Prevalence of Rota Virus Detection by Reverse TranscriptasePolymerase Chain R...IOSRJPBS
The present study was conducted for the period from 1/6/2016 to 20/1/2017 in Baquba city. The study aimed to detection of rotavirus in stool specimens of children fewer than five age and also explore the effects of certain demographic factors on the detection rates by revers transcriptase- polymerase chain reaction. The study included 49 patients with acute diarrhea, 32 were male and 17 were female. The age range was two months to 5 years. Demographic information on the patients regarding age, sex, residence, type of feeding and source of drinking water were collected from their parents. Stool specimens were collected from each patients and. Detection of rotavirus in stool specimens was done by conventional reverse transcriptase polymerase chain reaction (RT-PCR). The results of present study showed that the overall infection rate by rotavirus among patients with acute diarrhea by RT-PCR tests was 93.88%. The highest infection rate was recorded among those >10-≤15 months of age. None of the results showed significantly difference between female and male, PCR (88% vs 96.87%). Likewise, there was insignificantly difference between urban and rural residence, PCR (95.65% vs 92.30%). The results revealed insignificantly higher infection rate among patients (those below 2 years) feed mixing (91.66%) and bottled (100%) compared to that breast feeding (77.77%) by RT-PCR. The rotavirus infection rate was insignificantly higher among patients consuming municipal water for drinking (97.22%) compared to those consuming bottled water (84.61%) by the RT-PCR. The study concluded that rotavirus was detected in high rates among children less than 5 years old with acute diarrhea in Baquba city, particularly those less than 2 year old.
Prevalence of Rota Virus Detection by Reverse TranscriptasePolymerase Chain R...IOSRJPBS
The present study was conducted for the period from 1/6/2016 to 20/1/2017 in Baquba city. The study aimed to detection of rotavirus in stool specimens of children fewer than five age and also explore the effects of certain demographic factors on the detection rates by revers transcriptase- polymerase chain reaction. The study included 49 patients with acute diarrhea, 32 were male and 17 were female. The age range was two months to 5 years. Demographic information on the patients regarding age, sex, residence, type of feeding and source of drinking water were collected from their parents. Stool specimens were collected from each patients and. Detection of rotavirus in stool specimens was done by conventional reverse transcriptase polymerase chain reaction (RT-PCR). The results of present study showed that the overall infection rate by rotavirus among patients with acute diarrhea by RT-PCR tests was 93.88%. The highest infection rate was recorded among those >10-≤15 months of age. None of the results showed significantly difference between female and male, PCR (88% vs 96.87%). Likewise, there was insignificantly difference between urban and rural residence, PCR (95.65% vs 92.30%). The results revealed insignificantly higher infection rate among patients (those below 2 years) feed mixing (91.66%) and bottled (100%) compared to that breast feeding (77.77%) by RT-PCR. The rotavirus infection rate was insignificantly higher among patients consuming municipal water for drinking (97.22%) compared to those consuming bottled water (84.61%) by the RT-PCR. The study concluded that rotavirus was detected in high rates among children less than 5 years old with acute diarrhea in Baquba city, particularly those less than 2 year old.
Dr. Laura Miller - Comparative analysis of signature genes in PRRSV-infected ...John Blue
Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived dendritic cells at differential activation statuses - Dr. Laura Miller, Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, from the 2015 North American PRRS Symposium, December 4 - 5, 2015, Chicago, IL, USA.
More presentations at http://www.swinecast.com/2015-north-american-prrs-symposium
Identification of antibiotic resistance genes in Klebsiella pneumoniae isolat...QIAGEN
Antibiotic resistant strains of pathogenic bacteria are a growing worldwide health problem. To effectively combat the spread of difficult-to-treat bacterial infections, rapid surveillance methods for detection of antibiotic resistance genes is required to monitor both bacterial isolates and metagenomic samples. Additionally, identification of potential new sources for different antibiotic resistance genes is critical. Both of these goals require tools that can be used for profiling of antibiotic resistance genes from various types of samples. Real-time PCR has proven to be effective for the detection of antibiotic resistance genes. Using PCR array technology, simultaneous detection of 87 prevalent and important antibiotic resistance genes is possible and should prove to be an effective method for antibiotic resistance monitoring. This allows for a more comprehensive profiling of antibiotic resistance genes than is possible using individual PCR assays.
In vitro transcription and transfection of HCV genomic repliconBinodGupta27
Introduction: Hepatitis C virus (HCV) is a positive stranded RNA virus that causes acute and chronic hepatitis and hepatocellular carcinoma. Aims & Objectives: The study was conducted to establish the transfection of Huh 7.5 derived cell lines with In-vitro transcript of HCV pF6/JFH-1 for production of infectious virus particles in naïve Huh 7.5 cells, its detection by RT-PCR. Materials and Method: Huh 7.5 cells, a highly permissive cell lines for HCV replication, were grown in Dulbecco’s Modified Eagle’s Medium and pFL-J6/JFH plasmid was linearized with XbaI and subjected to in-vitro transcription using MEGAscript Kit (Ambion, USA) Huh-7.5 cells were transfected with 2.5 μg transcript using Lipofectamine 2000 transfection reagent (Invitrogen, USA) . The culture supernatant was collected after 24, 48 and 72 hr after incubation in fresh media and viral RNAs were isolated from it using Trizol LS reagent (Ambion, USA) and quantified by real-time quantitative RT-PCR. Total RNA was extracted from cells using Trizol reagent (Ambion, USA) and then RNA was subjected to cDNA synthesis using RevertAid reverse transcription (Thermo Fisher Scientific, USA). The PCR products were resolved by electrophoresis in 1.5% (w/v) agarose gels and images were captured by a Chemidoc XRS system (Bio-Rad, USA). Results: We observed Huh7.5 cells were cultured in DMEM. Plasmid FL-J6/JFH1 was linearized with the restriction enzyme XbaI and HCV RNA was obtained by In-vitro transcription and was transfected to grown Huh 7.5 cells shown by band on agarose gel and total RNA isolated after 24 hours of post infection followed by RT-PCR gave distinct band on gel whereas 48 and 72 hr did not. Infection of Huh 7.5 cells with cell culture supernatant from cells transfected with HCV in vitro transcript gave a distinct band. This will help in understanding entire viral life cycle and its non-structural gene products like NS4B and NS5A that enhance the replicative capacity of replicons in Huh 7.5 cell lines for development of drug and vaccines.
In vitro transcription and transfection of HCV genomic repliconBinodGupta27
ABSTRACT:
Introduction: Hepatitis C virus (HCV) is a positive stranded RNA virus that causes acute and chronic hepatitis and hepatocellular carcinoma. Aims & Objectives: The study was conducted to establish the transfection of Huh 7.5 derived cell lines with In-vitro transcript of HCV pF6/JFH-1 for production of infectious virus particles in naïve Huh 7.5 cells, its detection by RT-PCR. Materials and Method: Huh 7.5 cells, a highly permissive cell lines for HCV replication, were grown in Dulbecco’s Modified Eagle’s Medium and pFL-J6/JFH plasmid was linearized with XbaI and subjected to in-vitro transcription using MEGAscript Kit (Ambion, USA) Huh-7.5 cells were transfected with 2.5 μg transcript using Lipofectamine 2000 transfection reagent (Invitrogen, USA) . The culture supernatant was collected after 24, 48 and 72 hr after incubation in fresh media and viral RNAs were isolated from it using Trizol LS reagent (Ambion, USA) and quantified by real-time quantitative RT-PCR. Total RNA was extracted from cells using Trizol reagent (Ambion, USA) and then RNA was subjected to cDNA synthesis using RevertAid reverse transcription (Thermo Fisher Scientific, USA). The PCR products were resolved by electrophoresis in 1.5% (w/v) agarose gels and images were captured by a Chemidoc XRS system (Bio-Rad, USA). Results: We observed Huh7.5 cells were cultured in DMEM. Plasmid FL-J6/JFH1 was linearized with the restriction enzyme XbaI and HCV RNA was obtained by In-vitro transcription and was transfected to grown Huh 7.5 cells shown by band on agarose gel and total RNA isolated after 24 hours of post infection followed by RT-PCR gave distinct band on gel whereas 48 and 72 hr did not. Infection of Huh 7.5 cells with cell culture supernatant from cells transfected with HCV in vitro transcript gave a distinct band. This will help in understanding entire viral life cycle and its non-structural gene products like NS4B and NS5A that enhance the replicative capacity of replicons in Huh 7.5 cell lines for development of drug and vaccines.
Dr. Laura Miller - Comparative analysis of signature genes in PRRSV-infected ...John Blue
Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived dendritic cells at differential activation statuses - Dr. Laura Miller, Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, from the 2015 North American PRRS Symposium, December 4 - 5, 2015, Chicago, IL, USA.
More presentations at http://www.swinecast.com/2015-north-american-prrs-symposium
Identification of antibiotic resistance genes in Klebsiella pneumoniae isolat...QIAGEN
Antibiotic resistant strains of pathogenic bacteria are a growing worldwide health problem. To effectively combat the spread of difficult-to-treat bacterial infections, rapid surveillance methods for detection of antibiotic resistance genes is required to monitor both bacterial isolates and metagenomic samples. Additionally, identification of potential new sources for different antibiotic resistance genes is critical. Both of these goals require tools that can be used for profiling of antibiotic resistance genes from various types of samples. Real-time PCR has proven to be effective for the detection of antibiotic resistance genes. Using PCR array technology, simultaneous detection of 87 prevalent and important antibiotic resistance genes is possible and should prove to be an effective method for antibiotic resistance monitoring. This allows for a more comprehensive profiling of antibiotic resistance genes than is possible using individual PCR assays.
In vitro transcription and transfection of HCV genomic repliconBinodGupta27
Introduction: Hepatitis C virus (HCV) is a positive stranded RNA virus that causes acute and chronic hepatitis and hepatocellular carcinoma. Aims & Objectives: The study was conducted to establish the transfection of Huh 7.5 derived cell lines with In-vitro transcript of HCV pF6/JFH-1 for production of infectious virus particles in naïve Huh 7.5 cells, its detection by RT-PCR. Materials and Method: Huh 7.5 cells, a highly permissive cell lines for HCV replication, were grown in Dulbecco’s Modified Eagle’s Medium and pFL-J6/JFH plasmid was linearized with XbaI and subjected to in-vitro transcription using MEGAscript Kit (Ambion, USA) Huh-7.5 cells were transfected with 2.5 μg transcript using Lipofectamine 2000 transfection reagent (Invitrogen, USA) . The culture supernatant was collected after 24, 48 and 72 hr after incubation in fresh media and viral RNAs were isolated from it using Trizol LS reagent (Ambion, USA) and quantified by real-time quantitative RT-PCR. Total RNA was extracted from cells using Trizol reagent (Ambion, USA) and then RNA was subjected to cDNA synthesis using RevertAid reverse transcription (Thermo Fisher Scientific, USA). The PCR products were resolved by electrophoresis in 1.5% (w/v) agarose gels and images were captured by a Chemidoc XRS system (Bio-Rad, USA). Results: We observed Huh7.5 cells were cultured in DMEM. Plasmid FL-J6/JFH1 was linearized with the restriction enzyme XbaI and HCV RNA was obtained by In-vitro transcription and was transfected to grown Huh 7.5 cells shown by band on agarose gel and total RNA isolated after 24 hours of post infection followed by RT-PCR gave distinct band on gel whereas 48 and 72 hr did not. Infection of Huh 7.5 cells with cell culture supernatant from cells transfected with HCV in vitro transcript gave a distinct band. This will help in understanding entire viral life cycle and its non-structural gene products like NS4B and NS5A that enhance the replicative capacity of replicons in Huh 7.5 cell lines for development of drug and vaccines.
In vitro transcription and transfection of HCV genomic repliconBinodGupta27
ABSTRACT:
Introduction: Hepatitis C virus (HCV) is a positive stranded RNA virus that causes acute and chronic hepatitis and hepatocellular carcinoma. Aims & Objectives: The study was conducted to establish the transfection of Huh 7.5 derived cell lines with In-vitro transcript of HCV pF6/JFH-1 for production of infectious virus particles in naïve Huh 7.5 cells, its detection by RT-PCR. Materials and Method: Huh 7.5 cells, a highly permissive cell lines for HCV replication, were grown in Dulbecco’s Modified Eagle’s Medium and pFL-J6/JFH plasmid was linearized with XbaI and subjected to in-vitro transcription using MEGAscript Kit (Ambion, USA) Huh-7.5 cells were transfected with 2.5 μg transcript using Lipofectamine 2000 transfection reagent (Invitrogen, USA) . The culture supernatant was collected after 24, 48 and 72 hr after incubation in fresh media and viral RNAs were isolated from it using Trizol LS reagent (Ambion, USA) and quantified by real-time quantitative RT-PCR. Total RNA was extracted from cells using Trizol reagent (Ambion, USA) and then RNA was subjected to cDNA synthesis using RevertAid reverse transcription (Thermo Fisher Scientific, USA). The PCR products were resolved by electrophoresis in 1.5% (w/v) agarose gels and images were captured by a Chemidoc XRS system (Bio-Rad, USA). Results: We observed Huh7.5 cells were cultured in DMEM. Plasmid FL-J6/JFH1 was linearized with the restriction enzyme XbaI and HCV RNA was obtained by In-vitro transcription and was transfected to grown Huh 7.5 cells shown by band on agarose gel and total RNA isolated after 24 hours of post infection followed by RT-PCR gave distinct band on gel whereas 48 and 72 hr did not. Infection of Huh 7.5 cells with cell culture supernatant from cells transfected with HCV in vitro transcript gave a distinct band. This will help in understanding entire viral life cycle and its non-structural gene products like NS4B and NS5A that enhance the replicative capacity of replicons in Huh 7.5 cell lines for development of drug and vaccines.
SARS2 CoVID-19 is so far the latest endemic that has hit the humanity. This presentation is a sincere approach to understand about this class of viruses and the methods that can be used to prevent their further upgradation or genetic modification.
Objective: To probe into the influence of miR-21 on the proliferation as well as apoptosis of oral squamous cell carcinoma (OSCC) and its causative role.
Study Design: We adopted microarray for detecting the differentially expressed genes in OSCC tumor tis-sues and paracancerous tissues. We assessed the link of miR-21 expression with tumor size, lymph node metastasis, and tumor differentiation. We employed CCK-8 and EdU assay for detecting the impact of miR-21 inhibitor and miR-21 mimic on Cal-27 cell proliferation, as well as TUNEL and AnnexinV-FITC/PI double staining for detecting miR-21 expression on cell apoptosis. We forecasted the possible target of miR-21 via TargetScan, as well as detected the interaction of miR-21 with PTEN via luciferase reporter experiment. The function of miR-21 expression in PTEN signaling pathway was monitored via western blot. We constructed PTEN overexpression plasmid and conducted rescue experiment to evaluate overexpressed PTEN on miR-21–induced proliferation.
Results: Microarray and RT-qPCR indicated that miR-21 expression increased demonstrably in OSCC. Subsequently, statistical analysis showed that miR-21 expression was plainly correlated with tumor size, lymph node metastasis, tumor differentiation, and smoking history. CCK-8 and EdU method exhibited that miR-21 mimics manifestly promoted Cal-27 cell proliferation, while miR-21 inhibitor blatantly inhibited Cal-27 cell proliferation. TUNEL and V-FITC/PI double staining assay showed that miR-21 inhibitor conspicuously promoted Cal-27 cell apoptosis. CCK-8 and EdU assay exhibited that overexpressed PTEN abolished the pro-proliferation influence of miR-21 mimic. TUNEL and V-FITC/PI experiments pointed out that knocking down PTEN abrogated the pro-apoptosis impact of miR-21 inhibitor.
Conclusion: miR-21 contributes to OSCC cell proliferation via targeting PTEN and inhibits its apoptosis.
Keywords: Akt/PKB signaling pathway; apoptosis; biomarkers, tumor; carcinoma, squamous cell; cell line, tumor; cell proliferation; microRNAs; miR-21; miRNA-21; mouth neoplasms; oral cancer; oral squamous cell carcinoma; proliferation; real time PCR
Chronic Hepatitis C Virus Infection and Carcinoma Cervix – Report of a Case ...Apollo Hospitals
We report a case of a 54 year old woman with carcinoma cervix and chronic hepatitic C infection. Hepatitis C Virus was isolated from the malignant cervical tissue which caused Chronic Hepatitis and may have had a direct role in the development and pathogenesis of cervical cancer.
potassium, chloride, bicarbonate, blood urea nitrogen (BUN), magnesium, creatinine, glucose, and sometimes calcium. Tests that focus on cholesterol levels can determine LDL and HDL cholesterol levels, as well as triglyceride levels.[6]
Novel research aimed at finding a cure for AIDS requires animal models responding to human antiretroviral drugs. However, there have been few antiretrovirals cross-active against the simian viruses. In this study, we expanded the arsenal of drugs active against the simian retrovirus SIVmac251 and showed that this virus is inhibited by the protease inhibitor, darunavir, and the CCR5 blocker, maraviroc. Administration of these two drugs in combination with the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the integrase inhibitor, raltegravir, resulted in prolonged plasma viral loads below assay detection limits, and, surprisingly, restricted the viral reservoir, a marker of which is viral DNA. We then decided to employ this multidrug regimen (termed “highly intensified ART”) in order to increase the potency of a previous strategy based on the gold drug auranofin, which recently proved able to restrict the viral reservoir in vivo. A short course of highly intensified ART following the previous treatment resulted, upon therapy suspension, in a remarkably spontaneous control of the infection, that may pave the way to a persistent suppression of viremia in the absence of ART. These results corroborate the robustness of the macaque AIDS model as a vanguard for potentially future treatments for HIV in humans.
670501 global health program for executivesPattie Pattie
Integration of Global Health Program for Higher Education เป็นบ่ายวันที่ ๑ พฤษภาคม ๒๕๖๗ โดย ศ.นพ.วิจารณ์ พานิช ในการจัดการอบรม THAILAND HEALTH LEADERSHIP FORUM Global Health Program for Executives “Charting the Future of Global Health: Bridging Gaps & Building Sustainability” ระหว่างวันที่ ๓๐ เมษายน - ๒ พฤษภาคม ๒๕๖๗
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
1. Copyright 2016 American Medical Association. All rights reserved.
Hepatitis C Virus—From Discovery to Cure
The 2016 Lasker-DeBakey
Clinical Medical Research Award
The 2016 Lasker-DeBakey Clinical Medical Research Award
has been presented to Ralf F. W. Bartenschlager, Charles M.
Rice, and Michael J. Sofia for the development of a system
to study the replication of the virus that causes hepatitis C
virus and for use of this system to revolutionize the treat-
ment of this chronic, often lethal disease.
The liver is the largest organ in the human body and is
central for metabolism and many other functions. Sev-
eralvirusesspecializeininfectingtheliverandarecalled
hepatitis viruses. Five such viruses are known, includ-
ing hepatitis C virus (HCV), which was originally recog-
nizedasanagentofposttransfusionnon-A,non-Bhepa-
titis. Given that about 6% of patients receiving blood
transfusionsdevelopednon-A,non-Bhepatitis,tremen-
dous efforts were mounted to isolate and molecularly
clone this filterable agent, likely a virus.
Inalandmarkpaperin1989,Houghtonandhisteam
isolated the first molecular clone of HCV and provided
aglimpseoftheHCVgenome:apositive-strandRNAvi-
rus with a genome length of around 9500 nucleotides
encoding a long polyprotein that was likely cleaved co-
translationally and posttranslationally into 8 to 10
products.1
Work in many laboratories, subsequently
identified 10 HCV proteins generated by the action of
host cell and viral proteases, including 2 viral enzymes,
thenonstructuralproteins(NS)3-4Aserineproteaseand
the NS5B RNA-dependent RNA polymerase, highly at-
tractive HCV drug targets. Subsequent research by
Drs Bartenschlager, Rice, and Sofia led to the develop-
ment of new and effective treatments for HCV.2-7
The bottleneck in drug development was the lack
of cell culture systems for HCV, but the availability of
molecular HCV clones raised hope because the RNA
genome of positive-strand RNA viruses is infectious.
Introducing genome RNA or a genome RNA equivalent
transcribed from a plasmid into permissive cells can ini-
tiate an entire viral life cycle. The genome RNA is recog-
nized by cellular ribosomes, translated to produce the
viral proteins, and, in concert with additional factors
from the host cell, amplified and used to make infec-
tious virus. However, this approach, which had suc-
ceeded for many other viruses, failed for HCV. One rea-
son was a missing piece at the 3′ end of viral genome
finally discovered by the laboratories of Kunitada
Shimotohno and Charles M. Rice. With the HCV
genome now likely complete, making a functional
complementary DNA (cDNA) clone should be easy, but
how would this be tested without a cell culture system?
In 1997, clones reflecting a “consensus” sequence were
used to filter out possible lethal mutations present in
the patient-derived HCV population or acquired during
cDNA cloning in the laboratory. Injection of this syn-
thetic, naked genome RNA into the liver of chimpan-
zees gave rise to a productive HCV infection and pro-
vided the first genetic system for proving that possible
HCV-specific drug targets were essential for the virus.
With virtually unlimited quantities of HCV ge-
nome RNA, validated as infectious in vivo, it might be
expected that finding a suitable cell culture system
would quickly follow, but that was not the case. The
solution came from work in the laboratory of Ralf
Bartenschlager that used another HCV consensus
genome cloned from the liver of a chronically infected
patient. With the aim to isolate rare cells supporting ro-
bust HCV replication, “selectable minigenomes,” called
replicons,wereengineered.Theserepliconsencodethe
minimal set of viral proteins assumed to be required for
autonomousreplicationand,inaddition,ageneconfer-
ringresistanceagainstthecytotoxicdrugG418.Byusing
drug selection, cells supporting efficient and long-term
HCV replication could be isolated. This first robust HCV
cellculturemodelrecapitulatedalltheintracellularsteps
of the HCV replication cycle and because replication of
these HCV RNAs relied on the viral enzymes, most no-
tably the NS3 protease and the NS5B polymerase, the
replicon system was suitable for drug development.
Subsequent studies conducted in the Rice and
Bartenschlager laboratories unveiled the reasons for
such high replication efficiency. First, the most HCV-
permissive individual cells in a given cell pool had been
selected; second, the replicons present in selected cell
clones harbored mutations that enhanced HCV RNA
replication by orders of magnitude. Insertion of these
mutations into the parental replicon allowed direct
measurement of HCV replication. Thus, the first widely
useful genetic systems for studying HCV biology were
created. Subsequent work by Bartenschlager, Rice, and
others refined this approach.
With the robust HCV replicon whole-cell system
availableforscreeningofsmallmolecules,thesearchfor
inhibitors of HCV became a major focus of pharmaceu-
tical and biotech companies. This was propelled by the
desire to identify direct-acting antivirals with the ulti-
mategoalofreplacingthethencurrentstandardofcare
for treating HCV infection, the combination of inject-
able interferon plus ribavirin, which was limited by se-
vere adverse effects, modest cure rates, and limited
genotype coverage.
In 2005 efforts in HCV drug discovery were fo-
cused on several key viral targets, including the NS5B
RNA-dependent RNA polymerase (NS5B RdRp). The
Ralf F. W.
Bartenschlager, PhD
Heidelberg University
Hospital, Heidelberg,
Germany.
Charles M. Rice, PhD
Laboratory of Virology
and Infectious Disease
and Center for the
Study of Hepatitis C,
Rockefeller University,
New York, New York.
Michael J. Sofia, PhD
Arbutus Biopharma,
Doylestown,
Pennsylvania.
Viewpoint
pages 1252 and 1256
Supplemental
content
Corresponding
Author: Michael J.
Sofia, PhD, Arbutus
Biopharma, 3805 Old
Easton Rd, Doylestown,
PA 18902 (msofia
@arbutusbio.com).
VIEWPOINT
Opinion
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2. Copyright 2016 American Medical Association. All rights reserved.
search for nucleoside inhibitors of HCV replication at Pharmasset
identified a unique 2′-α-F-2′-β-C-methylcytidine derivative
PSI-6130 (an inhibitor of HCV). Targeting of the HCV RdRp with a
nucleoside drug held particular promise for providing broad geno-
type coverage and for preventing formation of resistant virus. This
nucleoside was shown to be active as an inhibitor of HCV using the
repliconsystemanddemonstratedhighselectivityforHCVvsother
viruses,exhibitedapangenotypicprofile,anddemonstratedahigh
barrier to resistance. However, PSI-6130 lacked sufficient oral bio-
availabilityandwasmetabolizedtoformasubstantialamountofan
inactiveuridinenucleoside—thuslimitingtheamountofactivedrug
available to target HCV.
An initial attempt to improve on PSI-6130 led to the develop-
ment of a PSI-6130 prodrug. In a clinical study, PSI-6130 prodrug
demonstrated proof of concept that the 2′-α-F-2′-β-C-methylcyti-
dinenucleosideinhibitedHCVinpatientsandthat,forthefirsttime,
a direct-acting antiviral was effective in non–genotype 1 patients.
However, the limitations of this drug candidate were potency, the
requirement for a large amount of drug given twice daily to show
efficacy, and the inactive uridine metabolite still persisted.
To address the deficiencies of the PSI-6130 prodrug a radical
redesign of this nucleoside inhibitor was developed by Sofia and
colleagues. Studies showed that the triphosphate of the uridine
nucleoside metabolite was a potent inhibitor of the HCV RdRp
and also exhibited a long half-life in primary human hepatocytes.
A long triphosphate half-life would lead to high active drug con-
centrations inside cells. It was determined that a block in the
metabolic conversion of the uridine nucleoside to the active tri-
phosphate was the reason for its inactivity. The block was specifi-
cally in the conversion of the uridine nucleoside to the mono-
phosphate intermediate.
To address the problem of delivering a highly charged, un-
stable, and membrane-impermeable uridine monophosphate into
cells and ultimately into the body, a “Trojan horse” strategy was de-
veloped that masked the uridine monophosphate in such a way as
toimpartstabilityandfacilitatetransportintothebodyandintoliver
cells. Once inside the liver cell, the “mask” would need to fall off re-
vealing the monophosphate that would then be converted by the
cell to the triphosphate inhibitor. At the same time, the mask was
designedwiththeintentionoffacilitatinglivertargetingofthedrug
byleveragingliverfirst-passmetabolism—usingliverenzymestose-
lectively remove the mask and ultimately trap the drug inside liver
cells. This would increase the concentration of the drug in the liver
and reduce drug exposure to the rest of the body.
Afterextensiveinvitroandinvivopreclinicaldevelopmentthat
evaluated numerous versions of masked uridine nucleoside mono-
phosphates, the clinical candidate PSI-7851 was selected. Subse-
quently, PSI-7851 was shown to be highly efficacious in HCV pa-
tientswhendosedorallyoncedailyinashort-durationstudywithout
any observed drug-related adverse events or drug resistance. This
resultprovidedproofofconceptforaliver-targetednucleosidemono-
phosphate prodrug. In a landmark clinical study named “Electron,”
theinterferon-freecombinationofPSI-7977(thesingle-isomericver-
sion of PSI-7851) plus ribavirin dosed for 12 weeks resulted in a
100% cure rate (ie, defined as sustained virologic response at the
completion of therapy) in patients with HCV genotype 2 and 3. This
result established a new approach for how clinicians could treat pa-
tientsinfectedwithHCV.Nolongerwasinjectableinterferonneeded
as part of the drug combination. Phase 3 clinical studies with
PSI-7977(nowcalledsofosbuvir)plusribavirindemonstratedhighcure
rates, and, subsequently, sofosbuvir plus ribavirin was approved by
theUSFoodandDrugAdministrationasthefirstinterferon-freetreat-
mentregimenforpatientswithHCVgenotype2and3.However,so-
fosbuvir plus ribavirin for 12 weeks was not quite good enough to
achieve high cure rates in patients with HCV genotype 1.
With the development of reporter replicons containing both a
selection marker and a reporter gene, high-throughput screens
against millions of compounds were enabled, and this led to iden-
tification of a new class of very potent HCV inhibitors, the NS5A in-
hibitors.Thisdevelopmentdemonstratedtheversatilityoftherepli-
con system and the identification of a peculiar drug target lacking
enzymaticactivity.WithfurtherdevelopmentofNS5Ainhibitorsand
next-generation NS3-4 protease inhibitors, new and potent drug
combinations with sofosbuvir as the backbone were now available
for clinical study. This led to the approval of multiple sofosbuvir-
based drug combinations for treating HCV, and the approval of the
firstsingle-pill,fixed-dosecombinationofsofosbuvirplustheNS5A
inhibitor ledipasvir that provided more than 95% cure rates for pa-
tients infected with HCV genotype 1.
The journey from the identification of a virus that causes de-
bilitatingliverdamagetoasafeandhighlyeffectivecureforHCVhas
taken more than 24 years. The possibility now exists that with time
and commitment, HCV infection can one day be given the designa-
tion of a rare disease.
ARTICLE INFORMATION
Published Online: September 13, 2016.
doi:10.1001/jama.2016.13713
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest. For a
full list of disclosures for each author, see the
Supplement.
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Viewpoint Opinion
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