic rate. In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. Intraretinal concentrations of glutamate and its main transporter glutamate/aspartate transporter (GLAST) were also determined. Treatment with SST eye drops prevented ERG abnormalities, glial activation, apoptosis, and the misbalance between proapoptotic and survival signaling detected in STZ-DM rats. In addition, SST eye drops inhibited glutamate accumulation in the retina and GLAST downregulation induced by diabetes mellitus. We conclude that topical administration of SST has a potent effect in preventing retinal neurodegeneration induced by diabetes mellitus. In addition, our findings open up a new preventive pharmacological strategy targeted to early stages of DR.

Beneficial effects of neuropeptide galanin on reinstatement of exercise-induced somatic and psychological trauma.

PubMed

He, Biao; Fang, Penghua; Guo, Lili; Shi, Mingyi; Zhu, Yan; Xu, Bo; Bo, Ping; Zhang, Zhenwen

2017-04-01

Galanin is a versatile neuropeptide that is distinctly upregulated by exercise in exercise-related tissues. Although benefits from exercise-induced upregulation of this peptide have been identified, many issues require additional exploration. This Review summarizes the information currently available on the relationship between galanin and exercise-induced physical and psychological damage. On the one hand, body movement, exercise damage, and exercise-induced stress and pain significantly increase local and circulatory galanin levels. On the other hand, galanin plays an exercise-protective role to inhibit the flexor reflex and prevent excessive movement of skeletal muscles through enhancing response threshold and reducing acetylcholine release. Additionally, elevated galanin levels can boost repair of the exercise-induced damage in exercise-related tissues, including peripheral nerve, skeletal muscle, blood vessel, skin, bone, articulation, and ligament. Moreover, elevated galanin levels may serve as effective signals to buffer sport-induced stress and pain via inhibiting nociceptive signal transmission and enhancing pain threshold. This Review deepens our understanding of the profitable roles of galanin in exercise protection, exercise injury repair, and exercise-induced stress and pain. Galanin and its agonists may be used to develop a novel preventive and therapeutic strategy to prevent and treat exercise-induced somatic and psychological trauma. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Insulin and the polycystic ovary syndrome.

PubMed

Macut, Djuro; Bjekić-Macut, Jelica; Rahelić, Dario; Doknić, Mirjana

2017-08-01

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes. PCOS women show age-related existence of hypertension, and subtle endothelial and vascular changes. Adverse reproductive outcomes include anovulatory infertility, and unrecognised potentiation of the hormone-dependent endometrial cancer. The main therapeutic approach is lifestyle modification. Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment. Thiazolidinediones should be reserved for women intolerant of or refractory to metformin, while glucagon-like peptide 1 analogues has a potential therapeutic use in obese PCOS women. Randomised clinical trials and repetitive studies on different PCOS phenotypes for the preventive actions and therapeutic options are still lacking, though. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibodies against a peptide of cholera toxin differing in cross-reactivity with the toxin differ in their specific interactions with the peptide as observed by sup 1 H NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anglister, J.; Zilber, B.

1990-01-30

The interactions between the aromatic residues of the monoclonal antibody TE34, and its peptide antigen CTP3, have been studied by 2D TRNOE difference spectroscopy. The sequence of CTP3 corresponds to residues 50-64 of the B subunit of cholera toxin (VEVPGSQHIDSQKKA). Unlike two previously studied anti-CTP3 antibodies (TE32 and TE33), the TE34 antibody does not bind the toxin. The off-rate of CTP3 from TE34 was found to be too slow to measure strong TRNOE cross-peaks between the antibody and the peptide. Much faster off-rates, resulting in a strong TRNOE, were obtained for two peptide analogues: (a) CTP3 with an amide inmore » the C-terminus (VEVPGSQHIDSQKKA-NH{sub 2}) and (b) a truncated version of the peptide (N-acetyl-IDSQKKA). These modifications do not interfere significantly either with the interactions of the unmodified part of the peptide with the antibody or with intramolecular interactions occurring in the epitope recognized by the antibody. The combined use of these peptides allows us to study the interactions between the antibody and the whole peptide. Two tyrosine residues and one or more tryptophan and phenylalanine residues have been found to interact with histidine-8, isoleucine-9, aspartate-10, lysine-13 and/or lysine-14, and alanine-15 of the peptide. The strong interaction of TE34 with the negatively charged C-terminus of CTP3 is one of the main reasons for its lack of cross-reactivity with the native toxin. Similar use of modified peptides may extend the applicability of 2D TRNOE difference spectroscopy to the study of other antibody-peptide complexes involving slow peptide off-rates.« less

Molecular mechanism for the effects of trehalose on beta-hairpin folding revealed by molecular dynamics simulation.

PubMed

Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

2008-11-01

Recent work has shown that trehalose can facilitate and inhibit protein folding, but little is known about the molecular basis of these effects. Molecular-level insights into how the osmolyte affects protein folding are of significance for the rational design of small molecular additives for enhancing or hindering the folding of proteins. To investigate the molecular mechanisms of the facilitation and inhibition effects of trehalose on protein folding, molecular dynamics (MD) simulation of a beta-hairpin peptide (Trp-Arg-Tyr-Tyr-Glu-Ser-Ser-Leu-Glu-Pro-Glu-Pro-Asp) in different trehalose concentrations (0-0.26 mol/L) is performed using an all-atom model. It is found that at a proper trehalose concentration (0.065 mol/L), the peptide folds faster than that in water, but it cannot fold to the beta-hairpin at higher trehalose concentrations. Free energy landscape analysis indicates the presence of three intermediate states in both pure water and in 0.065 mol/L trehalose, but the potential energy barriers in the folding pathway decrease greatly in 0.065 mol/L trehalose, so the peptide folding is facilitated. Moreover, at this trehalose concentration, there is a favorable balance between the peptide backbone hydrogen bonds (H-bonds) and the peptide-trehalose H-bonds, leading to the stabilization of the folded peptide. At higher trehalose concentrations, however, trehalose molecules cluster in the peptide region and interact with the peptide via many H-bonds that prevent the peptide from folding to its native structure. The energy landscape analysis indicates that the potential energy barriers increase so greatly that the peptide cannot overcome it, getting trapped in a local free energy basin. The work reported herein has elucidated the molecular mechanism of the peptide folding in the presence of trehalose.

Bacterial expression of self-assembling peptide hydrogelators

NASA Astrophysics Data System (ADS)

Sonmez, Cem

For tissue regeneration and drug delivery applications, various architectures are explored to serve as biomaterial tools. Via de novo design, functional peptide hydrogel materials have been developed as scaffolds for biomedical applications. The objective of this study is to investigate bacterial expression as an alternative method to chemical synthesis for the recombinant production of self-assembling peptides that can form rigid hydrogels under physiological conditions. The Schneider and Pochan Labs have designed and characterized a 20 amino acid beta-hairpin forming amphiphilic peptide containing a D-residue in its turn region (MAX1). As a result, this peptide must be prepared chemically. Peptide engineering, using the sequence of MAX1 as a template, afforded a small family of peptides for expression (EX peptides) that have different turn sequences consisting of natural amino acids and amenable to bacterial expression. Each sequence was initially chemically synthesized to quickly assess the material properties of its corresponding gel. One model peptide EX1, was chosen to start the bacterial expression studies. DNA constructs facilitating the expression of EX1 were designed in such that the peptide could be expressed with different fusion partners and subsequently cleaved by enzymatic or chemical means to afford the free peptide. Optimization studies were performed to increase the yield of pure peptide that ultimately allowed 50 mg of pure peptide to be harvested from one liter of culture, providing an alternate means to produce this hydrogel-forming peptide. Recombinant production of other self-assembling hairpins with different turn sequences was also successful using this optimized protocol. The studies demonstrate that new beta-hairpin self-assembling peptides that are amenable to bacterial production and form rigid hydrogels at physiological conditions can be designed and produced by fermentation in good yield at significantly reduced cost when compared to chemical synthesis.

A Cocoa Peptide Protects Caenorhabditis elegans from Oxidative Stress and β-Amyloid Peptide Toxicity

PubMed Central

Martorell, Patricia; Bataller, Esther; Llopis, Silvia; Gonzalez, Núria; Álvarez, Beatriz; Montón, Fernando; Ortiz, Pepa; Ramón, Daniel; Genovés, Salvador

2013-01-01

Background Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. Methodology/Principal Findings A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ1–42 peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24–47 h period after Aβ1–42 peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. Conclusions/Significance These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals. PMID:23675471

An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain

PubMed Central

Yin, Yanting; Zhou, X Edward; Hou, Li; Zhao, Li-Hua; Liu, Bo; Wang, Gaihong; Jiang, Yi; Melcher, Karsten; Xu, H Eric

2016-01-01

The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation. In contrast to this model, here we demonstrate that glucagon-like peptide-1 receptor can be activated by N-terminally truncated glucagon-like peptide-1 or exendin-4 when fused to the receptor, raising the question regarding the role of N-terminal residues of peptide hormone in glucagon-like peptide-1 receptor activation. Mutations of cysteine 347 to lysine or arginine in intracellular loop 3 transform the receptor into a G protein-biased receptor and allow it to be activated by a nonspecific five-residue linker that is completely devoid of exendin-4 or glucagon-like peptide-1 sequence but still requires the presence of an intact extracellular domain. Moreover, the extracellular domain can activate the receptor in trans in the presence of an intact peptide hormone, and specific mutations in three extracellular loops abolished this extracellular domain trans-activation. Together, our data reveal a dominant role of the extracellular domain in glucagon-like peptide-1 receptor activation and support an intrinsic agonist model of the extracellular domain, in which peptide binding switches the receptor from the auto-inhibited state to the auto-activated state by releasing the intrinsic agonist activity of the extracellular domain. PMID:27917297

Cardiac distribution of the binding sites for natriuretic peptides in vertebrates.

PubMed

Cerra, M C

1994-12-01

Natriuretic peptides are hormones that play an important role in the cardiovascular control of mammalian and non-mammalian vertebrates. They have been classified into four groups. Of these, ANP (atrial natriuretic peptide), BNP (brain atriuretic peptides), CNP (C-type natriuretic peptide) are detected in cardiac and non cardiac tissues of all vertebrates; while VNP (ventricular natriuretic peptide) has been isolated only from the fish ventricle. All peptides have shown a high degree of sequence homology. The expression of the three principal types of natriuretic peptide (ANP, BNP and CNP) in cardiac tissues is developmentally and functionally regulated in a highly tissue-specific manner. Three types of natriuretic peptide receptors have been identified in numerous target tissues. Two receptors are transmembrane guanylyl cyclases (ANPR-A and ANPR-B) that mediate biological effects of natriuretic peptides; the third one (ANPR-C) has no guanylyl cyclase and is called "clearance receptor." The presence of natriuretic peptide binding sites in the heart suggests new aspects of paracrine control of cardiac function. A relevant localization of natriuretic peptide receptors was found in those cardiac regions particularly suitable for monitoring blood volume and pressure oscillations such as the inflow tract and the outflow tract. For example, in birds (quail) the highest levels of natriuretic peptide receptors were detected in the inflow tract represented by the vena cava. In both fish and birds, the outflow chamber, the bulbus cordis, had a high number of natriuretic peptide binding sites. In mammals, a remarkable concentration of natriuretic peptide receptors was also observed in the coronary vessels. This zoning of cardiac natriuretic peptide receptors indicates an intracardiac action of the hormones and adds a humoral dimension to the morphofunctional design of the vertebrate heart.

Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition.

PubMed

Davis, Katherine M; Schramma, Kelsey R; Hansen, William A; Bacik, John P; Khare, Sagar D; Seyedsayamdost, Mohammad R; Ando, Nozomi

2017-09-26

Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules known as RiPPs (ribosomally synthesized and posttranslationally modified peptides). Although the leader sequence of the precursor peptide is often required for turnover, the exact mode of recognition by the modifying enzymes remains unclear for many members of this class of natural products. Here, we have used X-ray crystallography and computational modeling to examine the role of the leader peptide in the biosynthesis of a homolog of streptide, a recently identified peptide natural product with an intramolecular lysine-tryptophan cross-link, which is installed by the radical S -adenosylmethionine (SAM) enzyme, StrB. We present crystal structures of SuiB, a close ortholog of StrB, in various forms, including apo SuiB, SAM-bound SuiB, and a complex of SuiB with SAM and its peptide substrate, SuiA. Although the N-terminal domain of SuiB adopts a typical RRE (RiPP recognition element) motif, which has been implicated in precursor peptide recognition, we observe binding of the leader peptide in the catalytic barrel rather than the N-terminal domain. Computational simulations support a mechanism in which the leader peptide guides posttranslational modification by positioning the cross-linking residues of the precursor peptide within the active site. Together the results shed light onto binding of the precursor peptide and the associated conformational changes needed for the formation of the unique carbon-carbon cross-link in the streptide family of natural products.

Sequence Elucidation of an Unknown Cyclic Peptide of High Doping Potential by ETD and CID Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Guan, Fuyu; Uboh, Cornelius E.; Soma, Lawrence R.; Rudy, Jeffrey

2011-04-01

Identification of an unknown substance without any information remains a daunting challenge despite advances in chemistry and mass spectrometry. However, an unknown cyclic peptide in a sample with very limited volume seized at a Pennsylvania racetrack has been successfully identified. The unknown sample was determined by accurate mass measurements to contain a small unknown peptide as the major component. Collision-induced dissociation (CID) of the unknown peptide revealed the presence of Lys (not Gln, by accurate mass), Phe, and Arg residues, and absence of any y-type product ion. The latter, together with the tryptic digestion results of the unusual deamidation and absence of any tryptic cleavage, suggests a cyclic structure for the peptide. Electron-transfer dissociation (ETD) of the unknown peptide indicated the presence of Gln (not Lys, by the unusual deamidation), Phe, and Arg residues and their connectivity. After all the results were pieced together, a cyclic tetrapeptide, cyclo[Arg-Lys-N(C6H9)Gln-Phe], is proposed for the unknown peptide. Observations of different amino acid residues from CID and ETD experiments for the peptide were interpreted by a fragmentation pathway proposed, as was preferential CID loss of a Lys residue from the peptide. ETD was used for the first time in sequencing of a cyclic peptide; product ions resulting from ETD of the peptide identified were categorized into two types and named pseudo-b and pseudo-z ions that are important for sequencing of cyclic peptides. The ETD product ions were interpreted by fragmentation pathways proposed. Additionally, multi-stage CID mass spectrometry cannot provide complete sequence information for cyclic peptides containing adjacent Arg and Lys residues. The identified cyclic peptide has not been documented in the literature, its pharmacological effects are unknown, but it might be a "designer" drug with athletic performance-enhancing effects.

Phosphorylation-induced conformational changes in short peptides probed by fluorescence resonance energy transfer in the 10A domain.

PubMed

Sahoo, Harekrushna; Nau, Werner M

2007-03-26

Phosphorylation-induced conformational changes in short polypeptides were probed by a fluorescence resonance energy transfer (FRET) method by employing a short-distance FRET pair (R(0) approximately 10 A) based on tryptophan as natural donor and a 2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine (Dbo) as synthetic acceptor. Two substrates for kinases, LeuArgArgTrpSerLeuGly-Dbo (peptide I) and TrpLysArgThrLeuArgArg-Dbo (peptide II), were investigated, with serine and threonine, respectively, as phosphorylation sites. Steady-state and time-resolved fluorescence experiments in H(2)O revealed a decrease in FRET efficiency for peptide I and an increase for peptide II; this suggested that the effective distances between donor and acceptor increased and decreased, respectively. The same trends and similar absolute variations in effective donor-acceptor distances were observed in propylene glycol, a less polar and highly viscous solvent; this suggested that the variations are due to intrinsic structural preferences. Fitting of the time-resolved decay traces according to a distribution function model (Gaussian distribution) provided the mean donor-acceptor distances, which showed an increase upon phosphorylation for peptide I (from 9.7 to 10.5 A) and a decrease for peptide II (from 10.9 to 9.3 A) in H(2)O. The broadness (half-width) of the distributions, which provides a measure of the rigidity of the peptides, remained similar upon phosphorylation of peptide I (3.0 versus 3.1 A), but decreased for peptide II (from 3.1 to 0.73 A in H(2)O); this suggests a more compact, structured conformation upon phosphorylation of the latter peptide. The elongation of the peptide backbone (by ca. 0.7 A) for peptide I is attributed to an increase in steric demand upon phosphorylation, which favors an extended conformation. The contraction (by ca. 1.4 A) and structural rigidification of peptide II is attributed to attractive Coulombic interactions and hydrogen bonding between the phosphate group and the arginine residues.

Atypical Signaling and Functional Desensitization Response of MAS Receptor to Peptide Ligands

PubMed Central

Tirupula, Kalyan C.; Desnoyer, Russell; Speth, Robert C.; Karnik, Sadashiva S.

2014-01-01

MAS is a G protein-coupled receptor (GPCR) implicated in multiple physiological processes. Several physiological peptide ligands such as angiotensin-(1–7), angiotensin fragments and neuropeptide FF (NPFF) are reported to act on MAS. Studies of conventional G protein signaling and receptor desensitization upon stimulation of MAS with the peptide ligands are limited so far. Therefore, we systematically analyzed G protein signals activated by the peptide ligands. MAS-selective non-peptide ligands that were previously shown to activate G proteins were used as controls for comparison on a common cell based assay platform. Activation of MAS by the non-peptide agonist (1) increased intracellular calcium and D-myo-inositol-1-phosphate (IP1) levels which are indicative of the activation of classical Gαq-phospholipase C signaling pathways, (2) decreased Gαi mediated cAMP levels and (3) stimulated Gα12-dependent expression of luciferase reporter. In all these assays, MAS exhibited strong constitutive activity that was inhibited by the non-peptide inverse agonist. Further, in the calcium response assay, MAS was resistant to stimulation by a second dose of the non-peptide agonist after the first activation has waned suggesting functional desensitization. In contrast, activation of MAS by the peptide ligand NPFF initiated a rapid rise in intracellular calcium with very weak IP1 accumulation which is unlike classical Gαq-phospholipase C signaling pathway. NPFF only weakly stimulated MAS-mediated activation of Gα12 and Gαi signaling pathways. Furthermore, unlike non-peptide agonist-activated MAS, NPFF-activated MAS could be readily re-stimulated the second time by the agonists. Functional assays with key ligand binding MAS mutants suggest that NPFF and non-peptide ligands bind to overlapping regions. Angiotensin-(1–7) and other angiotensin fragments weakly potentiated an NPFF-like calcium response at non-physiological concentrations (≥100 µM). Overall, our data suggest that peptide ligands induce atypical signaling and functional desensitization of MAS. PMID:25068582

The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1.

PubMed

Sosenko, Jay M; Geyer, Susan; Skyler, Jay S; Rafkin, Lisa E; Ismail, Heba M; Libman, Ingrid M; Liu, Yuk-Fun; DiMeglio, Linda A; Evans-Molina, Carmella; Palmer, Jerry P

2018-05-01

The extent of influence of BMI and age on C-peptide at the diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body mass index Z-scores (BMIZ) and age on C-peptide measures at and soon after the diagnosis of T1D. Data from Diabetes Prevention Trial-Type 1 (DPT-1) participants <18.0 years at diagnosis was analyzed. Analyses examined associations of C-peptide measures with BMIZ and age in 2 cohorts: oral glucose tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was utilized. Fasting and area under the curve (AUC) C-peptide from OGTTs (n = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age were included as independent variables in regression models (P < .001 for all). BMIZ and age explained 31%-47% of the variance of C-peptide measures. In an example, 2 individuals with identical AUC C-peptide values had an approximate 5-fold difference in values after adjustments for BMIZ and age. The association between fasting glucose and C-peptide decreased markedly when fasting C-peptide values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). C-peptide measures are strongly and independently related to BMIZ and age at and soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial changes in C-peptide values, and impact the association between glycemia and C-peptide. Such adjustments can improve assessments of β-cell impairment at diagnosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis of peptide .alpha.-thioesters

DOEpatents

Camarero, Julio A [Livermore, CA; Mitchell, Alexander R [Livermore, CA; De Yoreo, James J [Clayton, CA

2008-08-19

Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

Effect of gender on awareness of cardiovascular risk factors, preventive action taken, and barriers to cardiovascular health in a group of Austrian subjects.

PubMed

Haidinger, Teresa; Zweimüller, Martin; Stütz, Lena; Demir, Dondue; Kaider, Alexandra; Strametz-Juranek, Jeanette

2012-04-01

The incidence of cardiovascular disease (CVD) is increasing in industrialized countries. Preventive action is an important factor in minimizing CVD-associated morbidity and mortality. However, it is not known whether gender differences affect CVD or risk factor awareness influencing self-assessment of personal risk and preventive action. This study was performed to assess individual CVD and risk factor awareness, preventive action taken, and barriers to cardiovascular health. The study included 573 women and 336 men, randomly chosen to complete an anonymous questionnaire to assess individual CVD and risk factor awareness, preventive action taken, and barriers to cardiovascular health. The data were analyzed using SAS software. Cardiovascular disease was identified in 75% of patients, in both sexes, as the leading cause of death; however, both groups showed significant lack of knowledge about CVD risk factors. Type 2 diabetes was identified correctly in only 27.5%. Preventive action was linked more often to family members in 66.5% of women and 62.8% of men. The primary barrier to cardiovascular health in adults was incorrect assessment of personal CVD risk. More than half of female respondents (56.4%) and male respondents (52.7%) underestimated their risk of CVD. Knowledge about risk factors for CVD needs to be improved in members of both sexes. Because women, in particular, have difficulty in correctly assessing their personal CVD risk, future education programs are warranted to inform both women and men about CVD and its risk factors, thereby helping them to correctly assess their individual risk. However, greater effort is needed to inform men, compared with women, about the various ways in which to prevent CVD and to motivate them to take preventive action. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Differences in Receipt of Three Preventive Health Care Services by Race/Ethnicity in Medicare Advantage Plans: Tracking the Impact of Pay for Performance, 2010 and 2013.

PubMed

Jung, Daniel H; Palta, Mari; Smith, Maureen; Oliver, Thomas R; DuGoff, Eva H

2016-09-08

In 2012, the Centers for Medicare and Medicaid Services (CMS) introduced the Quality Bonus Payment Demonstration, a pay-for-performance (P4P) program, into Medicare Advantage plans. Previous studies documented racial/ethnic disparities in receipt of care among participants in these plans. The objective of this study was to determine whether P4P incentives have affected these disparities in Medicare Advantage plans. We studied 411 Medicare Advantage health plans that participated in the Medicare Health Outcome Survey in 2010 and 2013. Preventive health care was defined as self-reported receipt of health care provider communication or treatment to reduce risk of falling, improve bladder control, and monitor physical activity among individuals reporting these problems. Logistic regression stratified by health care plan was used to examine racial/ethnic disparities in receipt of preventive health care before and after the introduction of the P4P program in 2012. We found similar racial/ethnic differences in receipt of preventive health care before and after the introduction of P4P. Blacks and Asians were less likely than whites to receive advice to improve bladder control and more likely to receive advice to reduce risk of falling and improve physical activity. Hispanics were more likely to report receiving advice about all 3 health issues than whites. After the introduction of P4P, the gap decreased between Hispanics and whites for improving bladder control and monitoring physical activity and increased between blacks and whites for monitoring physical activity. Racial/ethnic differences in receipt of preventive health care are not always in the expected direction. CMS should consider developing a separate measure of equity in preventive health care services to encourage health plans to reduce gaps among racial/ethnic groups in receiving preventive care services.

Low Levels of Knowledge, Attitudes and Preventive Practices on Leptospirosis among a Rural Community in Hulu Langat District, Selangor, Malaysia.

PubMed

Nozmi, Noramira; Samsudin, Suhailah; Sukeri, Surianti; Shafei, Mohd Nazri; Wan Mohd, Wan Mohd Zahiruddin; Idris, Zawaha; Arifin, Wan Nor; Idris, Norazlin; Saudi, Siti Nor Sakinah; Abdullah, Nurul Munirah; Abdul Wahab, Zainudin; Tengku Jamaluddin, Tengku Zetty Maztura; Abd Rahman, Hejar; Masri, Siti Norbaya; Daud, Aziah; Osman, Malina; Awang Hamat, Rukman

2018-04-06

Little is known on the knowledge, attitudes and preventive practices (KAP) of leptospirosis worldwide. This study embarked on assessing the KAP of leptospirosis among rural communities in Malaysia. A total of 444 participants (223 male; 221 female) aged between 18 and 81 years old were surveyed by using a self-administered questionnaire. A majority of participants had poor knowledge level (57.0%), unacceptable attitudes (90.3%) and unacceptable preventive practices (69.1%) on leptospirosis, and only 29.7% knew "rat-urine disease" as leptospirosis. Only 34.2% of the participants knew the bacteria could enter via wound lesions. Ethnicity and income were strongly associated with knowledge level and preventive practices, respectively ( p -values < 0.05). As for attitudes, ethnicity, income and education type were significantly associated ( p -values < 0.05). Only 36.5% of the participants were willing to see a doctor and did not mind if their house or surrounding area is dirty (59.7%). Surprisingly, only 32.9% had used rubber boots during floods. By logistic regression analysis, ethnicity was the only significant predictor for both knowledge level (an odds ratio (AOR) = 0.39, 95% confidence interval (CI) = 0.222-0.680) and preventive practices (AOR = 1.81, 95% CI = 1.204-2.734). Ethnicity (AOR = 0.40, 95% CI = 0.239-0.665), income (AOR = 1.58, 95% CI = 1.041-2.385) and education type (AOR = 3.69, 95% CI = 1.237-10.986) were strong predictors for attitudes. Among the KAP variables, attitude (AOR = 4.357, 95% CI = 2.613-7.264) was the only predictor for the preventive practices by logistic regression analysis. The KAP elements on leptospirosis are still lacking and poor health seeking behavior and attitudes are of our utmost concern. Thus, effective strategies should be planned to impart knowledge, and develop proactive approaches and good preventive modules on leptospirosis to this leptospirosis-prone community.

Dutch monitor on stress and physical load: risk factors, consequences, and preventive action.

PubMed

Houtman, I L; Goudswaard, A; Dhondt, S; van der Grinten, M P; Hildebrandt, V H; van der Poel, E G

1998-02-01

Due to recent changes in legislation on occupational health and safety, a national monitor on stress and physical load was developed in The Netherlands to monitor (a) risks and consequences of stress and physical load at work, (b) preventive actions in companies to reduce these risks, and (c) organisational and environmental variables that facilitate preventive actions. Information was gathered from employers, employees, and employees' representatives. The monitor was used with a nationally representative sample of companies in industry, wholesale trade, and banking and finance, 782 companies in total. The information from the employees, aggregated at the company level, was not found to be correlated with that from the employer from the same companies. Although many employers do recognise risk factors for both physical load and stress as a problem they often seem to underestimate the problem when compared with employees or their representatives. This is particularly the case for psychosocial risk factors. Also, the perception of outcome measures, especially employers who consider emotional exhaustion to be work related, were fewer than the employees' representatives of the same organisation. Preventive measures on physical load are much more popular than measures against stress. It is the responsibility of the employer to take more preventive action of all kinds. They need to recognise risk factors as problems and health outcomes to be related to work. Employees of larger companies should participate with employers to consider effective measures, and more use should be made of support at branch level. For specific preventive measures, specific predictors emerged. Except for measures to prevent work stress, information from employees did not sufficiently contribute to the initiation of preventive measures in the workplace.

Changes in children's oral health status and receipt of preventive dental visits, United States, 2003-2011/2012.

PubMed

Mandal, Mahua; Edelstein, Burton L; Ma, Sai; Minkovitz, Cynthia S

2013-12-05

Oral health represents the largest unmet health care need for children, and geographic variations in children's receipt of oral health services have been noted. However, children's oral health outcomes have not been systematically evaluated over time and across states. This study examined changes in parent-reported children's oral health status and receipt of preventive dental visits in 50 states and the District of Columbia. We used data from the 2003 and the 2011/2012 National Survey of Children's Health. National and state-level estimates of the adjusted prevalence of oral health status and preventive dental visits were calculated and changes over time examined. Multivariable logistic regression was used to compare outcomes across all states and the District of Columbia for each survey year. The percentage of parents who reported that their children had excellent or very good oral health increased from 67.7% in 2003 to 71.9% in 2011/2012. Parents who reported that their children had preventive dental visits increased from 71.5% in 2003 to 77.0% in 2011/2012. The prevalence of children with excellent or very good oral health status increased in 26 states, and the prevalence of children who received at least 1 preventive care dental visit increased in 45 states. In both years, there was more variation among states for preventive dental visits than for oral health status. State variation in oral health status and receipt of preventive dental services remained after adjusting for demographic characteristics. Understanding these differences is critical to addressing the most common chronic disease of childhood and achieving the oral health objectives of Healthy People 2020.

Dissemination and Implementation Strategies of Lower Extremity Preventive Training Programs in Youth: A Clinical Review.

PubMed

DiStefano, Lindsay J; Frank, Barnett S; Root, Hayley J; Padua, Darin A

Neuromuscular preventive training programs effectively reduce injury and improve performance in youth athletes. However, program effectiveness is directly linked to program compliance, fidelity, and dosage. Preventive training programs are not widely adopted by youth sport coaches. One way to promote widespread dissemination and compliance is to identify implementation strategies that influence program adoption and maintenance. It is unknown how previously published programs have followed the elements of an implementation framework. The objective of this review was to evaluate how elements of the 7 steps of implementation, developed by Padua et al, have been performed in the evidence of lower extremity preventive training programs. A systematic review of the literature from 1996 through September 2016 was conducted using electronic databases. Investigations that documented implementation of a sport team-based neuromuscular preventive training program in youth athletes and measured lower extremity injury rates were included. Clinical review. Level 4. A total of 12 studies met the inclusion criteria and were reviewed. Information regarding the completion of any of the 7 steps within the implementation framework developed by Padua et al was extracted. None of the 12 articles documented completion of all 7 steps. While each study addressed some of the 7 steps, no study addressed maintenance or an exit strategy for youth athletes. Program implementation appears limited in obtaining administrative support, utilizing an interdisciplinary implementation team, and monitoring or promoting fidelity of the intervention. Despite strong evidence supporting the effectiveness of preventive training programs in youth athletes, there is a gap between short-term improvements and long-term implementation strategies. Future interventions should include all 7 steps of the implementation framework to promote transparent dissemination of preventive training programs.

Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose.

PubMed

Hao, Wei; Gitelman, Steven; DiMeglio, Linda A; Boulware, David; Greenbaum, Carla J

2016-10-01

We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individuals with stimulated C-peptide ≥0.2 nmol/L, especially in children. Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of disease-modifying therapy on preservation of β-cell function. © 2016 by the American Diabetes Association.

Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose

PubMed Central

Gitelman, Steven; DiMeglio, Linda A.; Boulware, David; Greenbaum, Carla J.

2016-01-01

OBJECTIVE We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. RESULTS The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individuals with stimulated C-peptide ≥0.2 nmol/L, especially in children. CONCLUSIONS Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of disease-modifying therapy on preservation of β-cell function. PMID:27422577

Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

PubMed

Wang, Zhejun; de la Fuente-Núñez, Cesar; Shen, Ya; Haapasalo, Markus; Hancock, Robert E W

2015-01-01

Human oral biofilms are multispecies microbial communities that exhibit high resistance to antimicrobial agents. Dental plaque gives rise to highly prevalent and costly biofilm-related oral infections, which lead to caries or other types of oral infections. We investigated the ability of the recently identified anti-biofilm peptide 1018 to induce killing of bacterial cells present within oral multispecies biofilms. At 10 μg/ml (6.5 μM), peptide 1018 was able to significantly (p<0.05) prevent biofilm formation over 3 days. The activity of the peptide on preformed biofilms was found to be concentration-dependent since more than 60% of the total plaque biofilm cell population was killed by 10 μg/ml of peptide 1018 in 3 days, while at 5 μg/ml 50% of cells were dead and at 1 μg/ml the peptide triggered cell death in around 30% of the total bacterial population, as revealed by confocal microscopy. The presence of saliva did not affect peptide activity, since no statistically significant difference was found in the ability of peptide 1018 to kill oral biofilms using either saliva coated and non-saliva coated hydroxyapatite surfaces. Scanning electron microscopy experiments indicated that peptide 1018 induced cell lysis in plaque biofilms. Furthermore, combined treatment using peptide 1018 and chlorhexidine (CHX) increased the anti-biofilm activity of each compound compared to when these were used alone, resulting in >50% of the biofilm being killed and >35% being dispersed in only 3 minutes. Peptide 1018 may potentially be used by itself or in combination with CHX as a non-toxic and effective anti-biofilm agent for plaque disinfection in clinical dentistry.

The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick hair in Japanese men with androgenetic alopecia.

PubMed

Iwabuchi, Tokuro; Takeda, Shunsuke; Yamanishi, Haruyo; Ideta, Ritsuro; Ehama, Ritsuko; Tsuruda, Akinori; Shibata, Hideaki; Ito, Tomoko; Komatsu, Nobuyuki; Terai, Keiko; Oka, Syuichi

2016-06-01

A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. This study focused on the ability of the peptide to promote human hair growth. We used a human hair keratinocyte proliferation assay and organ cultures of human hair follicle as in vitro systems. The lotions with and without the penta-peptide were administered to 22 Japanese men with androgenetic alopecia (AGA) for 4 months in a double-blind and randomized clinical study. The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μm (P < 0.01), and 5.0 μm of this peptide had a marked effect on hair shaft elongation in the organ culture (P < 0.05). The change in the proportion of thick hair (≥60 μm) compared to baseline in patients that received the peptide was significantly higher than in the placebo (P = 0.006). The change in the proportion of vellus hair (<40 μm) was also significantly lower in the peptide group than in the placebo (P = 0.029). The penta-peptide also significantly improved the appearance of baldness (P = 0.020) when blinded reviewers graded photographs of the participants according to a standardized baldness scale. No adverse dermatological effects due to treatment were noted during this clinical study. This penta-peptide promotes proliferation of human hair keratinocytes and hair shaft elongation of human hair follicles, in vitro. This peptide increases thick hair ratio in vivo, and this compound is useful for the improvement of AGA. © 2016 Wiley Periodicals, Inc.

Biophysical Investigation of the Membrane-Disrupting Mechanism of the Antimicrobial and Amyloid-Like Peptide Dermaseptin S9

PubMed Central

Caillon, Lucie; Killian, J. Antoinette; Lequin, Olivier; Khemtémourian, Lucie

2013-01-01

Dermaseptin S9 (Drs S9) is an atypical cationic antimicrobial peptide with a long hydrophobic core and with a propensity to form amyloid-like fibrils. Here we investigated its membrane interaction using a variety of biophysical techniques. Rather surprisingly, we found that Drs S9 induces efficient permeabilisation in zwitterionic phosphatidylcholine (PC) vesicles, but not in anionic phosphatidylglycerol (PG) vesicles. We also found that the peptide inserts more efficiently in PC than in PG monolayers. Therefore, electrostatic interactions between the cationic Drs S9 and anionic membranes cannot explain the selectivity of the peptide towards bacterial membranes. CD spectroscopy, electron microscopy and ThT fluorescence experiments showed that the peptide adopts slightly more β-sheet and has a higher tendency to form amyloid-like fibrils in the presence of PC membranes as compared to PG membranes. Thus, induction of leakage may be related to peptide aggregation. The use of a pre-incorporation protocol to reduce peptide/peptide interactions characteristic of aggregates in solution resulted in more α-helix formation and a more pronounced effect on the cooperativity of the gel-fluid lipid phase transition in all lipid systems tested. Calorimetric data together with 2H- and 31P-NMR experiments indicated that the peptide has a significant impact on the dynamic organization of lipid bilayers, albeit slightly less for zwitterionic than for anionic membranes. Taken together, our data suggest that in particular in membranes of zwitterionic lipids the peptide binds in an aggregated state resulting in membrane leakage. We propose that also the antimicrobial activity of Drs S9 may be a result of binding of the peptide in an aggregated state, but that specific binding and aggregation to bacterial membranes is regulated not by anionic lipids but by as yet unknown factors. PMID:24146759

The critical role of peptide chemistry in the life sciences.

PubMed

Kent, Stephen B H

2015-03-01

Peptide chemistry plays a key role in the synthesis and study of protein molecules and their functions. Modern ligation methods enable the total synthesis of enzymes and the systematic dissection of the chemical basis of enzyme catalysis. Predicted developments in peptide science are described. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Research on Clinical Preventive Services for Adolescents and Young Adults: Where Are We and Where Do We Need to Go?

PubMed

Harris, Sion K; Aalsma, Matthew C; Weitzman, Elissa R; Garcia-Huidobro, Diego; Wong, Charlene; Hadland, Scott E; Santelli, John; Park, M Jane; Ozer, Elizabeth M

2017-03-01

We reviewed research regarding system- and visit-level strategies to enhance clinical preventive service delivery and quality for adolescents and young adults. Despite professional consensus on recommended services for adolescents, a strong evidence base for services for young adults, and improved financial access to services with the Affordable Care Act's provisions, receipt of preventive services remains suboptimal. Further research that builds off successful models of linking traditional and community clinics is needed to improve access to care for all youth. To optimize the clinical encounter, promising clinician-focused strategies to improve delivery of preventive services include screening and decision support tools, particularly when integrated into electronic medical record systems and supported by training and feedback. Although results have been mixed, interventions have moved beyond increasing service delivery to demonstrating behavior change. Research on emerging technology-such as gaming platforms, mobile phone applications, and wearable devices-suggests opportunities to expand clinicians' reach; however, existing research is based on limited clinical settings and populations. Improved monitoring systems and further research are needed to examine preventive services facilitators and ensure that interventions are effective across the range of clinical settings where youth receive preventive care, across multiple populations, including young adults, and for more vulnerable populations with less access to quality care. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Research on Clinical Preventive Services for Adolescents and Young Adults: Where Are We and Where Do We Need to Go?

PubMed Central

Harris, Sion K.; Aalsma, Matthew C.; Weitzman, Elissa R.; Garcia-Huidobro, Diego; Wong, Charlene; Hadland, Scott E.; Santelli, John; Park, M. Jane; Ozer, Elizabeth M.

2017-01-01

We reviewed research regarding system- and visit-level strategies to enhance clinical preventive service delivery and quality for adolescents and young adults. Despite professional consensus on recommended services for adolescents, a strong evidence base for services for young adults, and improved financial access to services with the Affordable Care Act’s provisions, receipt of preventive services remains suboptimal. Further research that builds off successful models of linking traditional and community clinics is needed to improve access to care for all youth. To optimize the clinical encounter, promising clinician-focused strategies to improve delivery of preventive services include screening and decision support tools, particularly when integrated into electronic medical record systems and supported by training and feedback. Although results have been mixed, interventions have moved beyond increasing service delivery to demonstrating behavior change. Research on emerging technology—such as gaming platforms, mobile phone applications, and wearable devices—suggests opportunities to expand clinicians’ reach; however, existing research is based on limited clinical settings and populations. Improved monitoring systems and further research are needed to examine preventive services facilitators and ensure that interventions are effective across the range of clinical settings where youth receive preventive care, across multiple populations, including young adults, and for more vulnerable populations with less access to quality care. PMID:28011064

Synthesis and characterization of Her2-NLP peptide conjugates targeting circulating breast cancer cells: cellular uptake and localization by fluorescent microscopic imaging.

PubMed

Cai, Huawei; Singh, Ajay N; Sun, Xiankai; Peng, Fangyu

2015-01-01

To synthesize a fluorescent Her2-NLP peptide conjugate consisting of Her2/neu targeting peptide and nuclear localization sequence peptide (NLP) and assess its cellular uptake and intracellular localization for radionuclide cancer therapy targeting Her2/neu-positive circulating breast cancer cells (CBCC). Fluorescent Cy5.5 Her2-NLP peptide conjugate was synthesized by coupling a bivalent peptide sequence, which consisted of a Her2-binding peptide (NH2-GSGKCCYSL) and an NLP peptide (CGYGPKKKRKVGG) linked by a polyethylene glycol (PEG) chain with 6 repeating units, with an activated Cy5.5 ester. The conjugate was separated and purified by HPLC and then characterized by Maldi-MS. The intracellular localization of fluorescent Cy5.5 Her2-NLP peptide conjugate was assessed by fluorescent microscopic imaging using a confocal microscope after incubation of Cy5.5-Her2-NLP with Her2/neu positive breast cancer cells and Her2/neu negative control breast cancer cells, respectively. Fluorescent signals were detected in cytoplasm of Her2/neu positive breast cancer cells (SKBR-3 and BT474 cell lines), but not or little in cytoplasm of Her2/neu negative breast cancer cells (MDA-MB-231), after incubation of the breast cancer cells with Cy5.5-Her2-NLP conjugates in vitro. No fluorescent signals were detected within the nuclei of Her2/neu positive SKBR-3 and BT474 breast cancer cells, neither Her2/neu negative MDA-MB-231 cells, incubated with the Cy5.5-Her2-NLP peptide conjugates, suggesting poor nuclear localization of the Cy5.5-Her2-NLP conjugates localized within the cytoplasm after their cellular uptake and internalization by the Her2/neu positive breast cancer cells. Her2-binding peptide (KCCYSL) is a promising agent for radionuclide therapy of Her2/neu positive breast cancer using a β(-) or α emitting radionuclide, but poor nuclear localization of the Her2-NLP peptide conjugates may limit its use for eradication of Her2/neu-positive CBCC using I-125 or other Auger electron emitting radionuclide.

Tuning Curvature and Stability of Monoolein Bilayers by Designer Lipid-Like Peptide Surfactants

PubMed Central

Yaghmur, Anan; Laggner, Peter; Zhang, Shuguang; Rappolt, Michael

2007-01-01

This study reports the effect of loading four different charged designer lipid-like short anionic and cationic peptide surfactants on the fully hydrated monoolein (MO)-based Pn3m phase (Q224). The studied peptide surfactants comprise seven amino acid residues, namely A6D, DA6, A6K, and KA6. D (aspartic acid) bears two negative charges, K (lysine) bears one positive charge, and A (alanine) constitutes the hydrophobic tail. To elucidate the impact of these peptide surfactants, the ternary MO/peptide/water system has been investigated using small-angle X-ray scattering (SAXS), within a certain range of peptide concentrations (R≤0.2) and temperatures (25 to 70°C). We demonstrate that the bilayer curvature and the stability are modulated by: i) the peptide/lipid molar ratio, ii) the peptide molecular structure (the degree of hydrophobicity, the type of the hydrophilic amino acid, and the headgroup location), and iii) the temperature. The anionic peptide surfactants, A6D and DA6, exhibit the strongest surface activity. At low peptide concentrations (R = 0.01), the Pn3m structure is still preserved, but its lattice increases due to the strong electrostatic repulsion between the negatively charged peptide molecules, which are incorporated into the interface. This means that the anionic peptides have the effect of enlarging the water channels and thus they serve to enhance the accommodation of positively charged water-soluble active molecules in the Pn3m phase. At higher peptide concentration (R = 0.10), the lipid bilayers are destabilized and the structural transition from the Pn3m to the inverted hexagonal phase (H2) is induced. For the cationic peptides, our study illustrates how even minor modifications, such as changing the location of the headgroup (A6K vs. KA6), affects significantly the peptide's effectiveness. Only KA6 displays a propensity to promote the formation of H2, which suggests that KA6 molecules have a higher degree of incorporation in the interface than those of A6K. PMID:17534429

Peptide selectivity between the PDZ domains of human pregnancy-related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes.

PubMed

Sun, Mei-Ling; Sun, Li-Mei; Wang, Yong-Qing

2018-06-01

The human HtrA family of serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) are the key enzymes associated with pregnancy and closely related to the development and progression of many pathological events. Previously, it was found that halogen substitution at the indole moiety of peptide Trp-1 residue can form a geometrically satisfactory halogen bond with the Drosophila discs large, zona occludens-1 (PDZ) domain of HtrA proteases. Here, we attempt to systematically investigate the effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains. The complex structures, interaction energies, halogen-bonding strength, and binding affinity of domain-peptide systems were modeled, analyzed, and measured via computational modeling and fluorescence-based assay. It is revealed that there is a compromise between the local rearrangement of halogen bond involving different halogen atoms and the global optimization of domain-peptide interaction; the substitution position is fundamentally important for peptide-binding affinity, while the halogen type can effectively shift peptide selectivity between the 4 domains. The HtrA1-PDZ and HtrA4-PDZ as well as HtrA2-PDZ and HtrA3-PDZ respond similarly to different halogen substitutions of peptide; -Br substitution at R2-position and -I substitution at R4-position are most effective in improving peptide selectivity for HtrA1-PDZ/HtrA4-PDZ and HtrA2-PDZ/HtrA3-PDZ, respectively; -F substitution would not address substantial effect on peptide selectivity for all the 4 domains. Consequently, the binding affinities of a native peptide ligand DSRIWWV -COOH as well as its 4 R2-halogenated counterparts were determined as 1.9, 1.4, 0.5, 0.27, and 0.92 μM, which are basically consistent with computational analysis. This study would help to rationally design selective peptide inhibitors of HtrA family members by using different halogen substitutions. Copyright © 2017 John Wiley & Sons, Ltd.

Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

NASA Astrophysics Data System (ADS)

Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

2015-07-01

We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02240a

Loop propensity of the sequence YKGQP from staphylococcal nuclease: implications for the folding of nuclease.

PubMed

Patel, Sunita; Sasidhar, Yellamraju U

2007-10-01

Recently we performed molecular dynamics (MD) simulations on the folding of the hairpin peptide DTVKLMYKGQPMTFR from staphylococcal nuclease in explicit water. We found that the peptide folds into a hairpin conformation with native and nonnative hydrogen-bonding patterns. In all the folding events observed in the folding of the hairpin peptide, loop formation involving the region YKGQP was an important event. In order to trace the origins of the loop propensity of the sequence YKGQP, we performed MD simulations on the sequence starting from extended, polyproline II and native type I' turn conformations for a total simulation length of 300 ns, using the GROMOS96 force field under constant volume and temperature (NVT) conditions. The free-energy landscape of the peptide YKGQP shows minima corresponding to loop conformation with Tyr and Pro side-chain association, turn and extended conformational forms, with modest free-energy barriers separating the minima. To elucidate the role of Gly in facilitating loop formation, we also performed MD simulations of the mutated peptide YKAQP (Gly --> Ala mutation) under similar conditions starting from polyproline II conformation for 100 ns. Two minima corresponding to bend/turn and extended conformations were observed in the free-energy landscape for the peptide YKAQP. The free-energy barrier between the minima in the free-energy landscape of the peptide YKAQP was also modest. Loop conformation is largely sampled by the YKGQP peptide, while extended conformation is largely sampled by the YKAQP peptide. We also explain why the YKGQP sequence samples type II turn conformation in these simulations, whereas the sequence as part of the hairpin peptide DTVKLMYKGQPMTFR samples type I' turn conformation both in the X-ray crystal structure and in our earlier simulations on the folding of the hairpin peptide. We discuss the implications of our results to the folding of the staphylococcal nuclease. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Transformation and trends in preventive and social medicine education at the undergraduate level in a Brazilian medical school.

PubMed

Forster, A C; Passos, A D; Dal-Fabbro, A L; Laprega, M R

2001-01-01

In the present study we discuss some transformations in undergraduate training in Preventive and Social Medicine in the Department of Social Medicine of the Faculty of Medicine of Ribeiro Preto, University of So Paulo, from 1993 to 1999. Aspects of the relationship between medical training and the reorganization of local services of the Brazilian national health system, and between graduate teaching in Preventive and Social Medicine and medical education as a whole are discussed. The crisis in Preventive and Social Medicine and its influence of medical training are evaluated. Trends for the application of a body of knowledge of the specialty and for the relationship between the department and the medical school are discussed.

"What about FH of my child?" parents' opinion on family history collection in preventive primary pediatric care.

PubMed

Syurina, Elena V; Gerritsen, Anne-Marie Jm; Hens, Kristien; Feron, Frans Jm

2015-08-01

Family history (FH) in Preventive Primary Pediatric Care is to identify children at risk for complex diseases and provide personal preventive strategies. This study was to assess parents' opinion on FH collection. Semi-structured interviews were conducted. Among issues addressed were: former experiences with FH, knowledge about FH, family definition and sharing information about FH. The importance of FH for participants depended on their knowledge, perceived family health status and former experiences. After insight into FH, parents shift to believing it to be important, but certain barriers exist in reporting FH. Parents suggest that the importance of FH should be more emphasized and more trusting relationship with Preventive Primary Pediatric Care should be invested in.

[Employment opportunities and education needs of physicians with specialty training in Hygiene and Preventive Medicine.].

PubMed

Fara, Gaetano M; Nardi, Giuseppe; Signorelli, Carlo; Fanti, Mila

2005-01-01

This survey was carried out under the sponsorship of the Italian Society of Hygiene (SItI), to evaluate the current professional position of physicians who completed their post-graduate professional training in Hygiene and Preventive Medicine in the years 2000 through 2003. An ad-hoc questionnaire was administered to 689 such specialists across Italy with a response rate of 40%. The results show that specialists in Hygiene and Preventive Medicine are generally satisfied with their professional choice though most specialists were found to have only temporary employment. Post-specialty training courses of major interest to specialists in Hygiene and Preventive medicine are those regarding occupational health, statistical analysis and epidemiology, and quality of health care.

Inactivation of the cloned potassium channel mouse Kv1.1 by the human Kv3.4 'ball' peptide and its chemical modification.

PubMed Central

Stephens, G J; Robertson, B

1995-01-01

1. This study used the whole-cell patch clamp technique to investigate the action of a 28-mer 'inactivation peptide' based on part of the N-terminal sequence of the human Kv3.4 K+ channel (hKv3.4 peptide) on the cloned mouse brain K+ channel mKv1.1 expressed in Chinese hamster ovary (CHO) cells, and compared this with the inactivation produced by Shaker B inactivation peptide (ShB peptide). 2. Inclusion of the hKv3.4 peptide in the patch electrode (320 microM) transformed non-inactivating mKv1.1 into a rapidly inactivating current. The voltage dependence of time constants of decay and steady-state inactivation induced by hKv3.4 peptide were characteristic of an 'A-type' K+ current. 3. The hKv3.4 peptide had no effect on the voltage dependence of activation of mKv1.1, with a mid-point of activation of -8 mV, and a slope factor of 15 mV. Steady-state inactivation curves had a mid-point of inactivation of -36 mV and a slope factor of -7 mV; the time constant of recovery from inactivation at -90 mV was 1.3 s. 4. The chemical modification reagents N-bromoacetamide (NBA, 100 microM) and chloramine-T (CL-T, 500 microM) had no effect on the fast inactivation of mKv1.1 induced by ShB peptide. In contrast, the inactivation caused by hKv3.4 peptide was removed by brief exposure to NBA and CL-T. 5. Chemical modification resulted in a hyperpolarizing shift of -8 mV (CL-T) and -11 mV (NBA) in the voltage dependence of activation of mKv1.1 in the presence of hKv3.4 peptide. 6. Chemical modification was critically dependent on the presence of a cysteine residue at position 6, and not position 24, of hKv3.4 peptide. 7. NBA and CL-T caused only a slight inhibition of unmodified mKv1.1 current with no significant effect on the voltage dependence of mKv1.1 activation, and also had no effect on channel deactivation at -90 mV. 8. Chemical modification experiments were consistent with a selective action on the hKv3.4 peptide itself, specifically at the cysteine residue at position 6. PMID:7602512

Quantifying the impact of accessibility on preventive healthcare in sub-Saharan Africa using mobile phone data.

PubMed

Wesolowski, Amy; O'Meara, Wendy Prudhomme; Tatem, Andrew J; Ndege, Samson; Eagle, Nathan; Buckee, Caroline O

2015-03-01

Poor physical access to health facilities has been identified as an important contributor to reduced uptake of preventive health services and is likely to be most critical in low-income settings. However, the relation among physical access, travel behavior, and the uptake of healthcare is difficult to quantify. Using anonymized mobile phone data from 2008 to 2009, we analyze individual and spatially aggregated travel patterns of 14,816,521 subscribers across Kenya and compare these measures to (1) estimated travel times to health facilities and (2) data on the uptake of 2 preventive healthcare interventions in an area of western Kenya: childhood immunizations and antenatal care. We document that long travel times to health facilities are strongly correlated with increased mobility in geographically isolated areas. Furthermore, we found that in areas with equal physical access to healthcare, mobile phone-derived measures of mobility predict which regions are lacking preventive care. Routinely collected mobile phone data provide a simple and low-cost approach to mapping the uptake of preventive healthcare in low-income settings.

[Mind-body approach in the area of preventive medicine: focusing on relaxation and meditation for stress management].

PubMed

Kang, Yunesik

2010-09-01

Emotional support and a stress management program should be simultaneously provided to clients as effective preventive services for healthy behavioral change. This study was conducted to review various relaxation and meditation intervention methods and their applicability for a preventive service program. The author of this paper tried to find various relaxation and meditation programs through a literature review and program searching and to introduce them. The 'Relaxation Response' and 'Mindfulness Based Stress Reduction (MBSR)' are the most the widely used meditative programs in mainstream medical systems. Abdominal breathing, Progressive Musclular Relaxation (PMR), Relaxative Imagery, Autogenic Training (AT) and Biofeedback are other well-known techniques for relaxation and stress management. I have developed and implemented some programs using these methods. Relaxation and meditation classes for cancer patients and a meditation based stress coping workshop are examples of this program. Relaxation and meditation seem to be good and effective methods for primary, secondary and tertiary preventive service programs. Program development and standardization and further study are needed for more and wider use of the mind-body approach in the preventive service area of medicine.

Peptide nanotube-modified electrodes for enzyme-biosensor applications.

PubMed

Yemini, Miri; Reches, Meital; Gazit, Ehud; Rishpon, Judith

2005-08-15

The fabrication and notably improved performance of composite electrodes based on modified self-assembled diphenylalanine peptide nanotubes is described. Peptide nanotubes were attached to gold electrodes, and we studied the resulting electrochemical behavior using cyclic voltammetry and chronoamperometry. The peptide nanotube-based electrodes demonstrated a direct and unmediated response to hydrogen peroxide and NADH at a potential of +0.4 V (vs SCE). This biosensor enables a sensitive determination of glucose by monitoring the hydrogen peroxide produced by an enzymatic reaction between the glucose oxidase attached to the peptide nanotubes and glucose. In addition, the marked electrocatalytic activity toward NADH enabled a sensitive detection of ethanol using ethanol dehydrogenase and NAD+. The peptide nanotube-based amperometric biosensor provides a potential new tool for sensitive biosensors and biomolecular diagnostics.

Near infrared optical biosensor based on peptide functionalized single-walled carbon nanotubes hybrids for 2,4,6-trinitrotoluene (TNT) explosive detection.

PubMed

Wang, Jin

2018-06-01

A near infrared (NIR) optical biosensor based on peptide functionalized single-walled carbon nanotubes (SWCNTs) hybrids for 2,4,6-trinitrotoluene (TNT) explosive detection was developed. The TNT binding peptide was directly anchored on the sidewall of the SWCNTs using the π-π interaction between the aromatic amino acids and SWCNTs, forming the peptide-SWCNTs hybrids for near infrared absorption spectra measurement. The evidence of the morphology of peptide-SWCNTs hybrids was obtained using atomic force microscopy (AFM). The results demonstrated that peptide-SWCNTs hybrids based NIR optical biosensor exhibited sensitive and highly selective for TNT explosive determination, addressing a promising optical biosensor for security application. Copyright © 2018. Published by Elsevier Inc.

The roles of peptide hormones during plant root development.

PubMed

Yamada, Masashi; Sawa, Shinichiro

2013-02-01

Peptide hormones are a key mechanism that plants use for cell-cell interactions; these interactions function to coordinate development, growth, and environmental responses among different cells. Peptide signals are produced by one cell and received by receptors in neighboring cells. It has previously been reported that peptide hormones regulate various aspects of plant development. The mechanism of action of peptides in the shoot is well known. However, the function of peptides in the root has been relatively uncharacterized. Recent studies have discovered important roles for peptide hormones in the development of the root meristem, lateral roots, and nodules. In this review, we focus on current findings regarding the function of peptide hormones in root development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery

NASA Technical Reports Server (NTRS)

Bai, J. P.; Amidon, G. L.

1992-01-01

The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/tripeptide)-type drugs with or without an N-terminal alpha-amino group, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed.

Effect of Curcumin on the metal ion induced fibrillization of Amyloid-β peptide

NASA Astrophysics Data System (ADS)

Banerjee, Rona

2014-01-01

The effect of Curcumin on Cu(II) and Zn(II) induced oligomerization and protofibrillization of the amyloid-beta (Aβ) peptide has been studied by spectroscopic and microscopic methods. Curcumin could significantly reduce the β-sheet content of the peptide in a time dependent manner. It also plays an antagonistic role in β-sheet formation that is promoted by metal ions like Cu(II) and Zn(II) as observed by Circular Dichroism (CD) spectroscopy. Atomic force microscopic (AFM) images show that spontaneous fibrillization of the peptide occurs in presence of Cu(II) and Zn(II) but is inhibited on incubation of the peptide with Curcumin indicating the beneficial role of Curcumin in preventing the aggregation of Aβ peptide.