There are promising new agents coming to treat colorectal cancer, including biomarkers to guide treatment selection, targeted therapies, immunotherapy, and new ways to deliver chemotherapy and targeted therapies. Specifically, targeted therapies work by targeting molecular pathways involved in cancer development and survival. Biomarkers like KRAS, BRAF, and EGFR help determine which targeted therapies may work best. Immunotherapy and combinations of targeted agents and chemotherapy also show promise. Molecular profiling of tumors is helping to better understand colorectal cancer subtypes and identify new treatment opportunities.
This class covers what all physicians need to know about colorectal cancer (except prevention and screening, dealt with elsewhere). It is exceedingly simple, but accurate to the best of my knowledge. It is based on Harrison's 19th, Edition.
This class covers what all physicians need to know about colorectal cancer (except prevention and screening, dealt with elsewhere). It is exceedingly simple, but accurate to the best of my knowledge. It is based on Harrison's 19th, Edition.
Our team of 8 undergrads spent a summer conceiving, designing, constructing, and testing a new system for sensing and reporting alternative fuel source concentrations. We were lucky enough to be invited to the world championship jamboree at MIT in Cambridge, MA, and this was our presentation for our 20 minute talk. Let me just say, I absolutely love how these slides turned out. However, it definitely makes more sense with our explanations, so check the whole talk out at the iGEM results website: http://2011.igem.org/files/video/Wisconsin-Madison_Championship.mp4
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Deborah K. Armstrong, MD, covering the most clinically relevant new data reported from The Future of Antiangiogenic Therapies in Ovarian Cancer: A Series of Community and Academic Grand Rounds.
Target Audience
This activity has been designed to meet the unique learning needs of oncologists, surgeons, gynecologists, and other healthcare professionals involved in the treatment of patients with ovarian cancer.
Format: Microsoft PowerPoint (.ppt) | File size: 9.7 MB | Date posted: 8/06/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Activity Overview
Although progress continues to be made in the treatment of ovarian cancer, making clinical decisions remains a challenge due to the many treatment options available in several different settings. Selective inhibitors of the VEGF/PDGF/FGF pathways have shown activity in patients with ovarian cancer in phase II and III clinical trials either as monotherapy or in combination with other chemotherapy. Community and academic oncologists who treat patients with ovarian cancer need to stay abreast of the latest research that can affect treatment decisions and patient outcomes.
As controversy still exists regarding how and when to incorporate the use of antiangiogenic agents into the treatment paradigm for ovarian cancer patients, this case-based activity developed by expert faculty will provide clinicians with the practical application of new data into community and academic practice settings.
The presentation I gave in the plenary session at the ICCS (Presentation A3). It has been slightly modified for publishing. Please contact me if you have any questions!
Kevin R. Fox, M.D., Director, Rena Rowan Breast Center, Perelman Center for Advanced Medicine at Penn Medicine - Newest Approach to Breast Cancer
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Our team of 8 undergrads spent a summer conceiving, designing, constructing, and testing a new system for sensing and reporting alternative fuel source concentrations. We were lucky enough to be invited to the world championship jamboree at MIT in Cambridge, MA, and this was our presentation for our 20 minute talk. Let me just say, I absolutely love how these slides turned out. However, it definitely makes more sense with our explanations, so check the whole talk out at the iGEM results website: http://2011.igem.org/files/video/Wisconsin-Madison_Championship.mp4
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Deborah K. Armstrong, MD, covering the most clinically relevant new data reported from The Future of Antiangiogenic Therapies in Ovarian Cancer: A Series of Community and Academic Grand Rounds.
Target Audience
This activity has been designed to meet the unique learning needs of oncologists, surgeons, gynecologists, and other healthcare professionals involved in the treatment of patients with ovarian cancer.
Format: Microsoft PowerPoint (.ppt) | File size: 9.7 MB | Date posted: 8/06/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Activity Overview
Although progress continues to be made in the treatment of ovarian cancer, making clinical decisions remains a challenge due to the many treatment options available in several different settings. Selective inhibitors of the VEGF/PDGF/FGF pathways have shown activity in patients with ovarian cancer in phase II and III clinical trials either as monotherapy or in combination with other chemotherapy. Community and academic oncologists who treat patients with ovarian cancer need to stay abreast of the latest research that can affect treatment decisions and patient outcomes.
As controversy still exists regarding how and when to incorporate the use of antiangiogenic agents into the treatment paradigm for ovarian cancer patients, this case-based activity developed by expert faculty will provide clinicians with the practical application of new data into community and academic practice settings.
The presentation I gave in the plenary session at the ICCS (Presentation A3). It has been slightly modified for publishing. Please contact me if you have any questions!
Kevin R. Fox, M.D., Director, Rena Rowan Breast Center, Perelman Center for Advanced Medicine at Penn Medicine - Newest Approach to Breast Cancer
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Dr. Murphy presents slides discussing general screening trends in the US, including how the US compares to other countries, different screening modalities, and differences in screening by:
-Age
-Gender
-Geography
-Race/Ethnicity
Looking to kick start your physical activity? Hoping to learn about how body movement can be a huge benefit for CRC patients and survivors? Curious about Climb for a Cure? Join this interactive webinar featuring Karia Coleman, MSK, personal trainer and athletic strength coach, and Fight CRC advocates as they discuss the importance, challenges, and joys of physical activity.
From bowel frequency, pain, and more, many colorectal cancer treatments lead to digestive side effects. Join this webinar with Dr. Cathy Eng to learn all about the digestive system, the side effects that are common due to CRC treatment, and how to manage those side effects.
Maine recently passed major colorectal cancer (CRC) policy at the state level. Join us to listen to their story and learn what worked well for CRC state advocacy!
Indiana just passed major colorectal cancer (CRC) policy this year. Join us to listen to their story and learn what worked well for CRC advocacy in Indiana!
Kentucky was one of the first states in the US to pass major colorectal cancer (CRC) policy. Join us to listen to their story and learn what worked well for CRC state advocacy!
Join Fight CRC in a webinar about biomarkers. In this session, Dr. Chris Lieu will focus the discussion on the NTRK biomarker, in addition to ctDNA, and Next-Generation Sequencing.
Join us as Eden Stotsky-Himelfarb, BSN, RN from Johns Hopkins Medicine discusses how to manage after a colorectal cancer diagnosis. In this session, she will cover understanding diagnoses, shared decision making, managing mental health, talking to family and colleagues, and more.
Some colorectal cancer treatments lead to side effects of the skin. In this webinar, Dr. Nicole LeBoeuf will discuss these specific side effects. She will talk about why they occur, how to prepare for them, and how to manage them.
Hear about the latest breaking colorectal cancer research! Fight CRC will be joined by Dr. Axel Grothey who will spend the hour detailing the research presented at the 2020 Gastrointestinal (GI) Cancers Symposium hosted by the American Society of Clinical Oncology.
Anticipating the end of life and making decisions about medical care at this time can be difficult and distressing for people with cancer and their loved ones. However, it is incredibly important to plan for the transition to end-of-life care.
In this webinar, we will discuss questions to ask when considering an end to curative treatment, what to expect with hospice and end-of-life care, a new medical care team, advance directives and healthcare proxies, options for pain, the role of caregivers and loved ones, and more.
In this webinar, Dr. Angela Nicholas, Dr. Chris Heery, and Wenora Johnson discuss all things clinical trials. Dr. Nicholas, a family practitioner and caregiver to her late husband, John MacCleod will dive into her experience searching for clinical trials along with advice to those currently searching, or planning on searching in the future. Dr. Heery, Chief Medical Officer for Precision Biosciences will spend time dispelling myths around clinical trials and challenges to enrollment, and Wenora Johnson, a stage III colon cancer survivor will describe the process and her point of view curating trials in the Fight CRC trial finder.
In this webinar, Dr. Popp will discuss everything you need to know about palliative care! This is an important webinar for colorectal cancer patients and their loved ones.
eeling worn out and exhausted all the time? You may be experiencing cancer-related fatigue. Tune in to this webinar to learn what cancer-related fatigue is, how to spot it, and how to manage it.
In this webinar, Dr. Azad discusses colorectal cancer recurrence. She addresses things to do to help reduce the risk of recurrence, in addition to what steps should be taken if colon or rectal cancer returns.
Join Fight CRC and Dr. Scott Kopetz to learn about the latest breaking colorectal cancer research from the American Society of Clinical Oncology 2019 Annual Conference.
May 2019 – What You Need to Know About Chemotherapy Induced Neuropathy WebinarFight Colorectal Cancer
Neuropathy is a common side effect for colorectal cancer patients. It is a side effect that can be incredibly challenging to manage, and can affect daily living. Join this informative webinar to learn all about neuropathy—why it happens, how to prepare for it, and methods to try and reduce its effects. This is an important webinar for all survivors and patients! Dana will speak from both the medical professional and patient angle, as she is a colon cancer survivor herself!
A cancer diagnosis and cancer treatment can be traumatic. An experience with cancer can lead to serious psychological distress that should be addressed. In this webinar, Schuyler Cunningham, Clinical Social Worker, talks about what trauma is, how to identify it, and what steps to take next.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Johanna Bendell Call-on Congress panel speaker
1. THERE ARE SO MANY
PROMISING AGENTS COMING
TO TREAT COLORECTAL
CANCER
Johanna Bendell, MD
Director, GI Oncology Trials
Sarah Cannon Research Institute
Nashville, TN
2. What is on the horizon?
• Biomarkers and molecular profiling to
guide treatment selection
• “Targeted therapies”
• Combination therapies
• Immunotherapy
• New ways of delivering chemotherapy
and targeted therapies
3. Why targeted therapy?
• Going after what makes the
cancer a cancer
• Our drug development is
catching up with the lab
• Identification of certain pathways
that are key in cancer
development and survival
• We are still learning
– One set of targets does not
fit all
– All of the pathways talk to
each other
– Side effect profiles are
different, but can be just as
toxic to the patient
– Chronic cancer treatment?
6. What biomarkers are we
already using in colorectal
cancers?
• Biomarkers can be prognostic or predictive
• Microsatellite instability (MSI)
• K-ras
• B-raf
• Rash
• And more to come…
• New drugs that are in early development
are looking at companion diagnostics and
specifying biomarker status early on
7. EGFR Pathway Signaling in CRC
P P Ras KRAS mutation (40%–50%)
EGFR Sos
P P Grb2 Mutually exclusive
Raf
BRAF mutation (10%)
MEK
ERK
Proliferation Metastasis
Survival Angiogenesis
MAPK: mitogen-activated protein kinase
8. KRAS as a Biomarker for Panitumumab
Response in Metastatic CRC
Patients With Wild-Type KRAS Patients With Mutant KRAS
1.0 Pmab + BSC
Median Mean 1.0
Proportion With PFS
BSC alone Events/N (%) Pmab + BSC
0.9 in Wks in Wks Mean
0.9 BSC alone Median
Proportion With PFS
0.8 12.3 19.0 Events/N (%) in Wks in Wks
115/124 (93) 0.8
0.7 114/119 (96) 7.3 9.3 9.9
0.7 76/84 (90) 7.4
0.6 95/100 (95) 7.3 10.2
HR: 0.45 (95% CI: 0.34–0.59) 0.6
0.5 Stratified log rank test: P < .0001 0.5
HR: 0.99 (95% CI: 0.73–1.36)
0.4 0.4
0.3 0.3
0.2 0.2
0.1 0.1
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 3436 38 4042 44 46 48 50 52 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 3436 38 4042 44 46 48 50 52
Weeks Weeks
Amado et al., JCO 2008.
9. Amphiregulin/Epiregulin
• EGFR ligands:
– 1 in C. Elegans
– 4 in Drosophila
– 7 in mammals: EGF, TGF-α, HB-
EGF, amphiregulin
(AREG), betacellulin, epiregulin
(EREG) and epigen1
– EREG and AREG bind more
weakly to EGFR than EGF
but much more potently
and prolonged
– EREG preferentially activates
heterodimers2
• High gene expression levels of
EREG and AREG predict response to
cetuximab3
– High levels define tumors that are
EGFR-dependent?
1. Singh AB, et al. Cell Signal. 2005;17(10):1183-1193.
2. Shelly M, et al. J Biol Chem. 1998;273(17):10496-10505.
3. Khambata-Ford S, et al. J Clin Oncol. 2007;25(22):3230-3237,
10. EREG as a Predictive Marker for Cetuximab
Efficacy
• Combimarker: KRAS wildtype and high EREG
– The right predictive test
– High EREG predicts cetuximab benefit for OS
High EREG by minimum-P threshold Low EREG by minimum-P threshold
100
100
Cetuximab + BSC Cetuximab + BSC
80 80
Proportion Alive
Proportion Alive
60 60
40 40
BSC alone BSC alone
20 20
HR 0.46 [0.32-0.65], P<.0001 HR 0.93 [0.51-1.71], P = .81
0 0
0 2 4 6 8 10 12 14 0 2 4 6 8 10
84 80 76 66 43 28 18 8 30 25 16 13 8 5
85 73 54 26 19 14 10 5 26 18 15 10 5 3
Time From Randomization, months Time From Randomization, months
Jonker D, et al. J Clin Oncol. 2009;27(15S): Abstract 4016.
11. Combimarker: KRAS Wildtype
PLUS EREG High
–All comers n = 394 (100%) HR: 0.7
–KRAS wildtype n = 230 (58%) HR: 0.55
–Combimarker n = 169 (44%) HR: 0.46
Could use of the combimarker effectively “stack the
deck” to choose patients who would benefit from
cetuximab use in earlier lines of therapy?
Jonker D, et al. J Clin Oncol. 2009;27(15S): Abstract 4016.
12. BRAF Mutations in CRC
• BRAF is primary effector of EGF
KRAS signaling
Tumor Cell
• BRAF mutations:
– Occur most frequently in
exon 15 (V600E) P P Ras
– Found in 4% to 14% of
patients with CRC P P
Raf
– Mutually exclusive with
KRAS mutations MEK
Tumor cell
proliferation Erk
and survival
Yarden Y, et al. Nat Rev Mol Cell Biol. 2001; 2(2):127-137. Di Nicolantonio F, et al. J Clin Oncol. 2008; 26(35):5705-5712.
Artale S, et al. J Clin Oncol. 2008;26(25):4217-4219..
13. CRYSTAL plus OPUS: Pooled analysis of OS in
patients with
KRAS wt/BRAF mt tumors
1.0 KRAS wt/BRAF wt
HR [95% CI]: 0.840 [0.710–0.993]
0.9 p=0.041
FOLFIRI / FOLFOX4 + cetuximab: (n=349) median 24.8 months
0.8 FOLFIRI / FOLFOX4: (n=381) median 21.1 months
Probability of overall survival
KRAS wt/BRAF mt
0.7 HR [95% CI]: 0.633 [0.378–1.060]
p=0.079
0.6 FOLFIRI / FOLFOX4 + cetuximab: (n=32) median 14.1 months
FOLFIRI / FOLFOX4: (n=38) median 9.9 months
0.5
0.4
0.3
0.2
0.1
0.0
0 6 12 18 24 30 36 42 48 54 60
Number of patients Time (months)
CT + cetuximab 349 317 268 225 163 120 80 63 19 4 0
CT 381 350 283 212 149 107 63 46 17 2 0
CT + cetuximab
CT
32 25 16 12 8 5 2 2 2 0 0
38 24 14 6 6 3 3 1 0 0 0
Van Cutsem E, et al. N Engl J Med 2009;360:1408-17; Bokemeyer C, et al. J Clin Oncol 2009;27:663-71 HR, hazard ratio
14. Vemurafenib in V600E+ mCRC
100
75
1 PR and 4 MRs (≥10% shrinkage)
%Change From Baseline
50
(Sum of Lesion Size)
25
0
-25
(RECIST cutoff for PR, 30%)
-50
-75
-100
n=19 Evaluable Patients Interim - 12/31/09
17. EGFRi+BRAFi has in vivo activity on
BRAFV600E mutant CRC xenografts
Corcoran RB et al, Cancer Discov 2012;2:227-35
Prahallad A et al, Nature 2012;483:100-3
19. Activity of Tivantinib (ARQ197) +
cetuximab/irinotecan
Median # prior
therapies: 2 (range
1-4)
19
Eng et al. ASCOGI 2011
20. GI155 - ACCOMPLISH Schema &
Regimen
Schema Regimen
Drug Induction Regimen Maintenance Regimen
MetMAb (or
10 mg/kg IV Day 1 10 mg/kg IV Day 1
placebo)
Bevacizumab 5 mg/kg IV Day 1 5 mg/kg IV Day 1
Oxaliplatin 85 mg/m2 IV Day 1 Discontinued
Leucovorin 400 mg/m2 IV Day 1 400 mg/m2 IV Day 1
400 mg/m2 IV bolus 400 mg/m2 IV bolus then
5-FU then 2400 mg/m2 over 2400 mg/m2 over 46 hours
46 hours starting Day 1 starting Day 1
a Objective response or stable SD after 4 cycles – mFOLFOX-6 continued
for a further 4 cycles;
b Patients with measurable disease in lesions between cycles 4 and 8
may elect to continue treatment for a maximum of 12 cycles prior to
commencing maintenance treatment if in the best interests of the
patient and after consultation with the Study Chair;
c Objective response or SD at cycle 8 – commence maintenance
treatment.
21. Immune-Modulating Therapies
• Immune system contains receptor-ligand pairs that
inhibit or stimulate immune response
• Balance necessary to fight infections but not
develop autoimmunity
Infection-fighting Autoimmunity
22. PD-1 and PD-1-Like Inhibitors
Tumor cell T cell
B7H1/B7DC PD1
3.
4. 2.
B7-CD28 family
B7-1/B7-2 CTLA-4
1.
B7H3 ?
5.
TNFR/ligand family
CD27L CD27
6.
1. FDA-approved Ipilimumab
2. Monoclonal antibody that targets PD1 (receptor)
3. Recombinant fusion protein of B7DC (PD-L2 ligand), targets PD1
4. Monoclonal antibody that targets B7H1 (PD-L1 ligand)
5. Monoclonal antibody that targets B7H3 ligand
6. Agonist anti-CD27 monoclonal antibody
23. Immunotherapy: PD-1 Inhibitor
Suppressive/dysfunctional T cells are
Tumor present in tumors
CD8+PD-1+ PD-1 inhibitor
CD8+PD-1-
1. Functional anti-tumor response with
CD8+PD-1- T cells infiltrate and kill tumor
cells.
2. T cell memory is established
What about combinations? Bevacizumab?
24. Genomic Landscape of CRC… 2006
PIK3CA FBXW7
TP53
Facts:
11 colorectal tumors
First Generation Sequencing
KRAS 13,023 genes
APC 21 Mb target sequence
135,483 primer pairs
~90 mutated genes/tumor
11 recurrent mutations/tumor
The List of Candidate Genes: Total 142
Usual suspects APC, KRAS, PIK3CA, PTEN, SMAD4, TGFBR2, TP53…
Wood L et al, Science (2007); Sjoblom T et al, Science (2006)
28. Molecular Profiling and Matched Targeted Agents
in Colorectal Cancer Patients enrolled in Phase I
trials
BRAF inh
BRAF mut
mTOR inh + anti-IGFR1 mAb
PTEN low 3
5
anti-HGF mAb
pMET high 10
42 PI3K pathway inh
Second-generation 11 PIK3CA mut or PTEN low
anti-EGFR mAb
KRAS wt refractory to
cetuximab/panitumumab
11
Dienstmann et al. Mol Cancer Ther. 2012;11:2062-71.
29. There is so much more to
come…
• We are learning at an exponential rate
• We finally have drugs to hit the right
targets
• And the targets may change over time
• We are learning more about specific
colorectal tumors
– Are there people more at risk?
– Location of the tumor, etc
• Clinical trials are essential to ending this
disease
Editor's Notes
Provided by Tona Gilmer– GSK212 inhibits both non-activated MEK1/2 (IC50 ~ 0.71 nM) and the activated-MEK1/2 (IC50 ~13 nM) (reference Gilmartin A et al. Clin Cancer Res 2011 17:989-1000). Cell growth inhibition was determined after 3 days of compound treatment. pERK western blot was determined after 24 hours of compound treatment (cell growth inhibition should be referenced as Eastman S, unpublished and the Western blot should be referenced as Greger J, unpublished).Tona Gilmer: Constitutive activation of the RAS/RAF/MEK/ERK MAPK signaling pathway in melanoma can occur primarily through oncogenic mutations in BRAF or NRAS, or through autocrine growth factor stimulation. Activating mutations of BRAF at valine (V) 600 to glutamic acid (E) or lysine (K) occur in ~50% of melanoma cases, and promote downstream MEK–ERK signaling, resulting in cell proliferation, survival, invasion and metastasis. Both GSK2118436 and GSK1120212 are selective and potent kinase inhibitors. GSK436 targets RAF including the mutant forms of BRAF V600E (with IC50 value of 0.65 nM) and V600K with IC50 value of 0.5 nM. GSK212 inhibits both non-activated and the activated-MEK1/2 with IC50 values from 0.7-13 nM. Recent clinical trials with both (GSK2118436 and GSK1120212) as monotherapy have shown activity in melanoma patients with tumorsharboring BRAFV600E/K mutations. However, some tumors do not respond or develop resistance to these agents. Thus, an approach combining these two agents with different mechanisms of action to block the MAPK signaling pathway, may provide more effective treatment for this disease. In fact, GSK436 plus GSK212 has a synergistic effect on cell growth inhibition as exemplified in A375PF11 melanoma cells (shown at the right side of the slide), with combination index value ~ 0.65. The combination demonstrated more effective blockade of the MAPK signaling measured by a reduction in phospho ERK (western blot). *Cell growth inhibition was determined after 3 days of compound treatment. pERK western blot was determined after 24 hours of compound treatment.