Comparison of Local versus General Anaesthesia for Carpal Tunnel Release

          http://austinpublishinggroup.com/musculoskeletal-disorders/fulltext/ajmd-v4-id1043.php

Carpal tunnel syndrome(CTS) is a common neuropathy, affecting the median nerve as it passes under the transverse carpal ligament. CTS is described as a nerve compression at the wrist plane, CTS causes numbness and tingling in the hand and fingers. Sir James Paget defined CTS first in1853, and since then, in the 1950s a scientist named George Phalen popularized the diagnosis and treatment of CTS. The aetiology of CTS is considered idiopathic in most cases but it is still controversial.

Conservative treatment consists of splinting or corticosteroid injections and surgical release of the carpal tunnel are the treatment method options. There has been continued debate over the optimal management of this disease. Decision of the surgeon has consistently varied.Carpal tunnel release (CTR) is known as an effective treatment for idiopathic CTS. CTR is performed with a variety of techniques such as endoscopic (ECTR) or open (OCTR). Literature has not got consensus on the superiority of any one technique to another.

Local anaesthesia (LA) and general anaesthesia (GA) are anaesthetic options on the surgical treatment of CTS. LA is safe, fast, and effective, but the injection could be painful. In one recent series, about 10% of patients indicated that they would prefer another form of anaesthesia. When applying the local anaesthetics under the skin patient could have pain and pain could make the patient uncomfortable. Also from the surgeon side discomfort of the patient could affect the surgical procedure and sometimes visualization of the surgical area could be difficult due to oedema caused by local anaesthetics. These problems in surgical procedure could affect the clinical results of the surgery. Sedation or GA could make the procedure more comfortable.

The aim of the present study was to compare the effects of the anaesthetic methods on the patient’s clinical results. To our knowledge this is the first report that compares the clinical outcomes of the open CTR with GA or LA.Computerized patient database was searched to identify all patients with CTS who underwent open CTR between January 2009 and January 2013 at Fatih Sultan Mehmet Training and Research Hospital. The year 2013 was selected to ensure a minimum one-year follow-up. At the result of the search total of 148 patients (169 CTS hands) were found. Of the 148 patients (169 CTS hands) 21 patients were operated bilaterally and excluded from study. Of the 127 patient operated monolaterally. One patient died from another reason and 14 patients was not available and excluded from the study. Fifty five patients operated with GA (group A) and 57 patients with LA (group B). The last available 50 monolateral patient operated by the same surgeon for each group included to the study.

Chemical Imaging by NanoSIMS Provides High-Resolution Localization of the G-Quadruplex Interactive Drug (Br)-PhenDC3 on Human Chromosomes

                                            http://austinpublishinggroup.com/molecular-biology/

Determining thedistribution of biologically active compounds within cells is a major issue to understand their mechanism of action and to optimize their properties. Over the past decade DNA secondary structures called G-quadruplexes (G4) have been identified as key modulators of genomic functions. This very active research field has led to the development of G4-targeted molecular probes that are used to track quadruplex forming domains in cells, which is achieved, in most cases, by conventional fluorescence microcopy. However, the intrinsic low resolution of fluorescence microcopy as well as the necessity to tag the drugs with fluorophores represent strong limitations. Here we present the use of secondary ion mass spectroscopy imaging (nanoSIMS) for mapping within metaphase human chromosomes the distribution of a bromo-bisquinolinium phenanthroline derivative (Br- PhenDC3) used as G-quadruplex probe. In addition a statistical approach to increase the accuracy and the spatial resolution of the nanoSIMS imaging was implemented as a plug in for the image analysis software ImageJ. The results demonstrate the presence of Br-PhenDC3both at terminal and interstitial regions of chromosomes and constitute a demonstration of the effectiveness of nanoSIMS imaging as an alternative method for accurate genome-wide mapping of DNA interactive drugs.

Most anticancer chemotherapeutic agents used in the clinic as frontline drugs act as nuclear DNA binders. These agents are considered to bind more or less randomly on the polymeric structure of DNA, or at least in a non-controllable manner thereby hitting both crucial target regions and off-target regions. This uncontrollable distribution is assumed to be responsible for the high cytotoxicity and the potential mutagenicity frequently associated with DNA interactive drugs, two features often used as decisive arguments to decrease research and development studies on this class of compounds. Therefore, determining whether DNA drugs localize uniformly or show preference for certain genomic regions has become a crucial issue for the development of optimized DNA binding anticancer agents in the future. Surprisingly this topic remains largely unexplored so far, essentially due to the lack of genome-wide analytical methods. However this has been recently challenged by the emergence of Chemical-Sequencing (Chem-Seq) methodologies which propose to map the genomic distribution of drugs by identifying drug-induced DNA damages or repair protein recruitment using chemical capture and sequencing. Nevertheless, although powerful and highly promising, Chem-Seq approaches are still technically challenging, highly expensive in the case of whole-genome studies and require extreme caution in data analysis with stringent bioinformatics procedures [5,6]. In addition, they provide indirect read out and not direct visualization of drug DNA binding targets. Consequently, there is a strong need for new complementary imaging methods for identifying the distribution of DNA interactive drugs at the genomic level.

Although drugs can be labelled with fluorescent tags (or be intrinsically fluorescent) routine fluorescence microscopy provides resolution limited by light diffraction thereby enabling only the detection of spots (foci) corresponding to the presence of at least 20-40 fluorophores or more. This works fine for immunostaining strategies, in which the fluorescent signal is amplified by heavily labelled antibodies, but it is not applicable to the detection of small molecules unless these are confined in sub compartments (e.g. nucleus, mitochondria, lysosomes),which increases the density of fluorescent markers. Moreover, the labelling of drugs represents an issue as most fluorophores impact target recognition and may modify drug intracellular localization and penetration. Although super resolution microscopies hold great potential for chromosome and cellular imaging with high spatial resolution, they are far from being routine imaging techniques and they are highly dependent on the specific photophysics of the dyes.

Darwinian Factors in the Clinical Expression of Multiple Sclerosis

                      http://austinpublishinggroup.com/multiple-sclerosis/currentissue.php

Manypredisposing factors for multiple sclerosis (MS), such as HLA types and geomagnetic fields have been described but the search for a single essential factor has been like searching for the rainbow’s end. The most notable feature in the epidemiology of MS in the Western world has been its rise from unknown to the most prevalent disabling neurodegenerative disease of young adults. We suggest that this may be largely or entirely attributable to societal changes that have increasingly isolated populations from micro-organisms that form part of the human microbiome and which are essential for an effective maturation of immune defence mechanisms. This Darwinian explanation suggests a rational approach to both prevention and treatment of MS, by substituting for the loss or absence of factors that millions of years of evolution have led the immune system to ‘expect’ to encounter early in life.

BCG: Bacille Calmette-Guérin; CDMS: Clinically Definite Multiple Sclerosis; CIS: Clinically Isolated Syndrome; EBV: Epstein- Barr virus; HERV: Human Endogenous Retrovirus; HLA: Human Leucocyte Antigen; IL: Interleukin; INF-α: Interferon Alpha; MAIT: Mucosal-associated Invariant T Cells; MAMP: Microbe-associated Molecular Pattern; MHC: Major Histocompatibility Complex; MRI: Magnetic Resonance Imaging; MS: Multiple Sclerosis; TCR: T Cell Antigen Receptor; TNF-α: Tumour Necrosis Factor Alpha; Treg: Regulatory T Cell; PRR: Pattern Recognition Receptor; TLR: Toll-like Receptor; RA: Retinoic Acid.

Current treatment strategies for multiple sclerosis (MS) are essentially empirical because no single clear underlying cause of the disease has been determined. Numerous genomic and environmental risk factors for MS have been described, but problems of cause and effect remain unresolved. It has indeed been stated, with considerable justification, that MS research is “low on fact, high on fiction” .

Although there is a well-described genetically determined predisposition to MS, the association is far from complete as, for example, the risk of an identical twin sibling of an affected person developing MS is only 30%. Thus any genes involved are likely to be of low penetration and influenced by the expression of some or many other genes. Notwithstanding, a large number of genetic loci, including many coding for HLA, have been determined and fine-mapped. These studies have demonstrated a central role for the immune system in the aetiopathogenesis of MS but the highly complex nature of the data will require novel tools for their analysis before any unifying factor can be delineated.

Intersection of Apoptosis and Autophagy Cell Death Pathways

                    http://austinpublishinggroup.com/molecular-cellular-biology/currentissue.php

Thebalance between cell survival and death is a critical parameter in the regulation of cell and tissue homeostasis. Autophagy is an evolutionarily conserved mechanism for the gross disposal and recycling of intracellular proteins in mammalian cells. Autophagy also kills cells under certain conditions, in a process called autophagic cell death; this involves pathways and mediators different from those of apoptosis. Therefore, three different mechanisms of cell death have been identified in mammalian cells; namely, apoptosis (type I), autophagic cell death (type II), and necrosis (type III). Whether and how these different processes of cell death interconnected each other has not been fully clarified. In this review we discuss the evidence supporting a mechanistic link especially focusing between apoptosis and autophagy associated cell death—including the possibility of cross–talk between the relevant signaling pathways—that could serve to maintain cellular homeostasis in mammals.

In recent decades, insight into the molecular regulation of autophagy in mammalian cells has come from the discovery and functional analysis of Autophagy-Related Gene (ATG). Autophagy is an evolutionally conserved homeostatic process for intracellular degradation by which intracellular proteins are sequestered in a double–membrane–bound autophagosome and delivered to the lysosome during stress conditions; this process facilitates both degradation and recycling of intracellular proteins in mammalian cells. The molecular machinery of autophagy co-ordinates diverse aspects of cellular and organismal responses to other dangerous stimuli such as infection. Defective autophagy underlies a wide variety of human disease and physiology including cancer, neurodegeneration, and infectious diseases. Mammalian orthologues of ATG family proteins have been identified and various functions of ATG proteins have been elucidated, including how these proteins control the formation of autophagosomes. Although autophagy was originally characterized as a cytoprotective process in yeast under starvation conditions, it is now thought to be a form of cell death along with the two classical mechanisms of apoptosis and necrosis in mammalian cells.

Three possible mechanisms for cell death have been known to exist in mammalian cells, namely apoptosis (type I cell death), autophagic cell death (type II cell death), and necrosis (type III cell death). Apoptotic cell death (type I cell death) is characterized by rounding up of the cell and reduction of cell volume, chromatin condensation, nuclear fragmentation, no modification of cytoplasmic organelle, and plasma membrane blebbing without involvement of gene activity. Since autophagy is thought to be a pro-survival pathway, whether or not autophagy indeed induce cell death is still under debate. However, under certain circumstances, autophagy can induce cell death (type II cell death) which is characterized by presence of massive autophagic vacuole in the cytoplasm. Necrosis (type III cell death) is most classical form of cell death with characteristic morphological feature of a gain of cell volume, swelling of organelles with plasma membrane rupture without blebbing.

Compliance with Biosafety and Biosecurity Protocols in Academic and Healthcare Institutions

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

Lack of compliance with biosafety and biosecurity protocols in academic and healthcare institutions is the top ranking health security concern today. A little breach of protocol while working with deadly pathogens put the whole system at risk. Biosafety is personal safety and protection from dangerous biological agents, while biosecurity is restricting unauthorized access to harmful biological agents. In other words, biosafety is to protect ourselves from germs while biosecurity is to protect germs from people. In either case, protective and monitoring measures are extremely crucial in the working environment where pathogens are found.

It has been observed as a common practice in the healthcare institutions that healthcare workers in the hospitals do not comply with SOPs while managing patients. Proper and necessary infection control precautions are not followed in touching patients, changing gloves between patients, touching the beds, bed sheets, and bedside equipment in hospitals. The healthcare workers do not really care about it. This practice could partly be because of lack of basic necessary knowledge, underestimating or not realizing the possible threats, or lack of necessary hospital resources with the staff. In either ways, the consequences are extremely threatening and the germs dissemination poses a consistent threat to humanity. Same malpractice is seen in the laboratories in the academic institutions. Students experimenting with deadly pathogens do not strictly comply with the safety protocols. Even the donning and doffing of gloves and coats are not properly followed. This practice not only risks their own lives but they also help spread the pathogens in the environment thereby risking the very lives of the entire community. Infectious diseases are considered the greatest health security threat today, and are been widely predicted as the leading cause of deaths in the near future. Thus there is an urgent need of the day to make policies that not only define the Principles, Practice and Protocols (PPP) for biosafety and biosecurity but such protocols should be legally binding too.

One of the obvious issues in working with pathogens or lack of compliance to any SOPs, in general, is that the policies that define such practices are not legally binding. There should be strict legislations in this regard. And to implement and ensure sustainability of the policies, every institution must establish an Institutional Biosafety and Biosecurity Monitoring Department (IBMD). Few of the developed countries have ensured that all institutions working with hazardous or potentially hazardous substances to the public health and environment must have institutional review boards to check the working environment in the laboratory for compliance with safety protocols so that environmental health and safety is guaranteed. However, majority of the developing countries do not have any such infrastructure and that is very devastating because infectious agents respect no boundaries. A biothreat in a small unit in an isolated place in a healthcare or academic institution is a threat to the whole community, and to the entire population at large.

Modern Workforce in Academic Radiation Oncology: Challenges and Opportunities

                                  http://austinpublishinggroup.com/medical-oncology/

Cancer care for themodern patient has become increasingly complex with the competing need to deliver care in closer approximation to the home of the patient. This raises challenges for the modern department of radiation oncology in balancing geographically determined cancer care with academic growth. Career development had uniformly been symbiotic with practice locations at central academic medical centers. The modern workforce needs to adapt and achieve academic growth in centers aligned with health care networks. This manuscript addresses many of the challenges posed by this dichotomy and offers potential problem-solving strategies and solutions to ensure academic success.

The practice of radiation oncology has undergone significant change over the past thirty years. Today, over 60% of cancer patients receive curative/palliative radiation therapy as a component of their disease management. More than 75% of these patients receive radiation therapy with intent to cure, an increase from 50%, thirty years ago. This has significantly changed the modern practice of radiation oncology. Clinical decision strategies are now inherently more complex with influence from patient-specific medical comorbidities, tumor-related information, and image-based information of normal tissue function. These factors define the extent of normal tissue sparing and need for complex volumetric treatment planning. This has promoted, in part, subspecialty practice with multidisciplinary partners including radiation oncology. The time and effort associated with team-patient management should be acknowledged as part of team-oriented metrics for measuring clinical productivity and professional academic growth of each faculty member. 

The technology of radiation therapy has become exceptionally complex and patient expectations for both outstanding clinical service and clinical outcome have never been higher as measured by patient satisfaction surveys. Modern oncology patient care has become a concierge clinical practice. Because we interact with patients and almost all medical/surgical service subspecialties on a near daily basis, often radiation oncologists are called upon to bridge gaps in service between multiple health care providers, patients, and families. Radiation therapy treatment planning is volumetric and image driven with treatment execution uniquely image guided, making radiation oncology dependent on many imaging tools. As radiation oncology technology has evolved, the skill set of the modern radiation oncologist has had to adapt at multiple levels including acquiring personal real-time expertise in specific work-related information previously reserved for colleagues in other medical, surgical, and radiology practices. Radiation oncologists now often bridge information between surgical and medical colleagues to reconcile issues in daily patient care. To be an effective member of the oncology multidisciplinary team, the radiation oncologist must be fluent in the strengths and limitations of surgical and medical team members as well as understand how advanced technology imaging tools and other evolving biomarkers will affect modern practice. Although radiation oncology functions as a department, individual faculty are now woven into a matrix of patient-centered multidisciplinary partners. An important aspect of modern practice is to learn how to function in a team-oriented patient care approach when team members may not fully appreciate the strengths and training limitations of the radiation oncologist. As a result, radiation oncology department leaders need to understand the challenges imbedded within the workforce and apply guidelines for department function to 1) ensure patient care needs are met 2) the intradepartmental workforce and workflow needs are met and 3) productivity expectations are balanced with individual faculty academic growth and career development.

Comparative Nano-indentation Creep Study of Ductile Metal, Ductile Polymer and Polymer-fly Ash Composite

                               http://austinpublishinggroup.com/material-science-engineering/

Anew study is conducted under same experimental creep conditions to investigate and compare the response of dissimilar materials (metals, polymers and composites) in relation to properties such as hardness and (unloading) ‘reduced modulus’ on changing the nano-indentation test parameters. The research uses nano-indentation technique to determine the resistance to plastic deformation in these broadly different materials as a function of maximum load, holding time and loading rate. Wear rate and cutting efficiency of these materials are examined and it is found that only maximum load alters these properties in the three materials. Hardness and ‘reduced modulus’ are found to be directly affected by increase or decrease in maximum load, holding time and loading rate.

H: Hardness;E_r: Effective Modulus; h: Indentation Depth; h_max: Maximum Indentation Depth at Maximum Load; h_c: Indentation Depth in contact with Indenter; hp: Height of Sink-in/pile-up; h_e: Elastic Recovery Height after Unloading; h_c/h_max: Degree of Sink-in/ pile-up; H/E_r ²: Rate of wear or Resistance to Plastic Deformation; A: Area of Indentation; S: Stiffness; β: Correction Factor for Indentation Shape; n value: Work Hardening Coefficient Value.

A concept of determining the mechanical properties of material on nano scale has given rise to the development of a powerful depth sensing nano-indentation technique which is capable of studying the various material properties such as unloading ‘reduced’ modulus, hardness, creep properties, and fracture toughness. Nano-indentation test procedure involves application of predetermined load in the range of μN to mN with the help of either spherical or pyramidal indenter in order to produce the indentation of the order of a few microns (measured in terms of nano-meters), followed by controlled unloading. The contact area of indentation is used to calculate hardness (H) of the material and the slope of unloading curve on load-displacement can be used for determining the ‘effective’ modulus or ‘reduced’ modulus (E_r). Later modification in the method was achieved by holding at maximum load constant for some time before unloading (creep). This modification was done in order to study the visco-elastic and visco-plastic behavior of the materials where conventional nano-indentation method was based on the assumption that material behave in an elastic-plastic manner.

LECT2 – A New Cause of Hepatic Amyloidosis

                                   http://austinpublishinggroup.com/liver/online-first.php

Amyloidosis is caused by an abnormal deposition and accumulation of insoluble protein fibrils in multiple organs, often leading to diverse clinical presentations, and possible organ failure. On Congo-Red staining, amyloid fibrils form characteristic betapleated sheets that typically show apple, green birefringence upon polarization under light microscopy. The kidney is the most common organ affected in systemic amyloidosis. The liver is involved less frequently than the kidney. In this editorial we present a recently discovered amyloid protein - LECT2 (leukocyte chemotactic factor 2) that has been documented to affect the kidney and the liver. Of more than 30 types of amyloid protein fibrils discovered thus far, LECT2 is one of the most recently described. It was initially reported to present with slowly progressive renal failure and nephrotic syndrome.

In the United States, LECT2 protein has been found to be especially prevalent among people of Hispanic ethnicity. In an autopsy series, LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanics, and could represent an important but under-recognized etiology of chronic kidney disease in this population. Two large case series focusing on renal amyloidosis identified LECT2 as the second and third most common form of renal amyloidosis respectively. LECT2 fibrils are found in the glomeruli, renal vessels, and interstitium. Other organs including the liver, spleen, adrenals, and lungs but not myocardium or brain have been reported to be involved with LECT-2 amyloid protein.

A recent large case series identified LECT2 as the second most common form of hepatic amyloidosis. In this series LECT2 accounted for up to 25% of hepatic amyloid cases. LECT2 is synthesized mainly by the liver and is considered to be a hepatokine. The exact biological function of LECT2 is not precisely known. In the liver, it acts as is an eutrophilic chemotactic factor. It also plays a role in hepatocyte regeneration. Increased expression of LECT2 has been found in hepato cellular tumors. The LECT2 gene has been mapped to chromosome 5q31.1-q32 by fluorescence in situ hybridization. This region contains a cluster of cytokine genes that include IL-4, IL-5, and IL-9. Recently it was discovered that LECT2 may play an important role in insulin resistance and may promote atherosclerosis. As such, it is also suggested to play a role in the development of fatty liver and obesity.

Hepatic amyloid, when identified, is usually located in the sinusoids, portal tracts, and arterioles. Various morphological patterns of amyloid including linear, globular and mixed types have been identified. The Globular Hepatic Amyloid (GHA) sub-type is composed of round to oval globules, 5 to 40 micrometer in diameter that are found within the space of Disse as well as aggregated within the portal tracts. Chandran et al. found that GHA, although uncommon, is highly sensitive and specific for LECT2 amyloidosis and was also found more often in Hispanics. LECT2 has been described in a patient with non-cirrhotic portal HTN. It is possible that deposition of GHA in the vascular spaces of the liver can cause obstruction of the blood flow at the sinusoidal level resulting in non-cirrhotic portal hypertension.

A New History: The 2016 Revision of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissuess

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

Classification is thelanguage of medicine: diseases must be described, defined and named before they can be diagnosed, treated and studied. However, a critical feature of any classification of diseases is that it be periodically reviewed and updated to incorporate new information. For many years the diagnosis of leukemia was based solely on pathologic and cytological examination of bone marrow and peripheral blood smears; however, this classification does not always reflect the genetic and clinical diversity of the disease. In this way, the World Health Organization (WHO) proposed a classification to recognize and classify different subgroups of leukemia through clinical, morphological and genetic correlation.

The “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues” is one of the “blue book” monographs published by the International Agency for Research on Cancer (IARC; Lyon, France), created in collaboration with the Society for Hematopathology and the European Association for Haematopathology. Eight years have elapsed since the current fourth edition of the monograph was published in 2008, and remarkable progress has been made in the field in this time period. Despite this, a truly new fifth edition cannot be published for the time being, as there are still other volumes pending in the fourth edition of the WHO tumor monograph series. Therefore, the Editors of the “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues,” with the support of the IARC and the WHO, decided to publish an updated revision of the fourth edition that would incorporate new data from the past 8 years which have important diagnostic, prognostic, and therapeutic implications.

The major changes in the classification and their rationale are presented by Swerdlow S. et al. and Arber D. et al. for lymphoid and myeloid neoplasm respectively, however it’s important to note that although some provisional entities have been promoted to definite entities and a few provisional entities have been added to the revised WHO classification, no new definite entities were permitted according to IARC guidelines. The current revision is a much needed and significant update of the 2008 WHO classificationto incorporate clinical features, morphology, immunophenotyping, cytogenetics, and molecular genetics to provide better diagnostic categories and criteria, together with biological and clinical correlates, and facilitate state-of-theart patient care, future therapeutic advances, and basic research in this field. The WHO effort to keep up-dating the classification will continue on, and hopefully provide a model of cooperation between clinicians, pathologists, scientists and hematologists from all over the world. In the field of leukemia, many questions remain unanswered, however, this update is the first step toward a closer integration of genetic data into a clinicopathological classification. Based in this, the journal “Austin Leukemia” aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Leukemia that could be the basis for future classifications.

Lung Cancer Activity of Caralluma Species, an Overview

                        http://austinpublishinggroup.com/lung-cancer-research/currentissue.php

Genus Caralluma a perineal herb of Asclepiadaceae family, it is used as traditional medicine for the treatment number of diseases like diabetes, inflammation, leprosy, obesity, rheumatism, diseases of the blood helminthic diseases, stomach disorders, abdominal pains, septics, chronic lung diseases, such as tuberculosis and cancer. We focus critical evaluation of genus Caralluma use in the lung cancer treatment in this review.

Uncontrolled cell division that spreads throughout the body is cancer; it’s a group of diseases which can lead to death if not controlled. External factors (tobacco, infectious organisms, and unhealthy diet) and internal factors (inherited genetic mutations, hormones, and immune conditions) are the main causes of cancer. These i.e. external and internal may act composed or in order resulting cancer, it may pass a decade from exposure to detection of cancer. Among all types of cancers lung and breast cancers are most diagnosed and leading cause of deaths in men and women. WHO report states that the common causes of cancer deaths are cancers of lung (1.59 million deaths), liver (745 000 deaths), stomach (723 000 deaths), colorectal (694 000 deaths), breast (521 000 deaths), oesophageal cancer (400 000 deaths). Mainly cancer arises from the interaction of person’s genetic factors and three types of external factors like physical carcinogens (Ultraviolet and Ionizing radiation), chemical carcinogens (Tobacco, asbestos, smoke, aflatoxin, and arsenic) and biological carcinogens (virus, bacteria and parasites). 

The incidence of cancer is more in developed nations than less developed nations but mortality is more (65%) in less developed nations. Prostate cancer in men and lung cancer in women is leading death cause of cancer in more developed Nations, the burden of cancer is slowly shifting to less developed Nations due to the aging of the population and increasing pervasiveness. The genus Caralluma of Asclepiadaceae comprises of approximately 350 species all around the globe. Genus Caralluma normally prefers a dry habitat and decay when they are exposed to an excess of water. The support may be necessary, as they do not contain fibrous tissue. Some of the plants grow even up to a height of 100 cm under protection. Review of literature revealed medicinal uses of genus Caralluma. The distribution of Carallumas ranges from the Mediterranean to East Indies, mostly found in Southern Europe, Iran, Iraq, African countries like Kenya, Somalia, Sudan and Ethiopia, Arabian countries like Oman, UAE and Yemen and Asian countries like Afghanistan, Pakistan, India, Nepal, Burma and Sri Lanka.

From Bench to Bedside: The Growing Use of Arabinoxylan Rice Bran (MGN-3/Biobran) in Cancer Immunotherapy

                     http://austinpublishinggroup.com/austin-immunology/currentissue.php

MGN-3/Biobran is a denatured hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. Over the last 24 years, our fundamental research objective has been to study the biotherapeutic activity of MGN-3 as a treatment for cancer based on its ability to activate the immune system. This objective has been pursued in vitro, and in animal and human studies. This review is focused on the immunomodulatory effects of MGN-3 and on its potential as an anticancer agent. In vitro studies showed that culturing different human and murine cancer cell lines with MGN-3 resulted in a reduction of the survival rate of cancer cells. In vivo studies have also shown that MGN-3 induces tumor regression in several models of animal bearing tumor, including gastric cancer, neuroblastoma, and Ehrlich carcinoma. In addition, the anti-cancer activity of MGN-3 has been shown in human clinical trials and in several case reports on patients with Hepatocellular Carcinoma (HCC) and progressive and partially metastasized cancer. Patients that were treated with MGN-3 in addition to Conventional Therapy (CT), as compared with CT alone, showed: 1) less recurrence of cancer, 2) higher survival rate and 3) improved Quality of Life (QOL) as characterized by improvements in physical activity, appetite, sleep, and digestion, and a decrease in pain and anxiety.

This review summarizes the preclinical and clinical research on MGN-3/ Biobran since it was first patented in 1992. Various animal studies and human clinical trials including different types of malignancies have demonstrated that MGN-3 is a potent Biological Response Modifier (BRM). MGN-3 enhances the cytotoxic reactivity of immune cells with anti-cancer activity such as NK and CD8+ T cells via increasing cell granularity, stimulates the production of interferons, IL-2 and IL-12, and functions as a natural adjuvant for Dendritic Cells (DC). Therefore, MGN-3 may be used in DC-based vaccine strategies against infections and cancer. Importantly, MGN-3 is a unique BRM because it is a safe non-toxic agent and does not exhibit hyporesponsiveness. MGN- 3 has the potential to be a novel and promising immune modulatory adjuvant that could complement the existing immunotherapeutic modalities for cancer patients.

Despite the last decade of advances in treatment options, cancer remains the second leading cause of death in the United States. Unfortunately the outcome of standard cancer treatments is often poor due to the emergence of Multidrug Resistance (MDR) during the course of treatment. MDR cells are a significant factor in the failure of chemotherapeutics as evidenced by high relapse rates for the majority of patients. Therefore, to increase cancer survival and improve symptom control, there is a strong need for new and better approaches to cancer treatment. Today, the National Cancer Institute (NCI) has acknowledged the importance of immune therapy for the treatment of cancer. NCI, other health organizations, and professionals in the field of oncology are currently working to harness the immune system to fight cancer and to expand immunotherapy in combination with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy.

Two Cases of Peritonitis due to Pantoea Species at One Center with Different Outcomes

                  http://austinpublishinggroup.com/austin-internal-medicine/currentissue.php

Peritonitisis a serious complication of peritoneal dialysis. A variety of microorganisms are identified in these cases and during recent years a new one was included, Pantoea species. In our report, we present 2 cases of patients on CCPD with a peritonitis episode caused by this organism. The source of infection in one of the cases was thought to be due to gardening of the plant Basil, while unknown in the other case. In microbiologic culture, this organism was identified and the patients were started on antibiotics with success in one case while the other requiring catheter removal. The number of reported cases with this organism has increased in last years and various infection localizations and clinical progress patterns have been identified. In peritoneal dialysis patients presenting with peritonitis, this organism must be kept in mind.

For patients on peritoneal diaysis, peritonitis is an important cause of mortality and morbidity. The treating physician needs to keep a high index of suspicion and treat peritonitis early to improve outcome and reduce complications. While usual gram positive and gram negative organisms make most of the cases, recently one unusual environmental gram negative family appeared to be the cause. The organism Pantoea, belongs to the family Enterobacteriaceae and is responsible for infectious diseases mainly from plant-thorn injuries, causing arthritis, osteoitis, osteomyelitis to bacteremia. Until now a number of clinical cases of peritonitis caused by this organism have been described. We present two cases (Case A and B) of peritonitis with Pantoea species at our center, both of which had different course and outcomes requiring different treatments.

Upon evaluation, there was diffuse abdominal tenderness but there were no signs of exit site or tunnel infection. The PD fluid was found to be cloudy and analysis showed White cell count of 1000 with 92% neutrophils. Other investigations revealed serum WBC count 7.6k/ul, ESR 30mm/hr, CRP 0.4mg/dl, Lactic acid 3.1mmol/L. Patient was started on empirical treatment including Intraperitoneal Ceftriaxone and Vancomycin. The Blood cultures were negative; however the PD fluid culture grew Pantoea species sensitive to Cephalosporins, Gentamycin and Tazobactam. The patient showed significant improvement and disappearance of symptoms on the third day. The PD fluid WBC dropped to 22k/ul with normalization of ESR and lactic acid levels and the fluid culture became negative after 5 days of treatment. Patient was discharged home and he completed 14 days of antibiotic therapy. Over the next one year, patient did not have any further episodes of peritonitis, and the repeated PET test did not show any changes on the membrane characteristics.

Response of Potato to Water Stress in Southern Serbia

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

Aninvestigation was carried out on alluvium soil type in the river valley of Southern Morava, Southern Serbia during the seasons of 2008 and 2009, aiming to determine the response of potato to soil water deficit, using yield response factor. The values of yield response factor were derived from the linear relationship between relative seasonal evapotranspiration deficits and relative yield loss. Values of seasonal crop response factor of 1.14 indicate that potato is moderately sensitive to soil water stress in the climatic conditions of the Southern Serbia. Seasonal evapotranspiration was 495.0 mm and 291.2 mm in irrigated and rain-fed conditions respectively. A linear relationship was found between seasonal evapotranspiration and tuber yield. Potato yield in the variant with irrigation was 48.31 t ha-1 or 88.3% higher than in the variant without irrigation.

Production of potato (Solanum tuberosum L.) takes a very important place in world agriculture, with a production potential of about 368 million t harvested and 19.3 million ha planted area with an average yield of 19.1 t ha-1. Potato production ranks fourth in the world after rice, wheat and maize. In Serbia potato is grown at about 77,000 ha with an average yield of 10.2 t ha-1, and total production of 786,000 tones. In southern Serbia potato crop land is 55,000 ha with an average yield of 9.2 t ha-1, and total production of 55,000 tones. The yield of potato in Serbia is fourth times lower than this achieved in the leading potato growing countries. The low yields are the consequence of inadequate management practices, insufficient amount and unfavorable arrangement of precipitation in the growing season and inappropriate irrigation scheduling applied. In Serbia potato is cultivated under both irrigated and non-irrigated conditions. Portable sprinkler irrigation systems are commonly used. Due to the unpredicted amount and distribution of precipitation in the growing season, irrigation in Serbia is mainly supplemental. It is used primarily to supplement infrequent or irregular precipitation during drought periods.

Several authors and research groups reported results of experiments aimed at determining optimum soil moisture under different environmental and technical conditions. Bošnjak and Pejić, Milić et al., Pejić et al. found that the lower limit of optimum soil moisture for potatoes is 70% of field water capacity when this crop is grown in a soil with medium texture. Wright and Stark, King and Stark, Costa et al.  indicated that maximum yield of high quality potato tubers could only be achieved if the soil’s available water in the maximum active root zone would not drop below the 50% limit.

Which Criteria to use for the Diagnosis of Behcet’s Disease: International Study Group (ISG) Criteria or International Criteria for Behcet’s Disease (ICBD)?

                                 http://austinpublishinggroup.com/immune-research/currentissue.php

It is interesting to note that Behcet’s Disease (BD) is one of those diseases which had an early diagnostic criteria (9 years after its official recognition, with the Curth criteria in 1946), having one of the largest number of classification/diagnosis criteria (17 sets, in 70 years, till 2016), among them only 2 real International Criteria (ISG and ICBD), and having one of the largest international participation (27 countries for ICBD). The ISG criteria were created by the collaboration of 7 countries (France, Iran, Japan, Tunisia, Turkey, UK, and USA) in 1990. The ICBD was first presented in 2006 to the International Conference on Behcet’s Disease in Portugal and the revised version in 2010 to the International Conference on Behcet’s Disease in London, and published in 2014.

The sensitivity of ISG criteria was very good, at 92%, when checked on the patients gathered from the 7 countries. The specificity was excellent at 97%. Originally, the accuracy was not checked and instead the relative value, which was 189 (the sum of sensitivity and specificity). When the performance of the criteria was checked, for validation, in different countries, the sensitivity was low, while the specificity was high. The problem came from two main biases. First, as the majority of BD patients gathered from the seven countries had oral aphthosis (OA), this manifestation was put as a mandatory symptom to be present for diagnosis, while all over the world, when patients are diagnosed by expert opinion, around 5% of patients diagnosed as having BD miss OA. Second, the patients’ selection: overall 886 BD patients and 97 control patients were selected from the seven collaborating countries, with 366 (41.3%) from Iran, 285 (32.2%) from Turkey, and 141 (16.9%) from Japan, which made 90.4% from 3 countries and less than 10% of the remaining 4 countries. From Western countries, only 5% had BD. To be classified as having BD, a patient must have oral aphthosis (mandatory), and two of he following manifestations: genital aphthosis, skin manifestations (pseudo-folliculitis, erythema nodosum), ophthalmologic manifestations (anterior uveitis, posterior uveitis, retinal vasculitis), positive pathergy test.

For ICBD, patients were gathered from 27 countries, all over the world. This time, it was paid enough attention to not make the same error in the patient selection, and to have enough patients from the Western world. A total of 2556 BD and 1163 controls were gathered, with 35.1% from 9 countries of the Western world. The revised ICBD performance in the cohort of the international patients was: sensitivity 96%, specificity 91.2%, and accuracy 94.5%. ICBD was validated in Germany, China, Iran, and Italy. The revised ICBD was validated in Iran with sensitivity 96.8% (ISG 78.1%), specificity 97.2% (ISG 98.8%), and accuracy 97% (ISG 85.5%). To be classified as having BD, a patient must get 4 points from the ICBD. Oral aphthosis, genital aphthosis, and ophthalmologic manifestations (anterior uveitis, posterior uveitis, retinal vasculitis) get each 2 points. Skin manifestations (paseudo-folliculitis, erythema nodosum, skin aphthosis), vascular manifestations, neurological manifestations, and positive pathergy test get each one point.

Vitrified-Warmed Blastocyst Score Effects Pregnancy Outcomes: Towards a Single Blastocyst Vitrification and Transfer

                             http://austinpublishinggroup.com/invitro-fertilization/currentissue.php

No a referable quality selection criteria for a single vitrified-warmed blastocyst transfer. Therefore, the present study aimed to investigate the relationship between vitrified-warmed blastocyst score and clinical pregnancy outcomes. This retrospective analysis consisted of 221 patients undergoing two blastocysts transfer on thawing day. Implantation rate, fetal heart pregnancy rate, live-birth rate, multiple birth rate were analyzed.

When a patient received two high-quality vitrified-warmed blastocysts (=3BB), implantation rate and fetal heart pregnancy rate were 48.2% and 65.5%, respectively. The multiple birth rates in this group were 44.4%. When two vitrified-warmed blastocysts (one =3BB and another <3BB) were available for transfer, implantation rate and fetal heart pregnancy rate were 34.5% and 52.7%. The multiple birth rate for this group was 29.6%. When only two generalquality vitrified-warmed blastocysts (<3BB) were transferred, implantation rate and fetal heart pregnancy rate were 21.7% and 35.9%, and the multiple birth rate was 21.7%.

The ability to transfer one good-quality vitrified-warmed blastocyst (=3BB) should lead to fetal heart pregnancy rates greater than 52% and live birth rates greater than 36%. Results of the present study can provide guidelines for a single vitrified-warmed blastocyst transfer, which is an effective means of eliminating multiple gestations and avoiding the complications associated with such pregnancies.

Searching Anti Leprosy Vaccine: Views to go Forward

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

Apreventive anti leprosy vaccine can contribute considerably towards global control and even elimination of leprosy. However, there is no successful vaccine available as yet. M.leprae is known to evade/subvert the antimicrobial activity of the invaded antigen presenting cells (APCs; macrophages and dendritic cells). Therefore, the cause for failure towards developing anti leprosy vaccine could be lack of presentation of M leprae antigens to re-stimulate the candidate vaccine generated CD4+Th1 type of memory cells against M.leprae. Since, autophagy is known to kill M.leprae and present its antigens, intermittent induction of autophagy might help in improving vaccine efficacy by re-stimulation of vaccine induced memory cells and thereby persistence of vaccine generated immunity. On the other hand, T cell subsets other than CD4+Th1 are also known to be protective in leprosy. A strategy involving such immune cells towards formulating anti leprosy vaccine may also prove to be advantageous. Hence, investigations on these aforementioned approaches are worthwhile exploring.

Leprosy is a chronic contagious disease caused by infection with Mycobacterium leprae (M.leprae), an obligate intracellular microbe which harbours, primarily, macrophages and Schwann cells. During this disease, mainly, skin and nerves are affected where immunological complications can result in nerve damage and thereby neuropathy leading to disabilities. Over the years, despite remarkable global decrease in leprosy cases the new case detection rates have not changed much. The data from 106 countries documented occurrence of 210758 new cases during 2015. Of these, 22 countries have been reported to be high burdened. Though Multi Drug Therapy (MDT) has brought down the global number of leprosy patients, persistence of new cases could be due to limitations of MDT and/or due to prevalence of undetected leprosy cases.

The existing scenario points-out that leprosy infection is still going on in community and for many countries it is still an important public health problem. Though, leprosy has been controlled significantly; nevertheless, its further control and finally, elimination can be boosted by anti M.leprae vaccine. As yet, no efficient anti leprosy vaccine is available for its use for prevention of occurrence of leprosy. Hence, efforts towards searching better vaccine are underway in several laboratories. Through this communication, an attempt has been made to share views to further refine research on developing anti leprosy vaccine.

The Dual of Porphyria Cutanea Tarda and Hemochromatosis

                        http://austinpublishinggroup.com/austin-hematology/currentissue.php

Porphyria Cutanea Tarda (PCT) is a condition characterized by accumulation of the carboxyl group substituent’s uroporphyrin I and heptacarboxyl porphyrin III resulting in increased iron storage and photosensitivity dermatitis. Here we present a case of a 51-year-oldman who presented with bilateral dorsal hand lesions and iron overload toxicity. Further screening revealed PCT resulting from a mutation in Uroporphyrinogen Decarboxylase (UROD) as well as from genetichemochromatosis (HFE) caused by C282Y homozygosity. The patient was treated successfully with phlebotomy.

Porphyria is an encompassing term for diseases in which Uroporphyrinogen Decarboxylase (UROD) deficiency results in overproduction of 4-8 carboxyl group substituents. Porphyria Cutanea Tarda (PCT) is characterized by the accumulation of uroporphyrin I, heptacarboxyl porphyrin III and iron overload toxicity. Deposition and photoexcitement of these porphyrins in the skin cause oxidative damage to the surrounding tissues resulting in classical PCT photosensitivity dermatitis. We present a case of a man who presented with sporadic season dependent bilateral cutaneous lesions on his dorsal hands and nailbeds, who was found to have new onset porphyria cutanea tarda as well as C282Y mutation homozygosity resulting in genetichemochromatosis (HFE) and underlying Hepatitis C (HCV) with undetectable viral load.

A 51-year-old male with a long-standing history of hepatitis C secondary to past intravenous drug use with undetectable viral load, and diabetes Type II presented to his primary care physician with worsening cutaneous lesions that had been appearing on his hands. During the past 7summershe would experience painful dorsal upper extremities resulting in disfiguration of his hands and nails (Figure 1). The patient’s daily medications were Lisinopril 20mg and Linagliptin 5mg once daily, Metformin 1000mg twice daily and insulin Detemir subcutaneously. He denied any supplemental iron usage or previous erythrocyte transfusions and denied any similar family history. At the time of his initial visit he had been referred to a dermatologist who performed a shave biopsy of the right index finger.

Yap Regulation of Hepatic Stellate Cells: Is there a Role for Metabolic Stress?s

                        http://austinpublishinggroup.com/austin-hepatology/currentissue.php

Mannaerts et al. recently reported that the effect or protein, Yap of the Hippo pathway regulates liver fibrosis by controlling the activation of hepatic stellate cells. The authors elegantly demonstrate that Yap activation induces fibrotic phenotype using in vitro as well as in vivo models. Besides contributing to liver failure, cirrhosis an advanced stage of fibrosis is known to be a major underlying disease of primary liver cancer, Hepatocellular Carcinoma (HCC). Thus experimental characterization of Yap’s role in fibrogenesis is clinically relevant due to the necessity for a viable antifibrotic therapy.

Emerging data show that Yap and hippo pathway in general are involved in liver enlargement and the associated clonal expansion of HCC. Yet, detailed mechanistic insights on the molecular regulation of fibrogenesis by Yap remain unclear. Recent reports document that energy producing pathways are altered in early/late cirrhotic stages and selective deregulation/ disruption of such metabolic alteration block fibrotic phenotype in vitro and in vivo.Thus, accumulating data indicate that metabolic alteration is indispensable for the progression of fibrosis/ cirrhosis.

Corroborating this, Yap and Hippo signaling mechanism have also been found to be regulated by energy stress. Importantly, glucose-mediated energy homeostasis has been shown to regulate Hippo pathway which in turn affects pro-glycolytic function of Yap. Multiple lines of evidence have established that metabolism-related oxidative stress is a major facilitator of fibrosis. Intriguingly, evidences also show that Yap- Hippo pathway is affected by oxidative stress. Taken together, it is thus far evident that cellular stress contributes for fibrogenesis and Yap-Hippo pathway is affected by such cellular stress during fibrogenesis. Future investigations focusing on molecular intricacies of Yap regulation by metabolic stress will be critical and relevant to identify potential therapeutic target (s) and development of any viable and translatable strategy to treat liver fibrosis/cirrhosis.