Tag: Academic research

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First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy

Huntington’s disease therapeutics have reached a historic milestone—the first patient has successfully received an experimental neural stem cell therapy at UCI Health. This groundbreaking dose marks the world’s first human trial of embryonic stem cell-derived neural stem cells for the devastating neurodegenerative disorder.

The treatment, performed in May at University of California Irvine (UCI) Health, represents the culmination of more than 12 years of laboratory research and eight years of clinical planning led by scientists and physicians at the University of California, Irvine. Researchers hope the treatment, known as hNSC-01, could eventually slow disease progression, protect vulnerable brain cells and potentially restore damaged neural circuits.

To date, the first participant has not reported any serious adverse effects, according to the clinical team. A second patient is expected to receive the therapy in July.

Leslies Thompson - Huntington's
Leslie M. Thompson, PhD, Donald Bren Professor of psychiatry and human behavior, as well as neurobiology and behavior, at the University of California, Irvine [UC Irvine]

“This clinical trial highlights the important role that an interdisciplinary academic and clinical team, together with the HD families, plays in advancing medicine,” Leslie M. Thompson, PhD, clinical trial sponsor as well as the Donald Bren Professor of psychiatry and human behavior UC Irvine, told Inside Precision Medicine. “We are grateful to our patients and their incredible families for their bravery to provide hope for others with very few options.”

hNSC-01

Huntington’s disease, caused by a mutation in the huntingtin gene, destroys brain cells, causing involuntary movements, cognitive decline, and psychiatric symptoms that begin between 35 and 50 and worsen over time. Without a cure, the fatal disorder burdens patients and families emotionally, physically, and financially, often requiring daily and long-term care.

Current treatments for Huntington’s disease primarily focus on managing symptoms rather than altering the underlying disease process. Drugs such as tetrabenazine and deutetrabenazine can reduce involuntary movements known as chorea, while antidepressants, antipsychotics and mood stabilizers help address psychiatric symptoms. Physical therapy, speech therapy and occupational therapy can also improve quality of life. However, none of these approaches has been shown to slow or stop the progressive loss of neurons that drives the disease.

Over the past decade, researchers have pursued several experimental disease-modifying strategies. Among the most advanced are gene-targeting therapies designed to reduce production of the mutant huntingtin protein. These include antisense oligonucleotides (ASOs), which are delivered through repeated spinal injections, as well as RNA-targeting and gene-editing approaches intended to suppress or correct the faulty gene. While these strategies directly target the genetic cause of Huntington’s disease, clinical results have been mixed, and questions remain about long-term effectiveness, safety and the need for lifelong treatment.

The hNSC-01 neural stem cell therapy being tested at UCI Health takes a different approach. Rather than targeting the mutant gene itself, the therapy aims to protect vulnerable neurons, replace lost cells, rebuild damaged neural circuits and provide supportive factors that promote brain health. 

The UCI researchers believe stem cell-based therapies may offer a new approach by addressing multiple aspects of the disease simultaneously. The experimental treatment, hNSC-01, consists of pluripotent neural stem cells derived from embryonic stem cells and manufactured through the UC Davis Good Manufacturing Practice facility.

Preclinical studies in animal models suggested the cells could perform several functions relevant to Huntington’s disease, including protecting existing neurons, replacing cells that have been lost, rebuilding damaged neural networks and releasing beneficial proteins such as brain-derived neurotrophic factor (BDNF). The cells were also shown to reduce harmful protein accumulations associated with neurodegeneration and demonstrated long-term safety in mice.

Unlike conventional drug therapies, the stem cells are delivered directly into the brain. During the approximately six-hour procedure, performed under general anesthesia, patients lie face down within an MRI scanner while neurosurgeons use a specialized stereotactic navigation and delivery system to implant the cells into the striatum, a deep brain structure heavily affected by Huntington’s disease.

The striatum plays a central role in motor control, decision-making, motivation and learning. Degeneration of this region contributes significantly to the hallmark symptoms of the disorder. The first intervention was delivered by UCI Health neurosurgeon Jefferson W. Chen, MD, and a multidisciplinary surgical team.

Tracking treatment impact

As a Phase Ib/IIa study, the trial’s primary objective is to evaluate safety. However, researchers will also track biomarkers and clinical indicators that may provide early clues about whether the treatment is affecting disease progression.

When asked which biomarkers would help identify how the therapy is working in patients, Thompson emphasized that current measurements are focused more on assessing treatment impact than revealing biological mechanisms. “We will be including HD relevant clinical endpoints and biomarkers, including NfL in plasma and NfL and PENK in CSF; however, these are geared to understanding whether the treatment is having a benefit to these outcome measures versus informing the mechanism of action,” Thompson said.

One of the most important early indicators will be whether disease-related biomarkers remain stable rather than continuing their expected decline. “The earliest sign first and foremost is safety in this initial trial,” Thompson said. “Initial signs that the therapy could be meaningfully altering disease progression would be if the blood-based or CSF-based biomarkers do not show progression.”

Reaching the point of treating the first patient required overcoming a series of scientific, manufacturing and logistical hurdles. According to Thompson, selecting the optimal cell line was among the most significant challenges, testing multiple cell lines in vitro and in vivo.

Researchers also had to establish quality-control standards for the final therapeutic product and create Good Manufacturing Practice cell banks following extensive testing in Huntington’s disease mouse models. The COVID-19 pandemic introduced additional delays. “Disruptions caused by COVID-19, in particular the safety and tumorigenicity studies, delayed the timeline,” Thompson explained.

Another major undertaking involved creating the clinical infrastructure necessary for a first-of-its-kind procedure. Thompson said that it’s not really a challenge, but getting the overall procedural pipeline in place is the first study of this kind at the UCI Health–Irvine hospital in the MRI suite.

Despite the complexity of the project, Thompson said interactions with regulators proceeded smoothly. “We actually had a very good experience in terms of regulatory activities. A very helpful pre-pre-IND, pre-IND and relevant feedback from the FDA on the clinical trial.”

Scalability and competitive landscape

Whether hNSC-01 will ultimately compete with or complement emerging gene-targeting therapies remains unclear. Gene-silencing approaches may be easier to distribute because they do not require brain surgery, but repeated administrations over many years could result in substantial cumulative costs. In contrast, hNSC-01 involves a specialized MRI-guided neurosurgical procedure that may initially be limited to major medical centers, but it is designed as a one-time treatment whose long-term costs could compare favorably with chronic therapies if benefits prove durable.

Thompson believes the infrastructure requirements may be less of a barrier than many assume. “Yes, major medical centers can eventually offer it, and several medical centers are now using this system for other indications,” she said. “The other aspect is this would be a one-time administration so an individual could even travel to a medical center that offers the procedure.”

The REGEN4HD trial plans to enroll 21 adults aged 18 to 65 with early-stage Huntington’s disease. Twelve participants will be included in a Phase Ib dose-escalation cohort, while nine additional participants will be enrolled in a Phase IIa expansion group. The study is funded through a $12 million grant from the California Institute for Regenerative Medicine and coordinated through the UC Irvine Alpha Clinic, one of nine state-supported regenerative medicine clinical research centers.

Even if the therapy proves safe and beneficial, researchers caution that it remains unclear whether stem cell transplantation alone will be sufficient to combat Huntington’s disease over the long term. “At this point we do not know whether this will be sufficient alone or will need to be delivered with other disease-modifying therapies,” said Thompson. “For example, ones that specifically target an HD mechanism such as somatic repeat instability,” Thompson said. “However, these cells also have the potential to exert therapeutic effects directly while serving as vehicles for the delivery of additional interventions.”

For families affected by Huntington’s disease, the first successful treatment in the REGEN4HD trial represents more than a scientific milestone. It marks the beginning of a new chapter in regenerative medicine—one that researchers hope could eventually transform the outlook for a disease that has long remained untreatable.

The post First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy appeared first on Inside Precision Medicine.

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SMILE: neural signal acquisition and intra-body transmission for facial nerve bypass—An acute feasibility study and proof-of-concept in a rat model

Facial paralysis is a disabling condition with severe functional and aesthetic consequences. Facial paralysis affects approximately 1.8% of individuals over their lifetime, with approximately 30% of affected patients developing persistent deficits; among these, patients with permanent flaccid paralysis and severe facial asymmetry do not resolve with pharmacological treatment and require surgical intervention. It is specifically this surgically relevant subgroup that represents the target population of the SMILE framework. The SMILE framework (bypaSs of a facial nerve lesion through intra-body biocoMpatIbLE communication technologies) validates the feasibility of the communication infrastructure required to establish a functional neural bypass link between the healthy side and a surgically reinnervated contralateral side of the face. This work presents a preliminary interdisciplinary experimental and engineering approach underlying the SMILE framework, combining neurophysiological validation in 15 adult Wistar rats with the design of ultra-low-power intra-body communication links based on galvanic coupling (GC) and ultrasound (US). Microsurgical cuff electrodes were implanted around the buccal branch of the healthy facial nerve to record odor-evoked motor outputs. ENG signals recorded from the intact buccal branch of the facial nerve on one side were transmitted to the contralateral side, across the animal’s facehead. Engineering evaluations demonstrated robust transmission capabilities, with the GC link achieving a mean equivalent SNR of 18.2 ± 0.6 dB and a mean normalized cross-correlation of r = 0.72 ± 0.09 between transmitted and reconstructed ENG signals, with MSE on the order of 10−2. The US link achieved an equivalent SNR around 12 dB with MSE around 5 · 10−2, supporting the feasibility of intra-body neural signal relay through biological tissues.
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Building tech in the world’s secret R&D hub

Apple. Anthropic. Disney Research. Google. Meta. Microsoft. NVIDIA. OpenAI. Few places outside Silicon Valley can claim R&D hubs from all of these companies. Fewer still are concentrated in a city of just over 400,000 people—roughly half the size of San Francisco.

Over the past two decades, however, many of the world’s most influential technology companies have established R&D operations in and around Zurich, Switzerland. What began with Google’s decision to build its largest R&D hub outside the United States has evolved into one of the world’s most concentrated centers for AI research, talent, and commercialization, in certain areas at a higher density than Silicon Valley. 

The question is why so many technology leaders keep choosing the same place to build and scale.

Located at the center of Europe, Greater Zurich Area, a region spanning the cantons of Glarus, Graubünden, Schaffhausen, Schwyz, Solothurn, Tessin, Uri, Zug, and Zürich, the region of Winterthur, and the city of Zurich, combines access to major markets with political stability, regulatory predictability, and strong intellectual property protection. And Zurich Airport connects the region directly with key business hubs across Europe, North America, and Asia, making it an efficient base for international operations.

The country’s innovation performance reinforces this position. Switzerland has ranked first in the Global Innovation Index for more than a decade, leads the world in patents per capita, and invests over 3.3% of GDP in research and development. Earlier this year, google.org pledged a $1 million grant to the Swiss National AI Institute, a joint effort to advance AI research for the public good.

Switzerland’s venture ecosystem reflects a similar focus. Over 60% of Swiss venture capital is invested in deep tech—the highest share globally by a large margin and nearly twice the share of major economies like Germany, France, and the UK. And, according to the Swiss Deep Tech Report 2026, at $1,470 invested per capita, Switzerland commits more to deep tech per capita than any other country in Europe.

The economics of specialization

While Switzerland is one of Europe’s most expensive locations for talent and operations, salaries remain at a fraction of those in Silicon Valley. The talent pool is small by global standards. Scaling a team quickly is harder in Zurich than in London, Paris, or Amsterdam. For early-stage companies that need to hire fast and burn lean, that trade-off is real. For companies building specialized AI capabilities, however, the equation works: The objective is to assemble the right team, not the largest one.

Switzerland’s economy is built around high-value, knowledge-intensive work. Productivity is among the highest in the world, and companies concentrate on functions that depend on specialized expertise rather than large workforces. For companies developing advanced AI capabilities, cost is often weighed against factors that are harder to replicate elsewhere: direct access to leading universities and research institutions, regulatory stability, and a quality of life that helps attract and retain skilled international talent.

A high-density AI ecosystem

Within Switzerland, the Greater Zurich Area concentrates many of the ingredients required to build and deploy AI systems.

The defining characteristic of this region is density. Many of the world’s leading AI companies, research institutions, investors, and startups operate in close proximity, creating connections between talent, capital, and ideas.

For example, Google engineers teach at ETH Zurich. ETH graduates join companies such as Anthropic. Researchers launch startups, while former employees of global technology firms go on to found new ventures of their own. Investors, founders, academics, and corporate teams encounter each other repeatedly through shared networks, industry events, and professional circles. In a region of this size, collaboration often happens less through formal introductions than through proximity. While talent flows freely, it rarely leaves the ecosystem.

One indicator of the region’s maturity is its ability to convene. Events such as the Zurich AI Festival will bring together more than 6,500 guests this September 28 to October 3. With more than 35 confirmed events across AI and the arts, AI literacy, health, technology, and policy, it is designed as a platform for cross-sector exchange. Its flagship events, the AI + X Summit, AI + Environment, and the AI + Policy Summit, will bring together internationally recognized leaders alongside researchers, policymakers, venture capitalists, and entrepreneurs, convening international voices and fostering dialogue across sectors.

Research, talent, and company creation

At the center of the country’s AI capabilities are institutions such as ETH Zurich, the University of Zurich, École Polytechnique Fédérale de Lausanne (EPFL), Scuola Universitaria Professionale della Svizzera Italiana (SUPSI), and Zürcher Hochschule für Angewandte Wissenschaften (ZHAW).

ETH Zurich ranks among Europe’s leading universities for deep tech commercialization, generating more than 40 spin-offs and startups in 2025 alone, helping create some of the continent’s most valuable technology companies.

The Stanford AI Index 2026 reinforces that picture: Switzerland ranks first globally for AI researchers and inventors per capita, with 110.5 per 100,000 inhabitants—ahead of Singapore (109.5), Sweden (80.6), and the United States (64.8). And the IMD World Talent Ranking ranked Switzerland as number 1 for the 10th consecutive year, leading globally in investment, development, and talent appeal.

Engineers, researchers, and founders move frequently between universities, startups, and established technology firms, creating strong knowledge flows across organizations. That density is increasingly attracting companies from outside the region too. Even before formally announcing their Zurich office, Exa.ai received a strong pipeline of candidate applications. ‘To assemble the greatest search team in the world, you’ve got to meet people where they are,’ says Will Bryk, the company’s CEO and co-founder. ‘And many are in Greater Zurich.’

Former Google Switzerland employees alone have founded approximately 210 companies and created around 2,600 jobs over the past two decades. For a country of around nine million inhabitants, the multiplier effect is significant. Large technology firms contribute not only through direct employment, but also through the creation of new companies and the transfer of expertise.

Why the Greater Zurich Area complements Silicon Valley

For many technology companies, Switzerland is not a substitute for Silicon Valley. The two serve different functions within the AI value chain.

Silicon Valley remains unmatched in scale, venture capital, and frontier model development, but for global technology companies, an R&D presence in Switzerland has increasingly become a strategic complement: a way to access specialized talent, stay close to leading research, and build capabilities that will shape the next generation of products and services.

This is particularly relevant for companies working at the intersection of AI and the physical world. Switzerland offers direct access to leading universities, industrial partners, and sectors such as healthcare, finance, manufacturing, and robotics, where reliability, compliance, and precision are often as important as raw model performance.

Geography is strategy

Global AI leaders came to the Greater Zurich Area because the region concentrates capabilities that are often distributed across multiple locations: world-class research, specialized talent, industrial partners, capital, and pathways to deployment. Those advantages were built over decades, not years.

For companies evaluating where to build the next generation of AI products, the answer may not be another larger ecosystem. It may be one where the distance between research, talent, capital, and deployment is measured in minutes rather than hours.

Learn more about the Greater Zurich Area.

This content was produced by the Greater Zurich Area. It was not written by MIT Technology Review’s editorial staff.

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Two Proteins with Opposing Functions Found to Support Healthy Skin Maintenance

Research headed by a team at Stanford Medicine has identified two proteins with opposing functions that are involved in orchestrating the development and maintenance of healthy skin.

The proteins, NEDD8 and SUMO2, are part of a family called ubiquitin-like proteins (UBLs), and the researchers believe that modulating their activity with topical drugs could reduce inflammation, aid wound healing, and slow or halt the growth of skin cancer.

“These two ubiquitin-like protein systems are remarkably dedicated and opposite in their functions,” said Paul Khavari, MD, PhD, chair of dermatology at the Stanford School of Medicine and senior author of the study. “One promotes the stem-cell state while the other drives differentiation. It’s like having two opposing forces that determine a cell’s fate.”

Added clinical instructor of dermatology Mårten Winge, MD, PhD, “What’s really exciting is how specific these effects are. When we manipulate one system or the other, we see very clear and opposite outcomes. This specificity is unusual for ubiquitin-like pathways and makes these systems particularly attractive for therapeutic targeting.”

Khavari, who is the Carl J. Herzog Professor in Dermatology in the School of Medicine, chief of dermatology at Veterans Affairs Palo Alto, and a member of the Stanford Cancer Institute, is senior author, and Winge is co-lead author of the researchers’ published paper in Science, titled “Ubiquitin-like proteins NEDD8 and SUMO2 control epithelial homeostasis, regeneration, and inflammation.” The work was carried out in collaboration with researchers at Icahn School of Medicine at Mount Sinai.

Stratified epithelial tissues, such as the skin’s epidermis, differentiate to form protective barriers against environmental attacks, the authors wrote. “This process involves coordinated modulation of thousands of genes and is disrupted in many inflammatory or neoplastic diseases.

Ubiquitination controls the targeted destruction and disposal of unneeded proteins in a cell. “Ubiquitin and related ubiquitin-like proteins (UBLs) comprise a major layer of protein regulation,” the team continued. The study by Khavari and colleagues has now found that in the skin, certain ubiquitin-like proteins switch on or off wide swaths of genes involved in cellular growth and development. In particular, they trigger progenitor, or stem, cells in the lower layer of the skin to either mature and migrate to the skin surface or to self-renew.

The outer layer of your skin can be considered as two distinct compartments. On the lower level, progenitor cells or skin-specific stem cells wait to transform into keratinocytes, a more specialized cell type forming the critical skin barrier that keeps moisture in (and out),  excludes infection-causing pathogens, repels DNA-damaging ultraviolet rays, and harbors the nerve endings that allow us to sense our surroundings.

These progenitor cells divide just enough to keep their numbers robust. But when needed—after injury or infection or when skin cells naturally slough off—a subset of progenitor cells differentiate and migrate to the skin’s surface. Disruptions in this delicate balance between stem cell maintenance and their maturation into adult keratinocytes can lead to psoriasis, poor wound healing, and skin cancer.

The researchers were interested in understanding how the differentiation switch is flipped. “We hypothesized that differentiation-dependent proteomic remodeling diverges from RNA-level effects due to posttranslational protein modifications,” they noted. They used a wide swath of experimental approaches to assess dynamic changes in the expression of thousands of genes and proteins at various stages of keratinocyte differentiation. The results found that the maturing cells expressed increasing levels of genes and proteins involved in skin formation and decreasing levels of others associated with stem cell maintenance. Many of the proteins that decreased during differentiation bore small molecular tags that identify locations recognized by other proteins in the ubiquitin pathways—giving a hint that ubiquitination may be involved in the differentiation switch the researchers were seeking.

Disrupting the expression of more than 200 genes in the ubiquitin pathway during keratinocyte maturation highlighted two subpathways essential for proper differentiation: NEDDylation and SUMOylation. Hobbling the NEDDylation pathway supercharged differentiation, while blocking SUMOylation prevented differentiation. Similar results were obtained when the pathways were blocked pharmacologically with existing drugs in both human keratinocytes grown in the laboratory and in human skin organoids—three-dimensional sheets of tissue about the size of a quarter that mimic the multicellular structure of human skin.

Next, the researchers genetically engineered laboratory mice such that the expression of either Nedd8 or Sumo2—two key proteins in the NEDDylation and SUMOylation pathways—could be blocked when a triggering molecule is applied to the animals’ skin. They found that the skin of the mice developed abnormally when either Nedd8 or Sumo2 expression was halted, showing that both proteins are necessary for proper skin development.

“Generation of conditional knockout mice established essential roles for NEDD8 in progenitor maintenance, skin regeneration, and inflammation, whereas SUMO2 was required for differentiation,” they commented. Mice unable to make Nedd8 had an overgrowth of keratinocytes on their skin’s surface (similar to psoriasis), and animals lacking Sumo2 showed impaired differentiation and a loss of the distinct layers that make up healthy skin.

In addition to changes in the skin cells, the loss of Nedd8 and Sumo2 led to striking changes in the amounts and kinds of immune cells populating the skin. Nedd8 loss resulted in an increase in the numbers of immune cells called neutrophils in the skin and caused inflammation, while Sumo2 loss caused an increase in the numbers of another immune cell called a T cell. “In skin, NEDD8 maintained the undifferentiated epidermal state, enabled wound healing, and restrained neutrophilic inflammation,” they said. “SUMO2 promoted proper epidermal differentiation and suppressed T lymphocyte infiltration.”

Khavari commented: “We’re not just changing individual cells—we’re changing the whole tissue microenvironment. Manipulating these pathways could have therapeutic applications for wounds, inflammation, skin aging, and even cancer.”

Further experiments showed that the effect of Nedd8 on cell differentiation is due to its association with an RNA-binding protein called HNRNPU. “NEDD8 loss modulated the RNA binding and stabilizing functions of HNRNPU,” the team explained. In the absence of Nedd8, HNRNPU latches onto and stabilizes sets of RNA messages encoding genes for proteins essential for the differentiation of progenitor cells into keratinocytes, but when Nedd8 attaches to HNRNPU, the protein instead binds to and stabilizes RNA messages encoding proteins necessary for progenitor cell maintenance.

“Thus, NEDD8 and SUMO2 play opposite roles in epithelial homeostasis, regeneration, and inflammation, demonstrating multiple ways ubiquitin-like networks govern tissue homeostasis,” the team reported in their paper. “The researchers are now exploring whether topical drug treatments targeting the NEDDylation or SUMOylation pathways could tilt the balance of keratinocyte differentiation to progenitor cell maintenance and to treat a variety of skin diseases and disorders.

“The beauty of understanding these fundamental switches is that we can apply them to multiple disease states,” said co-lead author Leandra Jackrazi, an MD/PhD student. “Whether it’s promoting wound healing, reducing inflammation, or controlling cancer growth, having the ability to toggle between stemlike and differentiated states opens many doors.”

The post Two Proteins with Opposing Functions Found to Support Healthy Skin Maintenance appeared first on GEN – Genetic Engineering and Biotechnology News.

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The effect of weather on unscheduled healthcare utilisation for mental health conditions in England, 2014–2022

BackgroundWeather conditions have been linked to adverse mental health outcomes, and rising concern about climate change has increased interest in these associations. However, most existing research focuses on extreme weather events, such as heatwaves, or on acute clinical outcomes, such as suicide. Evidence is more limited regarding population-level variations in mental health–related healthcare utilisation across the full range of daily weather conditions.ObjectiveTo examine associations between daily weather conditions and unscheduled mental health–related healthcare contacts in England using large-scale national surveillance data.MethodsWe conducted a retrospective observational study across nine English regions from 1 January 2014 to 31 December 2022. Outcomes were daily counts of unscheduled mental health–related contacts to emergency departments (EDs), general practice out-of-hours (GP OOH) services, and the NHS 111 telephone advice line. Weather exposures included mean daily temperature (°C), hours of full sunshine, and total daily rainfall (mm). Associations were estimated using distributed lag non-linear models at regional level and combined through two-stage multivariate meta-analysis. Models were adjusted for seasonality, long-term trends, day of week, public holidays, and population size.ResultsMental health–related unscheduled healthcare contacts showed modest but consistent associations with temperature and sunshine. Across services, relative risks (demand) increased with rising temperatures up to around 18 °C and were higher on days with fewer hours of sunshine. Sunshine demonstrated the clearest pattern, with increased utilisation on low-sunshine days across all healthcare settings. Rainfall was not consistently associated with healthcare contacts. Age-stratified analyses showed a U-shaped relationship between temperature and ED attendances among adults aged over 64 years, with higher utilisation during both colder and warmer conditions. Overall variations in daily healthcare demand were modest, typically within ±10–20% of baseline levels.ConclusionIn England, short-term variations in temperature and sunshine are associated with changes in unscheduled mental health–related healthcare utilisation, whereas rainfall shows little consistent effect. Although effect sizes were modest, these findings highlight the role of everyday weather conditions in influencing mental health–related healthcare demand and may support planning and preparedness efforts for mental health services under current and future climate conditions.
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Treating ADHD With Methylphenidate (Ritalin, Concerta)

Methylphenidate is a stimulant medication used to treat symptoms of ADHD. It helps the brain regulate attention, focus, and impulsive behaviors.

It’s one of the two stimulants widely used in ADHD medications. Methylphenidate is the active ingredient in Ritalin and Concerta, among others. The other commonly used stimulant, amphetamine, is the active ingredient in Adderall and Vyvanse, among others. Both stimulants work by increasing levels of dopamine and norepinephrine, chemicals in the brain that control attention, focus, and impulsivity. If a child doesn’t do well on the first stimulant medication they try, they may respond better to a different formulation of that type or the other type of stimulant.

How is methylphenidate different from amphetamine?

Methylphenidate is somewhat less powerful than amphetamine and tends to have milder side effects.

If your child is under 12 and has just been diagnosed with ADHD, a doctor is likely to prescribe a methylphenidate medication first, to see how well the medication reduces their ADHD symptoms, and whether the side effects are problematic.

Methylphenidate is also many doctors’ first choice for younger children because it has been used to treat ADHD much longer than amphetamine. Ritalin (methylphenidate-based) was FDA approved in 1955, while Adderall (amphetamine-based) wasn’t approved until 1996. In countries outside the United States, amphetamine-based ADHD medications are less widely approved than those based on methylphenidate.

How methylphenidate works vs amphetamine

The two stimulants target the same brain chemicals but work slightly differently, says Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. Methylphenidate increases the levels of dopamine and norepinephrine by blocking what’s called reuptake — the process by which nerve cells reabsorb these chemicals after they’ve been released. As Dr. Mitrani describes it, methylphenidate “enhances” the norepinephrine and dopamine the brain naturally releases by making the chemicals stay around longer. It boosts the stimulation the brain is already getting from whatever activity the child is engaged in.

Amphetamine, on the other hand, not only blocks reuptake but stimulates the release of more dopamine and norepinephrine, which is why it’s considered stronger. “Adding stimulation with amphetamine sometimes helps,” he notes. “But sometimes that added stimulation is too much, and it increases side effects the child experiences.”

Kids vary in how they respond to methylphenidate vs amphetamine

There is individual variation in how children respond to the two stimulants. So if methylphenidate doesn’t give the desired symptom relief or produces problematic side effects, it’s recommended practice to try amphetamine, or vice versa. Research shows that 70 percent of children with ADHD respond to a trial of methylphenidate. More than 90 percent will have a beneficial response to one of the stimulants if both methylphenidate and amphetamine are tried. Studies also show that approximately 41 percent respond equally well to both types of stimulant.

Children can also vary in their response to different formulations of the same stimulant, which affect the rate at which the medication goes into the bloodstream.  For instance, a short-acting form of Ritalin will kick in quickly and last for 3-4 hours, while Concerta, a delayed-release formula, lasts as long as 10-12 hours. It’s very common for kids to try several before finding the best fit.

What are the side effects of stimulant medications?

Methylphenidate and amphetamine have the same side effects, though they may be less intense with the former.

Appetite suppression

The most common side effect of stimulants is appetite suppression. It can be especially concerning with long-acting forms of the medication, which are often preferred to get better coverage through the school day. Kids who take a long-acting stimulant in the morning tend to lose their appetite for lunch and may not be interested in eating until after dinnertime.

When this is a problem, Dr. Mitrani notes that taking a shorter-acting form of the medication can help. “For instance, Concerta is a methylphenidate medication that lasts for a long time and can suppress appetite for 10–12 hours.” An alternative might be a medication that lasts for 6–8 hours, such as Metadate CD or Ritalin LA. Some children with more pronounced problems with appetite will do better on a short-acting dose in the morning and then another after lunch, he adds, since it gives them a break during the day where they can eat better.

Sleep issues

Kids who take stimulant medication can have trouble falling asleep. This can happen when a long-acting medication or an afternoon dose of a short-acting medication wears off and they get restless or hyperactive around bedtime. Difficulty falling asleep can get better after a few weeks, but if it doesn’t, it may be helpful to change either the timing or the type of the medication that is given. It’s also important to explore whether there are other contributors to sleep challenges, such as worry, screen time too close to bedtime, or lack of a consistent evening routine that helps kids calm down.

Irritability

Stimulant medications can generate agitation and irritability, which can be especially problematic in kids who are already anxious. For children with anxiety, this can be another reason to start treatment with methylphenidate, because amphetamines can feel more activating.

But Dr. Mitrani notes that treating ADHD can also reduce anxiety: “Some kids are so stressed about school — because they can’t pay attention or arealways getting in trouble — that when you treat the ADHD, they are better able to manage the demands of school and become less anxious.”

That reduction in school anxiety can also affect what happens when they get home from school. “When there is anxiety, it’s like kids are holding it together at school, and then they come home after a stressful day and just let it out,” he says. “So if the school day is less stressful, you may also see that come down at the end of the day.”

Mood changes

Some children report that stimulant medications seem to dull their personality. Dr. Mitrani suggests that this may be connected to the medication stimulating the prefrontal cortex, the part of the brain that not only manages attention and focus, but also helps regulate emotions and impulse control in other brain areas. “Enhanced control of the emotional part of the brain can cause this feeling of dullness,” he notes. “Some people will even say they feel depressed, that they’re just not like themselves because they don’t have the same energy or personality.”

If this happens to a child on methylphenidate, Dr. Mitrani will recommend trying an amphetamine or a non-stimulant medication.

Rebound effects

Some families report that their child is irritable or emotional after school or at the end of the day, when the stimulant medication is wearing off. Dr. Mitrani notes that this can coincide with the child being hungry after missing lunch. It can also be connected to the medication level dropping too quickly, and strategies that create a more gradual decrease may help take it away. For example, he might suggest adding a small dose of  short-acting form of the stimulant a half hour before the morning medication wears off.

Starting children on methylphenidate

Dr. Mitrani usually starts a child on a short-acting form of methylphenidate for two reasons: as a quick test to see if the child will experience side effects and to have an opportunity to try it twice in a day, to have more chances to assess for positive changes.

He recommends starting the medication on a weekend or a break from school and giving the child some tasks that are challenging for them because of their ADHD, like reading or something else that requires concentration, such as cleaning their room or doing household chores. “After lunch you want to try it again, to have another time point to check on. Because if you only give one dose of the medication, you don’t know if the child’s behavior was a result of the medication or some other factor. The more data points that we have, or more trials, the more information we get.”

He recommends keeping the child on short-acting doses for at least several days before trying a longer-acting formula.

Starting children on a low dose

Practice guidelines for psychiatrists recommend starting children on a low dose to assess any side effects the child might experience and gradually increasing it over 1-2 weeks with careful monitoring of response until you reach the minimum dose that will give the best symptom relief.

There is a great deal of variation in how children respond to these medications, so starting with an “average” effective dose, even adjusted by body weight, would be under-medicating some kids and overmedicating others.

For instance, for a 6- or 7-year-old child, a common starting dose of a short-acting medication might be about 2.5 mg, going up to 5 mg if more is needed for symptom relief and side effects are not an issue, Dr. Mitrani says. 

Liquid versions of either stimulant have an advantage when it comes to getting exactly the right dose, he notes: “You can do, 1 milliliter, 1.5, 1.6, depending on the syringe.”

Long-acting formulations that come in capsules can be especially frustrating, he adds — since they come in set doses and can’t be opened and divided effectively, because the beads inside are made to be triggered at different time periods.

Trying different formulations

Dr. Mitrani stresses that small differences in the formulation of a medication can make a difference in a child’s reaction.

For instance, Focalin (dexmethylphenidate) is a refined form of methylphenidate. Standard methylphenidate medications contain two mirror-image forms, or isomers, but most of the benefit comes from one of them. Focalin contains only this more active isomer. For some children, it works better, causes fewer side effects, or feels smoother.

He also notes that variations in the release patterns among long-acting formulations can affect a child’s experience. “Take Concerta, which has a unique mechanism for the extended release,” he explains. “There are three phases: a really immediate phase, then a regular Ritalin kind of phase and, then a slow extrusion of the remaining methylphenidate throughout the day that helps it last as long as 12 hours.”

By contrast, he describes Ritalin LA, which tends to last for 6-8 hours, as “50-50” — 50 percent of the dose is immediate released and the other half is delayed release. Other formulations are “40-60” or “30-70.” “These subtle differences can result in some kids responding better to one than the other, while other kids can do well on any of them.”

So even within the methylphenidate group, there may be reason to try a child on number of different formulations to get the best fit. And, of course, other reasons for trying different versions are limits on what insurance covers —which can change suddenly — and what’s available because of shortages. “And that can be really frustrating for families,” he says. “What I hear is, ‘My child was on Concerta or on Metadate CD and they made me switch to this one and now my kid’s not doing as well.’ “


When families cannot get a medication that has been working, finding another medication that’s available, that’s effective, and that insurance will approve can be a lot of hoops to jump through, he adds.

The post Treating ADHD With Methylphenidate (Ritalin, Concerta) appeared first on Child Mind Institute.

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Improving Semantic Interoperability in Health Care Through Translation and Contextualization of International Organization for Standardization 13940 (ContSys) in Estonia: Qualitative Document- and Artifact-Based Study

<strong>Background:</strong> Event-based digital health data and information exchange are a complex sociotechnical challenge because they rely on the existence of stable, shared meanings for care process concepts such as mandate, responsibility, episode boundaries, and referral, across clinical, administrative, financing, and technical stakeholders. International Organization for Standardization 13940:2015 System of Concepts to Support Continuity of Care (ContSys) provides a conceptual framework for continuity-of-care processes, but national translations and contextualization, along with their governance implications, remain largely undocumented in the scholarly literature. <strong>Objective:</strong> This study aimed to document Estonia’s translation and contextualization of ContSys and to identify and interpret recurring patterns of conceptual discrepancy that are relevant to the durable governance of event meanings. <strong>Methods:</strong> We conducted a qualitative study of a national standards implementation project by using document and artifact analysis. Materials included the source standard, the translated manuscript, mapping notes and spreadsheets, review records, and public commentary inputs. We preserved ContSys concepts while documenting local counterparts through country-specific notes (including scope differences and contextual legal use) and synonymous terms. We summarized implementation outputs by concept domain and interpreted discrepancy patterns by using the Levels of Conceptual Interoperability Model and Blobel’s Generic Component Model as a cross-domain reference architecture lens. <strong>Results:</strong> The Estonian publication covers all ContSys concept domains and includes extensive contextualization outputs (46 country-specific notes and 82 synonyms), with the highest concentrations in time- and responsibility-related domains, indicating where semantic pressure is the greatest. Mapping and review discussions repeatedly revealed conflation of local legal or organizational terms with distinct ContSys concepts, especially where mandate and responsibility shift over time. A familiar referral artifact label (Estonian: <i>saatekiri</i>) was inconsistently interpreted as (1) a mandate transfer, (2) joint involvement while retaining the original mandate, or (3) episode initiation, demonstrating why event meanings cannot be safely encoded as event triggers in specifications without an explicit, versioned meaning decision. <strong>Conclusions:</strong> Translating and contextualizing a conceptual standard can support cross-domain semantic alignment by making mismatches explicit while preserving conceptual fidelity. However, durable event meanings require an explicit stewardship model—decision rights, resourcing, conflict resolution, and change control—to maintain coherence as they evolve. <strong>Trial Registration:</strong>
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Framework for Health-Promoting Environments for Office Workers: Photovoice Study

Background: Office work is increasingly carried out outside conventional office settings, particularly during and after the COVID-19 pandemic. This highlights the need to understand the complexity of aspects that may influence health across different office work environments. Objective: This study aimed to (1) identify aspects that office workers perceive as supporting or hindering their health during office work, and (2) formulate novel questions about office work for quantitative studies. Methods: In February 2021, we conducted a digitally distributed photovoice study in Sweden, in which a convenience sample of 17 office workers from 5 companies took photos and provided written comments on what they perceived as supporting or hindering their health in places where they performed office work. For objective 1, we carried out both qualitative formal analysis and analysis without a theoretical frame, as well as quantified the content of the photos and comments. The identified aspects and their interactions were summarized in a visual framework. For objective 2, findings from the photovoice study were used to adapt selected items from the 2019 Swedish Work Environment Survey, capturing office work performed across multiple settings. Results: Of a total of 63 photos, 70% (44/63) were taken at home, 24% (15/63) in an office, and 6% (4/63) outdoors. The comments on photos taken in conventional office settings largely highlighted health-promoting aspects, while the interpretations of home office photos showed greater variability regarding their impact on health. We identified 9 aspects and categorized them into two groups: (1) environmental perspective, including space, ergonomic, technical, and aesthetic-sensuous aspects and (2) behavioral perspective, including flexibility, focus, breaks-recovery, physical activity, and eating habits. Whether the aspects supported or hindered health depended on the environment where office work was performed and the employees’ living conditions. Our visual framework illustrates how these two perspectives interact with each other, bridged by space and flexibility. The study also resulted in a battery of multiple-choice questions about work in offices, at home, in public places, and outdoors that can be used in future research to better capture variation in modern work arrangements. Conclusions: This study extends the notion that office environments play a central role in supporting employee health by suggesting that this also applies to home offices. The results emphasize the need for tailored health-promoting interventions that account for the diverse environments in which office work is performed and for individual needs. The developed visual framework for analyzing health-promoting work environments for office workers and the battery of survey questions can contribute to future research and the advancement of sustainable, health-promoting office environments.
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Schistosomiasis Vaccine Shows Strong Immune Memory in Early Clinical Trials

Helminth parasites of the Schistosoma genus cause roughly 290,000 deaths annually, primarily in tropical and subtropical regions. In addition, an estimated 250 million people are currently chronically infected with Schistosoma parasites—with an additional 800 million people at risk of getting the infection—making schistosomiasis second only to malaria among the world’s deadliest tropical parasitic diseases.

The larvae, which live in fresh water, penetrate the skin and develop into adults. Schistosomiasis can be found in nearly 80 countries and is common in sub-Saharan Africa.

Now, new research shows promise for a vaccine being tested to prevent and treat schistosomiasis. SchistoShield® (Sm-p80 + GLA-SE) is a leading vaccine candidate for schistosomiasis that has successfully completed Phase I (USA) and Phase Ib (Africa) safety and immunogenicity clinical trials. Findings in a new report suggest that the vaccine triggered an adaptive immune effector and memory responses.

This work is published in npj Vaccines in the paper, “Schistosomiasis vaccine SchistoShield® induces functional immune memory responses in U.S. and African populations.”

Afzal Siddiqui, PhD, director of the Center for Tropical Medicine and Infectious Diseases and chair of the Department of Immunology and Molecular Microbiology at the TTUHSC School of Medicine has devoted decades to creating SchistoShield.

In this study, samples taken from people who’ve received trial doses of the vaccine in both the United States and Africa now demonstrate the vaccine’s effectiveness. Using Peripheral Blood Mononuclear Cells (PBMCs) obtained from intercontinental Phase I and Phase Ib trial participants, the team analyzed adaptive immune effector and memory responses to SchistoShield.

“The SchistoShield vaccine,” Siddiqui notes, “induced robust cell-mediated effector and memory responses, hallmarks of a potentially efficacious vaccine against schistosome/helminth parasites.”

More specifically, the paper reports results demonstrating that “the vaccine induced pronounced effector and memory T-cell responses. Upon recall with Sm-p80 antigen, cytokines including IFN-γ, TNF-α, IL-17A, IL-9, and granzyme B were produced, indicating the generation of functionally heterogeneous CD4 T-helper and cytotoxic lymphocyte responses. Consistent with T-helper responses that promote humoral immunity, Sm-p80 antigen-specific antibody-secreting plasmablasts were detected in vaccinated volunteers who were tracked longitudinally.”

“The people we have vaccinated, in both the U.S. and in Africa, have the memory response, both B-cell and T-cell-based,” Siddiqui said. “The vaccine is doing what it is supposed to. But always remember that these trials are very small 50 to 100 people. Now it has to go to thousands of people. So that’s where we are moving into.”

Schistosomiasis is considered a “neglected disease” because it predominantly affects impoverished communities in tropical and subtropical regions. There’s only one drug available to treat people, but it does not prevent re-infection. Through his efforts, and the support of TTUHSC, federal grants and national and international charitable and non-profit groups, Siddiqui has been able to develop SchistoShield as a humanitarian effort, rather than making it for profit.

“Our purpose from the beginning has been to expand access to care,” Lori Rice-Spearman, PhD, president of TTUHSC said. “Dr. Siddiqui’s work reflects that commitment through research that could help address a disease affecting millions of people around the world.”

The post Schistosomiasis Vaccine Shows Strong Immune Memory in Early Clinical Trials appeared first on GEN – Genetic Engineering and Biotechnology News.