Day 1 :
Keynote Forum
Gerald C. Hsu
Eclaire MD Foundation, USA
Keynote: Methodology of math-physical medicine
Time : 11:25-12:05
Biography:
The author received an honorable PhD in mathematics and majored in engineering at MIT. He attended different universities over 17 years and studied seven academic disciplines. He has spent 20,000 hours in T2D research. First, he studied six metabolic diseases and food nutrition during 2010-2013, then conducted research during 2014-2018. His approach is “math-physics and quantitative medicine” based on mathematics, physics, engineering modeling, signal processing, computer science, big data analytics, statistics, machine learning, and AI. His main focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.
Abstract:
Math-physical medicine approach (MPM) utilizes mathematics, physics, engineering models, and computer science in medical research. Initially, the author spent four years of self-studying six chronic diseases and food nutrition to gain in-depth medical domain knowledge. During 2014, he defined metabolism as a nonlinear, dynamic, and organic mathematical system having 10 categories with ~500 elements. He then applied topology concept with partial differential equation and nonlinear algebra to construct a metabolism equation. He further defined and calculated two variables, metabolism index and general health status unit. During the past 8.5 years, he has collected and processed 1.5 million data. Since 2015, he developed prediction models, i.e. equations, for both postprandial plasma glucose (PPG) and fasting plasma glucose (FPG). He identified 19 influential factors for PPG and five factors for FPG. He developed the PPG model using optical physics and signal processing. Furthermore, by using both wave and energy theories, he extended his research into the risk probability of heart attack or stroke. In this risk assessment, he applied structural mechanics concepts, including elasticity, dynamic plastic, and fracture mechanics, to simulate artery rupture and applied fluid dynamics concepts to simulate artery blockage. He further decomposed 12,000 glucose waveforms with 21,000 data and then re-integrated them into three distinctive PPG waveform types which revealed different personality traits and psychological behaviors of type 2 diabetes patients. Furthermore, he also applied Fourier Transform to conduct frequency domain analyses to discover some hidden characteristics of glucose waves. He then developed an AI Glucometer tool for patients to predict their weight, FPG, PPG, and A1C. It uses various computer science tools, including big data analytics, machine learning, and artificial intelligence to achieve very high accuracy (95% to 99%).
Keynote Forum
Clyde A Smith,
Stanford University, USA
Keynote: Structural studies on Carbapenem-Hydrolyzing Class D serine β-lactamases from Acinetobacter baumannii
Time : 12:05-12:45
Biography:
Clyde Smith has over 30 years’ experience in the determination of small molecule and protein structures using X-ray crystallography. Dr Smith gained his PhD in Protein Crystallography at Massey University (New Zealand) in 1993, where he studied the structure and metal binding properties of lactoferrin from human milk. He then undertook a two-year NIH-funded postdoctoral fellowship at the University of Wisconsin, working on the structure of the major skeletal muscle protein, myosin. He returned to New Zealand as a FRST postdoctoral fellow studying the structures of thermostable enzymes. In 1997 he was appointed as a Lecturer in Biochemistry in the School of Biological Sciences at the University of Auckland. In late 2003, he moved to the US to take up a Staff Scientist position in the Chemistry Department at Stanford University, working at the Stanford Synchrotron Radiation Lightsource (SSRL). He is currently a Senior Staff Scientist at SSRL. His scientific research in the field of structural biology includes work in antibiotic resistance, folate metabolism and vitamin B12 chemistry.
Abstract:
The class D serine β-lactamases comprise a superfamily of almost 800 enzymes capable of conferring high-level resistance to β-lactam antibiotics, predominantly the penicillin’s including oxacillin and cloxacillin. In recent years it has been discovered that some members of the class D superfamily have evolved the ability to deactivate carbapenems, “last resort” β-lactam antibiotics generally held in reserve for highly drug resistant bacterial infections. These enzymes are collectively known as Carbapenem-Hydrolyzing Class D serine β-Lactamases or CHDLs (1). The mechanism of β-lactam deactivation by the class D serine β-lactamases involves the covalent binding of the antibiotic to an active site serine to form an acyl-enzyme intermediate (acylation). This is followed by hydrolysis of the covalent bond (deacylation), catalyzed by a water molecule activated by a carboxylated lysine residue (2). It was initially thought that the carbapenems acted as potent inhibitors of the class D enzymes since the formation of the covalent acyl-enzyme intermediate effectively expelled all water molecules from the active site, thus preventing the deacylation step. Our structural studies on two CHDLs (3,4) have indicated that their carbapenem hydrolyzing ability may be due to two surface hydrophobic residues which allow for the transient opening and closing of a channel through which water molecules from the milieu can enter the binding site to facilitate the deacylation reaction (Figure). Although the hydrophobic residues responsible for the channel formation are present in all class D β-lactamases, sequence and structural differences nearby may be responsible for the evolution of carbapenemase activity in the CHDLs. These mechanisms will be presented, including some insights into the carbapenemase activity of non-Acinetobacter CHDLs which show a variation in how deacylation is activated. Future work aimed at improved inhibitor design will also be explored.
Keynote Forum
A. C. Matin
Stanford University School of Medicine USA
Keynote: Role of bacterial antioxidant defense in their resistance to bactericidal antibiotics
Time : 12:30-12:50
Biography:
A.C. Matin got his PhD from University of California in Microbiology (1969). He is serving as the Chair of MS senate task force on postdoctoral affairs (2009- present), Member of MS senate steering committee (2008-present) & Senator of Medical School senate (2006-present). He is a Fellow of the American Academy of Microbiology. He got 16 Honors and Awards which are Star Award in Environmental Protection Agency (1991-1997), Review Committee Member in Accreditation Board for Engineering and Technology (1992) and Foundation for Microbiology Lecturer in American Society for Microbiology (1991-1993). He has authored about 37 Publications that include review articles. His Community & International Work involved in Bacterial antibiotic resistance in space flight, Stanford University; NASA Ames and Nuclear waste remediation.
Abstract:
Statement of the problem: Bacterial antibiotic resistance is a world-wide public health problem requiring and new approaches. Background: Sigma S (σs) controls the synthesis of proteins that contribute to the resistance of bacteria like uropathogenic Escherichia coli (UPEC) in the stationary phase of growth, where bacteria are most virulent; σs is encoded by the rpoS gene. Methodology: Colony forming unit formation was used to determine antibiotic sensitivity; a novel microfluidic device determined sensitivity at single-cell level. Results: Lack of rpoS increased UPEC sensitivity to bactericidal antibiotics: gentamicin (Gm), ampicillin and norfloxacin. Gm will be discussed to illustrate the findings with the three antibiotics. Global proteomic analysis implicated weakened antioxidant defense. Use of the psfiA genetic reporter, 3-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more oxidative stress in the mutant. Cell elongation can compromise the results of HPF, but the antibiotic treatment did not affect the dimensions of stationary phase bacteria. The antioxidant, N-acetyl cysteine (NAC), & anaerobiosis decreased drug lethality. Thus, greater oxidative stress caused by insufficient quenching of endogenous ROS and/or respiration-linked electron leakage contributed to the increased sensitivity of the mutant; this was confirmed also in vivo. Eliminating of quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, (source of NADPH required by the quenchers), also generated greater oxidative stress and killing by Gm. The results were confirmed at single-cell level, as well as under microgravity during space flight where astronaut immune response is compromised. Conclusion and Significance: Besides their established mode of action, bactericidal antibiotics also kill bacteria by oxidative stress. Targeting the antioxidant defense will therefore enhance their efficacy. Bioinformatic approaches have identified small molecules that inhibit these proteins and are under study.
- The Emergence of Antimicrobial Resistance
Location: Wright
Session Introduction
Yuan Liu
Farmland Irrigation Research Institute, Chinese Academy of Agricultural Sciences, China
Title: Long-term application of farmyard manure to arable soils does not, in itself, promote the spread of antibiotic resistance genes
Time : 10:00-10:30
Biography:
Yuan Liu is mainly engaged in the research of rhizospheric electrochemistry and chemical behavior of nutrients and pollutants such as heavy metals, antibiotics and antibiotic resistance genes during farmland irrigation with unconventional water resources such as livestock wastewater and reclaimed water. .
Abstract:
Misuse of antibiotics has exacerbated the development and spread of antibiotic resistance in microbes in the environment, promulgating calls for nations to adopt mitigation strategies. Farmyard manure (FYM) has a long history in soil fertility management which is being re-evaluated because of a combination of rising mineral fertilizer costs, concerns for sustainable soil management and ecological stability. However, FYM may act as a reservoir of antibiotic resistance genes (ARGs) and resistant organisms: the effect of long-term application of FYM on ARGs in soil needs to be established. We studied ARGs in arable soil treated for 175-years with FYM or chemical fertilizer (CF) and native woodland (W). Metagenomic analysis showed that the abundance of fox5, blaCTX-M-4, vgb, tetG, sul1, vanA and floR genes were significantly lower in FYM than W, and the abundance of fox5, vgb and tetX genes in FYM were also significantly lower than CF. The phylogenetic diversity of individual ARGs was also typically lower in FYM than either CF and W. Despite this, there were no significant differences in the abundance of integrase genes (intI1 and intI2). There were also no significant differences in the abundance of metal resistance genes, except merB associated with Hg-resistance, which was more abundant and had an increased phylogenetic diversity in FYM soils. Overall, FYM did not increase the abundance and diversity of ARGs significantly and there was only limited association between ARGs and metal resistance genes in the soils.
- Antibiotic Resistance: Opportunities and Challenges
Location: Wright
Session Introduction
Zhongyang Li
Farmland Irrigation Research Institute, Chinese Academy of Agricultural Sciences, China
Title: The impact of alternate-furrow irrigation with livestock wastewater on antibiotic resistance gene abundance in soil
Biography:
Professor Zhongyang Li is mainly engaged in the research on agricultural safety utilization of livestock wastewater and reclaimed water and the amelioration technology of soil polluted with heavy metals, antibiotics in farmland.
Abstract:
One effective approach to treating large amounts of wastewater produced during livestock production is to use it to irrigate crops. However, antibiotics and antibiotic resistance genes (ARGs) associated with wastewater may enter the soil and plants. ARGs are spread readily among microbial populations by mobile genetic elements, and may pose threats to human health. Compared with conventional furrow irrigation (CFI), alternate-furrow irrigation (AFI) can reduce water use and still achieve high yields. These different irrigation methods may influence the fate of ARGs in soil, but few reports have studied the combined effects of AFI and livestock wastewater upon the distribution of ARGs in soil. Here, swine wastewater was used to irrigate cultivated peppers, and compared to relatively ARG-free groundwater. AFI was compared to CFI (100%) at three AFI irrigation rates (80%, 65% and 50% of CFI). The results showed that wastewater irrigation resulted in greater accumulation of antibiotics and ARGs in soil than groundwater irrigation. The effect of wastewater was much more pronounced in rhizosphere than in the bulk soils. Compared with CFI, AFI using wastewater reduced the relative abundance of ARGs in rhizosphere, but the concentration of antibiotics was largely unaffected; though antibiotic concentrations in roots were significantly lower, the abundance of ARGs in roots at 50% and 65% rates and in fruits at 50% rate were significantly increased when using wastewater. The soil bacterial communities did not change significantly between the different irrigation rates, but different behaviours were observed between ARGs and antibiotics at different irrigation rates. Antibiotic availability plays an important role in the diffusion of ARGs. In conclusion, AFI with livestock wastewater can reduce the relative abundance of ARGs in rhizosphere, but reducing irrigation amount should be employed carefully for the safe agricultural production.
- Antibiotics: In Pregnancy and Lactation
Location: Wright
Session Introduction
Carmen Mannuccia
University of Messina, Italy
Title: Fosfomycin treatment during pregnancy
Biography:
Carmen Mannucci is a Post-doc in Pharmacology at the Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy. His area of expertise are: Pharmacology, toxicology, pharmacology and toxicology of herbal medicine, food supplements and nutraceuticals.
Abstract:
Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteraemia, sepsis, pyelonephritis and kidney dysfunction with a reported mortality rates of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them requires antimicrobials treatment for at least 1 episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy. Use of fosfomycin to treat cystitis in pregnancy is generally considered safe and for the fetus and mothers, even thought this opinion is not based on specific studies monitoring the relationship of between urinary infections, consumption of antibiotics and pregnancy outcomes. On this basis we analyzed data from the database of a multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken in consideration. Women who have been treated with urinary antibiotics during the pregnancy were 187 (3.49%). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight and neonatal Apgar index did not show any significant difference. At the same time analysis of data of pregnancy complicancies (such as, urgent cesarean delivery, use of general anesthesia, need to induce labour) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. Our data, confirm the safety use of fosfomycin use in pregnancy.
- Advances in Infectious Antibiotics
Location: Wright
Session Introduction
Gershon Y. S. Sekley
G2 Medical Laboratory, Ghana
Title: Antimicrobial resistance-mediated complications in wound infections in Accra, Ghana
Biography:
Gershon Yao Sena Sekley is the Chief Executive Officer of G2 Medical Laboratory, a leading referral laboratory for most clinics and hospitals in Ghana. He helped establish G2 Medical Labs in 1997 with the sole vision of providing quality and accurate diagnosis service for both clients and healthcare professionals. Before then, he worked as a medical laboratory scientist and a senior supervisor in various establishments including The Trust Hospital (1990-1992), Swan Clinic (1992- 1997) and, Mendel Medical Laboratory (1993-1997). During this period, Gershon has contributed to different research studies that involved Sickle cell disease, Prostate Disorder in adults, Sexually Transmitted Infections and Renal Disorders in Diabetic patients. Besides analyzing clinical specimen in the laboratory, he is into health advocacy using the electronic media e.g. radio, television as a platform to educate the nation on topics like, Breast Cancer, Prostate Cancer, Cervical Cancer etc and also educate corporate organizations and churches on healthy life style and if you do not find him in the laboratory working hard to find solutions to serve patients and physicians, he will be found in the Library reading, teaching colleagues and students. Currently he is involved with research and findings in various disciplines in the field of medicine and academia. He would be seen spending time with his family during his leisure time.
Abstract:
Background: Wound infection is a major global health problem because it poses serious complications that result in difficulty in treatment and wounds bacterial contamination are common hospital acquired infections causing more than 80% of mortality. The aim of this study was to identify common bacteria infecting five different types of wounds and their resistance to commonly used antibiotics.
Methodology: Clinical swabs were received from hospitals and/ or clinics and some were obtained directly from patients visiting the G2 Medical Laboratory from 2015 to 2018. Specimens were obtained from wounds including Buruli ulcer, lupus, surgical, diabetes and burns. Conversional method of culturing on CLED, BLOOD AND CHOCLATE AGAR, incubated in an aerobic and anaerobic condition between 18 and 24 hours at 37°C. The microbial were identified through the gram staining and various biochemical reactions. Antibiotics sensitivity test was done for both gram negative and positive microbial.
Results: A total of 10629 specimen were analyzed and different types of bacteria were isolated, Pseudomonas aeruginosa was the most predominant pathogen isolated from all wound type infection: Buruli ulcer =3493 (32.9%); lupus =2180 (20.5%); surgical =2911 (27.4%); diabetes =1503 (14.1%); and burn =609 (5.7%). A total of microbial resistance n=9657. P. aeruginosa showed the highest rate of resistance to the tested antibiotics of n=5396 (55.9%): Gentamicin=963 (17.8%); amikacin=960 (17.8%); cefotaxime=813 (15.1%), ceftriaxone=850 (15.8%); ciprofloxacin=947 (17.6%) and levofloxacin=863 (16.0%) and other multidrug resistance strains identified were Enterobacter spp., n=2105 (21.8%); S. aureus, n=974 (10.1%); Klebsiella spp., n=571 (5.9%); Proteus spp., n=356 (3.7%) and E. coli, n=255 (2.6%).
Conclusion: Among other pathogens, we found P. aeruginosa to be the predominant bacteria in all wound infections and also shows the highest resistance to all tested antibiotics. A fugal elements (Aspergillius there was also isolated but no susceptibility testing was done). This study indicates that wound infections are typically polymicrobial comprising both Gram negative and positive bacterial with increased multidrug resistance to commonly used antibiotics for treatment.