Background: Long-term care facilities are increasingly caring for persons living with dementia as this population grows. Frontline care workers provide most hands-on support, yet they often have limited access to formal dementia education and training. Traditional training formats frequently fail to support experiential learning or accommodate the linguistic, cultural, and demographic diversity of the long-term care workforce. Objective: This mixed methods pilot study examined the effects of the combined use of online learning, immersive virtual reality (VR) simulation, and facilitated group discussions on the training and preferred learning formats. In particular, this study tested whether training based on relationship-centered care (eg, emphasizing the importance of mutual respect, empathy, and shared humanity) in care relationships embodied in the immersive VR simulation allows staff to experience dementia-related cognitive and sensory changes from the perspective of persons living with dementia. Methods: A total of 21 certified nursing assistants from 1 US nursing home participated in a 3-month mixed methods intervention. Empathy and knowledge were measured using pre- and postintervention standardized tests; qualitative feedback was collected through open-ended surveys and group discussions. Results: Participants were predominantly female, Black certified nursing assistants with approximately 68% reporting 8 years or more of care experience. Among the 76.2% (16/21) of the participants who completed the pre- and postintervention surveys, empathy scores increased from pretest (mean 5.31, SD 0.74) to posttest (mean 5.51, SD 0.61). The mean difference of 0.20 (SD 0.43) did not reach statistical significance (=1.88; =.08), but the effect size was moderate (Cohen =0.47, 95% CI −0.03 to 0.43). Dementia knowledge scores also increased from pretest (mean 5.50, SD 2.37) to posttest (mean 5.94, SD 2.11), with a mean difference of 0.44 (SD 1.63), which was not statistically significant (=1.07; =.30), and demonstrated a small effect size (Cohen =0.27, 95% CI −0.43 to 1.31). Qualitative findings revealed that participants perceived the VR training as engaging and emotionally impactful. Participants described reframing their understanding of dementia, reporting reduced stigma and increased empathy toward persons living with dementia. Many noted that experiencing dementia-related symptoms through VR helped them better understand residents’ behaviors and respond with greater compassion. Participants expressed a strong preference for immersive VR and facilitated group discussions over online modules, and cultural differences in the VR scenarios were not perceived as barriers to learning. Conclusions: While preliminary, these findings suggest that combining relationship-centered care with immersive VR may enhance empathy and engagement among staff, particularly when paired with facilitated discussion and plain language explanations. This multimodal model appears particularly valuable for supporting empathic learning within diverse and experienced workforces. Larger, multisite studies with sustained follow-up are needed to determine long-term effects and optimize training for linguistically and culturally diverse workforces.
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Comparing Perceptions of ChatGPT Use in Health Attitude Contexts Among Users and Nonusers: Cross-Sectional Study
Background: In light of the growing use of artificial intelligence (AI) in health care, individuals’ access to and use of health information are transforming. ChatGPT, an AI chatbot, provides immediate responses to health queries, with the potential to influence health-related attitudes, thereby raising concerns related to privacy, reliability, and security. Objective: This study aimed to investigate the perceived usefulness, risks, anxiety, and social influence of ChatGPT on health attitudes among users and nonusers in Saudi Arabia. Methods: A cross-sectional study was conducted using an online survey based on a validated tool. In total, 337 participants aged 18 years and older responded to questions assessing their perceptions of ChatGPT on health-related attitudes. Results: Data showed that 76.1% (194/255) of the respondents used ChatGPT, with the majority being younger and more highly educated. The main uses for health-related purposes were health education (43/194, 22.2%) and physical activity guidance (31/194, 16%). The analysis showed that users considered ChatGPT useful for health-related decisions, with 45.9% (89/194) finding it easy to learn and use, but concerns about privacy (106/194, 54.7%) and reliability (87/194, 44.9%) remained. Among nonusers, security risks (39/61, 63.9%) were the major barrier to using AI-based tools for health purposes, and 68.9% (42/61) found such tools attractive and engaging. There were no statistically significant differences between users and nonusers across all examined sociodemographic characteristics (>.05). Conclusions: The study established the potential of ChatGPT in improving health decision-making and revealed cultural, privacy, and trust issues that may affect its implementation. These findings underscore the importance of strengthening the security of AI-based applications to enhance public acceptability of related health policies and to support the safe integration of tools such as ChatGPT into the health care system.
The Effectiveness and Mechanisms of Action of App-Based Interventions for Improving Mental Health and Workplace Well-Being: Randomized Controlled Trial
Background: Depression is the most common mental health disorder worldwide and frequently leads to workplace absence. As face-to-face treatment can be difficult to access, app-based interventions are a popular solution, although their effectiveness in working populations and their mechanisms of action are unclear. Deficits in executive function may contribute to the onset and maintenance of depression, and executive function training is proposed to improve symptoms by enhancing executive function. Responders to cognitive behavioral therapy (CBT) show improvements in executive function, suggesting that this may be one mechanism of action. Objective: This study investigated the effectiveness of app-based interventions (executive function or CBT-based) for reducing depressive and anxiety symptoms and improving workplace well-being, and assessed whether changes in executive function mediated improvements. Methods: A total of 228 participants (147 female participants) with mild-to-moderate symptoms of depression and anxiety were recruited online and randomly assigned to a waitlist control group, an executive function training group (NeuroNation app, Synaptikon GmbH), or a self-guided CBT group (Moodfit app, Roble Ridge LLC) for a 4-week intervention period. Participants assigned to the active intervention groups were asked to use their apps a minimum of 21 times during the intervention. Participants completed measures of depressive symptoms, anxiety symptoms, and workplace well-being, and a working memory task at baseline, postintervention, and follow-up (12 weeks). Results: Executive function training reduced anxiety (β=−2.79; =.004) and depressive (β=−2.77; =.02) symptoms at follow-up but not at postintervention, and it did not affect workplace well-being. There were no reductions in depressive or anxiety symptoms in the self-guided CBT group, though workplace well-being was improved at postintervention (β=3.72; =.02) and follow-up (β=4.46; =.02). Improvements in executive function did not mediate intervention-related changes in symptoms or workplace well-being. Self-reported adherence rates were high (executive function training: 48/54, 89%; self-guided CBT: 52/54, 96%), although attrition was high at follow-up (58% missing). Conclusions: These results suggest that app-based executive function training may be effective at managing symptoms of anxiety and depression in a working population, while self-guided CBT apps may improve workplace well-being. However, improving executive function did not appear to be a mechanism of action of either intervention. Trial Registration: ISRCTN 12730006; https://www.isrctn.com/ISRCTN12730006
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PD-L1 Inhibitors for Cancer Treatment Could Be Repurposed to Treat Bone Loss in Obesity
Bone loss related to obesity is partly caused by changes inside the bone marrow fat compartment that reshape immune signaling and increase osteoclast formation, according to researchers at the MaineHealth Institute for Research. In a study published in Bone Research, the team found that expansion of bone marrow adipose tissue in obese people changes the marrow environment toward immunosuppression through PD-L1 signaling, which in turn promotes bone-resorbing osteoclast activity that reduces bone volume.
“We discovered that bone marrow fat is not simply a passive tissue but actively reshapes immune signaling in ways that accelerate bone loss in obesity,” said senior author Clifford J. Rosen, MD, senior scientist at the MaineHealth Institute for Research.
The team noted that obesity influences bone health not just due to a higher body weight but also by altering the bone marrow environment. The increase in bone marrow fat promotes immunosuppressive PD-L1 signaling, which enhances osteoclast formation and accelerates bone loss.
The study identified a pathway in which bone marrow adipocytes increase expression of MCP-1, a signaling molecule that recruits myeloid immune cells. These recruited cells shift toward a PD-L1–expressing phenotype, with PD-L1 interacting with PD-1 receptors, which are found not only on T cells but also on osteoclast precursors. In immune biology, PD-1/PD-L1 signaling is typically known for suppressing T-cell activation and promoting immune braking. This new study shows that this same form of suppressive signaling also directly enhances osteoclast differentiation.
According to the study results, as PD-L1+ myeloid cells accumulate, they suppress T-cell activity in bone marrow, creating an immunosuppressive environment. At the same time, PD-L1 engagement with PD-1 on osteoclast precursors promotes their maturation into active osteoclasts, which break down bone tissue, increase resorption and reduce bone density.
To learn more about this mechanism, the investigators used diet-induced obese mouse models, co-culture systems, and genetic depletion approaches. An important model in this work were mice lacking bone marrow adipocytes, which allowed the researchers to isolate the role of marrow fat. The team also blocked PD-1/PD-L1 signaling during early osteoclast formation in vitro. In both cases, osteoclast differentiation decreased and bone structure improved. The mice lacking bone marrow adipocytes showed fewer PD-L1+ myeloid cells, fewer PD-1+ osteoclast precursors, and higher trabecular bone volume even under high-fat diet conditions.
Earlier research has shown a link between obesity and bone loss, but studies reported trabecular bone loss without cortical effects, while others found no significant bone changes under diet-induced obesity. The MaineHealth team noted that these earlier studies often focused on shifts in osteoblast activity as opposed to their approach which identified a pro-osteoclastic mechanism driven by immune signaling.
In addition, the Maine Health finding also added to evidence that has established that obesity is associated with impaired immune responses, including reduced vaccine effectiveness and altered macrophage activity. In this study, the marrow environment in obese mice resembled features seen in tumor-associated immune suppression, where PD-L1 expression is elevated and immune activity is dampened. The researchers wrote that “the increase in PD-L1 expression seen in OB-HFD mice is related to the increase in Mcp-1 in part because previous cancer research has suggested the recruitment of myeloid cells via Mcp-1 creates an immunosuppressive tumor microenvironment.”
The findings suggest potential strategies for preserving bone bones in obese people by targeting bone marrow adiposity or the PD-1/PD-L1 pathway. Because PD-1/PD-L1 inhibitors are already used in oncology, there is a compelling case for repurposing or adapting immune checkpoint modulation therapies already approved for cancer treatment for bone disorders linked to metabolic disease. The authors also noted another strategy could be to reduce the amount of bone marrow fat itself to restore immune balance and limit osteoclast-driven bone loss.
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Removing Harmful Protein from Blood Helps Women with Preeclampsia
An early stage clinical study shows removing a protein known as soluble Fms-like tyrosine kinase 1 (sFlt-1) from the blood of pregnant women with early stage, severe preeclampsia seems to help both mothers and babies with no significant side effects.
The treatment, which involved filtering the patient’s blood through a machine to remove the harmful protein, reduced blood pressure and allowing pregnancies to continue for around 10 extra days.
Up to 5% of pregnancies in the U.S. are affected by preeclampsia, a condition where a woman develops high blood pressure during pregnancy, and organs like the kidneys, liver, or brain can also be affected. It can be life threatening in some cases and there are currently no available treatments, so the only real option is to deliver the baby, which can cause problems for the baby if delivered preterm.
The single exact cause of preeclampsia is unknown, but most evidence points to problems with how the placenta and its blood vessels develop early in pregnancy, which then triggers widespread damage in the mother’s blood vessels. Women with preeclampsia seem to have high levels of sFlt-1 in their blood and research suggests it binds and neutralizes VEGF and PlGF, key proteins that normally help keep blood vessels healthy and relaxed.
In this study, published in Nature Medicine, the researchers tested whether filtering the blood of women with early onset preeclampsia (at 24-32 weeks gestation) to remove the excess sFlt-1 protein could help improve their symptoms and prolong pregnancy.
This was an early stage study to check safety and tolerability and included 16 women in total. Seven women were in an initial group to test the safety of the filtering process and to assess how much protein could be removed. This showed the treatment was safe and well tolerated with no major side effects observed.
The second group of nine women had several treatments and the researchers looked at how effective the treatment was in this group. In the second group, the women’s symptoms improved; blood pressure went down by 4.1 mmHg on average and pregnancy was extended by 3-19 days (median 10 days).
“Even a few extra days in the womb can make a meaningful difference in outcomes for premature infants,” said co-lead study author Ananth Karumanchi, MD, professor of medicine and director of the Renovascular Research Center at Cedars-Sinai, in a press statement. “We found a way to potentially buy that time safely. Our approach could shift how we manage very early preeclampsia.”
The researchers acknowledge the treatment needs to be tested further but are hopeful it could be a good treatment option for women with this condition in the future, particularly as it does not involve introducing a drug or therapy into the body and therefore reduces the risk of side effects for both mother and baby.
The post Removing Harmful Protein from Blood Helps Women with Preeclampsia appeared first on Inside Precision Medicine.
Trump administration warns against using federal dollars on fentanyl test strips
The Trump administration is doubling down on its opposition to harm reduction services for people who use illicit drugs.
In an open letter on April 24, the federal agency overseeing addiction and mental health policy warned its grantees against using federal funds to buy harm reduction supplies including sterile syringes and pipes, or to distribute test strips for common drug supply adulterants like fentanyl, xylazine, and medetomidine.
Emotional Training via Telerehabilitation After Surgical Treatment for Facial Palsy: Prospective, Assessor-Blinded, 2-Arm Pilot Cohort Study
Background: Peripheral facial nerve palsy is a debilitating condition that may necessitate surgical intervention. Although motor rehabilitation is considered essential, the most effective approach has not yet been determined. Objective: This study aimed to evaluate the feasibility and effectiveness of emotional training, a novel telerehabilitation-based treatment, on motor, functional, and psychological outcomes in patients with unilateral facial palsy following triple innervation surgery. Methods: A prospective, assessor-blinded, 2-arm pilot cohort study was conducted at the rehabilitation unit at University Hospital San Paolo, Milan, Italy, from January to October 2024. Participants (N=16) received 1 treatment session every 2 weeks over 20 weeks, each lasting 45 minutes, according to standard clinical procedures in place at the rehabilitation unit. Participants were nonrandomly assigned to either an in-person group (n=8) or an online group (ie, telerehabilitation; n=8) based on their ability to attend in-person sessions. The primary outcomes assessed at baseline (T0) and after treatment (T1) included facial symmetry (Sunnybrook Facial Grading System; SFGS), facial disability (Facial Disability Index; FDI), and anxiety levels (Beck Anxiety Inventory). Results: Statistical analysis revealed significant improvements at T1 for both groups in the FDI social and well-being function subscale, Beck Anxiety Inventory, SFGS resting symmetry score, SFGS symmetry of voluntary movement score, SFGS composite score, SFGS with bilateral masseter contraction symmetry of voluntary movement score, and SFGS with bilateral masseter contraction composite score (<.001 for all). Only the FDI physical function subscale showed a differential improvement at T1 for the in-person group treatment (ANOVA for time × treatment: =14.356; =.002; Holm-Bonferroni post hoc test: <.001). Finally, a strong positive correlation was observed between the time elapsed from surgery to rehabilitation and SFGS composite score improvement at T1 (=0.94; =.005). Conclusions: These results suggest that the online emotional training protocol is as feasible and effective as the in-person emotional training protocol in improving facial motor function, reducing anxiety, and enhancing facial expression spontaneity in patients who had undergone surgery for peripheral facial palsy. These findings support the validity of telerehabilitation approaches as a feasible, accessible, and sustainable alternative to conventional in-person therapy for facial nerve recovery.
Digital Phenotyping via Passive Network Traffic Monitoring: Prospective Observational Study in University Students
Background: Digital behaviors such as sleep, social interactions, and productivity reflect how individuals structure their daily lives. Among university students, online activity patterns mirror academic schedules, social rhythms, and lifestyle habits, with disruptions linked to sleep, stress, and well-being. Existing approaches—including wearables, apps, and surveys—depend on self-report or active participation, limiting long-term adherence. Passive sensing of network traffic offers a scalable alternative for the unobtrusive capture of smartphone usage patterns that preserves privacy. Objective: This study evaluated the degree to which encrypted smartphone network traffic, collected via a standard virtual private network (VPN), can capture patterns of digital behavior. We assessed feasibility (sustained data capture) and acceptability (usability, burden, and privacy perceptions) and examined how traffic-derived features reveal aspects of digital behavior—including timing, intensity, and regularity—relevant to health and daily functioning. Methods: We conducted a 2-week prospective observational study at New York University. Participants installed the WireGuard VPN client on personal smartphones, enabling passive capture of encrypted network traffic. Feasibility was assessed using a mixed methods approach combining quantitative measures of user retention and data coverage with qualitative analysis of semistructured exit interviews. Acceptability was evaluated using the System Usability Scale, NASA Task Load Index, and qualitative interview analysis. Exploratory analyses visualized traffic-derived features in relation to digital activity patterns. Results: Thirty-eight students consented, of whom 29 (76.3%) contributed valid network traffic data and formed the analytic cohort. Within this cohort, 93% of participants (27/29; Wilson 95% CI 78%‐98%) contributed at least 5 days of monitoring, corresponding to 71% retention relative to all consented participants (27/38; Wilson 95% CI 55%‐83%). The mean data coverage within the analytic cohort (n=24) was 74.1% (SD 19.3%; median 77.1%, IQR 63.6%-90.0%; bootstrap 95% CI 66.3%‐81.4%). These participants contributed an average of 311.6 (∼13 d, SD 3.5) hours of monitored traffic, ranging from 121 to 496 hours. Acceptability outcomes were evaluated among participants completing the exit survey and interview. Usability ratings were high (System Usability Scale score: mean 78, SD 14.96), and perceived workload was low (NASA Task Load Index scores were minimal). Participants described the system as easy to install, unobtrusive, and generally trustworthy, although some reported temporarily disabling the VPN during activities they considered private. No inferential statistical tests were conducted; analyses were descriptive. Exploratory analyses indicated that traffic-derived features reflected daily digital activity rhythms and revealed distinctive lifestyle patterns, including gaming and irregular late-night food delivery use. Conclusions: VPN-based monitoring of encrypted smartphone traffic was feasible and acceptable, enabling sustained passive data collection with minimal burden. This approach shows promise as a scalable, device-agnostic method for digital phenotyping that captures fine-grained behavioral rhythms while preserving privacy. With broader validation, this technique could expand the toolkit for studying health and well-being in everyday life.
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<![CDATA[Adial seeks FDA priority voucher to speed AD04 review, a biomarker-guided therapy aiming to curb heavy drinking in alcohol use disorder.]]>
Anticancer Strategy Targets Defense Mechanism in Senescent Cells
Scientists headed by a team at MRC Laboratory of Medical Sciences (LMS) and Imperial College London have found that a new set of drugs can exploit a recently-revealed weakness in senescent—or ‘zombie-like’—cells, a finding that could lead to new treatments for cancer and age-associated diseases.
Senescent cells walk a tightrope, risking cell death with high levels of iron and other damaging agents, but compensating for this by overproducing a protective protein, GPX4, which staves off death. The team showed that targeting this defense mechanism removes the shield and could be used to treat diseases that are associated with senescence, including cancer. Tests showed that combining anticancer therapies with GPX4 inhibitors eliminated senescent tumor cells in models of melanoma, prostate and ovarian cancer. This approach, they say, could complement existing treatments to bring much-needed improvements for cancer patients.
Mariantonietta D’Ambrosio, PhD, a postdoctoral researcher at the LMS, is first author of the international research team’s published paper in nature cell biology, titled “Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.”
Cancers grow as a result of unconstrained cell division. But within most tumors, there is a portion that does not divide at all: senescent cells. Chemotherapy often increases the proportion of senescent cells in a tumor as it aims to stem the rapid proliferation, the team explained. However, while these senescent cells don’t directly increase the size of a tumor, they can wreak havoc in their own way.
Senescent cells, which are also a defining feature of aging conditions such as fibrosis, influence neighboring cells by secreting molecules that increase proliferation, the spread of the cancer, and unwanted immune system activity. “Senescent cells drive aging and age-related pathologies, including cancer,” the team wrote. There is therefore an increasing interest in developing drugs that directly target and kill senescent cells, in cancer and beyond. “Consequently, senolytics, drugs that selectively kill senescent cells, have broad therapeutic appeal,” they continued. “Compounds that selectively kill senescent cells (senolytics) can treat different age-related pathologies.”
The study by D’Ambrosio and colleagues has identified a new approach to killing senescent cells in cancer. “Senescence was considered for a long time to be positive, because senescent cells don’t proliferate, which is the core feature of cancer,” D’Ambrosio explained. “Normal chemotherapy induces senescence blocking the proliferation of cancer cells, so the tumor doesn’t get bigger. But with time you also see the negative side of the senescent cells, because they secrete a lot of factors that influence neighboring cells and induce even more proliferation, metastasis, and recruitment of bad parts of the immune system that will provoke even more aggressiveness in the tumor. For this reason, we tried to find some drugs that were able to kill the senescent cells.”
The researchers cast a broad net in their search for new drugs that might kill senescent cells. Together with collaborators at the Department of Medicinal Chemistry at Imperial, they decided to examine covalent compounds, a class of inhibitors that can form a covalent bond with their target, which can result in the inhibition of proteins previously considered undruggable. The investigators introduced 10,000 different covalent compounds to both senescent cells and normal cells, looking for the ones that preferentially killed senescent cells and classing the drug as “senolytic,” or senescent-killing.
They narrowed their results down to just four promising compounds and found that three of them affected a particular protein, GPX4, which has a protective role in cells, helping stave off ferroptosis, a type of cell death associated with high levels of iron and destructive reactive oxygen species. To protect themselves against the high levels of iron and other ferroptosis-causing agents, senescent cells have high levels of GPX4. It is like proactively taking a painkiller so a person can keep running on an ankle. The damage and danger remains, but the immediate risks are bypassed. Removing the painkiller makes the pain unbearable.
“Senescent cells are primed for ferroptosis and upregulate GPX4 as a protective mechanism,” the team noted. Ferroptosis had only recently been revealed as a potential weakness of senescent cells. D’Ambrosio commented, “recent papers have shown this predisposition of senescent cells to ferroptosis, but it’s a new senescence vulnerability. That creates an opportunity for us to exploit. So now there is research to find senolytic drugs to kill cells through ferroptosis.”
The researchers found that blocking the activity of GPX4 removes the shield, making fatal ferroptosis unavoidable. The authors further commented, “We concentrated our studies on four chloroacetamides displaying senolytic activity in different models of senescence … GPX4 was a target of three of the four senolytic chloroacetamides. GPX4 is a glutathione peroxidase that prevents ferroptosis by reducing lipid peroxidation.”
The team tested their drugs with three different mouse models of cancer and saw improved outcomes as a result of senescent cell death in each case. Translating this to patients could be a huge asset to cancer treatments. “In mouse models we saw that these drugs reduced tumor size, and improved survival,” noted professor Jesus Gil, PhD, senior author and head of the senescence group at the LMS. “Now we need to see the effect on the immune system. Is the improvement also awakening the ‘good side’ of the immune system (T cells, natural killer cells) that helps to kill the tumor? … Once we know more, the next step is to understand which cancer cell types or specific patients might better respond to this treatment. For example, if a patient undergoing chemotherapy overexpressed GPX4 then you could use this approach in combination with existing drugs to improve efficacy.”
This approach offers a much-needed new perspective on cancer therapy, pinpointing senescent cells as an underexploited target. D’Ambrosio says it has potential to transform treatment. “Targeting senescence is a huge opportunity for cancer treatments, and ultimately it can play a supporting role in addition to chemotherapy and immunotherapy.”
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