Bronchial Thermoplasty (BT) Novel Treatment for Patients with Severe AsthmaBassel Ericsoussi, MD
Do our Asthma Patients Know What They Are Missing?Now, A Revolutionary Procedure Can Help Them Lead A Fuller Life.
Bronchial Thermoplasty (BT) Novel Treatment For Patients With Severe Asthma
Bronchial Thermoplasty (BT) Novel Treatment for Patients with Severe AsthmaBassel Ericsoussi, MD
Do our Asthma Patients Know What They Are Missing?Now, A Revolutionary Procedure Can Help Them Lead A Fuller Life.
Bronchial Thermoplasty (BT) Novel Treatment For Patients With Severe Asthma
Development of Biotechnology based on the Cloning Technology (Omalizumab). Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglobulin-E (IgE) in the blood and interstitial fluid and to membrane-bound form of IgE on the surface of mIgE-expressing B-lymphocytes.
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
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.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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
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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.
3. Pathogenesis in a glimpse…
• Asthma has traditionally been described as a Th2
lymphocyte mediated condition in which allergen
presentation by antigen presenting cells to naïve T cells
results in Th2 cell differentiation.
• The Th2 lymphocytes produce IL-4, IL-5, and IL-13 cytokines
that then drive B cells to secrete immunoglobulin E.
4. Available classes of biologicals…
Omalizumab Anti IL5 mab
Primary mechanism of
action
Anti IgE Anti IL5
Other potential MOA Anti rhinoviral
Bio-marker for patient
selection
IgE to indoor aero-
allergens
Eosinophils
Children ≥6yrs ≥12yrs
Patient selection Total IgE and BMI BMI for reslizumab
ROA s.c. Mepolizumab: s.c.
Reslizumab: I.V.
5. The drugs…
• Omalizumab, a monoclonal antibody against
immunoglobulin E (anti-IgE), was the first biologic
developed for the treatment of severe allergic asthma. It
binds to free IgE, which lowers free IgE levels and causes
FcεRI receptors on basophils and mast cells to be
downregulated.
• Mepolizumab or reslizumab, anti-interleukin-5 (anti-IL-5)
mAbs or benralizumab, an anti-IL-5 receptor mAb, are
effective in reducing exacerbations in patients with severe
eosinophilic asthma.
6. Anti IL-5 MOA…
• Mepolizumab specifically binds to the α-chain of IL-5 and disrupts
its interaction with the α-subunit of the IL-5 receptor, which is
present on the eosinophils and their early precursors.
• Reslizumab binds to the alpha chain of the IL-5 receptor on the
eosinophil surface.
• Benralizumab binds to the amino acid isoleucine-61 present
within the domain 1 of human IL-5Rα, thus interacting with the
extracellular IL-5Rα epitope. As a consequence, benralizumab
inhibits hetero-dimerization of IL-5 receptor α/βc subunits and the
following signal transduction mechanisms.
7. Severe Eosinophilic disease diagnosis..
Major Minor
Diagnosis of severe asthma Late onset of disease
Evidence of high load of eosinophilic
disease (persistent blood or sputum
eosinophilia detected on ≥2 occasions.
Upper airway disease
Frequent exacerbations (≥2 per yr.) Role of other biomarkers
Dependence on OCS to achieve asthma
control
Fixed airflow obstruction
Air trapping/presence of mucus plugs.
9. When to use what???
Omalizumab for treating severe persistent allergic asthma
A positive skin test or in vitro reactivity to a perennial aeroallergen
Reduced lung function (FEV1 <80% in adults and adolescents)
Frequent daytime symptoms or night-time awakenings
Multiple documented severe exacerbations despite daily high-dose plus LABA
10. Mepolizumab, as an add-on to optimised standard therapy, is recommended as an
option for treating severe refractory eosinophilic asthma in adults, only if:
The blood eosinophil count is ≥300 cells per μL or more in the previous 12 months, and
The person has agreed to and followed the optimised standard treatment plan, and
Has had four or more asthma exacerbations needing systemic corticosteroids in
the previous 12 months, or
Has had continuous oral corticosteroids of at least the equivalent of prednisolone
5 mg per day over the previous 6 months.
T
11. At 12 months of treatment:
Stop mepolizumab if the asthma has not responded adequately, or
Continue treatment if the asthma has responded adequately and assess response
each year
An adequate response is defined as:
At least 50% fewer asthma exacerbations needing systemic corticosteroids in those
people with four or more exacerbations in the previous 12 months, or
A clinically significant reduction in continuous oral corticosteroid use while
maintaining or improving asthma control
12. Reslizumab, as an add-on therapy, is recommended as an option for the treatment of
severe eosinophilic asthma that is inadequately controlled in adults despite
maintenance therapy with high-dose ICS plus another drug, only if:
The blood eosinophil count has been recorded as ≥400 cells per μL
The person has had three or more asthma exacerbations in the past 12 months, and
At 12 months:
Stop reslizumab if the asthma has not responded adequately, or
Continue reslizumab if the asthma has responded adequately and assess response
each year
An adequate response is defined as:
A clinically meaningful reduction in the number of severe exacerbations needing
systemic corticosteroids, or
A clinically significant reduction in continuous oral corticosteroid use while
maintaining or improving asthma control
13. Dosing…
• Omalizumab is administered subcutaneously every 2–
4 weeks at doses 75-375mg based on baseline total IgE level
and body weight.
• Reslizumab is administered intravenously every 4 weeks
based on body weight (3 mg·kg−1). The corresponding
volume must be injected slowly into a 50-mL bag of 0.9%
sodium chloride. It is then injected over 20-50min.
• Mepolizumab is administered as a fixed dose subcutaneous
injection (100mg) every 4 weeks.
15. • Benralizumab is given as 30 mg SC q4weeks for the first 3
doses, then q8weeks thereafter
16. If not IL5, then??...
• IL-4 and IL-13 expressed by Th2 cells, mast cells, basophils,
and innate lymphoid cells are key cytokines in the
pathogenesis of allergic asthma and atopic disease.
• IL-4 is responsible for many features of asthma, including
Th2 differentiation, mucus production, and B cell isotype
switching. Both IL-4 and IL-13 signal through two different
but overlapping heterodimeric receptors that share the
alpha subunit of the IL-4 receptor (IL-4Rα).
17. Drugs in the pipeline….
Drug MOA
Pascolizumab Anti IL4
Altrakincept Recombinant human IL-4Rα antagonist
Pitrakinra Antagonist against IL-4/IL-13 cytokine
heterodimeric receptor, composed of IL-
13Rα1 and IL-4Rα subunits
Dupilumab Humanized monoclonal antibody to the
IL-4Rα subunit
Lebrikizumab Anti IL-13
Tralokinumab Anti IL-13