Structure Activity Study of Clinically Observed Adverse Events and Oligomer Chemistry

                         http://austinpublishinggroup.com/drug-development/currentissue.php

The number and diversity of new nucleic acid based therapeutics in clinical trial illustrates the remarkable flexibility of this approach to therapy. The use of synthetic oligomers has the advantage of control of dose and duration of action over gene therapy and Cas9/CRISPR approaches that are developed in parallel. Further, synthetic compounds may contain a variety of modifications to fine tune their therapeutic purpose and define their mechanism of action. The expansion in diversity of nucleic acid therapeutics may also reflect the approaches to barriers observed in previous clinical trials. The objective of this review is to provide new insight into the clinical adverse event data reported for nucleic acid based therapeutics in advanced development, with the goal of establishing a comprehensive framework for evaluating the current implications, and future direction, of therapeutic antisense technologies. A pattern of adverse events, some sufficiently severe to require discontinuation of treatment, include Flu-Like Symptoms (FLS), Injection Site Reactions (ISR), kidney abnormalities, elevated liver enzymes, and thrombocytopenia are frequently observed with oligomer chemistries that have negatively charged phosphate linkages and naturally occurring sugars. Anti-Drug Antibodies (ADA) have been reported in high percentages following chronic treatment with oligomer chemistries designed to enhance duration of tissue residence time. However, these common adverse events are not observed with Phosphorodiamidate Morpholino Oliogmers (PMO) containing morpholino sugars and no negative charge in the phosphate linkage.

Oligonucleotide drug development must be viewed through a lens, which recognizes that humans are well equipped to recognize both foreign and endogenous DNA/RNA in the circulation. This protective recognition arises either as part of an innate, microbial DNA immune response or in response to cellular danger signaled by DNA Damage-Associated Molecular Patterns (DAMPs) [1,2]. Now that synthetic analogues of DNA and RNA are being developed as therapeutics for both acute and chronic treatment regimens, it is critical that we clarify the extent to which these emerging therapeutics result in chronic or inappropriate activation of these nucleic-acid sensors.

Information available to guide optimal therapeutic oligomer chemistry has transitioned from what chemical structures can be made to properties in biological systems and then on to efficacy in animal models. Recently, advanced therapeutic development of oligonucleotides has provided a wealth of information from well controlled clinical trials. Human data are the most pertinent information as, in some cases, the preclinical efficacy reports are discordant with human efficacy observations such as the case with TKM-100802 which was highly effective in nonhuman primates  but its use in patients from the recent Ebola outbreak were not effective  and off-target effects including activation of inflammatory cytokines were notable outcomes. In addition, detailed summaries are only recently publicly available for Ampligen, mipomersen, drisapersen, and eteplirsen which provide comprehensive evaluation of efficacy and safety from multiple human studies.

An Association of Insulin Resistance with Numerous of Circulating Microparticles Originated from Endothelial Cells in Cardiac Failure Individuals without History of Diabetes Mellitus

          http://austinpublishinggroup.com/disease-markers/fulltext/jdm-v2-id1032.php

ACEI: Angiotensin-Converting Enzyme Inhibitors; ARBs: Angiotensin Receptor Blockers; AUC: Area Under Curve; BMI: Body Mass Index; BNP: Brain Natriuretic Peptide; CHF: Chronic Heart Failure; CV: Cardiovascular; EMPs: Endothelial-Derived Microparticles; GFR: Glomerular Filtration Rate; hs-CRP: High Sensitive C-Reactive Protein; HbA1c: Glycated Hemoglobin; HDL-C: High-Density Lipoprotein Cholesterol; HFpEF: CHF with Precerved LVEF; HFrEF: CHF with Reduced LVEF; IR: Insulin Resistance; LDL-C: Low-Density Lipoprotein Cholesterol; LVEF: Left Ventricular Ejection Fraction; MetS: Metabolic Syndrome; T2DM: Type 2 Diabetes Mellitus.

 Chronic heart failure (CHF) remains a major public health problem worldwide leading to growth of cardiovascular (CV) morbidity and mortality. During the past decades prevalence and incidence of CHF has increased. Despite contemporary understanding of the underlying disease mechanisms of CHF there is knowledge gap with respect to nature evolution CHF under influence of co-existing CV risk factors. Indeed, the results of few population-based and epidemiological investigations have shown that multiple actual CV risk factors and various metabolic comorbidities presented in CHF patients may affect cardiac failure development. There is still debate in the scientific community about whether identification of numerous of CV risk factors / the metabolic co-morbidities improves ability to predict CHF development beyond use of single risk factor.

Recent clinical investigations have revealed insulin resistance (IR) is as a distinct cause of cardiac dysfunction and CHF in diabetic and non-diabetic patients. IR mediates excessive or inadequate proliferation of the extracellular matrix accelerates apoptosis via increased oxidative stress, neurohumoral and inflammatory activation that effect cardiac remodeling and endothelial function. Despite IR is considered a main component of metabolic syndrome (MetS) and type two diabetes mellitus (T2DM), a lot of individuals with CHF may present IR prior to other dysmetabolic conditions including MetS / T2DM. However, IR is persisted component of CV risk factors and it role in CHF development in the patients without history of T2DM is still unclear.

Maternal Smoking and Perinatal Outcomes

                  http://austinpublishinggroup.com/drug-abuse-addiction/online-first.php

Nicotine is one of the major components in tobacco smoke, and it can cross the placenta. It enters the fetal circulation and accumulates in the fetal compartments from as early as seven weeks of gestation, even with passive smoking. Elevated fetal carbon monoxide levels may result in hypoxia due to reduced availability of hemoglobin for oxygen transport. Exposure to hazardous substances in cigarette smoke could lead to adverse pregnancy and birth outcomes. In particular, maternal nicotine exposure is associated with many adverse fetal, placental, and postnatal health outcomes, including both shortterm and long-term complications. Despite increased awareness of the harmful effects of smoking during pregnancy, approximately 20% of women continue to smoke throughout pregnancy in the world. Reducing smoking in pregnancy is a global public-health priority. We recommend clinical and public-health strategies aimed at the primary and secondary prevention of tobacco exposure for fetuses and children.

The World Health Organization (WHO) estimates that the prevalence of smoking is approximately 22% of women in developed countries and 9% of women in underdeveloped countries. The 2011 Pregnancy Risk Assessment Monitoring System (PRAMS) polled women from 24 states in the US. The self-reported data showed that about 23% of reproductive-aged women smoked during the three months before pregnancy, and about 10% of women smoked during the last three months of pregnancy. About 55% of women who smoked before pregnancy reported they had quit smoking by the last three months of pregnancy. The highest prevalence of those smoking during the last three months of pregnancy (15-16%) was in the age groups of 24 years and younger (Figure 1). A strong correlation has been seen between maternal smoking during pregnancy and young age, unmarried status, and being from a low socioeconomic status.

The Centers for Disease Control and Prevention’s (CDC) PRAMS showed the trends of smoking three months before pregnancy, during, and after pregnancy data from 40 states in the US from 2000 to 2010. During this decade, the prevalence of smoking in the three months before pregnancy remained unchanged at about one in four women. However, the prevalence of smoking declined in the last three months of pregnancy from 13.2% to 11.6% and after delivery from 17.8% to 16.6%. The data showed that 40% of women who quit smoking during pregnancy relapsed within six months after delivery.

Other parts of the world had a greater decrease in smoking for women. Dias-Dame et al., conducted population-based survey in Brazil, data of 7,572 women showed that the prevalence of smoking before pregnancy decreased from 28% in 2007 to 22% in 2013, and the prevalence of smoking during pregnancy decreased from 22% in 2007 to 18% in 2013. In Australia, the prevalence of smoking in pregnancy in New South Wales declined from 22.1% in 1994 to 13.5% in 2007. The largest decrease in smoking in pregnancy rates was among the highest socioeconomic group, and smaller declines were observed among teenage and remote rural mothers.

THANKSGIVING DAY

THANKSGIVING DAY

Thanksgiving Day is a day of giving thanks for blessing them with the harvest and of the progressing year. It is a day of celebration in many countries like Canada, United States, Liberia, Japan and some of the Caribbean islands. It’s a time to be appreciative and grateful for all we've and a time to mirror on the year and acknowledge people who have provided the love, care, and a focus to create our lives higher. In most of the countries Thanksgiving Day is celebrated on the Fourth Thursday of November every year.

History

Prayers of thanksgiving ceremonies are common amongst all the religions during the time of harvests. The history of Thanksgiving stretches the entire manner back to a time long before America became a nation. During 1620, pilgrims came to settle down in the North America. At times brutal conditions were faced by them which lead to death of many people due to droughts. As the days moved on, they began to harvest the corn successfully and in order to show their gratitude and thankfulness to God they decided to celebrate the feast of Thanksgiving Day in the year 1621. In the year 1789, President George Washington declared 26^th November as national thanks giving day. During the rule of Abraham Lincoln, he proclaimed “last Thursday of November” as thanks giving day which everyone follows till today.

Raising the Self Esteem with the Oral Rehabilitation of a Child with Incontinentia Pigmenti Syndrome

                                              http://austinpublishinggroup.com/dentistry/

Incontinentia pigmenti (IP) is a rare X-linked dominant syndrome that mainly affects the skin, eyes, hair, central nervous system and teeth. Although dermatologic manifestations are among the most important aspects for the diagnosis of the syndrome, oral involvement characterized by hypodontia, conoid teeth and delayed eruption are also important for the diagnosis and patient aesthetic rehabilitation. These abnormalities may cause feeding problems influencing the patient quality of life. This study reported a case of a 10-year-old girl with cutaneous manifestations and hypodontia. The child´s main complaint was related to her smile. The treatment plan was the tooth restoration (conoid) and installation of the space maintainers. This case enhances the importance of integrated dental treatment, which combines pediatric dentistry, orthodontics and conventional prosthesis. In addition, hypodontia is frequently found in incontinentia pigmenti, and dentists should be aware of this condition in order to help with the diagnosis.

Incontinentia pigmenti (IP) syndrome is a rare X-linked dominant genodermatosis which mainly affects women and is usually lethal for males when in the mother’s utero. Synonyms of IP type 2 are: Bloch-Sulzberger syndrome, Bloch-Siemens syndrome, familial incontinentia pigmenti (pigment incontinence). The incidence of the disorder is 1 case per 40,000 populations. The name of the disease reflects morphological changes of the skin seen under a microscope system. The disease is systemic and involves tissues of ectodermic and mesodermic origin including coetaneous tissue, teeth, eyes and the central nervous system (CNS), amongst other organs. In 80% of the cases other defects are seen in the form of dental, skeletal, nail anomalies, microcephaly, seizures, psychomotor retardation, strabismus, opitc nerve atrophy, retinal detachment, cataracts, etc.

Cutaneous manifestations of IP are divided into the following four stages, although not all stages may be present in some cases: stage 1-erythema, vesicles and blisters appearing in a typically linear pattern; stage 2-papulae, verrucous lesions and hyperkeratosis; stage 3-hyperpigmentation; stage 4-hypopigmentation and cutaneous atrophy. In all of these stages, the cutaneous lesions tend to follow the lines of Blaschko.The blistering stage of the lesion needs to be differentiated from Herpes simplex and Bullous Impetigo. The lesions are linear and in clusters in classical Incontenentia Pigmenti. Warty phase needs to be differentiated from linear epidermal birthmarks or warts. Hyperpigmentary stage needs to be differentiated from moles and other causes of hyperpigmentation. Hyperpigmentation of Incontenentia Pigmenti is classically in whorls. affect both the primary and permanent dentitions. The most frequent alteration is hypodontia (up to 43% of patients), followed by pegged or conically crowned teeth (30% of patients). Other dental features were also reported as delayed eruption, partial anodontia, hypomineralization and gothic palate. All these manifestations are important because they persist throughout the patient’s life, thus requiring an adequate dental treatment plan when the diagnosis of the disease to oral rehabilitation is made by a multidisciplinary team. The majority of dental anomalies in IP patients could be successfully corrected. Some of these anomalies may greatly influence the quality of life causing psychological and feeding problems. This article reports a case of a 10-year-old girl with cutaneous manifestations and hypodontia. The diagnosis of incontinentia pigmenti in this patient was based on the description of vesiculobullous lesion at birth followed by hyperpigmented lesion overlapping the previous area of the vesicobullous lesion.

Stabilization versus Ablation of Tumor Vasculature: Implications in Radio and Chemo-Sensitization

                   http://austinpublishinggroup.com/carcinogenesis/currentissue.php

It is well established that tumors are unable to grow beyond certain size (1-2 mm) unless they acquire their own blood supply via. angiogenesis. In addition, angiogenesis helps tumors to invade adjacent tissues and metastasize to distant sites. Therefore, it has been postulated that interfering with the blood supply using antiangiogenic therapies will destroy the tumor. However, there is an emerging alternative concept that depriving the tumor of its blood supply interferes with the delivery of chemotherapeutic agents to the tumor and creates unfavorable hypoxic environment that compromises the action of radiotherapy. This concept was supported by the modest responses to anti-angiogenic therapies in clinical trials and the lack of any impact on patient’s survival when antiangiogenic drugs are administered as single agents. Although, Hurwitz, et al have shown that combining the antiangiogenic drug, Bevacizumab with chemotherapy significantly improved survival among metastatic colorectal cancer patients. Still, other studies demonstrated reductions in tumor concentrations of chemotherapy or effectiveness of radiotherapy when antiangiogenic drugs were co-administered. Even when antiangiogenic drugs yielded significant effects on the growth of some tumors such as renal cell carcinoma, cervical cancer and ovarian cancer, they failed to demonstrate significant improvements in patients’ survival. Furthermore, complete resistance to antiangiogenic therapies have been reported for prostate and pancreatic adenocarcinoma and melanoma. In order to explain this inconsistency, further research is needed for better understanding of the underlying cellular and molecular mechanisms of tumor vascularization and its interaction with cancer therapies in different tumor beds.

Tumors’ blood vessels are often larger and more conspicuous than those of normal tissues. However, tumors tend to actually have less blood supply than normal tissues because tumor blood vessels are fragile, leaky, morphologically abnormal and malfunctioning. While the normal vasculature consists of evenly spaced, well-differentiated arteries, arterioles, capillaries, venules and veins, the tumor vasculature is heterogeneous, unevenly distributed and chaotic with a tortious irregular course that leads to zones of hypoxia and acidosis. Tumors initiate a vascular supply through secreting angiogenic factors, mainly Vascular Endothelial Growth Factor (VEGF). Despite being of critical value in controlling the physiological processes of angiogenesis and vascular permeability, when continuously over-expressed in tumor tissues, VEGF induces accelerated and defective angiogenesis wherein vessels are immature, leaky, tortious and characterized by defective anatomy and physiology. These structural abnormalities contribute to spatial and temporal heterogeneity in tumor blood function, resulting in poorly perfused and subsequently hypoxic tumor microenvironment. Targeting tumor vessels via. Anti-VEGF/VEGFR drugs have not been effective as a cure since impeding tumor blood supply deprives the tumor of oxygen, leading to hypoxia and acidosis that, in turn, can promote tumor growth, abnormal angiogenesis, and metastasis and also compromise the cytotoxic functions of immune cells that infiltrate tumors. In addition, reduced tumor vascularity is a main contributor to therapeutic resistance in cancer since it interferes with the delivery of anti-cancer agents to the tumor targeted by chemotherapy or minimizes the production of Reactive Oxygen Species (ROS) in the tumor area, which is essential for radiation therapy induced cell killing [18,19]. Radiation-induced effects on cancer are brought about by inducing ROS production, DNA damage and apoptosis. However, poor vascularization and hypoxia that characterize solid tumors induce resistance to radiotherapy and are positively correlated with more invasion and metastasis. 

This is achieved by two mechanisms: first, through the lack of O2 and hence the interference with radiation-induced ROS production. Second, via. the hypoxia inducible factor-1a (HIF-1a) that provokes adaptive intracellular responses that, in turn, facilitate cell proliferation, interfere with apoptosis, provide protection from cell demise and ultimately rendering tumors radioresistant. As a result, increasing the chemotherapeutic doses or strategies to intensify radiotherapy have been employed to increase the treatment efficacy. However, these procedures can potentially lead to a higher risk of serious side effects. To raise the therapeutic ratio (the ratio between the desirable cytotoxic effects and normal tissue complications), new strategies to enhance chemo and radiosensitivity of cancer are needed. To this end, we need to develop methods to improve tumor blood perfusion and normalize vascular development in order to increase tumor vulnerability to anti-cancer therapy as a better alternative to starving a tumor of its blood supply, which is not curative. Furthermore, one needs to emphasize that antiangiogenic drugs are not without side effects. Indeed, they have been reported to induce a myriad of toxic effects such as hypertension, hemorrhage, thromboembolism, proteinuria, malaise, fatigue, biochemical hypothyroidism, and cardiac failure, all are related to the non-specific action of antiangiogenic drugs that affects both normal and cancer tissues.

Helicobacter pylori, A Sex Transmitted Bacteria

                    http://austinpublishinggroup.com/chronic-diseases/current-issue.php

Since oralsex is a very common sexual activity and recent evidence reported H. pylori exist in oral cavity as colonized site. Both facts indicated H. pylori may results sex transmitted disease such as vagina, breast and urethritis, However, further clinical studies and lab confirmation should be followed. Helicobacter pylori (H. pylori) passes through the mouth on its way to colonizing the stomach, where chronic infection is associated with ulcers, gastritis, and gastric adenocarcinoma. H. pylori is the only proven oncogenic bacterial species and detecting, preventing, or curing infection in the early stages is essential if gastric disease is to be prevented. However, beside of stomach H. pylori infection, there are several reports indicated non-gut organs have been harbored of H. pylori, such as vagina, nasopharyngeal sinus cavities, coronary plaque, otitis media, breast. Now it is time we should answer a question; is H. pylori a sex transmitted bacteria?

Helicobacter pylori (H. pylori) passes through the mouth on its way to colonizing the stomach, where chronic infection is associated with ulcers, gastritis, and gastric adenocarcinoma. H. pylori is the only proven oncogenic bacterial species and detecting, preventing, or curing infection in the early stages is essential if gastric disease is to be prevented. However, beside of stomach H. pylori infection, there are several reports indicated non-gut organs have been harbored of H. pylori, such as vagina, nasopharyngeal sinus cavities, coronary plaque, otitis media, breast. Now it is time we should answer a question; is H. pylori a sex transmitted bacteria?

Seroprevalence studies have shown that in sex partners with a man/woman who is infected with H. pylori the non-infected individual has an increased risk of transmitting the infection. Studies have shown that prevalence rates were statistically significant between couples with and without H. pylori infection (83.3% v 28.5%) respectively.

Ethnicity may also be an important predictor of sexual transmission of H. pylori infection. A number of studies have shown that the highest rates of sexually transmitted infections occur in ethnic minorities. The high prevalence of sexually transmitted infections correlates well with the high H. pylori prevalence rates that exist among these ethnic groups.

Inverted Dispersive Liquid–Liquid Micro Extraction of Nicotinic Acid from Human Plasma and its Determination by High-Performance Liquid Chromatography

http://austinpublishinggroup.com/chromatography/fulltext/chromatography-v3-id1038.php

Extractionand determination of nicotinic acid from human plasma was performed using inverted dispersive liquid-liquid microextraction and HPLC. The parameters affecting extraction recovery such as type and volume of extracting and disperser solvents, pH of sample solution, salt addition and extraction time were optimized. Optimal extraction conditions were: 150μL tributyl phosphate as extraction solvent, 400μL methanol as disperser solvent, and pH of sample = 4.5, concentration of NaCl = 3M, without effect of extraction time. Under the optimal conditions a linear range of 30-1000 ng mL-1 (R² = 0.9994) was obtained. Limit of detection, the extraction recovery and preconcentration factor were 10 ng mL^-1, 68% and 53 respectively. The method was successfully applied for the extraction and determination of nicotinic acid in human plasma sample.

Nicotinic acid (niacin or pyridine-3-carboxylic acid, Figure 1) is a water soluble B-complex vitamin present in many foods including fish, milk and green vegetables. The deficiency of nicotinic acid results in pellagra, affecting the skin and central nervous system. High-dose of nicotinic acid may cause thickening of the retina and increase the level of uric acid in the blood. Thus, determination of nicotinic acid in human plasma is very important for health.

The analytical techniques, such as flow injection analysis, thinlayer chromatography , liquid chromatography-mass spectrometry, capillary chromatography, and high-performance liquid chromatography were used for determination of nicotinic acid in human plasma. However, many of analytical techniques may need to preconcentrate target compounds before analysis. Preconcentration methods such as drop-to-drop solvent microextraction, solid phase extraction and Reactive Extraction are difficult and time consuming. Hence, simple and rapid preconcentration method is required to extract nicotinic acid from human plasma. Dispersive Liquid-Liquid Microextraction (DLLME) is a mode of Liquid- Liquid Extraction (LLE) in smaller level, which in comparison with the LLE method, its consumption of organic extracting solvent and environmental contamination significantly lower, and the obtained preconcentration factor is much higher. DLLME employs a mixture of a high-density extracting solvent and water miscible polar disperser solvent. In DLLME After a rapid injection of an appropriate mixture containing extracting and disperser solvents into the aqueous sample a cloudy state is formed. The contact area between the extracting solvent and the sample solution is very large. Thus the extraction equilibrium is achieved rapidly. After centrifugation, the extracted phase is settled at the bottom of the conical test tube. In 2009, Farajzadeh et al. designed inverted dispersive Liquid-Liquid Microextraction (IDLLME). IDLLME is invert of DLLME because in IDLLME the extracting solvent is lighter than water; therefore the separated phase was collected at the top of the sample solution. Thus in the present work, IDLLME-HPLC is used for the extraction and determination of nicotinic acid in plasma sample. This method is based on the extraction of nicotinic acid from plasma sample into an organic solvent. Parameters affecting extraction recovery of nicotinic acid, such as selection types and volume of extracting and disperser solvents, pH of sample solution, salt addition and extraction time were optimized.

Nicotinic acid was purchased from Sigma–Aldrich (Steinheim, Germany). HPLC grade (Methanol, acetonitrile, acetone), sodium hydroxide, hydrochloric acid, and sodium chlorid were obtained from Merck (Darmstadt, Germany). Xylene, n-hexan, toloen, dodecane, tributyl phosphate and 1-octanol were obtained from Aldrich (Milwaukee, WI, USA). Water used was double distilled deionized which purchased from Power Plant in sari city. Stock solution of nicotinic acid (1.0 mg/L) was prepared in methanol and stored in the dark at 4oC. Noted to the LC chromatogram this solution was stable for two months. Working standard solutions were diluted with deionizer double distilled water at concentration of 100.0 ngmL-1 when ever needed.

Textile Industry Wastewater Treatment Using DAP, Urea, and Polymer AQUATREAT @AR 06

                                            http://austinpublishinggroup.com/chemical-engineering/

TextileIndustry is one of the most important and largest industrial sectors in Pakistan. It has a high importance in terms of its environment impact, since it consumes large quantity of textile industrial processed water and produces highly polluted discharge water. The textile industry uses high volume of water throughout its operation, from the washing of fibers to bleaching, mercerizing, dyeing, printing and washing of finished products. A process data collection was performed and integrated with a characterization of the process effluents in terms of treatability and reusability. In this research we use 98% Concentrated Sulfuric Acid for the Neutralization i.e. to maintain pH, Di Ammonium Phosphate (DAP) and Urea for the bacterial growth i.e. to decrease Biological Oxygen Demand (BOD), and we use AQUATREAT @AR 06 for as an efficient coagulation and flocculation agent. The water treated and purified by using this method can be used for the agricultural purposes or can be drain to sewer without any hesitation.

The world’s water consumption rate is doubling every 20 years, outpacing by two times the rate of population growth. The availability of good quality water is on the decline and water demand is on the rise. Worldwide availability of fresh water for industrial needs and human consumption is limited. Various industrial and developmental activities in recent times have resulted in increasing the pollution level and deteriorating the water quality. Water shortages and unreliable water quality are considered major obstacles to achieve sustainable development and improvement in the quality of life. The water demand in the country is increasing fast due to progressive increase in the demand of water for irrigation, rapid industrialization, and population growth and improving life standards. The existing water resources are diminishing (i) due to unequal distribution of rain water and occasional drought, (ii) excessive exploitation of ground water sources and its insufficient recharge, (iii) deterioration of water quality due to the discharge of domestic and industrial effluents without adequate treatment. This is resulting into water stress/ scarcity. Country is currently passing through social and economic transition. The proportion of the population which is urban has doubled over the last thirty years (and is now about 30%), agriculture now accounts for about 25% of GDP and the economy has been growing at around 7-9% a year. Country has a highly seasonal pattern of rainfall, with 50% of precipitation falling in just 15 days and over 90% of river flows in just four months.

Textile Industry is one of the most important and largest industrial sectors in Pakistan. It has a high importance in terms of its environment impact, since it consumes large quantity of textile industrial processed water and produces highly polluted discharge water. The textile industry uses high volume of water throughout its operation, from the washing of fibers to bleaching, mercerizing dyeing, printing and washing of finished products .

Textile industry causes considerable higher impacts to water pollution by discharging their effluents into various receiving bodies includes ponds, rivers and other public sewer. Major pollutants load from the textile industries are from the several of their wet -processing operations like scouring, bleaching, mercerizing and dyeing. Among these various processes, dyeing process normally uses large amount of water for dyeing, fixing and washing processes. Thus, textile wastewater possess a high COD concentration, large amount of suspended solids, broadly fluctuating pH, strong color, high temperature and low biodegradability caused by varying contaminates within water environment. The textile industry is one of the most polluting industries in term of discharge volume and effluent composition. The dye effluent is characterized by strong color, high Chemical Oxygen Demand (COD) with pH varying from 2 to 12. The removals of color and COD reduction pose greatest problems in textile industry. Conventionally effluents containing organics are treated with adsorption, biological oxidation, coagulation, etc.

Femoral Endarterectomy against Iliofemoral bypass-Case Series

                             http://austinpublishinggroup.com/cardiovascular-diseases/

Thedecision for an ideal vascular procedure for occlusive peripheral arterial disease depends on type of lesion involved, patient factors and the options available to deal with it. Despite a dramatic increase in the use of endovascular techniques to treat chronic limb ischemia secondary to femoral arterial disease (FAD), femoral endarterectomy (FE) and profundaplasty remain the procedures of choice because long-term patency results are still superior to any other intervention. The American Heart Association  has recommended that angioplasty of the femoral artery be carried out only in single lesions of less than 10 cm, and better results are associated with short lesion length and good runoff, claudication, stenosis and the absence of diabetes. The immediate placement of a stent after angioplasty may address the issues of elastic recoil and dissections and improve the early success rate, but it has not been shown consistently to improve long-term patency. Even though the endarterectomy was the one of the first described procedures, autogenous long saphenous vein bypass has surpassed it as the preferred procedure for occlusive disease in the infrainguinal region. This is largely the result of several series reporting an inferior long term patency rate with endarterectomy. Further studies were conducted to compare the efficacy of available surgical options (vein by-pass, open endarterectomy and semi-closed endarterectomy) to combat the femoro-popliteal occlusion and it showed that the immediate failures and late cumulative patency/survival were similar for all three procedures. Studies supported the use of endarterectomy as available option for infrainguinal arterial diseases with very comparable results to vein grafts.

The longsaphenous vein is a very demanding conduit if coronary or vein bypass is required in future. Synthetic grafts and angioplasty studies has shown inferior results (high early and late restenosis rates). The present retrospective study is to evaluate the results of open endarterectomy in short atherosclerotic occlusion of the femoral artery against iliofemoral bypass grafting with long saphenous vein graft. Endarterectomy of localized lesions of the iliofemoral artery was performed in 5 male patients between May 2013 and May 2015, with a proven diagnosis of chronic occlusion of isolated external iliac artery or iliofemoral artery. The diagnosis was confirmed by angiography. The median age of the patients was 40 +/− 10 years. Risk factors for peripheral atherosclerosis were diabetes, electrocardiogram changes of past myocardial is chaemia, smoking and hypertension.

All patients suffered from atherosclerosis, and had thrombosis or stenosis of the external iliac artery associated with/without adjoining femoral artery and profunda femoris artery. All endarterectomies were performed as a primary procedure and not as an adjunct to a bypass procedure. Selection of patients the indications for operation in this series were disabling intermittent claudication, rest pain and gangrene. Out of five in two cases, the claudication distance was 100m or less and in two cases had rest pain severe enough to interfere with sleep and one case had established gangrene of the toes. In those with occlusive disease localized to the iliofemoral artery, the patient’s usually had with no pulses in the limb distally on the affected side. Occasion-ally, weak pedal pulses were present. All patients were investigated by Colour Doppler scan by CE FDA 3D 4D Doppler ultrasound and femoral angiography. Where unequal femoral pulses were present, or bruits were audible over the iliac or common femoral vessels, suggesting more proximal lesions, lumbar orthography was performed and if present these patients were excluded from the study.

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

                                  http://austinpublishinggroup.com/cancer-clinical-research/

Chemotherapyis the mainstay of treatment for advanced gastroesophageal cancer (AGC). There is no consensus whether doublet or triplet chemotherapy is better. Hence our study aimed to compare CAPOX (capecitabine and oxaliplatin) with EOX (epirubicin, oxaliplatin plus capecitabine) as first line treatment for AGC. From December 2012 to July 2014, total of 69 patients were randomly assigned; 35 to EOX arm (epirubicin 50 mg/m² on day1, capecitabine 625 mg/m² twice daily for 21 day and oxaliplatin 130 mg/m² on day1 three weekly for 8 cycle) and 34 to CAPOX arm (capecitabine 1000 mg/m² twice daily for 14 days and oxaliplatin 130 mg/m² on day 1 in a three weekly cycle for 8 cycle). Median age at diagnosis was 55 years. The median number of chemotherapy cycle delivered was 7.45% completed planned treatment. 63.8% patient needed dose modification and 33.3% had treatment discontinuation due to grade 3/4 toxicity. Incidence of grade 3/4 neutropenia was significantly more in EOX where as diarrhoea and vomiting were more in CAPOX group. The ORR (overall response rate) was 63% in the entire cohort and 54.5% and 71.4% in the CAPOX and EOX group respectively. Median follow up was 15.2 month. Median OS (overall survival) was 8.1 and 10.3 months in the CAPOX and EOX groups respectively; p=0.298, however there was a trend favouring PFS (progression free survival) in the EOX group (5.5 vs. 8.3 months in CAPOX and EOX respectively; p=0.06). No significant difference was observed between the two regimens with respect to ORR, PFS and OS. Doublet chemotherapy regimen (CAPOX) has similar efficacy as a triplet regimen (EOX), however, with higher incidence of gastrointestinal toxicity.

AGC:Advanced Gastroesophageal Cancer; ALT: Alanine Transaminase; ALP: Alkaline Phosphatise; AST: Aspartate Transaminase; CAPOX: Capecitabine and Oxaliplatin; CR: Complete Response; EOX: Epirubicin, Oxaliplatin Plus Capecitabine; ECOG: Eastern Co-Operative Group; GEJ: Gastro Esophageal Junction; HR: Hazard Ratio; NCI-CTCAE: National Cancer Institute - Common Terminology Criteria for Adverse Events; ORR: Overall Response Rate; OS: Overall Survival; PD: Progressive Disease; PFS: Progression Free Survival; PR: Partial Response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: Stable Disease; TTP: Time To Progression; ULN: Upper Limit of Normal.

Gastriccancer is the fifth most common cancer and third most common cause of death worldwide. Despite recent advances in the diagnosis and treatment of gastric cancer, many patients present with advanced disease and have poor survival. According to data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program, the five-year survival for patients with gastric cancer improved only modestly over the last 50 years, from 12 percent in the years 1950 to 1954, 22 percent during the period 1996 to 2003. The median survival for advanced gastric cancer is about four months without treatment, and this extends up to one year with current treatment modalities. Chemotherapy is the mainstay of treatment for advanced gastroesophageal cancer (AGC). Initial trials used single agent drugs versus best supportive care. Subsequent studies showed that combination chemotherapy result in superior outcomes compared to monotherapy. Triple drug regimen is better than double in the form of increased overall response rate (ORR) and time to progression (TTP) but is associated with increased myelosuppression and infectious complications. The recent REAL-2 trial has proven that capecitabine is equivalent to 5-FU and oxaliplatin is equivalent to cisplatin with comparable or even more response rate and survival. Combination therapies using cisplatin and fluoropyrimidines with or without epirubicin or docetaxel have been widely used as first-line treatments for AGC. There is no strong data whether doublet or triplet chemotherapy is better, though ORR and TTP favors triplet regimen, there is increased toxicity. We conducted a pilot study at our centre of capecitabine and oxaliplatin (CAPOX) in locally advanced and metastatic gastroesophageal cancer (unpublished data) that showed an ORR of 47.3%, and median survival of 8 months, which are at par with current literature. With this encouraging data we planned to conduct a randomized clinical study comparing CAPOX with epirubicin, capecitabine and oxaliplatin (EOX) in AGC.

Investigation of Bismuth Nanoparticles Antimicrobial Activity against High Pathogen Microorganisms

                               http://austinpublishinggroup.com/bioterrorism-biosecurity-biodefense/

Despite of the common efforts in biodefense around the world the problem of high dangerous pathogens distribution, especially under the threat of terrorist attacks, is still urgent. Among the biotoxins that could be used for dispersion, leading experts identify large number of high pathogen microorganisms of category A and B, such as well-known pathogens: Bacillus anthracis, Salmonella, Escherichia etc.

The most important problem in the struggle against biohazard is high effective defense of civil population. Such effective defense can be provided using safe drugs, which are effective against wide range of biotoxins.

Modern antimicrobial preparations and vaccines don’t possess by wide range of activity against different classes of pathogens. So, the search and development of new high effective antimicrobial substances with high effectiveness against wide spectra of high pathogen microorganisms - causative agents of most dangerous human and animals’ diseases is topical problem today. Metal nanoparticles are possessed by high potential in this area. The main goal of presented work was antimicrobial activity investigation of the synthesized bismuth nanoparticles against wide spectra of pathogen microorganisms - potential causative agents of high dangerous human and animals’ diseases.

Spherical Bismuth Nanoparticles (BiNP) have been synthesized by the method of chemical condensation in water medium. The concentration of obtained BiNP was 77.5 mg/ml by metal. The shape Transmission Electron Microscopy (TEM) (JEM-1230 «JEOL LTD», Japan). The method of energy-dispersive X-ray spectroscopy has been used for chemical composition’s X-ray microanalysis of the synthesized nanoparticles (IETEM 250 with detector X-Max 80, Oxford Instruments Analytical, UK for JEM-1230).iNP biosafety level has been estimated in vitro using parameters of cytotoxicity, genotoxicity, mutagenicity and biochemical markers according to the Guidelines «Safety assessment of medical nanopreparations.

Crossroad Intermediates as ‘Folding Pathway’ Control Mechanism of Gene Expression

http://austinpublishinggroup.com/biotechnology-bioengineering/fulltext/ajbtbe-v4-id1075.php

CrossroadIntermediates (CRI) are those folding pathway intermediates that are situated at crossroads between protein folding and aggregation. CRI can either lead to folding of protein into native functional state (if one pathway is followed) or lead to formation of aggregated non-functional state (if another pathway is followed). We propose here for the first time, that formation of CRI may be the last control mechanism of gene expression chosen by Nature (after transcriptional, post- transcriptional, translational control mechanisms) - an event that occurs just before formation of native state in order to maintain concentration of particular protein. Since this step occurs during folding of protein, we name it as ‘Folding Pathway’ Control Mechanism of gene expression. We also propose that switch mechanism, for these CRI following a particular pathway lies in the concentration of that protein. Notion that Protein Folding pathway should also be subjected to control mechanism has long been ignored in the history of biological sciences. Information in this article will help to reshape and strengthen our understanding of Control of Gene Expression.

Gene Expression is set of steps that starting from gene ultimately leads to production of proteins or functional RNA product. (In this communication, we are concerned with protein synthesis; hence in all further description gene expression would mean production of proteins from genes). It is the most important function of cell to maintain its structure and function. Gene Expression starts with Transcription (production of RNA from DNA) and then leads to Translation (production of proteins from RNA). When RNA is synthesized from DNA by process of transcription that occurs in nucleus of cell, it undergoes several modifications known as Post- Transcriptional Modifications and then transported out of nucleus. In cytoplasm, RNA is translated into protein sequence. Protein then undergoes Post-translational modifications (in some cases). Linear chain of amino-acids is then folded into 3-dimensional structure by process of Protein Folding before it becomes functionally active. Transcription, Post-Transcriptional Modifications, Translation, Post-translational modifications- all constitute the elaborate process of Gene Expression.

As much as Gene Expression is important, so is its control, in order to maintain timing and concentration of protein at a particular site in cell. Although same DNA sequence is present in all cells, it is control of gene expression that defines protein content (and subsequently content of other bio molecules) of a particular cell at a particular time and makes the cell specialized and distinct from other cells. Control of gene expression is exercised at each step involved in this process. Transcriptional control forms the first step of control and is usually the most important step. Post-transcriptional control occurs after mRNA is synthesized. Once protein is being synthesized from mRNA, translational control mechanism takes over and tries to maintain concentration of protein being synthesized. The protein can also be subjected to activity control mechanism switching it between active or inactive states.

After being synthesized by translation, native linear chain of polypeptide has to fold in order to achieve its functional state by the process known as Protein Folding. Protein folding is thus described as a process by which a disordered protein chain diffuses across a high-dimensional energy landscape and finally reaches the folded ensemble. It has been inferred that proteins must fold to their unique native state through multiple unpredictable routes and intermediate conformations. The search problem involved in folding however has been simplified through the evolution of folding energy landscapes that are funnelled. Funnel-shaped energy landscape pictures that proteins must fold energetically downhill along with decrease in entropy in order to form native conformation. The free energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Single molecule studies have provided novel insights about how the dynamic sampling of the free energy landscape dictates all aspects of protein behaviour; from its folding to function.

Advancement Towards Microfluidic Approach to Develop Economical Disposable Optical Biosensor for Lead Detection

http://austinpublishinggroup.com/biosensors-bioelectronics/fulltext/ajbb-v2-id1021.php

Aneconomical single use optical biosensor has been developed for lead detection using a microfluidic approach. The present study represents the initiative step for amalgamation of microfluidic and advanced biosensor technologies which offers rapid analysis with lab-on-a-chip policy. Urease producing Bacillus sphaericus was co-immobilized with phenol red (pH indicator) in the glass capillary which acted as a microchannel. For immobilization, a combination of sol-gel approach and calcium alginate method cited first time in literature was used which reduced the time of solidification to seconds as compared to hours with sol-gel alone. Bioassay principle was based on urease inhibition in the presence of lead. Fiber optic spectrophotometer was used as transducer which measured the intensity of color change. Linear relationship (10-1000 μg/L) was observed between logarithmic concentration of lead and absorbance. The study resulted in the development of cheap, miniaturized, sensitive and reliable lead biosensor with requirement of small sample volume (1 mL).

Increasedenvironmental awareness and stringent environmental regulation led to the dire need of the techniques for the fast, easy and economic detection of various pollutants like heavy metals, pesticides and toxic gases. Heavy metals are among the most hazardous pollutants due to their ubiquitous presence in the biosphere, their bioavailability from both natural and anthropogenic sources as well as their high toxicity even at trace level. Lead is among the toxic heavy metals which harm the body when present above the threshold concentration. The higher concentration of lead (>18 μM) in the blood may cause coma and death. It affects different parts of the body particularly brain and central nervous system. Accumulation of lead in the body produces damaging effects associated with hematology, neurology and nephrology which include paralysis, mental retardation and neural deafness. The substitution of calcium in the body with lead causes impairment in the development of bones and teeth. Human exposure to lead occurs primarily through leadbased paints, industrial waste, water from lead-laden pipes, soil and dust generated from gasoline and food items like milk, dairy products and imported candies. The cattle grazing on the metal contaminated fields transmit lead contamination in the milk and dairy products. A threshold lead limit of 10 μg/L was estimated in food and water by the International Agency for Research on Cancer (IARC) while 5 μg/L in drinking water by Environmental Protection Agency (EPA). It is mandatory, therefore, to detect the lead in food samples and drinking water to prevent the deleterious effects of lead. Conventional methods to detect heavy metals like differential pulse polarography, Atomic Absorption Spectrophotometry (AAS), Differential Pulse Cathodic Stripping Voltametry (DPCSV) are superseded by the use of biosensors.

Biosensorsare analytical tools capable of providing either qualitative or quantitative results, consisting of an immobilized biological recognition element such as an enzyme, antibody or cell receptor immobilized to a physicochemical transducer to create a single unit. Now-a-days biosensor technology has emerged as the most promising tool for detection of heavy metals being costeffective, fast, selective, sensitive, portable, easy to use and reliable. A number of lead biosensors have been developed using various transducers like conductometer, electrochemical and optical  based on whole cell, enzymes or DNAzyme.

Diversity-Oriented Synthesis of a Library of Podocarpic Acid Derivatives

                           http://austinpublishinggroup.com/bioorganic-organic-chemistry/

Podocarpic acid 1 (Figure 1) was first isolated from the resin of Podocarpus cupressins, an important timber tree which is endemic to Java, and later from Podocarpus dacrydioides (“Kahikatea”) and Dacrydium cupressinum (“Rimu”), trees which are found in the timber regions of New Zealand. Since 1968, more than forty oxygenated metabolites of podocarpic acid have been isolated from various species of Podocarpus.Interest in these naturally occurring and synthetic lactones, podolactones, and related podocarpic acid derivatives has been mainly due to the novel structures of these compounds and the various types of biological activity possessed by them.

Octahydrophenanthrene lactones 2 (Figure 1) and related podocarpic acid derivatives 3 have been reported to possess hormonal and anti-inflammatory properties. Other similar podolactones have been shown to inhibit the expansion and division of plant cells, to have antileukemic activity, to have antibacterial activity, to have insect toxicity properties, and to exhibit antitumor activity.Other reports have indicated that these types of compounds, as a class, possess significant antifungal properties. The lactone 6 (Figure1), first isolated as a mold metabolite, was found to have significant activity against a number of fungi. The momilactones A 7 and B 8 have been shown to be fungitoxic towards Cladosporium cucumerinum. In a recent report several oxidized resin acid derivatives of dehydroabietic acid 9 (a-c) and 13-hydroxypodocarpic acid 9 (d) were found to be highly fungistatic against Dothistroma pini, a conifer pathogenic fungi. It was observed that mature trees were more resistant to fungal infection and contained a greater quantity of oxidized resin acid derivatives in their resin suggesting greater resistance.

More recently, some podocarpic acid analogs have been reported as cytokine release inhibitors and this has consequently led to the discovery of novel anti-inflammatory drugs. Other compounds, including a podocarpic acid anhydride, have been shown to be liver.X receptor α and β agonists. These two nuclear oxysterol receptors in the liver are involved in cholesterol and lipid metabolism. Thus, any of their agonists could be useful in the development of drugs for the treatment of atherosclerosis.In view of their documented biological properties, it appeared worthwhile to prepare a series of synthetic intermediates derived from podocarpic acid for potential biological activity. This report describes the preparation and characterization of these derivatives.Commercial podocarpic acid is derived from natural sources. Several recent studies have been directed towards the total synthesis of this resin acid to assure adequate future supplies of this material for use in agriculture and medicine.The goal of the present study was to prepare a series of derivatives related to podocarpic acid for use in structure/activity studies designed to reveal functional groups responsible for the molecules fungistatic properties. Four specific modifications were planned.

Enhancing Cancer Radiation Therapy with Cell Penetrating Peptide Modified Gold Nanoparticles

                         http://austinpublishinggroup.com/biomedical-engineering/index.php

Radiotherapyis one of the most prevalent methods for cancer treatment. However, a challenge for cancer radiotherapy is that therapeutic doses used can damage neighboring normal cells. This paper describes a new method to enhance radiation therapy by delivering gold nanoparticles into cancer cells, where gold nanoparticles were modified with virus-derived cell penetrating peptides (CPPs) and Poly (Ethylene Glycol) (PEG). PEG was used to improve nanoparticles blood circulation time, and CPPs were used to enhance internalization of the nanoparticles into cells. The internalization of CPP-PEG modified gold nanoparticles in cancer cells (HeLa cells) was confirmed with differential interference contrast imaging. A variety of assays (such as bright field imaging, MTT, DNA damage, reactive oxygen species and immunofluorescence) were used to detect cellular and genetic damage in cancer cells. We found that CPP-PEG modified gold nanoparticles caused more cellular and DNA damage than gold nanoparticles at the same radiation doses due to enhanced generation of free radicals. In contrast, damage was not severe for normal fibroblasts cells under the same conditions. This method can potentially be used to severely damage DNA and other cellular structures of cancer cells, while minimizing damage to normal cells during radiation therapy.

Currently, chemotherapy, surgery and radiotherapy are the most effective methods to treat cancer. Radiotherapy targets and destroys tumor with ionizing radiation. The laser generates free radicals that damage various cellular components including DNA. One of the advantages of using radiotherapy is that it can kill tumor even though they are intermix with normal healthy tissue. Hence, more than 50% of cancer patients received radiotherapy treatment. However, the therapeutic doses used during radiotherapy can damage nearby normal cells. Various chemicals and nanoparticles were tested to act as radiosensitlzers to enhance radiotherapy.

Despite its essential role in maintaining cell function, cell membranes present a major barrier for intra-cellular delivery of therapeutic nanoparticles. Hence, even though ions or nanoparticles of high atomic number elements (such as gold, platinum and bismuth) have been used to enhance radiation therapy by absorbing ionizing radiation and generating free radicals at high yield, the measured enhancement effect due to nanoparticles has been negligible, likely because inefficient nanoparticles were present in cancer cells and X-ray generated free radicals cannot reach the vicinity of DNA to cause damage 

Nanoparticles can be modified to have desirable surface properties to allow for uptake and targeted delivery into cells and subcellular locations. Non-viral vectors such as amino-modified silica nanoparticles, iron oxide nanoparticles, carbon nanotubes and gold nanoparticles have been used to deliver nucleic acids in transfection assays. In particular, gold (Au) nanoparticles are stable, non-toxic and easy for surface modification, making them a suitable candidate to deliver molecules into cells. However, to reach their full potential in cellular applications such as radiotherapy, robust methods must be developed to allow for the controlled uptake of gold nanoparticles into cells. This requires the gold nanoparticles to be functionalized with engineered coatings to promote their cellular uptake and targeted delivery.

Poly ethylene glycol (PEG) was used to coat nanoparticles to improve their blood circulation. However, PEG interactions with cell surface ligands prevent nanoparticles intra-cellular uptake. One solution to use cell penetrating peptides (CPPs). CPPs are relatively short cationic and/or amphipathic peptides and are efficient cellular delivery vectors due to their intrinsic ability to enter cells and mediate uptake of a wide range of macromolecular cargo. The various molecular cargo delivered by CPPs ranges from nanosize particles to small chemical molecules and large fragments of DNA. The “cargo” is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions [26]. The function of the CPPs is to deliver the cargo into cells, a process that commonly occurs through endocytosis with the cargo delivered to the endosomes of living mammalian cells.

Proposing Asian Principles of Bioethics from Asian Perspectives

                 http://austinpublishinggroup.com/austin-anthropology/index.php

Much discussion and debate have taken place after the publication of Principles of Biomedical Ethics, co-authored by Georgetown University’s bioethicists, Beauchamp and Childress who implied that the four principles they promoted reflect not only the common concerns of the world but also are trans-cultural in nature. In other words, these four principles, based on common morality theory, can be universally valid.

At first glance, one cannot but agree with this argument. But on a closer examination, one will notice that these four principles are more western than eastern, let alone universally functional despite the fact that Asian religious and philosophical thought share similar concerns.

Biomedical ethics have been guided by a few broad principles, at least from the perspective of principle-ism which, though questioned by some has gradually been accepted by most bioethicists. Some biomedical ethicists list seven, veracity, autonomy, beneficence, nonmaleficence, fidelity, confidentiality and justice, but Beauchamp and Childress listed only four and see the other three as derivatives. Beauchamp and Childress have argued that these principles are trans-cultural in nature, yet Asians have different understandings of their implications. Confucianism, one of the dominate thinking’s in Asia will be selected as an example to illustrate the similarities and differences in the interpretation of these principles.

no harm” hence became the healthprofessionals’ obligation. If a physician cannot benefit someone, at least he/she should do no harm to them. Beneficence is the positive dimension of nonmaleficence. This principle claims that physicians have the duty to help others further their interests. It refers to a positive duty of promoting the health and welfare of patients above all other considerations.

These principles of “do good and do no harm” reflect Confucian teachings. “Do good” is the positive aspect of Jen, the foundation of Confucian ethics. “Do to others what you wish for yourself” is called by Confucius as Chung, or conscientiousness to others. “Do no harm” is the negative aspect -- “do not do to other what you do not wish yourself” which is called Shu, the way to practice Jen.

Furthermore, nonmaleficence and beneficence are understood not only as duties but also as inborn natures of man. Mencius, the second sage in Confucianism, believes that all men are endowed with a concern toward others. In his word: “All men have the mind which cannot bear to see the suffering of others”. He further explained: “When I say that all men have the mind which cannot bear to see the suffering of others, my meaning may be illustrated thus: now when men suddenly see a child about to fall into a well, they all have a feeling of alarm and distress, not to gain friendship with the child’s parents, nor to seek the praise of their neighbors and friends, nor because they dislike the reputation of lack of humanity if they did not rescue the child”. From such a case, we see that beneficence and nonmaleficience are expressions of the feeling of commiseration which Mencius asserted as the beginning of humanity. From this, we see that Confucian thought regards beneficence and malificence as more than principles to be promoted. They are part of human nature.