Beta-blocker use and risk of symptomatic bradyarrhythmias： a hospital-based case-control study

在与 -blockers use.MethodsA 的关系调查征兆的 bradyarrhythmias 的风险因素基于医院的盒子控制学习[228 个病人：108 与征兆的 bradyarrhythmias (案例) 和 120 控制] 在 Sultanah Aminah 医院，在 2011 年 1 月之间的马来西亚和 2014 年 1 月 .ResultsThe 平均数年龄里被进行是 61.1 ?? 業牴敩歮?? 呑 ?

pH-responsive magnesium- and carbonate-substituted apatite nano-crystals for efficient and cell-targeted delivery of transgenes

The short half-lives due to the enzymatic degradation in blood, the lack of tissue targetability and the incapability to passively diffuse across the plasma membrane and smoothly traffic across the harsh intracelluar environment are the major shortcomings for nucleic acid-based potential therapeutics, such as recombinant plasmid and antisense oligonucleotides or small interferring RNA (siRNA). Plasmid DNA containing a gene of interest could have immense impact as a promising therapeutic drug for treating genetic as well as acquired human diseases at the molecular level with high level of efficacy and precision. Thus both viral and non-viral synthetic vectors have been developed in the past decades to address the aforementioned challenges of naked DNA. While in the viral particles plasmid DNA is integrated into the viral genome, in most non-viral cases the DNA being anionic in nature is electrostatically associated with a cationic lipid or polymer forming lipoplex or polyplex, respectively, or a cationized inorganic gold, silica or iron oxide particle. Due to the potential immunogenicity and carcinogenicity issues with the viral particles, non-viral vectors have drawn much more attention for the clinical evaluation. However, the main concern of using non-biodegradable particles, specially the inorganic ones, is the adverse effects owing to their long term interactions with body components. We have recently developed biodegradable pH-sensitive inorganic nanoparticles of Mg/CaPi and carbonate apatite for efficient transgene delivery to primary, cancer and embryonic stem cells, by virtue of their high affinity binding with the DNA, ability to contact the cell membrane by ionic or ligand-receptor interactions and fast dissolution kinectis in endosomal acidic pH facilitating release of the DNA from the dissolving particles and also from the endosomes.

Application of chitosan-based nanoparticles in skin wound healing

The rising prevalence of impaired wound healing and the consequential healthcare burdens have gained increased attention over recent years.This has prompted research into the development of novel wound dressings with augmented wound healing functions.Nanoparticle(NP)-based delivery systems have become attractive candidates in constructing such wound dressings due to their various favourable attributes.The non-toxicity,biocompatibility and bioactivity of chitosan(CS)-based NPs make them ideal candidates for wound applications.This review focusses on the application of CS-based NP systems for use in wound treatment.An overview of the wound healing process was presented,followed by discussion on the properties and suitability of CS and its NPs in wound healing.The wound healing mechanisms exerted by CS-based NPs were then critically analysed and discussed in sections,namely haemostasis,infection prevention,inflammatory response,oxidative stress,angiogenesis,collagen deposition,and wound closure time.The results of the studieswere thoroughly reviewed,and contradicting findings were identified and discussed.Based on the literature,the gap in research and future prospects in this research area were identified and highlighted.Current evidence shows that CS-based NPs possess superior wound healing effects either used on their own,or as drug delivery vehicles to encapsulate wound healing agents.It is concluded that great opportunities and potentials exist surrounding the use of CSNPs in wound healing.

Enhancing Students’ Learning about Healthy Living through Community Participation

Introduction: The Health Enhancement Module (HEM) is taught as a core curriculum for all medical students at Monash University since 2002. In 2012 we moved the year three content of the program into a community setting, calling it the Health Enhancement Carnival (HEC). At the carnival, our undergraduates interacted with school students, their teachers, and their parents, involving them in a mix of discussions, poster presentations, and video presentations. In this paper we present our experience with the HEC. Specifically, we looked at the following two measures: how did the HEC influence the knowledge, attitude, and practice of healthy living among medical students? And, what were the learning experiences of the students during the HEC? Methods: Five themes (exercise, food, healthy sleep, workplace stress and ageing) were divided among students. They were asked to develop those themes with the help of posters, power point presentations, community talks as well as video presentations. The carnival was held in the setting of two nearby children’s schools. Students were evaluated by a panel of examiners with regards to learning objectives as well as preparation and presentation. As part of evaluation, we developed 2 questionnaires. The HEP Healthy Living Questionnaire provided feedback on how the program had improved students’ knowledge, attitudes, and practice of healthy living. The HEP Learning Style Questionnaire covered twelve areas, including collegiality, environment, leadership, community interaction and other facets of learning style. Analyses were performed using the IBM SPSS Statistics version 20 software in the Clinical School Johor Bahru. Results: 1) Influence of HEC on the knowledge, attitude, and practice of healthy living among medical students. From the interviews, the judges gave the students mean ratings of 4.0/5. We also received 77 out of 127 feedback questionnaires (response rate: 60.6%) from the students. Most students (range: 49.35% to 55.84%) were “satisfied/totally satisfied”, “achieved/totally achieved”, or “improved/totally improved” to 5 questions of the Healthy Living Questionnaire. Correlation coefficients between knowledge of healthy living, attitude towards healthy living, and practice of healthy living were large (exceeding 0.8) suggesting that these three measures were highly and positively inter-correlated. Most students (range: 60.28% to 71.43%) scored “a lot/almost all”, to 5 questions regarding achievement of learning objectives. 2) Learning experiences of the students during the HEC. Responding to the HEP Learning Style Questionnaire, most students (range: 66.24% to 85.72%) agreed or strongly agreed that the program provided an optimal environment for learning, encouraging students to assume leadership responsibilities and promoting self-directed learning. A correlation matrix of the 12 items showed medium to large correlations between all twelve variables. Conclusions: The Health Enhancement Program (HEP) is an innovative approach that has enabled students to learn about healthy living within the context of the local community.

Review Paper: Association between Social Network and Obesity among Adult Population

Objectives: Our main objective is to establish an association between obesity and social networks among the adult population as well as understanding the underlying mechanisms. We aim to provide suggestions for the development of future interventions to treat obesity. Methods: We carried out a literature search from 4 databases: PubMed, Embase, Scopus and Web of Science. We conducted a systematic search targeting on 3 main concept terms—“social network”, “obesity” and “adult”. A final pool of 11 articles best fitted for our topic was included. Results: We have established a clear association between obesity and social networks. Single women with the co-living arrangement have a higher waist circumference (WC), consistent with a higher predisposition to obesity seen among single individuals but lone living divorced men had lower WC compared to those with partners. Women with high incomes are less likely to be obese in comparison to highly social men with low income. The degree of the effect on social networks and obesity was inconclusive due to differences in the study population. Generally, women with low social participation tend to be obese. However, non-partnered women consistently showed a higher WC in comparison to their partnered counterparts regardless of participation rates except for divorced women. Living in a neighborhood with access to active transportation, high socioeconomic status, increased levels of social trust and social support reduces the prevalence of obesity. Mechanisms of cultural ideals, nature of employment, stress, gender, self-selection, network influence, social contagion and shared built environment may have contributed to the variation in results obtained. Conclusion: Association between social network and obesity exists. However, its overall effect on body weight is affected by a variety of factors. Sociodemographic factors and network characteristics of the population may influence the impacts on body weight. Therefore, a good understanding of the mechanisms associated will assist the development of effective network-based interventions.

PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells

Genetic intervention via the delivery of functional genes such as plasmid DNA(pDNA)and short-interfering RNA(siRNA)offers a great way to treat many single or multiple genetic defects effectively,including mammary carcinoma.Delivery of naked therapeutic genes or siRNAs is,however,short-lived due to biological clearance by scavenging nucleases and circulating monocytes.Low cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing activity.Development of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid delivery.Inorganic nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation activity.Here we introduce strontium salt-based nanoparticles,namely,strontium sulfate,strontium sulfite and strontium fluoride as new inorganic nanocarriers.Generated strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and siRNA.Degradation of the particles was seen with a drop in pH,suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic materials.While the particles are relatively nontoxic towards the cells,siRNA-loaded SrF 2 and SrSO 3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT,leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 cells.Strontium salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.

Seroprevalence of dengue among healthy adults in a rural community in Southern Malaysia:a pilot study

Background:The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia,with a shift in the age range predominance toward adults and an expansion to rural areas.Despite this,information pertaining to the extent of transmission of dengue virus(DENV)in the rural community is lacking.This communitybased pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia,and to identify influencing factors.Methods:In this study undertaken between April and May 2015,a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district.Sera were tested for immunoglobulin G(IgG)(Panbio®Dengue Indirect IgG ELISA/high-titer capture)and immunoglobulin M(IgM)(Panbio®)antibodies.The plaque reduction neutralization test(PRNT)was conducted on random samples of IgGpositive sera for further confirmation.Medical history and a recall of previous history of dengue were collected through interviews,whereas sociodemographic information was obtained from an existing database.Results:The overall seroprevalence for DENV infection was 86.6%(240/277)(95%CI:83-91%).Serological evidence of recent infection(IgM/high-titer capture IgG)was noted in 11.2%(31/277)of participants,whereas there was evidence of past infection in 75.5%(209/277)of participants(indirect IgG minus recent infections).The PRNT assay showed that the detected antibodies were indeed specific to DENV.The multivariate analysis showed that the older age group was significantly associated with past DENV infections.Seropositivity increased with age;48.5%in the age group of<25 years to more than 85%in age group of>45 years(P<0.001).No associations with occupation,study site,housing type,comorbidity,educational level,and marital status were observed,although the latter two were statistically significant in the univariate analysis.None of the studied factors were significantly associated with recent DENV infections in the multivariate analysis,although there was a pattern suggestive of recent outbreak in two study sites populated predominately by Chinese people.The majority of infections did not give rise to recognizable disease(either asymptomatic or nonspecific symptoms)as only 12.9%of participants(31/240)recalled having dengue in the past.Conclusions:The predominantly rural community under study had a very high previous exposure to dengue.The finding of a high proportion of unreported cases possibly due to subclinical infections underscores the need for enhanced surveillance and control methods.This finding also has implications for measuring disease burden,understanding transmission dynamics,and hypothesizing effects on DENV vaccine efficacy and uptake.

A community-based prospective cohort study of dengue viral infection in Malaysia: the study protocol

Background:Globally,dengue infections constitute a significant public health burden.In recent decades,Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes.The cyclical dominance of sub-types contributes to a pattern of major outbreaks.The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths.Understanding the complex interaction of the dengue virus,its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem.Methods:A prospective cohort study will be conducted in Segamat district of Johor State in Peninsular Malaysia.Researchers received approval from the Malaysian Medical Research Ethics Committee and Monash University Human Research Ethics Committee.The study will be conducted at a Malaysian based health and demographic surveillance site over a 1 year period in three different settings(urban,semi-urban and rural).The study will recruit healthy adults(male and female)aged 18 years and over,from three ethnic groups(Malay,Chinese and Indian).The sample size calculated using the Fleiss method with continuity correction is 333.Sero-surveillance of participants will be undertaken to identify asymptomatic,otherwise healthy cases;cases with dengue fever who are managed as out-patients;and cases with dengue fever admitted to a hospital.A genetic analysis of the participants will be undertaken to determine whether there is a relationship between genetic predisposition and disease severity.A detailed medical history,past history of dengue infection,vaccination history against other flaviviruses such as Japanese encephalitis and Yellow fever,and the family history of dengue infection will also be collected.In addition,a mosquito surveillance will be carried out simultaneously in recruitment areas to determine the molecular taxonomy of circulating vectors.Discussion:The research findings will estimate the burden of asymptomatic and symptomatic dengue at the community level.It will also examine the relationship between virus serotypes and host genotypes,and the association of the clinical manifestation of the early phase with the entire course of illness.

Strategies to assemble therapeutic and imaging molecules into inorganic nanocarriers

Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs,nucleic acid-based therapeutics,and imaging agents,influencing their blood half-lives,tumor targetability,and bioactivity.In addition to the high surface area-to-volume ratio,they exhibit excellent scalability in synthesis,controllable shape and size,facile surface modification,inertness,stability,and unique optical and magnetic properties.However,only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release,poor target specificity,and toxicity.To overcome these barriers,understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles(NPs)and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount importance.Therefore,we will shed light on various loading mechanisms harnessed for different inorganic NPs,particularly involving physical entrapment into porous/hollow nanostructures,ionic interactions with native and surface-modified NPs,covalent bonding to surface-functionalized nanomaterials,hydrophobic binding,affinity-based interactions,and intercalation through co-precipitation or anion exchange reaction.

Combating infectious diseases of poverty: a year on

The Infectious Diseases of Poverty journal,launched a year ago,is a platform to engage outside the traditional disciplinary boundaries,and disseminate high quality science towards the improvement of health.This paper reviews the milestone achievements during its first year of operation.The journal has filled an important niche,addressing some of the main priorities in the Global Report for Research on Infectious Diseases of Poverty.Highlights include the publication of three thematic issues on health systems,surveillance and response systems,as well as co-infection and syndemics.The thematic issues have foregrounded the importance and innovation that can be achieved through transdisciplinary research.The journal has been indexed by PubMed since April 2013,with the publication of a total of 38 articles.Finally,the journal is delivering to wider range readers both in developing and developed countries with sustained efforts with a focus on relevant and strategic information towards elimination of infectious diseases of poverty.

高产杀粉蝶菌素的链霉菌鉴定及其拮抗水稻白叶枯菌活性研究

【目的】为保证农业生产可持续性发展,研发和使用环境友好的生物农药受到全社会的高度重视。微生物代谢产物农药是我国目前应用最广的生物农药,也是未来发展绿色农药的一个重要方向。【方法】利用包含水稻白叶枯菌(Xanthomonas oryzae pv.oryzae,Xoo)PXO99A的NA培养基琼脂平板,从水稻根际土壤中筛选能抑制Xoo生长的链霉菌。通过高效液相色谱和质谱分析活性代谢产物的化学结构;采用剪叶法接种Xoo到水稻叶片后,再喷施杀粉蝶菌素溶液(0.1 g/L),2周后测定叶枯症状;采用响应面分析法优化高产杀粉蝶菌素的发酵培养基;采用PacBio SMRT测序平台+Illumina HiSeq X Ten平台开展全基因组测序。平均核苷酸一致性(average nucleotide identity,ANI)用于比较HSW2009与其他链霉菌在全基因组水平的亲缘关系。【结果】分离到一株对Xoo生长有强抑制活性的链霉菌HSW2009,其活性代谢产物为杀粉蝶菌素A1(piericidin A1,简称PIE);喷施PIE可以减轻Xoo在水稻叶片内的侵染;优化HSW2009高产PIE的发酵条件,得到MFM培养基;HSW2009在MFM培养中生长快、PIE发酵效价最高可以达到0.72 g/L;菌落表型分析、PIE生物合成基因簇分析、全基因组测序和ANI分析表明HSW2009与目前有效描述的PIE产生菌不同。【结论】HSW2009是一株高产杀粉蝶菌素A1的链霉菌属候选新种,命名为绍武链霉菌,可作为杀粉蝶菌素产业化研究的出发菌株。

Fructose promotes pyoluteorin biosynthesis via the CbrAB-CrcZ-Hfq/Crc pathway in the biocontrol strain Pseudomonas PA1201

Biocontrol strain Pseudomonas PA1201 produces pyoluteorin(Plt),which is an antimicrobial secondary metabolite.Plt represents a promising candidate pesticide due to its broad-spectrum antifungal and antibacterial activity.Although PA1201 contains a complete genetic cluster for Plt biosynthesis,it fails to produce detectable level of Plt when grown in media typically used for Pseudomonas strains.In this study,minimum medium(MM)was found to favor Plt biosynthesis.Using the medium M,which contains all the salts of MM medium except for mannitol,as a basal medium,we compared 10 carbon sources for their ability to promote Plt biosynthesis.Fructose,mannitol,and glycerol promoted Plt biosynthesis,with fructose being the most effective carbon source.Glucose or succinic acid had no significant effect on Plt biosynthesis,but effectively antagonized fructose-dependent synthesis of Plt.Promoter-lacZ fusion reporter strains demonstrated that fructose acted through activation of the pltLABCDEFG(pltL)operon but had no effect on other genes of plt gene cluster;glucose or succinic acid antagonized fructose-dependent pltL induction.Mechanistically,fructose-mediated Plt synthesis involved carbon catabolism repression.The two-component system CbrA/CbrB and small RNA catabolite repression control Z(crcZ)were essential for fructose-induced Plt synthesis.The small RNA binding protein Hfq and Crc negatively regulated fructose-induced Plt.Taken together,this study provides a new model of fructose-dependent Plt production in PA1201 that can help improve Plt yield by biosynthetic approaches.

Growth factor receptors: promising drug targets in cancer

Genetic,epigenetic and somatic changes deregulate the expression of growth factor receptors(GFRs),leading to cancer initiation and progression.Tumor cell growth and survival are orchestrated by clonal expansion and evasion of apoptotic signals in cancer cells.The growth of cells is further supported by angiogenesis and metastasis to distant organs.High expression of GFRs also contributes to the development of resistance.Therefore,therapeutics to target GFRs is a potentially attractive molecular approach to treat cancer more effectively.In this review,we have discussed the contribution of GFRs to cancer development and addressed molecular approaches undertaken to inhibit GFR-mediated pathways.A wide number of monoclonal antibodies(mAbs)and protein kinase inhibitors targeting these GFR-mediated functions are in clinical trials to treat human malignancies.However,most drugs that target GFRs lead to the development of drug resistance and generate adverse effects.Nucleic acid-based therapeutics,e.g.short interfering RNA(siRNA)could be harnessed to selectively silence GFR genes in cancer cells.Different polymer,liposome-based nanocarriers,and the most recently developed pH-sensitive inorganic carbonate apatite nanoparticles have been used in cell culture and preclinical trials for cytoplasmic delivery of the siRNAs targeting different GFR genes.siRNA-based therapeutics have been shown to have signifi cant potential to suppress GFR expression and functions and thus could be developed as molecular therapeutics.Multi-targeting of tumors at different levels by combining various approaches along with chemotherapy would be a promising therapeutic approach to fight the disease.Suitable nanocarriers capable of entrapping siRNA,mAb,GFR inhibitors and classical drugs targeting GFR have potential therapeutic applications.