Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors.
Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the
dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the longterm safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo- controlled trial in the future.
This paper demonstrates knowledge of the indirect connection between diet and autism-related behaviors and the anatomical reasoning behind the position. I am studying to be a pediatric occupational therapist - a career field that often has patients with developmental abnormalities that can be treated with therapy and supplemented by diet.
This paper demonstrates knowledge of the indirect connection between diet and autism-related behaviors and the anatomical reasoning behind the position. I am studying to be a pediatric occupational therapist - a career field that often has patients with developmental abnormalities that can be treated with therapy and supplemented by diet.
Simple Weight Loss Recipes
How You Can Safely and Naturally END Your Weight Issues WITHOUT Expensive Trips to the Doctor, Potentially Toxic Prescriptions, or Dangerous Side Effects.
http://rapbank.com/go/5254/75255/simple-weight-loss-recipes.html
A pilot study to evaluate nutritional influences on gastrointestinal symptoms...ivdacruz
A pilot study to evaluate nutritional influences on gastrointestinal symptoms and behavior patterns in children with Autism Spectrum Disorder1-s2.0-S0965229912001203-main
Body mass-index-quality-of-life-and-migraine-in-studentsAnnex Publishers
Migraine is reported globally with a higher prevalence in students. The present study aims to evaluate the association between nutritional status, quality of life (QL) and characteristics of migraine.
A cross-sectional study. Headache characteristics, level of disability caused by migraine crises (Pediatric Migraine Disability Assessment - PedMIDAS) and QL (Pediatric Quality of Life Inventory- PedsQL) were assessed. Anthropometric variables were also measured.
Data were collected from 98 students with a mean age of 11.2 ± 1.7 years. Migraine had the highest prevalence (54.8%). The average Body Mass Index (BMI) of the total sample was 20.0 ± 3.8 kg/m2, and among students with migraine and students with tension headache, the average BMIs were 20.4 ± 4.0 and 19.5 ± 3.4 kg/m2, respectively (p = 0.264, Student's t-test). Around 47.5% from migraineurs were overweight or obese. Regarding QL, the average total score in students with migraine was 74.4 ± 12.4, with no differences observed among normal weight, overweight or obese students, and no correlation between the scores of the PedsQL and BMI (r = -0.182, p = 0.165, Pearson correlation coefficient) was observed. There was a high percentage of overweight students with migraine. Analyses show no associations between the nutritional status, frequency, severity, disability caused by crises, or QL.
As a newly emphasized modality to treat infectious complications and also to folloew non-antibiotic regimens against infection, Probiotics has recieved more and more attention now a days.
Comparative Evaluation of the Effect of Doxycycline As An Adjunct to Non-Surg...QUESTJOURNAL
Background: The association between diabetes and periodontal disease has long been discussed with conflicting conclusions. Earlier studies demonstrating the relationship between diabetes and severity of periodontal disease has been equivocal. However, recent studies have clearly proven that diabetes increases the risk of periodontal disease progression. Less clear is the impact of periodontal disease on diabetes. It has been hypothesised that periodontal therapy may improve the metabolic control of diabetes. Aim: To determine the effect of doxycycline as an adjunct to non-surgical periodontal therapy in improving the metabolic control of poorly controlled type 2 diabetic subjects with chronic generalized periodontitis. Method: 30 poorly controlled type 2 diabetic subjects with chronic generalized periodontitis and receiving antidiabetic therapy were selected for the study. The subjects were randomly allotted to either of two treatment groups containing 15 subjects each: Group 1 (scaling and root planing(SRP)+ 15 days Doxycycline) or Group 2 (scaling and root planing(SRP). The Glycated haemoglobin (HbA1c) values, Gingival Index(GI), and Probing pocket depth of both the groups were assessed at baseline and after 3 months. Results: Both the treatment groups exhibited reductions in HbA1c, G I and Probing pocket depth compared to baseline over time. The amount of reduction in the glycated haemoglobin and gingival parameters was higher in Group I compared to group 2 after 3 months. Conclusion: Both treatments improved glycemic control in patients with type 2 diabetes; however, the reduction in HbA1c values reached statistical significance only in the group receiving doxycycline as an adjunct to scaling and root planing.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Nutritional Rehabilitation for Eating DisordersDavid Garner
This report describes our approach in sufficient detail to allow our outcomes to be replicated and compared with other programs. Our approach to meal planning has been referred to as “mechanical eating” and consists of a structured eating program in which quantity of food consumed, type of food consumed and spacing of meals, are all specified in advance. This report describes our approach in sufficient detail to allow our outcomes to be replicated and compared with other programs. We have anticipated potential criticisms of this
approach and have provided the theoretical and practical basis for our model.
In this Australian randomized trial, continued avoidance of gluten was associated with fewer and less severe symptoms among patients with irritable bowel syndrome
The Eating Attitudes Test (EAT-26) is probably the most widely used and cited standardized measure of symptoms and concerns characteristic of eating disorders . The original EAT appeared as a Current Contents Citation Classic in 1993. The 26-item version is highly reliable and valid according to Wikipedia. Many studies have used the EAT-26 as an economical first step in a two-stage screening process.
Metabolic effects of bariatric surgery in patients with moderate obesity and ...Apollo Hospitals
Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: Analysis of a randomized control trial comparing surgery with intensive medical treatment
Simple Weight Loss Recipes
How You Can Safely and Naturally END Your Weight Issues WITHOUT Expensive Trips to the Doctor, Potentially Toxic Prescriptions, or Dangerous Side Effects.
http://rapbank.com/go/5254/75255/simple-weight-loss-recipes.html
A pilot study to evaluate nutritional influences on gastrointestinal symptoms...ivdacruz
A pilot study to evaluate nutritional influences on gastrointestinal symptoms and behavior patterns in children with Autism Spectrum Disorder1-s2.0-S0965229912001203-main
Body mass-index-quality-of-life-and-migraine-in-studentsAnnex Publishers
Migraine is reported globally with a higher prevalence in students. The present study aims to evaluate the association between nutritional status, quality of life (QL) and characteristics of migraine.
A cross-sectional study. Headache characteristics, level of disability caused by migraine crises (Pediatric Migraine Disability Assessment - PedMIDAS) and QL (Pediatric Quality of Life Inventory- PedsQL) were assessed. Anthropometric variables were also measured.
Data were collected from 98 students with a mean age of 11.2 ± 1.7 years. Migraine had the highest prevalence (54.8%). The average Body Mass Index (BMI) of the total sample was 20.0 ± 3.8 kg/m2, and among students with migraine and students with tension headache, the average BMIs were 20.4 ± 4.0 and 19.5 ± 3.4 kg/m2, respectively (p = 0.264, Student's t-test). Around 47.5% from migraineurs were overweight or obese. Regarding QL, the average total score in students with migraine was 74.4 ± 12.4, with no differences observed among normal weight, overweight or obese students, and no correlation between the scores of the PedsQL and BMI (r = -0.182, p = 0.165, Pearson correlation coefficient) was observed. There was a high percentage of overweight students with migraine. Analyses show no associations between the nutritional status, frequency, severity, disability caused by crises, or QL.
As a newly emphasized modality to treat infectious complications and also to folloew non-antibiotic regimens against infection, Probiotics has recieved more and more attention now a days.
Comparative Evaluation of the Effect of Doxycycline As An Adjunct to Non-Surg...QUESTJOURNAL
Background: The association between diabetes and periodontal disease has long been discussed with conflicting conclusions. Earlier studies demonstrating the relationship between diabetes and severity of periodontal disease has been equivocal. However, recent studies have clearly proven that diabetes increases the risk of periodontal disease progression. Less clear is the impact of periodontal disease on diabetes. It has been hypothesised that periodontal therapy may improve the metabolic control of diabetes. Aim: To determine the effect of doxycycline as an adjunct to non-surgical periodontal therapy in improving the metabolic control of poorly controlled type 2 diabetic subjects with chronic generalized periodontitis. Method: 30 poorly controlled type 2 diabetic subjects with chronic generalized periodontitis and receiving antidiabetic therapy were selected for the study. The subjects were randomly allotted to either of two treatment groups containing 15 subjects each: Group 1 (scaling and root planing(SRP)+ 15 days Doxycycline) or Group 2 (scaling and root planing(SRP). The Glycated haemoglobin (HbA1c) values, Gingival Index(GI), and Probing pocket depth of both the groups were assessed at baseline and after 3 months. Results: Both the treatment groups exhibited reductions in HbA1c, G I and Probing pocket depth compared to baseline over time. The amount of reduction in the glycated haemoglobin and gingival parameters was higher in Group I compared to group 2 after 3 months. Conclusion: Both treatments improved glycemic control in patients with type 2 diabetes; however, the reduction in HbA1c values reached statistical significance only in the group receiving doxycycline as an adjunct to scaling and root planing.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Nutritional Rehabilitation for Eating DisordersDavid Garner
This report describes our approach in sufficient detail to allow our outcomes to be replicated and compared with other programs. Our approach to meal planning has been referred to as “mechanical eating” and consists of a structured eating program in which quantity of food consumed, type of food consumed and spacing of meals, are all specified in advance. This report describes our approach in sufficient detail to allow our outcomes to be replicated and compared with other programs. We have anticipated potential criticisms of this
approach and have provided the theoretical and practical basis for our model.
In this Australian randomized trial, continued avoidance of gluten was associated with fewer and less severe symptoms among patients with irritable bowel syndrome
The Eating Attitudes Test (EAT-26) is probably the most widely used and cited standardized measure of symptoms and concerns characteristic of eating disorders . The original EAT appeared as a Current Contents Citation Classic in 1993. The 26-item version is highly reliable and valid according to Wikipedia. Many studies have used the EAT-26 as an economical first step in a two-stage screening process.
Metabolic effects of bariatric surgery in patients with moderate obesity and ...Apollo Hospitals
Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: Analysis of a randomized control trial comparing surgery with intensive medical treatment
Teduglutida en el síndrome de intestino corto. Experiencia en PediatríaJavier González de Dios
La teduglutida, un análogo del péptido-2 similar al glucagón, pertenece a una nueva familia terapéutica y representa el primer abordaje no sintomático del síndrome de intestino corto.
En los ensayos clínicos realizados hasta la fecha se ha demostrado que la teduglutida recupera la función de absorción intestinal y que reduce significativamente la dependencia de la nutrición parenteral, consiguiendo incluso la independencia total en algunos pacientes. En el artículo adjunto se constata la experiencia española en 17 pacientes pediátricos en España, y esta efectividad en la vida real es superior en la población pediátrica que en adultos.
Effect of Antibiotics on The Gut Microbiota in Children with Chronic Pancreat...JohnJulie1
Little is known about the effect of antibiotic treatment on the gut microbiota in children with chronic pancreatitis (CCP). Our objective was to identify the effect of antibiotic treatment on the gut microbiota in children with chronic pancreatitis (CCP), the main gut microbiota genera and characterize the patients’ functional mutations after using antibiotics.
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
From metabolic syndrome to cachexia: what’s new about metabolic biomarkers?Bertin Pharma
What does Metabolic Syndrom really mean? What impact on world population? Which biomarkers can serve your studies? What treatments for tomorrow?...
These are just some of the questions Virginie Tolle and Odile Viltart, researchers at the INSERM (The French National Institute for Health and Medical Research ) answered in this very complete article for Bertin Pharma.
Good reading!
Gut Microbiota: The Missing Link in Obesity Induced Nonalcoholic Liver DiseaseIOSRJPBS
Background and objective: Recent research has elucidated a close association between intestinal microbiota, obesity, insulin resistance and nonalcoholic hepatic injury. Various studies have also indicated an increase in hepatic marker enzymes in obesity. Hence, this study aims to evaluate the association of gut microbiota with obesity, insulin resistance and hepatic marker enzymes. Material and Method: This case-control study was conducted during March 2015 to October 2016 At S.C.B Medical College, Cuttack, Odisha. The study included 186 subjects (86 irritable bowel syndrome patients as per the Rome III criteria and hundred matched controls). Plasma fasting glucose, serum lipid profile, hepatic marker enzymes were analysed by commercial kits adapted to automated clinical chemistry analyser and serum fasting insulin was estimated by kits adapted to Lisa Scan. Observation: Compared to controls the Irritable bowel syndrome patients had significantly higher Body mass index (20.9± 5.6 vs 30.1±0.22), Waist-hip ratio (0.9 ± 0.11 vs 1.02 ± 0.06), lipid profile, hepatic marker enzymes and insulin resistance. Conclusion: IBS patients were obese, and exhibited dyslipidemia, insulin resistance, elevated hepatic enzymes suggesting development of NAFLD.
Fast impact of lifestyle and functional interventions on adults affected by n...Metagenics Academy
Results of a observational study presented at the Australasian Congress of Lifestyle Medicine - Nov 4th 2016 . Autors L. Maselli, A. Saggioro, M.Salamone) Patients used MetaClear a formulation of vitamins, minerals and plant extracts that supports liver and detox function.
Conclusions reached from my involvement with the Canadian criminal justice system. 2011.
amd- 2021
References of papers published by Dr Mansfield Mela, and others regarding FASD, PAE, Mental Health, and the Justice System.
Dr Mela is one of the very few Forensic Psychiatrists who understands and advocates for those with FASD.
The Nomenclature of the Consequences of Prenatal Alcohol Exposure: PAE, and t...BARRY STANLEY 2 fasd
An historical account of the nomenclature relating to the effects of alcohol on the developing fetus.
The significance of facial features; the dose/threshold question; epigenetics, transgenerational consequences, and adult health issues, are raised.
The inadequacy of the present nomenclature is detailed
Effects of Hyperbaric Oxygen Therapy on Brain Perfusion, Cognition and Behavi...BARRY STANLEY 2 fasd
Abstract
A 15-year-old girl diagnosed with FASD underwent 100 courses of hyperbasic oxygen therapy (HBOT). Prior to HBOT, single motion emission compute tomographic begin imaging (SPECT)
revealed areas of hypo-perfusion bilaterally in the orbitofrontal region, temporal lobes and right dorsolateral—frontal, as well the medial aspect of the left cerebellum. Following two sets of HBOT treatments (60 plus 40), over 6 months, there was improvement in perfusion to the left cerebellum as well as the right frontal lobe. This was paralleled by improvement in immediate cognitive tests and an increase in functional brain volume. A follow-up 18 months after HBOT showed sustained
improvement in attention with no need for methylphenidate, as well as in math skills and writing.
This year as a priority of Proof Alliance’s legislative platform, major legislation that requires all children entering foster care be screened for prenatal exposure to alcohol in Minnesota was passed and signed into law. It is believed Minnesota is the first state in the nation to pass this legislation.
Four year follow-up of a randomized controlled trial of choline for neurodeve...BARRY STANLEY 2 fasd
Abstract
Background
Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial
Abstract
This presentation includes a brief review of research into boredom, normal brain resting state and corresponding default mode[s].
The possible equivalence to the brain activity of those with FASD in relation to “being bored” is explored, with reference to brain anatomy and function.
Actual FASD clinical cases are presented to illustrate what individuals with FASD mean by “boredom”: describing the role of perseveration as a relief process.
Finally, the manner in which these processes are misinterpreted is explored, with implications for Psychiatry and the Justice System.
Association Between Prenatal Exposure to Alcohol and Tobacco and Neonatal Bra...BARRY STANLEY 2 fasd
IMPORTANCE Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with
neurodevelopment.
OBJECTIVE To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns.
CONCLUSIONS AND RELEVANCE These findings suggest that even low levels of PAE or PTE are
associated with changes in offspring brain development.
Submitted to –
National Institute for Health and Care Excellence Fetal alcohol spectrum disorder
Consultation on draft quality standard – deadline for comments 5pm on 03/04/20
Clinical course and risk factors for mortality of adult inpatients with covid...BARRY STANLEY 2 fasd
Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help
clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale
for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Outcomes of Online Mindfulness-Based Cognitive Therapy for Patients With Residual Depressive SymptomsA Randomized Clinical Trial
Zindel V. Segal, PhD1; Sona Dimidjian, PhD2; Arne Beck, PhD3; et alJennifer M. Boggs, PhD3; Rachel Vanderkruik, MA2; Christina A. Metcalf, MA2; Robert Gallop, PhD4; Jennifer N. Felder, PhD5; Joseph Levy, BA2
Author Affiliations
JAMA Psychiatry. Published online January 29, 2020. doi:10.1001/jamapsychiatry.2019.4693
Significance for fasd
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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.
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 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
Long term benefit of microbiota transfer therapy on autism symptoms and gut microbiota
1. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota
Dae-Wook Kang 1,2,8, James B. Adams3, Devon M. Coleman3, Elena L. Pollard3, Juan
Maldonado1,2, Sharon McDonough-Means4, J. Gregory Caporaso 5,6 & Rosa Krajmalnik-
Brown 1,2,7
Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum
Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors.
Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and
behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the
dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal
microbes from a healthy donor. We previously performed an open-label trial of Microbiota
Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid
suppressant, and fecal microbiota transplant, and observed significant improvements in GI
symptoms, autism-related symptoms, and gut microbiota. Here, we report on
a follow-up with the same 18 participants two years after treatment was completed. Notably,
most improvements in GI symptoms were maintained, and autism-related symptoms improved
even more after the end of treatment. Important changes in gut microbiota at the end of
treatment remained at follow-up, including significant increases in bacterial diversity and
relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-
term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI
problems, and warrant a double-blind, placebo- controlled trial in the future.
The human gut and brain interact in complex ways, and abnormal conditions in the gut may
predispose individuals to neurodevelopmental disorders1,2. Individuals with Autism Spectrum
Disorders (ASD)3, Parkinson’s disease4, and Alzheimer’s disease5, for example, have been
known to experience chronic gastrointestinal (GI) symptoms as a common co-occurring
medical condition, suggesting the presence of a gut-brain axis. Hallmayer et al.6 investigated
192 twin pairs and found that both genetic and environmental factors contribute to the etiology
of ASD. The gut microbiome represents an important environmental factor that may exert an
influence on symptoms, and a growing number of research groups have observed that children
with ASD have distinctive gut microbiomes compared to neurotypical children7–11. Moreover,
multiple mouse studies have reported that gut microbes and their metabolites can impact
behavior through the gut-brain axis, including for ASD12–14.
Effective treatments for ASD include behavioral therapy, speech and social therapy, and
dietary/nutritional/ medical treatments, but no medical treatment has been approved to treat
core symptoms of ASD15, such as social communication difficulties and repetitive behaviors.
Considering the link between the gut and brain, modulating the gut microbiome by antibiotics,
probiotics, prebiotics, and/or fecal microbiota transplant (FMT) could be a viable therapeutic
option. In FMT, a large diversity and number of commensal microbes from a healthy donor are
used to transform a dysbiotic gut microbiome into a healthy microbiome. In fact, FMT is the
most effective therapy to treat recurrent Clostridium difficile infection16 and has shown varying
levels of success for treating other
1Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe,
AZ, 85287, USA. 2 Biodesign Center for Fundamental and Applied Microbiomics, Arizona State
University, Tempe, AZ, 85287, USA. 3School for Engineering of Matter, Transport and Energy,
Arizona State University, Tempe, AZ, 85287, USA. 4Integrative Developmental Pediatrics,
Tucson, AZ, 85701, USA. 5center for Applied Microbiome Science, Pathogen and Microbiome
Institute, Northern Arizona University, Flagstaff, AZ, 86001, USA. 6Department of Biological
2. Sciences, Northern Arizona University, Flagstaff, AZ, 86001, USA. 7School of Sustainable
engineering and the Built Environment, Arizona State University, Tempe, AZ, 85287, USA.
8Present address: Department of civil and Environmental Engineering, The University of
Toledo, Toledo, OH, 43606, USA. Correspondence and requests for materials should be
addressed to R.K.-B. (email: dr.rosy@asu.edu)
Figure 1. Changes in GI- and ASD-related symptoms of 18 children with ASD at two-year
follow-up after treatment stopped. Asterisks (at the top of the box plot) indicate whether
individuals (at each time point) have significantly changed since pre-treatment (Week 0 of
original Phase 1 trial). Based on two-tailed Wilcox on signed-rank test, ns indicates not
significant, single asterisk indicates p < 0.05, double asterisks indicate p < 0.01, triple asterisks
indicate p < 0.001. See also Supplementary Figs S1–S3.
GI disorders17, which has drawn attention to the method for use beyond GI-associated
disorders18. Previously, we performed a pioneering open-label modified-FMT trial with an
intensive combination called Microbial Transfer Therapy (MTT) consisting of two-week
vancomycin treatment followed by a bowel cleanse and then high dose FMT for 1–2 days and
7–8 weeks of daily maintenance doses along with a stomach-acid suppressant, administered
to children with ASD and chronic gastrointestinal problems19. After this 10-week MTT
treatment and an eight-week follow-up observation period (18 weeks in total), we observed an
80% reduction in GI symptoms and a slow but steady improvement in core ASD symptoms. At
the same time, we learned that gut microbial diversity, including potentially beneficial
microbes, significantly increased after MTT19. Two years after this original clinical trial was
completed, we re-evaluated the participants to determine whether observed improvements in
behavior and GI symptoms persisted, and to ascertain the long-term impact of MTT on the gut
microbiome of the study participants.
3. Results and Discussion
Improvements in GI and ASD symptoms remained two years after the MTT stopped. Two years
after the MTT was completed, we invited the 18 original subjects in our treatment group to
participate in a follow-up study, and all provided informed consent. We performed the same GI
and behavior tests that we employed previously19. 12 of 18 participants made some changes
to their medication, diet, or nutritional supplements, but these changes were well documented
and were mostly minor (Supplementary Table S1). We note that due to the open-label nature of
this initial trial, all of the assessments are subject to placebo effect, however the long- term
improvements we observed here are promising. Two years after treatment, most participants
reported GI symptoms remaining improved compared to baseline (Fig. 1a and Supplementary
Fig. S1). The improvement was on average 58% reduction in Gastrointestinal Symptom Rating
Scale (GSRS) and 26% reduction in % days of abnormal stools (Daily Stool Record or DSR)
relative to baseline, and this result is similar to what we observed at the end of treatment. The
improvement in GI symptoms was observed for all sub-categories of GSRS (abdominal pain,
indigestion, diarrhea, and constipation, Supplementary Fig. S2a) as well as for all sub-
categories of DSR (no stool, hard stool, and soft/liquid stool, Supplementary Fig. S2b),
although the degree of improvement on indigestion symptom (a sub-category of GSRS) was
reduced after 2 years compared with weeks 10 and 18. This achievement is notable, because
all 18 participants reported that they had had chronic GI problems (chronic constipation and/or
diarrhea) since infancy, without any period of normal GI health (Supplementary Table S2). The
families generally reported that ASD-related symptoms had slowly, steadily improved since
week 18 of the Phase 1 trial, and this was consistent with the data reported in Fig. 1b–f. Based
on the Childhood Autism Rating Scale (CARS) rated by a professional evaluator, the severity of
ASD at the two-year follow-up was 47% lower than baseline (Fig. 1b), compared to 23% lower
at the end of week 10. At the beginning of the open-label trial, 83% of participants rated in the
severe ASD diagnosis per the CARS (Fig. 2a). At the two-year follow-up, only 17% were rated
as severe, 39% were in the mild to moderate range, and 44% of participants were below the
ASD diagnostic cut-off scores (Fig. 2a). The parent-rated Social Responsiveness Scale (SRS)
assessment revealed that 89% of participants
4. Figure 2. CARS and SRS diagnostic category for ASD at baseline, 8 weeks after treatment,
and two-year follow-up after treatment stopped. (a) For CARS, Minimal-to-No Symptoms (15–
29.5 for ages less than 13; 15–27.5 for ages 13 or older), Mild-to-Moderate Symptoms (30–
36.5 for ages less than 13; 28–34.5 for ages 13 or order), and Sever Symptoms (37 and higher
for ages less than 13; 35 and higher for ages 13 or order)54. (b) For SRS, Normal (0–53), Mild
or High Functioning autism (54–86), Clinical diagnosis of autistic disorder, Asperger’s disorder,
or more severe cases of Pervasive developmental disorder not otherwise specified (PDD- NOS)
(>87)55. (c–g) Strong and significant correlations between improvements in GI symptoms
(GSRS) and behavior symptoms based on % changes in 2 years.
were in the severe range at the beginning of the trial, but the percentile dropped to 47% at the
two-year follow-up (Fig. 2b), with 35% in the mild/moderate range and 18% below the cut-off
for ASD. For the parent-rated Aberrant Behavior Checklist (ABC), total scores continued to
improve, and were 35% lower relative to baseline (versus 24% lower at the end of treatment,
relative to baseline; Fig. 1d). The Parent Global Impressions-III (PGI-III) scores remained similar
to the scores at the end of treatment (week 10) of the open-label (Fig. 1e). The Vineland
Adaptive Behavior Scale (VABS) equivalent age continued to improve (Fig. 1f), although not as
quickly as during the treatment, resulting in an increase of 2.5 years over 2 years, which is
much faster than typical for the ASD population, whose developmental age was only 49% of
their physical age at the start of this study. Moreover, we observed improvement in behaviors
5. in most sub-categories (Supplementary Figs S2c,d, and S3 for ABC, SRS, and VABS,
respectively).
Overall, the most substantial improvements observed were on the CARS assessments, which
was conducted by a professional evaluator and is less susceptible to placebo-effect20. CARS
is a stable and consistent diagnostic tool with high predictive validity21 and has been used to
evaluate participants before and after therapeutic interventions in multiple studies20,22,23. For
the follow up CARS, the evaluator collected current information based on each question’s
unique criteria. After the interview was complete for each question, the evaluator reviewed the
information initially collected at baseline and used it for calibrating the final evaluation.
Figure 3. Stool microbiota assessments at two-year follow-up after treatment stopped. (a)
Faith’s phylogenetic diversity (PD) in the microbiota of 18 children with ASD as measured from
stool samples. Orange lines indicate median PD of the donor samples (dashed line represents
initial donor samples (n = 5), and dotted line represents maintenance dose samples (n = 2)),
and green line indicates median PD of 20 neurotypical controls at week 0.
ns indicates not significant, single asterisk indicates p < 0.05, double asterisks indicate p <
0.01, triple asterisks indicate p < 0.001 (two-tailed Wilcoxon signed-rank test comparing weeks
3, 10, and 18 and two-year to week
0 values). (b) Unweighted Uni Frac distances between ASD gut microbiota and most relevant
donor sample (initial donor sample at weeks 0 and 3, most recent maintenance dose sample at
weeks 10 and 18, and 2 years). Green line indicates the median interpersonal variation between
neurotypical controls and illustrates that prior to treatment the difference in gut microbiota
composition between MTT recipients and donors was on the order of normal interpersonal
variation. Statistics are the same as those used in (a). See also Supplementary Figs S5 and S6.
Improvements in GI and ASD symptoms were significantly correlated. We performed statistical
analyses to assess whether improvements in GI and ASD severity were correlated. As shown in
6. Fig. 2c–e, percentage changes in CARS, SRS, and ABC scores were positively correlated with
percent changes in GSRS scores (Spearman correlation test, 2-tailed p < 0.005 and r > 0.7),
implying that GI relief provided by MTT may ameliorate behavioral severity in children with
ASD, or vice versa, or that both may be similarly impacted by another factor. Another GI
assessment, DSR, however, showed that there was no significant correlation. Although the
direction of the influence is not clear, a potential clinical link between GI and behavior severity
is consistent with what previous studies have reported24,25.
ASD fecal bacterial diversity was higher two years after the MTT stopped. 16 out of 18 original
ASD participants provided an additional fecal sample two years after the open-label trial.
Based on 16S ribosomal RNA (rRNA) gene amplicon sequencing analysis, most participants
maintained higher gut microbiota diversity two years after treatment relative to baseline.
Interestingly, for many individuals, the bacterial diversity was higher at two years than at the
week 18 follow up as measured by Faith’s Phylogenetic Diversity (Fig. 3a and Supplementary
Fig. S4a) and Observed OTUs (Supplementary Fig. S5a). Considering low gut bacterial diversity
in individuals with ASD26 and other human disorders27–29, an increase in diversity after MTT
may reflect that MTT intervention successfully transformed gut environment into a healthier
status and led to a long-term benefit on GI and behavior symptoms.
Upon completion of the original MTT treatment, we observed that the unweighted Uni Frac
distance30 between the gut microbiota of MTT recipients and their corresponding donors was
smaller than before treatment, suggesting some engraftment of the donor microbiome into the
recipients by MTT19. Interestingly, two years after the trial, the recipients were as different from
the donor microbiome as they were pre-treatment as measured by unweighted UniFrac
distance (Fig. 3b, Supplementary Fig. S4b) and several other metrics of community dissimilarity
(Supplementary Fig. S5b–e). This suggests that the recipients didn’t retain completely the
donated microbiome, but rather retained some features of it such as increased overall diversity,
and increase in some important microbes such as Prevotella, while finding a new state.
Bifidobacterium and Prevotella relative abundances remained higher in feces of participants
with ASD two-years after MTT stopped. Three taxa that were noticeably enhanced in MTT
recipients at the conclusion of the original clinical trial19 were revisited during the two-year
follow-up. Notably, compared to baseline, median relative abundances of Bifidobacteria and
Prevotella increased 4-fold and 712-fold at week 10, and 5-fold and 84-fold at two years,
respectively (Fig. 4a,b). Desulfobivrio relative abundance decreased since week 18 (Fig. 4c),
but at the two-year follow-up was still marginally higher compared to baseline (two-tailed
Wilcoxon signed-rank test, p = 0.07) and higher than neurotypical controls (two-tailed Mann-
Whitney U test, p < 0.05). An increase in Prevotella after MTT is noteworthy, since its lower
abundance in feces of children with ASD compared with neurotypical children has been
confirmed in two different cohorts26,31. A recent study also found reduced levels of Prevotella
in the oral microbiome of children with ASD32. Prevotella may be involved in butyrate
production33, a key nutrient for the intestinal epithelial cells34. In addition, its co-occurrence
with Desulfovibrio may reflect a synergistic advantage to outcompete other commensal
microbes that utilize mucin as nutrients35, although more research is needed on how their
ecological niche in mucin desulfation could
7. Figure 4. Changes in relative abundances of Bifidobacterium, Prevotella, and Desulfovibrio. ns
indicates not significant, single asterisk indicates p < 0.05 and double asterisks indicate p <
0.01 (two-tailed Wilcoxon signed- rank test comparing weeks 3, 10, and 8 and two-year to
week 0 values). Orange lines indicate median of the donor samples (dashed line represents
initial donor samples, and dotted line represents maintenance dose samples), and green line
indicates median of 20 neurotypical controls at week 0.
contribute to an integrity of gut epithelial cells36 as well as to the improvement on GI and
behavior symptoms we observed. Further mechanistic studies with multi-omic approaches are
warranted to define the roles of Prevotella and Desulfovibrio in the context of autism.
Further research with a placebo-control arm is warranted. To the best of our knowledge, long-
term follow-up studies are rare for medical treatment of individuals with ASD. In treatments
with vancomycin37 or phytochemical sulforaphane38, benefits were lost within two or four
weeks, respectively, of the treatments being discontinued. Thus, the long-term benefits
observed here two years after MTT stopped are very encouraging, and MTT-driven gut
microbiota transformation seems robust and long-lasting for the treatment of ASD. Despite
steady and continuous improvement in behaviors over two years, we must underscore that the
original clinical trial and current follow-up study are open-label trials without a control for
placebo effect. Autism symptoms are relatively stable over time without a major intervention:
for example, a trajectory study with 345 children with ASD showed that more than 80% of
participants with ASD retained unexpectedly stable core symptoms severity over 8 to 12
years39. The VABS observations indicate that the improvements in adaptive behaviors
observed here were substantially more than expected for children with ASD over two years. A
limitation of this study is that 12 out of 18 participants made one or more changes to their
medications, nutritional supplements, and diets between the end of the original MTT trial and
the two-year follow-up since the treatment stopped (Supplementary Table S1). As described in
detail in the methods section, participants were asked to rate the perceived effectiveness on GI
8. and ASD symptoms (on a scale of 0–4) caused by changes in medications, diet, or nutritional
supplements. Although the scale on the perceived effectiveness is still subjective and difficult
to interpret, low scores received (1.1 for GI and 0.8 for ASD symptoms) suggest that these
treatments on average could have only “slight effect”. Thus, it appears that most of the
changes observed were probably due to the MTT, although we still need follow-up studies to
understand whether the improvement by MTT were solely from vancomycin, MoviPrep,
Prilosec, Standardized Human Gut Microbiota (SHGM), or a combination of these individual
factors. For example, some participants in our study could have GI symptoms that were acid-
peptic in nature, and their improvements on GI symptoms might be solely attributed to the
administration of stomach-acid suppressant (Prilosec)40. We hypothesize that MTT may also
be beneficial for children with ASD who do not have obvious GI symptoms but have low
diversity of gut bacteria, as our previous study26 found that most children with ASD had low
gut bacterial diversity, regardless of whether they have GI problems.
Here, we also would like to address a potential study limitation interpreting the improvement on
GI symptoms after MTT, since these heterogeneous GI symptoms could reflect a wide range of
underlying etiological GI pathologies. Although we reviewed medical histories to exclude
children with known gastrointestinal diagnoses (such as ulcerative colitis, Crohn’s Disease,
celiac disease, eosinophilic gastritis, or similar conditions)19, we did not conduct additional GI
diagnostic evaluations, which is a limitation of this study. Thus, we want to underscore need of
follow-up studies embracing more thorough examination of participants’ GI pathologies in
order to better understand effectiveness of MTT.
Conclusions
In summary, all 18 participants with ASD were re-evaluated two years after MTT treatment
stopped, and we observed significant improvements both in GI and behavior symptoms as
compared with baseline measurements collected at the beginning of the original open-label
trial. GI benefits were mostly maintained from the end of treatment, and autism symptoms
were reported to have improved significantly since the end of treatment. Changes in gut
microbiota persisted at two years, including in overall community diversity and relative
abundances of Bifidobacteria and Prevotella. These encouraging observations demonstrate
that the intensive MTT
intervention is a promising therapy for treating children with ASD who have GI problems. We
recommend future research including double-blind, placebo-controlled randomized trials with a
larger cohort.
Methods
Ethics approval and consent to participate. The protocol for the original treatment study was
approved by FDA (Investigational new drug number 15886) and the Institutional Review Board
of Arizona State University (ASU IRB Protocol #: 00001053), as described in Kang et al.19. All
research methods were performed in accord- ance with the relevant guidelines and
regulations. For the follow-up study described in this paper, a new IRB protocol was approved
by the IRB of Arizona State University (ASU IRB Protocol # 00004890). The follow-up study
was only open to the 18 children with ASD who participated in the original Phase 1 trial study,
and no further inclusion or exclusion criteria was applied to what we employed in the original
trial19. For the consent process, we contacted past participants and their parents and
explained the study in detail by phone and/or email, and provided them with a copy of the
parent permission form and the child assent form. After the informed consent process, all 18
9. families agreed to participate and signed written parent permission and assent forms. We
maintained confidentiality of participants results by de-identifying all samples for the entire
analyses. The participant’s name and identifiers were removed and not used in all sections of
the manuscript, including supplementary information. The trial was registered at the
ClinicalTrials.gov (NCT02504554) on March 30, 2015.
Study objective. The purpose of the study was to conduct a 2-year follow-up on children with
ASD who participated in the original study and to determine long-term safety and efficacy of
the Microbial Transfer Therapy (MTT). In brief, the previous study was designed to perform an
open-label clinical trial for children with ASD and moderate to severe GI problems (ages 7–17
years)19. Eighteen children were enrolled in the previous study and treated with a combination
of vancomycin (to reduce pathogenic bacteria) for 2 weeks, MoviPrep (a bowel cleanse to
remove vancomycin and remaining bacteria), Prilosec (a proton pump inhibitor in order to
reduce stomach acidity and to increase the survival rate of high and maintenance doses of
SHGM), and Standardized Human Gut Microbiota (gut bacteria from healthy donors) for 7–8
weeks41. Participants were monitored during the 10 weeks of treatment, and again 8 weeks
after MTT stopped. There were no major adverse effects, and all 18 participants completed the
study. Most of the children had substantial reduction of their GI and ASD symptoms, and those
improvements remained at the follow-up at 8 weeks after the treatment ended. Further
information on the previous study design and outcomes are described in Kang et al.19. In this
current study, we followed up past participants approximately 2 years since the treatment
stopped, and requested parents to collect one stool sample from their child in order to
investigate changes in bacterial composition. After the study ended, 6 participants did not
make any changes in their treatments for the next two years, and 12 participants made one or
more changes (Supplementary Table S1). The changes (and the number of participants making
those changes) included dietary changes (gluten-free/casein-free diet (1), ketogenic diet (1),
and removing eggs(1)), GI treatments (magnesium citrate (2), digestive enzymes (1), dulcolax
(1), enteragam (1), probiotics (2)), medication changes (Abilify (1), birth control (1), IVIG (1),
Lamictal (1), lithium (1), Tenex (1), thryroid (1), and Vyvanse (1), and nutritional supplements
(amino acids (1), multivitamins (2), Bravo yogurt (1), citruline (1), fish oil (1), GABA (1), l-theanine
(1), magnesium (1), Oraimmune (1), and Rerum (1). Participants were asked to rate the
perceived effectiveness of each treatment on a scale of 0–4 for both GI and ASD symptoms,
where 0 = “No effect”, 1 = “Slight benefit”, 2 = “Moderate benefit”, 3 = “Good benefit”, and 4 =
“Great benefit”.
Assessments of gastrointestinal and autism-related symptoms. To be consistent with the previ-
ous assessments19, we evaluated GI symptoms using a revised version of Gastrointestinal
Symptom Rating Scale (GSRS) that employs 7-point Likert scale42 in 5 domains: Abdominal
Pain, Reflux, Indigestion, Diarrhea, and Constipation. We also collected Daily Stool Records
(DSR) that rates the stool using the Bristol Stool Form scale (1 = very hard, 7 = liquid) over 14
days. For the assessments of autism and related symptoms, we also employed the same
assessments that we used in the previous study including the Parent Global Impressions–III
(PGI-III)43, the Childhood Autism Rating Scale (CARS), the Aberrant Behavior Checklist (ABC),
the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale II (VABS-II).
The CARS evaluation was conducted by the same professional evaluator who conducted the
previous CARS evaluation, and parents assessed the GSRS, DSR, PGI-III, ABC, SRS, and
VABS-II at approximately 2 years after the therapy stopped.
10. Microbial DNA extraction and next generation sequencing. In order to be consistent with the
pre- vious work in Kang et al.19, we employed the same DNA extraction assay, library
preparation, and sequencing methods. We extracted microbial genomic DNA from stool
samples using a PowerSoil® DNA Isolation Kit (Mobio Carlsbard, CA) and constructed 16S
rRNA library for MiSeq Illumina platform according to the protocol from Earth Microbiome
Project (http://www.earthmicrobiome.org/protocols-and-standards/16s/). The barcoded primer
set 515f -806r was used for pair-ended sequencing to target the 16 s rRNA V4 region44.
Library preparation and sequencing work were performed at the Microbiome Analysis
Laboratory in the Biodesign Institute of Arizona State University
(http://krajmalnik.environmentalbiotechnology.org/microbiome-lab.html).
Microbiome bioinformatics. The 16S rRNA gene data from our previous sequencing run was
generated from four Illumina MiSeq runs, and the follow-up data (new to this study) was
sequenced on a single MiSeq run. To ensure consistent processing across all of these runs,
and to enable the use of the most recent bioinformatics methods for microbiome analysis, we
processed all five of these sequencing runs together in a single QIIME 2 analysis45.
Analyses were performed on the forward reads only, to retain as many sequences as possible
(i.e., to not dis- card sequences where forward and reverse reads could not be joined).
Sequence quality control was performed with two different processing pipelines, both
implemented in QIIME 2.
The first processing pipeline used DADA246 via the q2-dada2 QIIME 2 plugin (we’ll refer to this
as the DADA2 pipeline). In the DADA2 pipeline, the first 10 bases were trimmed from reads and
reads were truncated at 150 bases prior to processing with the dada2-single method, as
recommended by the DADA2 authors. All other DADA2 parameters were left with their default
settings. DADA2 was run on a per-sequencing run basis using the same parameters for all runs
of DADA2. The resulting feature tables were merged, such that we had one master “feature
table” containing counts of features on a per sample basis, where our features were unique
16S rRNA gene sequence variants. The “feature sequence” that defined each feature was the
unique 16S rRNA gene sequence var- iant. Microbiome analysis results based on this
processing pipeline are presented in Figs 3, 4 and Supplementary Figs S4, S5.
The second processing pipeline used the quality filtering approach described in Bokulich et
al.47 as imple- mented in the q2-quality-filter plugin using a min-quality of 20 (all other
parameters were defaults). We will refer to this pipeline as the Q20 pipeline. Sequence reads
were subsequently clustered into 97% OTUs using open-reference OTU picking as
implemented in the q2-vsearch plugin (which uses vsearch48 for clustering). Again, we had one
master “feature table” containing counts of features on a per sample basis, where in this case
our features were 97% OTUs. The “feature sequence” that defined each feature was the OTU
centroid sequence. As an additional quality control step, features that were only observed in a
single sample and features that could not be assigned to a phylum against the Silva
database49 (described further below) were filtered from the feature table. Microbiome analysis
results based on this processing pipeline are presented in Supplementary Fig. S6.
Following both the DADA2 and Q20 pipelines, feature sequences were aligned with mafft50
(wrapped in the q2-alignment plugin), high entropy positions were filtered from the resulting
alignment51, an unrooted tree was constructed with FastTree52 (wrapped in the q2-phylogeny
11. plugin), and the tree was rooted using midpoint root- ing. Taxonomy was assigned to each
feature sequence against the Silva 119 database using a Naïve Bayes classifier implemented in
the q2-feature-classifier plugin53. Feature tables were rarefied to 5,298 sequences per sample,
and diversity metrics were computed using the q2-diversity plugin.
For complete details on the bioinformatics methods, including the versions of all software and
dependencies, and all commands and parameter settings, readers can view the provenance
data contained in the Supplementary File S1. This information can be viewed visually at
https://view.qiime2.org.
The specific values of the microbiome richness and distance metrics differ between the DADA2
and Q20 bioinformatics pipelines. For example, Faith’s Phylogenetic Diversity is considerably
lower with the DADA2 pipe- line, likely because it does a much better job at raw sequence
quality control (as described in the original DADA2 paper). Despite this, it is encouraging to
observe that the different quality control and feature definition pipelines illustrate the same
trends in microbiome composition and richness.
Statistical analysis. We assumed the data as non-normally distributed because of a relatively
small sample size, and performed nonparametric analyses of Mann-Whitney U-test, Wilcoxon
signed-rank test, and Spearman correlation test. We reported all p values from two-tailed tests,
and accepted p values lower than 0.05 as significant. For the boxes in Figs 1, 3 and 4, the
cross line in the box indicates median values and the bottom and top edges of the box indicate
the 25th and 75th percentiles of the sample.
Data Availability
The 16S rRNA gene sequence reads are available in the open-source sequence data repository
‘Qiita’ with the study ID number 10532 (https://qiita.ucsd.edu) and the NCBI SRA under
BioProject ID PRJNA529598. For de- tails on obtaining and installing QIIME 2, see
https://qiime2.org. QIIME 2 is open source and free for all use. The analyses presented in Fig. 3
and Supplementary Figs S4–S6 were performed using Jupyter Notebooks. These notebooks
are available at https://github.com/caporaso-lab/autism-fmt1.
References
1. Rogers, G. B. et al. From gut dysbiosis to altered brain function and mental illness:
mechanisms and pathways. Molecular Psychiatry 21, 738–748,
https://doi.org/10.1038/mp.2016.50 (2016).
2. Sharon, G., Sampson, T. R., Geschwind, D. H. & Mazmanian, S. K. The central nervous
system and the gut microbiome. Cell 167, 915–932, https://doi.org/10.1016/j.cell.2016.10.027
(2016).
3. McElhanon, B. O., McCracken, C., Karpen, S. & Sharp, W. G. Gastrointestinal symptoms in
autism spectrum disorder: a meta- analysis. Pediatrics 133,
https://doi.org/10.1542/peds.2013-3995 (2014).
4. Braak, H., Rub, U., Gai, W. P. & Del Tredici, K. Idiopathic Parkinson’s disease: possible
routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown
pathogen. Journal of Neural Transmission 110, 517–536, https://doi.org/10.1007/ s00702-002-
0808-2 (2003).
12. 5. McCarthy, M., AddingtonHall, J. & Altmann, D. The experience of dying with dementia: A
retrospective study. International Journal of Geriatric Psychiatry 12, 404–409,
https://doi.org/10.1002/(SICI)1099-1166(199703)12:3<404::AID-GPS529>3.0.CO;2-2 (1997).
6. Hallmayer, J. et al. Genetic heritability and shared environmental factors among twin pairs
with autism. Archives of General Psychiatry 68, 1095–1102,
https://doi.org/10.1001/archgenpsychiatry.2011.76 (2011).
7. Finegold, S. M. et al. Pyrosequencing study of fecal microflora of autistic and control
children. Anaerobe 16, 444–453, https://doi. org/10.1016/j.anaerobe.2010.06.008 (2010).
8. De Angelis, M. et al. Fecal microbiota and metabolome of children with autism and pervasive
developmental disorder not otherwise specified. Plos One 8, 18,
https://doi.org/10.1371/journal.pone.0076993 (2013).
9. Williams, B. L., Hornig, M., Parekh, T. & Lipkin, W. I. Application of novel PCR-based
methods for detection, quantification, and phylogenetic characterization of Sutterella species in
intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio 3,
e00261–11, https://doi.org/10.1128/mBio.00261-11 (2012).
10. Gondalia, S. V. et al. Molecular characterisation of gastrointestinal microbiota of children
with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings.
Autism Research 5, 419–427, https://doi.org/10.1002/aur.1253 (2012).
11. Son, J. S. et al. Comparison of fecal microbiota in children with autism spectrum disorders
and neurotypical siblings in the Simons
simplex sollection. Plos One 10, e0137725, https://doi.org/10.1371/journal.pone.0137725
(2015).
12. Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities
associated with neurodevelopment disorders. Cell
155, 1451–1463, https://doi.org/10.1016/j.cell.2013.11.024 (2013).
(2019) 9:5821 | https://doi.org/10.1038/s41598-019-42183-0 7
13. Kim, S. et al. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse
offspring. Nature 549, 528–532, https:// doi.org/10.1038/nature23910 (2017).
14. Buffington, S. A. et al. Microbial reconstitution reverses maternal diet-induced social and
synaptic deficits in offspring. Cell 165, 1762–1775, https://doi.org/10.1016/j.cell.2016.06.001
(2016).
15. Lacivita, E., Perrone, R., Margari, L. & Leopoldo, M. Targets for drug therapy for autism
spectrum disorder: challenges and future directions. Journal of Medicinal Chemistry 60, 9114–
9141, https://doi.org/10.1021/acs.jmedchem.7b00965 (2017).
16. Bagdasarian, N., Rao, K. & Malani, P. N. Diagnosis and treatment of Clostridium difficile in
adults a systematic review. Jama-Journal of the American Medical Association 313, 398–408,
https://doi.org/10.1001/jama.2014.17103 (2015).
17. Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with
active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109,
https://doi.org/10.1053/j.gastro.2015.04.001 (2015).
18. Xu, M. Q. et al. Fecal microbiota transplantation broadening its application beyond
intestinal disorders. World Journal of Gastroenterology 21, 102–111,
https://doi.org/10.3748/wjg.v21.i1.102 (2015).
19. Kang, D.-W. et al. Microbiota Transfer Therapy alters gut ecosystem and improves
gastrointestinal and autism symptoms: an open- label study. Microbiome 5, 10,
https://doi.org/10.1186/s40168-016-0225-7 (2017).
20. Belsito, K. M., Law, P. A., Kirk, K. S., Landa, R. J. & Zimmerman, A. W. Lamotrigine therapy
for autistic disorder: A randomized, double-blind, placebo-controlled trial. Journal of Autism
and Developmental Disorders 31, 175–181, https://doi. org/10.1023/a:1010799115457 (2001).
13. 21. Nah, Y. H., Young, R. L. & Brewer, N. Using the Autism Detection in Early Childhood
(ADEC) and Childhood Autism Rating Scales (CARS) to predict long term outcomes in children
with autism spectrum disorders. Journal of Autism and Developmental Disorders 44, 2301–
2310, https://doi.org/10.1007/s10803-014-2102-1 (2014).
22. Gattino, G. S., Riesgo, R. D., Longo, D., Leite, J. C. L. & Faccini, L. S. Effects of relational
music therapy on communication of children with autism: a randomized controlled study.
Nordic Journal of Music Therapy 20, 142–154, https://doi.org/10.1080/080981 31.2011.566933
(2011).
23. Saad, K. et al. Randomized controlled trial of vitamin D supplementation in children with
autism spectrum disorder. Journal of Child Psychology and Psychiatry 59, 20–29,
https://doi.org/10.1111/jcpp.12652 (2018).
24. Adams, J. B., Johansen, L. J., Powell, L. D., Quig, D. & Rubin, R. A. Gastrointestinal flora
and gastrointestinal status in children with autism-comparisons to typical children and
correlation with autism severity. Bmc Gastroenterology 11, 22, https://doi. org/10.1186/1471-
230x-11-22 (2011).
25. Horvath, K. & Perman, J. A. Autistic disorder and gastrointestinal disease. Current Opinion
in Pediatrics 14, 583–587, https://doi. org/10.1097/01.mop.0000030221.71203.46 (2002).
26. Kang, D. W. et al. Reduced incidence of Prevotella and other fermenters in intestinal
microflora of autistic children. Plos One 8, e68322,
https://doi.org/10.1371/journal.pone.0068322 (2013).
27. Ilhan, Z. E. et al. Distinctive microbiomes and metabolites linked with weight loss after
gastric bypass, but not gastric banding. Isme Journal 11, 2047–2058,
https://doi.org/10.1038/ismej.2017.71 (2017).
28. Ahn, J. et al. Human gut microbiome and risk for colorectal cancer. Jnci-Journal of the
National Cancer Institute 105, 1907–1911, https://doi.org/10.1093/jnci/djt300 (2013).
29. Ott, S. J. et al. Reduction in diversity of the colonic mucosa associated bacterial microflora
in patients with active inflammatory bowel disease. Gut 53, 685–693,
https://doi.org/10.1136/gut.2003.025403 (2004).
30. Lozupone, C. & Knight, R. UniFrac: a new phylogenetic method for comparing microbial
communities. Applied and Environmental Microbiology 71, 8228–8235,
https://doi.org/10.1128/aem.71.12.8228-8235.2005 (2005).
31. Kang, D. W. et al. Differences in fecal microbial metabolites and microbiota of children with
autism spectrum disorders. Anaerobe 49, 121–131,
https://doi.org/10.1016/j.anaerobe.2017.12.007 (2017).
32. Qiao, Y. A. et al. Alterations of oral microbiota distinguish children with autism spectrum
disorders from healthy controls. Scientific Reports 8, 12, https://doi.org/10.1038/s41598-018-
19982-y (2018).
33. Esquivel-Elizondo, S., Ilhan, Z. E., Garcia-Pena, E. I. & Krajmalnik-Brown, R. Insights into
butyrate production in a controlled fermentation system via gene predictions. mSystems 2, 13,
https://doi.org/10.1128/mSystems.00051-17 (2017).
34. Donohoe, D. R. et al. The microbiome and butyrate regulate energy metabolism and
autophagy in the mammalian colon. Cell Metabolism 13, 517–526,
https://doi.org/10.1016/j.cmet.2011.02.018 (2011).
35. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180,
https://doi.org/10.1038/nature09944 (2011).
36. Derrien, M. et al. Mucin-bacterial interactions in the human oral cavity and digestive tract.
Gut Microbes 1, 254–268, https://doi.
org/10.4161/gmic.1.4.12778 (2010).
14. 37. Sandler, R. H. et al. Short-term benefit from oral vancomycin treatment of regressive-onset
autism. Journal of Child Neurology 15,
429–435, https://doi.org/10.1177/088307380001500701 (2000).
38. Singh, K. et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of
the National Academy of Sciences of the
United States of America 111, 15550–15555, https://doi.org/10.1073/pnas.1416940111 (2014).
39. Gotham, K., Pickles, A. & Lord, C. Trajectories of autism severity in children using
standardized ADOS scores. Pediatrics 130,
E1278–E1284, https://doi.org/10.1542/peds.2011-3668 (2012).
40. Jain, K. S. et al. Recent advances in proton pump inhibitors and management of acid-
peptic disorders. Bioorganic & Medicinal
Chemistry 15, 1181–1205, https://doi.org/10.1016/j.bmc.2006.07.068 (2007).
41. Hamilton, M. J., Weingarden, A. R., Sadowsky, M. J. & Khoruts, A. Standardized frozen
preparation for transplantation of fecal
microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 107, 761–767,
https://doi.org/10.1038/ajg.2011.482
(2012).
42. Revicki, D. A., Wood, M., Wiklund, I. & Crawley, J. Reliability and validity of the
gastrointestinal symptom rating scale in patients
with gastroesophageal reflux disease. Quality of Life Research 7, 75–83,
https://doi.org/10.1023/A:1008841022998 (1997).
43. Adams, J. B. et al. Effect of a vitamin/mineral supplement on children and adults with
autism. BMC Pediatr 11, https://doi.
org/10.1186/1471-2431-11-111 (2011).
44. Caporaso, J. G. et al. Ultra-high-throughput microbial community analysis on the Illumina
HiSeq and MiSeq platforms. Isme
Journal 6, 1621–1624, https://doi.org/10.1038/ismej.2012.8 (2012).
45. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing
data. Nature Methods 7, 335–336, https://
doi.org/10.1038/nmeth.f.303 (2010).
46. Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data.
Nature Methods 13, 581–583, https://
doi.org/10.1038/nmeth.3869 (2016).
47. Bokulich, N. A. et al. Quality-filtering vastly improves diversity estimates from Illumina
amplicon sequencing. Nature Methods 10,
57–59, https://doi.org/10.1038/nmeth.2276 (2013).
48. Rognes, T., Flouri, T., Nichols, B., Quince, C. & Mahe, F. VSEARCH: a versatile open
source tool for metagenomics. Peerj 4, e2584,
https://doi.org/10.7717/peerj.2584 (2016).
49. Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data
processing and web-based tools. Nucleic Acids
Research 41, D590–D596, https://doi.org/10.1093/nar/gks1219 (2013).
50. Katoh, K. & Standley, D. M. MAFFT Multiple Sequence Alignment Software Version 7:
Improvements in Performance and Usability.
Molecular Biology and Evolution 30, 772–780, https://doi.org/10.1093/molbev/mst010 (2013).
51. Lane, D. Nucleic Acid Techniques in Bacterial Systematics. 115–175 (John Wiley and Sons,
1991).
52. Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2-approximately maximum-likelihood trees
for large alignments. Plos One 5, e9490, https://doi.org/10.1371/journal.pone.0009490 (2010).