Researchers at the Institute for Biomedical Sciences at Georgia State University have developed a vaccine platform designed to provide protection against a range of influenza virus infections by targeting conserved viral structures and inducing immunity at mucosal surfaces. The study, published in ACS Nano, details how the development of the novel vaccine uses cell-derived extracellular vesicles (EVs) engineered to display multiple influenza hemagglutinins (HAs) in an inverted configuration, which allows the immune system to recognize conserved regions shared across viral strains. In mouse models, the vaccine elicited cross-reactive antibodies, cellular immune responses, and mucosal immunity, providing protection against heterosubtypic H5N1 and H7N9 influenza virus challenges following intranasal administration.
“The influenza virus is smart. They have evolved to evade the immune system by hiding their critical conserved structures, rendering these elements poorly immunogenic,” said senior author Bao-Zhong Wang, PhD, a professor at the Institute for Biomedical Sciences at Georgia State.
The vaccine’s design centers on two key features: the use of extracellular vesicles (EVs) as a delivery platform and the inversion of HA proteins on their surface. EVs are natural nanoparticles involved in cell-to-cell communication and have been researched extensively for therapeutic delivery due to their biocompatibility. In this study, they were engineered to display multiple HA subtypes simultaneously. The HAs were presented in an upside-down orientation, which partially shields the highly variable head domain while exposing the conserved stalk domain. This structural arrangement directs the immune response toward regions less prone to mutation, enabling broader protection across influenza strains.
“These (vaccine responses) highlight that the inverted HA is a smarter strategy for inducing protective immunity to the conserved HA stalk. Meanwhile, cell-origin EVs are a biocompatible platform for mucosal vaccine delivery. Using EVs simultaneously displaying multiple inverted HAs is a powerful approach for developing universal influenza vaccines,” Wang added.
To test their vaccine design the researchers immunized mice intranasally with the EV-based vaccine, allowing researchers to assess mucosal immunity in addition to systemic responses. The data showed that the vaccine induced cross-reactive antibodies targeting HA stalks, virus-specific T cell responses, and a balanced Th1/Th2 immune profile. Importantly, the vaccinated mice were fully protected against lethal infections from reassortant H5N1 and H7N9 viruses.
The new vaccine designed was based on previous research into EV-based vaccine delivery and different strategies to target the HA stalk. Earlier studies had shown that EVs could serve as adjuvants and antigen carriers for intranasal vaccines. In addition, other research seeking to develop a universal influenza vaccine has focused on the conserved HA stalk domain, which evolves more slowly than the immunodominant head. As the researchers noted, “the conserved HA stalk domain has emerged as a promising candidate for a universal influenza vaccine due to its low evolutionary rate and greater tolerance to mutations.” However, previous approaches had used isolated HA stalk constructs, but faced shortcoming related to structural stability and immunogenicity.
By preserving the full HA ectodomain while inverting its orientation, the new design addressed these limitations. “Our findings suggest that utilizing the entire HA ectodomain as an immunogen, while hiding the HA head and increasing exposure of the HA stalk, is an effective strategy to induce robust immune responses targeting conserved HA epitopes,” the researchers wrote, noting that this approach allows the immune system to access structurally intact conserved regions.
If this vaccine design can be shown effective in humans, it could provide a vaccine with broader and longer-lasting protection against influenza, and reduce the need for frequent reformulations. The use of intranasal delivery could also change how vaccines are administered by targeting immune responses at the site of viral entry. “Mucosal vaccination effectively induces local immune responses, protecting against respiratory virus infections at the site of invasion,” the team noted.
Next steps for the team include continued characterization of the immune responses induced by the vaccine, to include the specificity and neutralizing capacity of antibodies, as well as evaluation of anti-EV immunity with repeated dosing. More animal studies, and eventually clinical trials, will be needed to assess safety, scalability, and efficacy in humans.
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Background: The universal adoption of mobile technologies by households has created an opportunity to provide families with young children with access to high-quality oral health information at convenient times and locations. Using community agencies (eg, Head Start and public health programs) that offer parenting education is an effective approach to reaching families in low-income households. Objective: This study aimed to explore the extent to which a coordinated, in-person oral health prevention intervention, together with an accompanying smartphone app, BeReadyToSmile, is feasible to implement among caregivers of young children. Methods: The BeReadyToSmile program targeted parents of children aged 0 to 6 years attending parenting education classes. This study was designed as a single-group pre-post feasibility study that included quantitative surveys and open-ended feedback. A total of 30 parents attended an in-person session on child oral health and were invited to use the BeReadyToSmile smartphone app. Preintervention and postintervention surveys were administered to assess pediatric oral health knowledge, attitudes toward child toothbrushing, brushing intention, brushing efficacy, program satisfaction, and ease of use. Results: Significant effects were observed on parent-reported pediatric oral health knowledge, attitudes toward brushing, brushing intention, and toothbrushing efficacy. Out of the 30 parents invited to use the BeReadyToSmile app, 1 (3%) completed no sessions and 20 (67%) completed all sessions. Participants rated the app highly on measures of satisfaction and use. We found significant increases in pediatric oral health knowledge (.004), child brushing attitudes and intention (=.01), and parental efficacy regarding child toothbrushing (=.03). Conclusions: Caregivers reported positive experiences with the implementation of BeReadyToSmile, indicating the overall feasibility of delivering oral health prevention to households with young children both in person and through a facilitated smartphone app. Further studies should include a larger and more diverse sample, randomized comparison conditions, and a longer follow-up period to assess outcomes. Trial Registration: ClinicalTrials.gov NCT03637309;
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Background: Health care professionals’ perceptions of telemedicine, its usability, and the presence of organizational barriers are important determinants of the successful implementation of digital solutions in health care. In Kazakhstan, the use of international assessment instruments requires contextual adaptation. The Telehealth Usability Questionnaire-Model for Assessment of Telemedicine-Kazakhstan version (TUQ-MAST-KZ) questionnaire was previously developed and psychometrically validated by integrating elements of the TUQ and MAST frameworks to assess perceptions of telemedicine within the national context. Objective: The aim of this study was to conduct the first pilot application of the TUQ-MAST-KZ questionnaire with physicians in Kazakhstan and perform an initial assessment of the organizational, technical, and educational aspects of telemedicine implementation. Methods: This cross-sectional study involved an anonymous online survey using the TUQ-MAST-KZ questionnaire, which covers perceptions of telemedicine, formats of use, platform usability, communication-related aspects, telemonitoring, organizational conditions, and implementation barriers. Responses from 156 physicians were analyzed. Stratified nonparametric comparisons were performed by sex, age group, work experience (years), and workplace, adjusted for multiple comparisons. Results: The most used telemedicine formats were telephone consultations (78/156, 50%), video consultations (69/156, 44.2%), chats and messaging applications (57/156, 36.5%), and mobile apps (48/156, 30.8%). The Kazakhstan National Telemedicine Network was used by 14.7% (23/156). Wearable devices were used by 5.8% (9/156). Telemedicine technologies incorporating artificial intelligence elements were used regularly by 13.5% (21/156) and occasionally by 32.1% (50/156) and not used by 50.6% (79/156). Positive ratings were as follows: 48.7% (76/156) regarding the simplicity and intuitiveness of telemedicine platforms; 56.4% (88/156) regarding the timeliness of patient condition monitoring; 51.9% (81/156) regarding the effectiveness of telemedicine for the management of patients with chronic diseases. The potential usefulness of telemonitoring for earlier detection of deterioration of a patient’s condition was rated as fairly or very high by 48.7% (76/156); 41% (64/156) rated it as moderate. Only 35.9% (56/156) positively rated the connection’s reliability and stability. Regarding the accuracy of wearable device data transmission, 57.1% (89/156) responded neutrally, potentially indicating ambiguity in perception, limited personal experience, or difficulty evaluating this aspect. Readiness to recommend telemonitoring at the national level was more often rated as moderate, high, or very high (78/156, 50%; 42/156, 26.9%; 14/156, 9%, respectively). Conclusions: This pilot application of the TUQ-MAST-KZ questionnaire showed a generally moderately positive perception of telemedicine by physicians, who recognized its potential clinical and organizational value. However, we identified substantial technical and institutional barriers, including connection instability, concerns about the accuracy of data transmission, insufficient process formalization, and a need for additional training. These preliminary findings should be interpreted in light of the pilot study design; however, they may serve to inform future larger-scale research and the development of organizational measures related to physician training, protocol standardization, and infrastructure support for telemedicine implementation.
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Background: The widespread prevalence of chronic pain (CP) significantly impacts daily functioning worldwide. In mainland China, maintaining engagement in biopsychosocial interventions remains challenging. Gamification, designed based on self-determination theory, can enhance motivation, while machine learning (ML) algorithms can assist clinicians in dynamically optimizing pain management. Objective: This study aimed to (1) evaluate the preliminary effectiveness of a gamified pain management (GPM) program on CP and psychological outcomes and (2) identify key factors of significant pain improvements through the application of ML to guide intervention adjustments. Methods: A single-arm, pre-post study was conducted with 16 participants with CP in mainland China, recruited via social media using convenience sampling. Participants engaged in a 10-week web-based GPM intervention consisting of education, physical activities, and gamified elements, including points, avatars, and feedback. Primary outcomes were pain intensity and interference measured by the Brief Pain Inventory. Secondary outcomes included anxiety, depression, and quality of life. Analysis included paired tests, and ML models were trained to predict clinically meaningful pain reductions. Shapley additive explanations, least absolute shrinkage and selection operator regression, association rule mining, and Kaplan-Meier survival analysis were used to identify key predictors and optimal sessions and intervention durations across subgroups. Results: A total of 16 participants were engaged, with a mean age of 27.63 (SD 9.584) years. Results from paired tests reported significant improvements in pain intensity (decreased by 27.3%, 95% CI 1.061 to 3.064; =.001), pain interference (decreased by 27.3%, 95% CI 8.159-17.216; <.001), and psychological distress, including anxiety (=3.538, 95% CI 0.969 to 3.906; =.003) and depression (=4.559, 95% CI 2.230 to 6.145; <.001). The gradient boosting model demonstrated the highest predictive accuracy (area under the curve=0.89 and accuracy=0.82). Least absolute shrinkage and selection operator regression identified session 3 (β=−0.45, 95% CI −0.68 to −0.22; <.001) and session 5 (β=−0.32, 95% CI −0.59 to −0.05; =.02) as most predictive of clinical success, while association rule mining revealed effective session combinations for different patient subgroups. Time-to-event analyses indicated that individuals with low back pain and higher baseline severity required longer intervention durations for improvement (5 wk; =.03). Conclusions: This pilot study presents an innovative method that combines ML with dynamic engagement data from a GPM program during interventions, rather than relying on static baseline data in prior studies. The results show preliminary efficacy and identify specific optimal session combinations and personalized treatment durations for different pain subgroups. These exploratory findings contribute to the field by providing a data-driven method for adaptive, personalized digital health interventions that move beyond one-size-fits-all strategies, potentially enabling clinicians to modify content and dosage to improve engagement and outcomes if validated in larger sample trials. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400094247; https://www.chictr.org.cn/showprojEN.html?proj=245138
According to the World Health Organization, an estimated 1.4 billion adults aged 30–79 worldwide had hypertension in 2024, representing around one-third of the global population of that age. Of these, 44% were unaware that they were living with a leading risk factor for premature death and poor health worldwide due to its association with myocardial infarction, stroke, and kidney disease.
Despite the size of the hypertension problem, its diagnosis and treatment pathway has remained largely the same for decades.
A 60-year-old pathway
“The current pathway in hypertension diagnosis and treatment has really not changed in over 60 years,” said Sandosh Padmanabhan, MD, PhD, chair of pharmacogenomics and professor of cardiovascular genomics and therapeutics at the University of Glasgow in Scotland.
He explained that it is based on opportunistic detection of hypertension, which has traditionally been defined as a blood pressure (BP) of 140/90 mmHg in the clinic, although thresholds vary by measurement method and guideline. For example, out-of-office measures typically use lower cut-points (e.g., home/daytime ambulatory averages) of 135/85 mmHg.
Sandosh Padmanabhan, MD, PhD Professor University of Glasgow
Diagnosis typically occurs when a patient visits their primary care physician (PCP) or has a pharmacy BP check. Confirmation follows, ideally with out-of-office BP monitoring to avoid misclassification caused by one-off measurements.
Patients are then stratified by predicted 10-year cardiovascular risk, using risk calculators such as Q-risk or the PREVENT score, and treatment is based on a stepwise algorithm. First, patients are generally given lifestyle advice like reducing salt, alcohol, and caffeine intake, improving sleep, managing stress, and increasing exercise. This may give them a chance to reduce their BP without pharmacologic intervention.
If unsuccessful, depending on local guidelines, patients may be offered an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker if under 55 years of age. Those over 55 years or of Black African or Caribbean origin are started on a calcium channel blocker. The next steps combine ACE inhibitors and calcium channel blockers, then add a thiazide-like diuretic, followed by spironolactone or other drugs.
However, this approach uses “a population-level logic,” said Padmanabhan. Although age and ethnicity are considered, “these are broad demographic proxies that don’t include any understanding of the individuals’ underlying pathophysiology or the genetic makeup.”
He stresses that, on a public health basis, the system works. There are multiple effective, low-cost antihypertensive drug classes and many generic options available that effectively lower BP. Despite this, control rates are poor. “Fewer than one in four hypertensive adults globally have their BP adequately controlled,” he said.
The measurement problem
Part of the issue lies in how BP is measured. “To give you an idea about the scale of inertia, we diagnose BP using a device that was introduced in the late 19th century,” Padmanabhan noted, referring to the sphygmomanometer invented by Scipione Riva-Rocci in 1896. Not only that, the technique can also be flawed. Variables such as incorrect cuff size, improper positioning, and patient movement can distort readings. Even talking during measurement can increase BP values by 5–9 mmHg or even higher.
Crucially, a single measurement provides little insight into cumulative lifetime exposure to high BP and can be skewed by issues like white coat hypertension or masked hypertension. “We look at the BP number, but the patients don’t experience that number. What they experience is a lifelong vascular risk,” Padmanabhan explained. “Treatment is not about a short-term reduction in a number. It’s about long-term sustained risk reduction.”
Yet the current system remains reactive and is not working well enough. “We have to move away from reactive diagnosis to proactive identification,” Padmanabhan said. “The earlier we measure accurately and respond systematically, the fewer surprises we’ll see later.”
Continuous monitoring
The pitfalls of opportunistic, or even planned, BP measurement are driving the emergence of new technologies capable of continuous monitoring.
Josep Solà, PhD CTO and Co-founder Aktiia
Josep Solà, PhD, began working on optical sensing technology in 2004 at the Centre for Electronics and Microtechnology in Switzerland. By analyzing subtle changes in reflected light caused by arterial dilation, it became clear that BP could be measured using these light signals. In 2018, this research was spun out into Aktiia, where Solà is CTO and co-founder. The company has developed and commercialized the Hilo band: a CE-certified wearable medical device designed for continuous, cuffless, BP monitoring that has been clinically validated against traditional ambulatory BP monitoring.
The band tracks BP and heart rate automatically, about 25 times per day, without requiring any action from users. Paired with an app, the device shows users daily, nightly, and long-term BP trends. It is currently available as a certified medical device across Europe, Australia, and Canada, and, following FDA approval in July 2025, the company is preparing for a U.S. launch.
Solà said he and co-founder Mattia Bertschi, PhD, were convinced they could change how hypertension is being managed today. He believes there is no good reason why most people with hypertension cannot control the condition. The medication is cheap and effective; the problem is that there has been no technology that patients can use to properly manage their condition.
“No one wants to use a cuff every day for the next 30 years,” said Solà. “They’re just so inconvenient, and you cannot expect people to proactively measure something they don’t feel.”
The Hilo band gives wearers a feedback loop that has historically been missing from BP measurement. Users can immediately see that reducing their salt or alcohol intake, for example, lowers their BP. “We are empowering people,” said Solà. “We are empowering them to look at the intervention, or combination of interventions, with or without medication, to see what is effective for them, and this reinforces their willingness to continue with the changes they are making.”
Credit: Hilo
Data published by Aktiia has shown that this approach works. A study of 8,950 U.K.-based Hilo users indicated that individuals who monitored their BP continuously showed better control over time. Specifically, users over 50 years of age appeared able to prevent the age-related rise in systolic BP typically seen in the general population, which the researchers say “may reflect greater awareness, stronger treatment adherence, and lifestyle changes prompted by continuous feedback.”
Wearables at scale: Opportunity and caution
Beyond dedicated monitoring devices like the Hilo band, smartwatches and other devices are increasingly capable of detecting physiological signals associated with cardiovascular risk. The Apple Watch can detect potential signs of chronic hypertension by analyzing heart rate sensor data over 30-day periods, the Huawei Watch D provides on-demand and 24-hour ambulatory BP monitoring using an air-filled strap, while the team behind the Oura ring is developing a “Blood Pressure Profile” feature to detect early signs of hypertension.
Although this represents a significant step toward embedding cardiovascular monitoring into everyday life, the increasing use of these devices raises important questions about accuracy, interpretation, and clinical integration, particularly as they often rely on indirect signals rather than direct BP measurement.
Adam Bress, PharmD Researcher University of Utah
As Adam Bress, PharmD, from the Spencer Fox Eccles School of Medicine at the University of Utah, and colleagues have recently shown, translating wearable-derived signals into meaningful clinical information is not straightforward.
They evaluated the hypertension alert feature of the Apple Watch, which has a published sensitivity of 41% and specificity of 92%, meaning that approximately 59% of individuals with undiagnosed hypertension would not receive an alert, while about eight percent of those without hypertension would receive a false alert.
“The problem there, is that this data only tells you how the alert works in a very controlled, limited population,” said Bress. “In order to understand how it’s going to work in the real world, we need to know how the true prevalence of undiagnosed hypertension varies in the population and in subgroups and to what degree.”
Using data from nearly 4,000 adults in the U.S., Bress and colleagues showed that the pretest probability of having hypertension has a significant impact on the reliability of the alert. For example, among adults under 30 years of age, the pretest probability of having hypertension is 14%. A positive alert on the Apple Watch would increase this probability to 47%, whereas no alert reduces the probability to 10%.
However, for adults aged 60 years and older, an alert increases the probability of an individual having hypertension from a pretest level of 45% to 81%, whereas the absence of an alert only lowers it to 34%. This translates to large numbers of false negatives when applied across millions of users.
In Apple’s validation study, the company stresses that the watch is not intended to replace traditional diagnosis methods or to be used as a method of BP surveillance, and that the absence of a notification does not indicate the absence of hypertension.
“The concern is, if you’re not getting an alert, will people interpret that as them not having hypertension,” said Bress. “That’s the worry. … The groups in which the negative alert is the least trustworthy contain the people with the highest risk. We’re most worried about people being falsely reassured.”
At the same time, he is clear that wearables should not be dismissed. “This technology is an important step forward; we need more wearable tech that can screen,” he said.
Unfortunately, access to these devices is not universal. Advanced monitoring technologies are often first adopted by the “worried well”—people who are more affluent and health-conscious—rather than those at highest risk.
“The only thing that can change this is a clear political decision to make awareness of hypertension large scale,” said Solà. Devices like the Hilo band could be used much like the continuous glucose monitors for diabetes. The difference is that if someone with diabetes doesn’t keep their blood glucose levels under control through regular monitoring, they can become ill very quickly. With hypertension, the effects of poor control don’t become apparent for decades.
“We need the policymakers to understand that investing in this technology today will have a return on investment in 10 years from now, not in one year from now,” Solà remarked.
Targeted drug selection
Even when hypertension is detected early and monitored closely, treatment remains largely empirical and can lead to therapeutic inertia, one of the biggest current challenges in hypertension care. “BP is not like diabetes, it doesn’t cause symptoms, and because of that, we don’t escalate treatment often enough,” said Padmanabhan.
At the same time, treatment selection remains largely trial-and-error. Clinicians cycle through medications sequentially, adjusting regimens based on response rather than underlying biology. The issue is that failed attempts risk side effects and can erode trust. That lack of trust can then impact adherence and, therefore, cardiovascular risk.
Instead, Padmanabhan believes that we need to move toward mechanistically informed drug selection.
This approach is common in oncology, where targeted therapies have been matched to specific mutations, but the picture is more complex for BP. Genome-wide association studies (GWAS) have identified more than 30 genes associated with monogenic forms of hypertension or hypotension and more than 2,100 single nucleotide polymorphisms linked to BP regulation, underscoring its highly polygenic nature.
This, combined with the strong influence of environmental factors, means that there is no single pathway or biomarker that can be easily targeted to reduce BP.
Padmanabhan’s work on the uromodulin gene (UMOD), however, shows that GWAS data can translate into therapy. His team identified a signal on chromosome 16 linked to uromodulin, a protein that is only expressed in one part of the kidney and plays a role in salt regulation. In a clinical trial comparing people with low BP to those with high BP, they found that people with the UMOD allele that increases protein expression experienced a sustained reduction in BP when treated with the loop diuretic torasemide, whereas the effect was only temporary and followed by rebound in those carrying the UMOD allele that lowers protein expression.
Approximately two-thirds of the population carry the UMOD allele that increases protein expression, meaning that loop diuretics like furosemide or torasemide, which are more commonly used to treat heart failure, could potentially be used in hypertension personalized by the patient’s genotype.
So far, “this is the only clinical trial from a GWAS-identified genetic variant in hypertension,” Padmanabhan noted, highlighting both the promise and challenge of pharmacogenomics in hypertension.
Although clinical translation from GWAS of hypertension has been limited, research has shown that genetic variation in drug-metabolizing enzymes can significantly impact hypertension treatment efficacy and toxicity. For example, variants of CYP2D6 affect metoprolol metabolism whereas those in CYP2C9 influence responses to losartan. Research is needed to determine whether testing for these variants or others could reduce trial-and-error prescription, minimize side effects, and thus increase patient confidence and long-term engagement.
Teresa Castielo, MD Director MIAL Healthcare
On a more fundamental level, biological sex differences remain a significant consideration in cardiovascular medicine. “Biological factors are an integral part of the clinical picture,” noted Teresa Castiello, MD, consultant cardiologist and director of MIAL Healthcare in London. She points out that clinical trials have historically seen a predominance of male participants; as a result, many standard medication dosages are based on data primarily derived from men.
This can lead to challenges with tolerability and a higher incidence of side effects in women as the therapeutic dose required for efficacy often tends to be lower in female patients.
Castiello suggests that this area of management warrants further refinement in clinical practice. She also emphasizes that key aspects of female cardiovascular risk, including reproductive history, menopause, and conditions like polycystic ovary syndrome, are nuances that may not always receive the necessary focus in routine care.
Toward a precise, preventative system
Ultimately, transforming hypertension care will require more than new technologies or therapies. It will require a fundamental change in how care is delivered.
Padmanabhan argues that hypertension should be managed through a “precision prevention service,” that integrates early detection, continuous monitoring, and personalized treatment, and involves more than just PCPs.
This approach recognizes that the disease is not just a clinical condition but a societal one, influenced by factors such as diet, socioeconomic status, work patterns, and access to care. Equity remains another critical issue. “We treat the ideal average patient under ideal circumstances but that’s not reality,” said Padmanabhan.
There also needs to be a cultural shift, said Castiello. “It’s not just the doctor’s responsibility; we also need to take responsibility for our own health.”
Solà shares a similar vision for the future: he would like to see BP measurement to become as routine as brushing your teeth, supported by technologies that empower individuals and reduce the burden on healthcare systems.
If realized, this shift could transform hypertension from a silent, progressive disease into a manageable, preventable condition, saving millions of lives in the process.
Laura Cowen is a freelance medical journalist who has been covering healthcare news for over 10 years. Her main specialties are oncology and diabetes, but she has written about subjects ranging from cardiology to ophthalmology and is particularly interested in infectious diseases and public health.