Category Archives: Integrative Medicine

image:Co-first author and Anatomy & Neurobiology graduate student, Alexa Tierno, holds a mouse brain made transparent to visualize connections between nerve cells in the entire brain. An image of neurons in medial entorhinal cortex projecting to transplanted interneurons in damaged hippocampus is shown in the background. view more

Credit: UCI School of Medicine

Irvine, Calif., June 17, 2022 Scientists from the University of California, Irvine have discovered that an injury to one part of the brain changes the connections between nerve cells across the entire brain. The new research was published this week in Nature Communications.

Every year in the United States, nearly two million Americans sustain a traumatic brain injury (TBI). Survivors can live with lifelong physical, cognitive and emotional disabilities. Currently, there are no treatments.

One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.

In the new study, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent. The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialized microscopes.

With the enhanced brain clearing processes, the UCI team mapped neural connections throughout the entire brain. The researchers focused on connections to inhibitory neurons, because these neurons are extremely vulnerable to dying after a brain injury. The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus. In both cases, the imaging showed that inhibitory neurons gain many more connections from neighboring nerve cells after TBI, but they become disconnected from the rest of the brain.

Weve known for a long time that the communication between different brain cells can change very dramatically after an injury, said Robert Hunt, PhD, associate professor of anatomy and neurobiology and director of the Epilepsy Research Center at UCI School of Medicine whose lab conducted the study, But, we havent been able to see what happens in the whole brain until now.

To get a closer look at the damaged brain connections, Hunt and his team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.

The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.

It looks like the entire brain is being carefully rewired to accommodate for the damage, regardless of whether there was direct injury to the region or not, explained Alexa Tierno, a graduate student and co-first author of the study. But different parts of the brain probably arent working together quite as well as they did before the injury.

The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, Hunt and his team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the teams earlier research demonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.

The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, Hunt said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.

Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders, said Hunt. Some people have proposed interneuron transplantation might rejuvenate the brain by releasing unknown substances to boost innate regenerative capacity, but were finding the new neurons are really being hard wired into the brain.

Hunt hopes to eventually develop cell therapy for people with TBI and epilepsy. The UCI team is now repeating the experiments using inhibitory neurons produced from human stem cells.

This work takes us one step closer to a future cell-based therapy for people, Hunt said, Understanding the kinds of plasticity that exists after an injury will help us rebuild the injured brain with a very high degree of precision. However, it is very important that we proceed step wise toward this goal, and that takes time.

Jan C. Frankowski, PhD; Shreya Pavani; Quincy Cao and David C. Lyon, PhD also contributed to this study. Funding was provided by the National Institutes of Health.

###

About the UCI School of Medicine: Each year, the UCI School of Medicine educates more than 400 medical students, as well as 200 doctoral and master's students. More than 600 residents and fellows are trained at UC Irvine Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master's degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master's in public health, or an MD/master's degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

Nature Communications

Brain-wide reconstruction of inhibitory circuits after traumatic brain injury

15-Jun-2022

The authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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UCI neuroscientists create maps of the brain after traumatic brain injury - EurekAlert

As many as 2,650 students of Alvas Group of Institutions performed Yoga on the occasion of International Yoga Day at the Alvas Nudisiri Vedike in Moodbidri on Tuesday.

The Alvas Education Foundation had laid a red carpet in the 60,000 sq ft area of the vedike for students to do asanas.

The yoga session was held between 6.30 a.m. and 7.30 p.m. Nearly 10,000 students from 35 schools and colleges, who had been trained by students of Alvas Naturopaty and Yogic Sciences for a week, joined the session virtually.

Moodbidri Jain Mutt seer Charukeerti Bhattaraka Swami inaugurated the session. Chairman of Alvas Education Foundation M Mohan Alva and staff of Alvas Group of Institutions participated in the programme.

More than 2,000 people performed yoga at the popular Thousand Pillar Jain Basadi in Moodbidri. The session was conducted by Patanjali Yoga Shikshana Samiti.

Charukeerti Bhattaraka Swami took part in the session held between 5.30 a.m. and 7 a.m.

More than 800 cadets from Mangaluru Group NCC celebrated International Yoga Day by performing Yoga on the Blue Flag beach at Padubidri.

As many as 863 cadets from Army, Navy and Air NCC units took part in the programme held amid a drizzle.

Colonel N.R. Bhide, Colonel Amitabh Singh and Colonel Anilesh Kaushik were among the NCC officers and staff who took part in the event.

Personnel from the Department of Tourism, staff of the Blue Flag beach and representatives from AYUSH Department also attended.

A good number of students and Udupi city residents participated in the one-hour-long yoga session, which was a part of the Yoga day programme jointly organised by Manipal Academy of Higher Educations Yoga Division and Centre for Integrative Medicine and Research. The programme was held at the TMA Pai Hall in KMC, Manipal.

Members of Yuva Red Cross, NSS volunteers and other students took part in a programme held at the P. Dayanand Pai Satish Pai Government First Grade College, Car Street. Yoga guru Gopalakrishna Delampady was the resource person. Delampady also conducted yoga session for staff and students of the St. Aloysius College at the colleges Arrupe Block.

More than 150 students and staff members attended the yoga session organised jointly by St. Agnes Colleges Post-Graduate Department of Psychology and Clinical Psychology and Centre for Post-Graduate Studies and Research.

Chairman of Sharada Group of Institutions M.B. Puranik chaired the Yoga day celebrations held at Sharada Vidyalaya in Kodailbail.

Among the other institutions where the celebrations were held included Yenepoya Naturopathy and Yogic Science College and Hospital, St Theresas School and Shakti Residential School.

Udupi Principal District and Sessions Judge Shantaveera Shivappa led a group of judicial officers and advocates who performed Yoga on the Udupi District Court premises on Tuesday morning. Mangaluru advocates performed yoga at the Old District Court building on Tuesday evening.

Staff of Adani Airports, Central Industrial Security Force, Airport Customs personnel and staff of private airlines took part in the International Yoga Day celebrations held at the Mangaluru International Airport.

Staff of Employees Provident Fund Organisation celebrated the Yoga day at the Mangaluru RegionalOffices auditorium. Yoga teacher Kushalappa Gowda conducted the yoga session. Regional PF Commissioner (RPFC)-1 N. Gopalkrishnan and RPFC-2 Sandeep Kumar were among those who took part in the programme.

Essay and quiz competition were held for the staff, while painting competition was held for children of the staff members.

International Yoga Day was also celebrated at the New Mangalore Port Trust. Office-bearers of Dakshina Kannada Union of Working Journalists and other reporters from the district did asanas at the Press Club.

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More than 2,000 students perform asanas in Moodbidri - The Hindu

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Get to know Chiropractor Dr. Anthony Hardnett, who serves patients throughout the State of Maryland.

(ProNewsReport Editorial):- New York City, New York Jun 21, 2022 (Issuewire.com)An established chiropractor, Dr. Hardnett places his emphasis on treating the patient as a whole and finding the cause of the problem, not just the symptoms. He owns and operates the premier state-of-the-art Effective Chiropractic Health & Wellness Center in Maryland, and has an overwhelmingly high success rate in helping patients with their health concerns. He feels that offering the latest treatment options, efficient care plans and patient education are all keys to the patients ultimate success. In 11 short years, he has made his practice the premier state-of-the-art chiropractic health and wellness facility in Maryland.

Effective Chiropractic Health & Wellness Center has grown from a small, 2-person office to a staff of 16 with expanded services and providers to meet their patients needs. It provides a variety of services that make them a one-stop-shop for healthcare. And in an effort to further expand services, the doctor has now added a Medical Doctor and Nurse Practitioner establishing Effective Integrative Healthcare, LLC to provide more integrative services for the community. He also added another office in Prince Georges County to further expand the practices ability to reach and help more patients.

In regards to his educational background, Dr. Hardnett graduated with his Doctor of Chiropractic degree from Life University in 2007. He is board-certified in Integrative Medicine (BCIM), which is the practice of using multiple treatment options within traditional medicine and alternative medicine to help patients. He also has extensive post-doctorate education relating to MRI interpretation and treatment of disc-related injuries.

With an unwavering commitment to his specialty, the doctor has been recognized as a Diplomate of the College of Manipulative and Body-Based Practices (DMBBP), which enhances his knowledge of how manipulation of the spine can assist the body to heal, as well as a Diplomate of the American Academy of Medical Legal Professionals (DAAMLP).

Chiropractic is a form of alternative medicine that mainly deals with the diagnosis and treatment of mechanical disorders of the musculoskeletal system, especially the spine. A chiropractor uses spinal adjustments, manipulation, and other techniques to manage patients health concerns, including neck pain, back pain, headaches, vertigo, and a long list of other ailments and conditions. They aim to improve patients functionality and quality of life by properly aligning the bodys musculoskeletal structure and enabling the body to heal itself naturally, without the use of medication or surgery.

Learn More about Dr. Anthony Hardnett:Through his findatopdoc profile, https://www.findatopdoc.com/doctor/2610078-Anthony-Hardnett-Chiropractor, or through Effective Chiropractic Health & Wellness Center, https://www.eihmd.com/about-us/

About FindaTopDoc.comFindaTopDoc is a digital health information company that helps connect patients with local physicians and specialists who accept your insurance. Our goal is to help guide you on your journey towards optimal health by providing you with the know-how to make informed decisions for you and your family.

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Anthony Hardnett, DC, BCIM, DMBBP, DAAMLP, a Chiropractor with Effective Chiropractic Health Wellness Center - Pro News Report

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India is all set to unveil its first integrated Ayurveda nursing degree as an add-on to Allopathy or conventional nursing programme in an effort to offer the best of integrated medicine benefits to patients. Offered to nurses trained in Allopathy, the Ayurveda component will be a year-long add-on training capsule with specific subjects and hands-on training.

The proposal, which is in the last phase of its approval with the Nursing Council of India, is expected to become a reality by this year-end.

The syllabus has been created by the All India Institute of Ayurveda (AIIA), the apex tertiary care centre for Ayurveda in the country, said AIIA director Prof. Tanuja Nesari, who added that this will be a first of its kind programme which will be a breakthrough in integrative health care.

Giving details of the initiative Dr. Rajagopala S, medical superintendent, AIIA, said nursing care was one of the four important pillars of health care and the integrated knowledge of both the therapies would be an asset.

The syllabus has been prepared by top professionals in both allopathic and Ayurveda fields and the intake will be of nursing graduates who have finished their allopathic training. The syllabus has been submitted to the Nursing Council and the council has had several rounds of meetings on the issue, he said.

If all goes well we should be able to offer the course soon. Besides the AIIA, institutes that have the infrastructure and manpower to conduct the course will be offering this to students, he added.

Nursing superintendent at the AIIA Sindhu Rajesh said this would be a residency programme where students would take theory classes and work in hospital for hands-on training.

We are proposing a 80:20 ratio of practical and theory, she said, adding that the syllabus had been approved in-principle and the suggestions made by the council had been incorporated. The draft syllabus was now undergoing the approval process.

The notification for the course could come in by August-end if all goes well, said Ms. Rajesh.

India currently offers Ayurveda nursing for those having finished Class 12 with science subjects.

The courses being offered currently, both B.Sc programme and diploma, dont offer nurses trained in the Ayurvedic stream a licence and registration number, which allows them the flexibility to work in the national or international arena. Their university registration is not recognised by the Indian Nursing Council, said Ms. Rajesh.

She added that the Nursing Council wants rigorous training like that offered to allopathic nurses for those wanting to specialise in Ayurveda. This can be achieved by the add-on programme that we are offering. It also eliminates the lacunae of not being registered to work internationally. Also, for the integrated medical therapy that we offer to our patients allopathic training helps. The idea is to provide holistic and rigorous medical care for patients, said Ms. Rajesh.

Excerpt from:
India all set to offer Ayurveda add-on nursing programme - The Hindu

MADRID, June 21, 2022 /PRNewswire/ -- Idoven, a pioneering health tech company advancing early detection and precision medicine of cardiovascular disease, today announced that it has raised $19.8 million in funding. The funding consists of a $12.9 million Series A round co-led by global software investor Insight Partners and Northzone with participation from Wayra.

The round is also supplemented by $6.9 million in grant and equity funding awarded by the European Innovation Council (EIC) Accelerator. The new funding will be used to further develop the company's best-in-class AI platform to identify arrhythmias and cardiac abnormalities, as well as accelerate hiring to build on its mission to advance early diagnosis and precision medicine of cardiovascular diseases.

A prominent list of angel investors joined the round, including Ron Vianu, Founder and CEO of Covera Health; Brad Fluegel, Former SVP, Chief Healthcare Commercial Officer and Strategy Officer at Walgreens; and Vlad Lata, Founder and CEO of Avi Medical, among others. The round was also joined by existing angels, including Iker Casillas, captain of Spain's World Cup-winning football team and UNDP ambassador, and former senior executives from Amazon and Apple, Diego Piacentini and Sebastian Gunningham. This round follows a $2 million seed round raised 12 months ago from leading business angels, Wayra and the Accel Starter programme.

Cardiovascular disease is the leading cause of death and is expected to be a $1 trillion public health burden by 2035, based on a study by the American Heart Association1. Managing this public health challenge starts with early diagnosis, and the most ubiquitous point-of-care test to detect heart problems is the electrocardiogram (ECG). However, today's healthcare outdated systems are not sufficient to keep up with the demand for ECG interpretation. Over 1 million hours are spent by physicians just in Europe every day analysing patients' ECG data to diagnose arrhythmias and other heart conditions. Moreover, with the use of wearables and other biosensors rapidly accelerating, the healthcare industry requires new approaches to analyse data at unprecedented speed and scale. Idoven was born to solve this problem.

Story continues

Idoven's team of data scientists, engineers and cardiologists leverage a proprietary deep learning system applied to cardiology to develop the world's first cardiology-as-a-service platform powered by AI that augments a clinician's ability to identify, triage and diagnose patients at scale. The solution is cloud-based and hardware-agnostic, able to analyse ECGs of any duration and from any device, and is made available to customers via API. The algorithmsdetect heart conditions that affect over 90% of the global population.

Unlike other health technology companies using AI to detect heart problems that are proprietary to their own hardware, Idoven's technology is hardware agnostic. This ensures that Idoven's algorithms are trained on the most complete database of signals, from 1-lead smartwatch ECGs to 12-lead hospital ECGs and long-duration ambulatory ECGs. Interpreting all types of ECG data is critical for obtaining a complete and standardised picture of the patient's cardiac history at any moment during the patient journey.

Dr. Marina Manuel Breysse, cardiologist, co-founder and CEO of Idoven said "Our AI software, Willem, has been learning cardiology for years and today, can help diagnose heart disease, anywhere and at any time, dramatically increasing our capacity to identify people in need of care. Our vision is to transform the way cardiovascular diseases are identified by augmenting the physician's decision making through integration of AI algorithms into the everyday clinical workflow. Deep learning algorithms can significantly improve the diagnostic accuracy of software found in existing ECG hardware, and create new prediction capabilities. Our technology is being used by leading medical device manufacturers and pharmaceutical companies to standardise at scale the analysis of ECGs. ECGs are used in virtually all clinical trials, to track patients' heart conditions in almost any medical specialty, as well as to monitor the safety of treatments with cardiac effects, particularly prevalent in cardiac and cancer treatments. We are excited to be at the very forefront of this movement in cardiovascular care to help doctors and patients all over the world."

One of the company's early backers, Iker Casillas, legendary Real Madrid goalkeeper and World Cup-winning Spain football team captain, refers to Idoven as "the AI that saved my life." After suffering a life-changing heart attack during training in 2019, Casillas and his foundation have teamed up with Idoven to promote the early detection and intervention of cardiovascular diseases, particularly among the most vulnerable groups like children with Down Syndrome and patients with congenital heart diseases or at high risk of sudden cardiac death.

Scott Barclay, Managing Director at Insight Partners said, "The future of medicine requires deeply validated artificial intelligence deployed via API to augment clinicians, and this is especially true in cardiology given the importance of heart health and the explosion of monitoring technology. Idoven has the chance to improve healthcare and save lives, at scale. This is the essence of the type of software-driven technology and empathy that Insight looks for in early healthcare investments."

Michiel Kotting, Partner at Northzone said, "In meeting the team at Idoven we were instantly struck with how big the impact of their work can be on global health. Starting with cardiologist-level accuracy in seconds and at scale for hospital ECGs, saving cost and avoiding delays, the database they are building up will enable potential heart problems to be spotted in advance on everyday fitness trackers. The unique skill set of a phenomenal team with deep backgrounds in cardiology, statistics, AI/ML and operations will enable this exciting future. We are incredibly proud and excited to join the team on this journey."

Through exclusive partnerships and research collaborations with world-class research institutions, Idoven has developed one of the world's largest ECG databases for AI development and scientific innovations. Among them is the pan-European MAESTRIA Consortium (Machine Learning and Artificial Intelligence for Early Detection of Stroke and Atrial Fibrillation) that involves collaboration with 17 other leading European and US research centres, and industry partners to develop and validate the first European integrative diagnostic digital platform, starting with atrial fibrillation.

About IDOVEN

Idoven is a health technology company advancing early detection and precision medicine for cardiovascular diseases. Idoven's AI-powered platform, WillemTM, delivers substantial improvements to the speed, consistency and accuracy of electrocardiogram (ECG) interpretation and prediction. Its powerful, proprietary AI algorithms, which work with existing ECG devices, are also being applied to develop disease biomarkers towards patient identification, risk stratification and prognosis, as well as drug cardiac safety monitoring. Idoven partners with leading medical device and pharmaceutical companies on AI-driven innovations to develop a new standard of cardiovascular care. Idoven has been awarded with numerous distinctions for its AI technology in Europe and the US, including the prestigious European Innovation Council (EIC) Accelerator and Horizon 2020 (H2020) awards and the Healthy Longevity Catalyst Award from the US National Academy of Medicine. The company is backed by top tier investors including Insight Partners, Northzone and Wayra (Telefnica), the Accel Starters programme, leading business angels and EIT Health. For more information on Idoven, visit idoven.ai or follow us on LinkedIn @idoven.

About Insight Partners

Insight Partners is a global software investor partnering with high-growth technology, software, and Internet startup and ScaleUp companies that are driving transformative change in their industries. As of February 24, 2022, the closing of the firm's recent fundraise, Fund XII, brings Insight Partners' regulatory assets under management to over $90B. Insight Partners has invested in more than 600 companies worldwide and has seen over 55 portfolio companies achieve an IPO. Headquartered in New York City, Insight has offices in London, Tel Aviv, and Palo Alto. Insight's mission is to find, fund, and work successfully with visionary executives, providing them with practical, hands-on software expertise to foster long-term success. Insight Partners meets great software leaders where they are in their growth journey, from their first investment to IPO. For more information on Insight and all its investments, visit insightpartners.com or follow us on Twitter @insightpartners.

About Northzone

Northzone (northzone.com) is an early-stage venture capital fund built on experience spanning multiple economic and disruptive technology cycles and has over $1.7 billion under management. Founded in 1996 and with a team spread across three main hubs, New York, London and Stockholm, Northzone has to date raised nine funds and invested in more than 150 companies, including category-defining businesses like Spotify, iZettle, Avito, Kahoot!, Hopin, Klarna and Trustpilot.

1https://www.rti.org/news/cardiovascular-disease-costs-will-exceed-1-trillion-2035

Cision

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Idoven Raises $19.8 Million in Funding to Redefine Detection and Precision Medicine of Cardiovascular Diseases with AI - Yahoo Finance

Advances in genetic technology have rapidly changed healthcare delivery in low- and middle-income countries. NGS utilization has decreased the time to diagnosis, increased the diagnostic rate, and provided valuable insight into the genotypephenotype correlation of IEI in a timely and cost-effective way28,29. IEI is not uncommon in India; however, their diagnosis is either missed or delayed due to a lack of awareness and a paucity of diagnostic facilities. There is an urgent need to increase testing capacity for early recognition, diagnosis, and management of IEI in our country30,31,32.

We have been diagnosing patients with IEI at our centre for the past 25years. However, services for molecular diagnosis for IEI both in government and commercial sectors have not been available in India until 2016. For molecular diagnosis of IEI, we established academic collaboration with Service Hmatologie, Immunologie et de Cytogntique, Hpital de Bictre, Le Kremlin Bictre, at France in the year 2007. Later, we established collaboration with institutes at Japan (National Defense Medical College, Saitama) and Hong Kong (Department of Paediatric and Adolescent Medicine, University of Hong Kong) in the years 2008 and 2010, respectively. This has facilitated molecular diagnosis for many of our patients with IEI. Our centre was designated as Centre for Advanced Research in diagnosis and treatment for primary immunodeficiency diseases by the Indian Council of Medical Research, Government of India, in 2015. Until 2016, tests available for diagnosis of IEI at our centre include immunoglobulin estimation, NBT, and flow cytometry for several surface and intracellular proteins10. With the increase in patients diagnosed with IEI in the last few years, we felt the need to establish molecular analysis at our centre4. We initiated Sanger sequencing for BTK, CYBB, and WAS genes in our centre in 2016 (Fig.1).

Commercial laboratories in India came up with facilities (targeted exome) for molecular diagnosis of IEI in 2016. Costs incurred for sequencing in commercial laboratories were exorbitant (USD 400500) in 2016 that later reduced in the subsequent years (USD 200 currently). The introduction of targeted NGS for IEI in 2018 at our centre has enabled us to offer this diagnostic modality to many of our patients who could not afford the costs of commercial testing. We have also been able to diagnose more IEIs each year and at a much faster pace than in previous years. The cost of targeted genetic sequencing at our setup is USD 83 per sample. This is much less than the costs incurred at commercial laboratories in India33. In addition, infants less than one year are covered under the JSSK (Janani Sishu Suraksha Karyakram) scheme of the Government of India. They are entitled to avail of NGS free of cost. Our Institute also provides free diagnostic services to patients from low-income groups who cannot afford the NGS charges, and charges are minimal for those who can afford this facility.

We have worked upon and improvised the standard protocol of NGS to suit our setup. We made some ingenious modifications to the recommended protocol to reduce the cost per sample and accommodate more patient samples in each run. Towards this end, we have successfully used half the recommended volume of reagents (however, concentration remained the same) at each successive step by starting with an initial DNA volume of 2.5L instead of 5L. So, a larger number of patient samples could be accommodated in each run. We have effectively run 42 patient samples with a 24-reaction reagent kit for 24 samples.

NGS sample preparation is a tedious and labour-intensive process requiring focus and concentration at each successive step34,35. After chip-loading and sequencing, we did not get results for two runs. On both these occasions, instead of repeating from the start, we started after the library quantification step as we were sure about the quality of the library preparation. So, restarting with the template preparation step instead of beginning from the start in the case of a failed run could be a helpful strategy if we are sure about the quality of library preparation.

We describe preliminary results of targeted NGS in 121 patients with different forms of IEIs diagnosed and managed at our centre. Our variant pick-up rate of 63.6% is much higher than previous studies- 25% by Yska et al. in 2019 and 29% by Vorsteveld et al. in 202128,36. The pick-up rate of variants in other studies were 16%7 (Gallo et al., Italy, 2016), 14% (Kojima et al., Japan, 2016)37, 2.1% (Sun et al., China in a cohort of infants)38, 28.6% (Cifaldi et al., Italy, 2020)18 and 42.4% (Arunachalam et al., India, 2020)33.

There are several reasons for a higher diagnostic yield in our study. Careful patient selection with a high pre-test probability based on clinical manifestations and preliminary immunological investigations was done. Patients with a high likelihood of having a pathogenic variant in one of 44 genes included in the gene panel are sorted out in consultation with clinicians trained in immunology and have broad experience in caring and managing patients with IEI. Currently more than 400 genes are implicated in various IEI. However, we selected 44 genes based on the most common diseases we encounter at our centre and also since we aimed to provide genetic diagnosis to maximum number of patients at an affordable cost. A large panel although more desirable would be costlier to design and in addition fewer samples would be accommodated in each run. Samples of patients who are very likely to have genetic variants in the genes included in the panel were included based on clinical history and initial immunological investigations. Patients with IEI not clearly delineated upon initial immunological investigations are referred for a clinical exome or whole-exome analysis. This analysis is outsourced to commercial laboratories providing these services at an affordable cost.

NGS has facilitated the early diagnosis of patients with IEI in situations where flow cytometry was either not conclusive or did not match the clinical presentation. For instance, patient 56 was clinically suspected of having an autosomal recessive hyper-IgM was found to have biallelic variants in the ATM gene. Hence, relying solely on typical manifestations of the IEI may not be ideal, and a rapid genetic diagnosis is indispensable39.

There have also been instances when the initial analysis on the Ion Reporter did not reveal a pathogenic variant. In patient 8 with clinically suspected XLA, no pathogenic variant was detected at initial analysis. There was a strong clinical suspicion of XLA in this case; we manually visualized the data on Integrative Genomics Viewer (IGV). We found a large deletion of exon-10, 11 and 12 in the BTK gene (Fig.2)40. Similarly, in another patient with suspected CGD (Pt.27), a large deletion was found in the CYBA gene, which was missed by the ion reporter software but was detected on manual reanalysis and visualization on the IGV. Patient 42 had an indel in IL2RG gene. In patient 42, analysis by the Ion reporter software revealed two IL2RG variants in close proximity, which was confusing. However, upon visualization of the BAM file on IGV, we realized that it was an indel (insertion of 3 nucleotides and deletion of 8 nucleotides) which was misinterpreted as two variants by the ion Reporter software.

Large deletion of Exon- 10 to 12 in BTK gene on Integrative Genome Viewer.

Hence, manual data visualization on IGV and manual analysis of annotated vcf files instead of relying on variants detected by initial analysis by software is crucial. We have been able to detect these variants in these cases using this strategy.

Detection of genetic variants in genes with known pseudogene is another problem that we encountered in our patient cohort. We faced this difficulty in patients with autosomal recessive CGD due to NCF1 gene defect. The targeted NGS panel systematically missed the most common pathogenic variant in NCF1, i.e., deletion of two nucleotides at the start of Exon-2. NCF1 gene has two flanking pseudogenes (NCF1)41. We assume that the amplicon designed for exon-2 of the NCF1 gene was unable to bind to its target, and thus, there was no amplification of this region, resulting in no reads for exon-2 in these patients. We performed a gene scan in 3 patients who had no reads in Exon-2 of the NCF1 gene to check for this variant and confirmed NCF1 GT deletion in all 3 of these patients (Fig.3A,B).

(A) IGV snapshot showing no reads from Exon-2 of NCF1 gene in 2 patients with AR-CGD (B) Gene Scan for Exon 2 NCF1 gene from control and an AR-CGD patient with no reads from exon 2 of NCF1 gene.

We have also been able to offer prenatal services to many patients. Patient 40 was clinically suspected of having SCID but had expired before a genetic defect could be established. His mother was pregnant at this time, and the period of gestation was 13weeks. We were able to identify a splice-site variant in the IL2RG gene in this family with X-linked SCID, and the mother was offered prenatal diagnosis by chorionic villous sampling. Molecular confirmation of diagnosis helped the family to get timely antenatal testing and appropriate genetic counselling. For some patients, especially SCID, rapid diagnosis through targeted NGS has saved lives, or genetic counselling has prevented an affected child in the subsequent pregnancy.

Pt 76 was the mother of a deceased child suspected to have X-linked Hyper-IgM, but a genetic diagnosis could not be established during the childs life. Targeted NGS revealed a synonymous variant in exon 1 of the CD40LG gene proximal to donor splice-site. In-silico prediction for this variant was found to be damaging by Mutation Taster2. Synonymous variants involving canonical splice-sites can also be pathogenic and should not be filtered out.

Genetic findings were beneficial in providing genetic counselling to affected families, carrier screening, and prenatal diagnosis. Moreover, genetic information is required for devising appropriate transplantation related strategies. Genetic findings were also crucial in deciding the treatment modalities in a few cases. Cases harbouring defects leading to antibody deficiencies were placed on regular replacement intravenous immunoglobulin therapy.

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Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India | Scientific Reports -...

Because cannabis sativa contains only a small amount of delta-8 THC, its typically manufactured in concentrated amounts from hemp-derived cannabidiol (CBD). While CBD doesnt have any intoxicating effects, delta-8 THC has similar psychoactive properties to delta-9 THC, although it is generally less potent than delta-9.

Delta-8 THC products are available in many forms, including gummies, chocolate and other candies, cookies, tinctures, vaping cartridges, infused drinks and even breakfast cereal.

Some manufacturers market delta-8 THC products as treatments or cures for medical conditions; however, the Food and Drug Administration (FDA) has neither evaluated nor approved these claims. In fact, in May 2022, the FDA issued warning letters to five manufacturers of delta-8 THC products for violating the Federal Food, Drug, and Cosmetic Act.

The warning letters address misbranding, such as not providing adequate instructions for use, illegal marketing of products as treatments for medical conditions or other therapeutic uses and adding delta-8 THC to foods, such as gummies, chocolate and other consumables.

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A container has a 30-count amount of gummies, with every individual serving containing a 10mg dose of pure, THC-free CBD isolate.

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Making general statements about whether using cannabis is good or bad doesnt paint an accurate picture of delta-8 THC or delta-9 THC, says Dave Gordon, M.D., a double-board certified integrative and functional medicine physician with expertise in cannabis therapeutics and advisory board member for Leaf411, an online resource for using cannabis safely and effectively.

To understand the risks and benefits of delta-8 THC or delta-9 THC, according to Dr. Gordon, consider:

With that said, potential benefits of delta-8 THC may include:

Like any compound, consuming more delta-8 THC than the body wants or needs can cause some short-term adverse effects, says Dr. Gordon. These negative side effects tend to depend on dosage, meaning they become more severe with increased consumption, he adds.

According to Dr. Gordon, short-term adverse effects of overconsuming delta-8 THC may include:

Generally, adverse effects resolve within a couple of hours with inhalation and within several hours of edible consumption, says Dr. Gordon.

Individuals with preexisting conditions may have risks that others do not, adds Dr. Gordon. In patients with high risk for (or already diagnosed) psychotic diseases, over-consuming delta-8 THC could increase frequency or severity of psychosis.

Consuming large amounts of delta-8 THC, especially when smoked, could precipitate heart damage or abnormal heart rhythms in those with significant underlying cardiovascular disease, says Dr. Gordon.

Additional risks associated with delta-8 THC consumption are linked to the product manufacturers themselves. According to the FDA, delta-8 THC products may contain potentially harmful chemicals or contaminants, including household chemicals used during the chemical synthesis process that yields delta-8 THC.

When weighing the potential risks of consuming delta-8 THC, its important to consider that the FDA hasnt evaluated or approved any delta-8 THC products for safe use. Delta-8 THC manufacturers may also market their products with unproven claims of health benefits that could put public health at risk.

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Delta-8 vs. Delta-9: What's The Difference? Forbes Health - Forbes

A world-renowned author and expert in the field of integrative medicine, Andrew T. Weil, MD, founder and director of the Andrew Weil Center for Integrative Medicine at the University of Arizona College of Medicine Tucson, was recognized recently with the top award given by the Integrative Healthcare Symposium.

Im honored to receive the symposiums 2022 Leadership Award, Dr. Weil said. Integrative health care is the way of the future, and the University of Arizona Health Sciences is leading that way. Our Center for Integrative Medicine sets the standard for training physicians, nurses, and allied health professionals to provide this kind of care in order to improve health outcomes and lower health care costs.

The annual award was presented to Dr. Weil, who also gave the symposiums keynote address on The Evolution of Integrative Medicine, earlier this year in New York City.

Presenting the award to Dr. Weil was Aly Cohen, MD, a 2014 graduate of the centers Fellowship in Integrative Medicine, founder of Integrative Rheumatology Associates and The Smart Human LLC, and co-author of the book, Non-Toxic: Guide to Living Healthy in a Chemical World. Dr. Cohen is the guest on the latest Body of Wonder podcast with Dr. Weil and center executive director Victoria Maizes, MD.

In lauding Dr. Weil, Dr. Cohen told the tale of how his car broke down in Tucson in the 1970s while he was traveling across country, he fell in love with the desert and stayed. Well, lucky for us. Combining the number of patients reached through fellowship graduates, health coaches, residents in training, medical students and researchers, some 8 million patients are guided by your teachings and are quite grateful your car broke down in Tucson many moons ago, she said.

Commenting on his 15 books, Dr. Cohen said, In an era of plentiful, often radical guidebooks and scary health news flashes, he has provided an oasis for balance and common sense for readers. Dr. Weil, your long and brave history of challenging the status quo of Western medicine and your ongoing mission to educate others through print, social media, television and lectures is a testament to the beautiful and rich journey youve taken.

After graduating high school in Philadelphia in 1959, Dr. Weil won an American Association for the United Nations scholarship that allowed him to travel abroad for a year where he lived with families in India, Thailand and Greece. Upon his return, he did his undergraduate studies in biology and ethnobotany at Harvard University and earned his medical degree from Harvard in 1968.

He interned at Mount Zion Hospital in San Francisco, then took a post with the National Institute of Mental Health before writing his first book, The Natural Mind. As a fellow of the Institute of Current World Affairs from 1971-75, Dr. Weil traveled widely in the Americas and Africa, studying medicinal plants and alternative treatment methods for disease. From 1971-84, he also was on the research staff of the Harvard Botanical Museum and conducted investigations of medicinal and psychoactive plants.

Dr. Weil founded the Program in Integrative Medicine in 1994 at the UArizona College of Medicine Tucson. Fourteen years later, the program by then a division in the colleges Department of Medicine was designated a center of excellence by the Arizona Board of Regents. In 2019, the center was renamed as the Andrew Weil Center for Integrative Medicine. The center broke ground on its new $23 million, donor-funded building March 16.

A UArizona clinical professor of medicine and public health and the Lovell-Jones Endowed Chair in Integrative Medicine, Dr. Weil also is editorial director of DrWeil.com, a leading online resource for healthy living based on a philosophy of integrative medicine, and a founder and partner of True Food Kitchen restaurants, whose recipes are the basis for his New York Times best-selling book, True Food.

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Dr. Andrew Weil Receives Integrative Healthcare Leader Award - University of Arizona