Heart’s beat may help it beat cancer, mouse research suggests

Heart disease and cancer are the leading causes of death in the United States, but it is rare that cancer makes its way to the heart. 

It’s an observation that clinicians have been grateful for, though largely unable to explain. But in a paper published Thursday in Science, researchers propose one potential explanation: The constant pressure that the organ is under from beating thousands of times a day and pushing gallons of blood creates an environment that is hostile to cancers. The study, which was conducted in mice, is preliminary, but outside experts said it points to potential new approaches for cancer treatments. 

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STAT+: Trump’s boosting of psychedelics, cannabis signal a new era in GOP drug policy

The days of “Just Say No,” it seems, are long gone. 

Over the weekend, President Trump signed an executive order to increase the availability of certain psychedelics as treatments for mental health conditions, ordering that $50 million be spent, and that the Food and Drug Administration fast-track reviews to usher in their approval. At one point, the president joked to the motley assembly of administration officials, a former Navy SEAL, and the podcaster Joe Rogan:  “Can I have some, please?” 

On Wednesday, the Trump administration announced it had downgraded medical marijuana from the highest tier of controlled substances, and was pushing the Drug Enforcement Administration to do the same for recreational marijuana.

The president’s lenient tack on some mind-altering drugs ushers in a new world of right-wing drug policy. While the administration has emphasized hardline, militaristic tactics when it comes to fentanyl, its recent actions on “softer” drugs could represent a new era not just for Republican politics but also for American drug policy writ large. 

“With this imminent move, we are now confronted with the most pro-drug administration in our history,” Kevin Sabet, the CEO of the anti-legalization advocacy group Smart Approaches to Marijuana, said in a statement. “Policy is now being dictated by marijuana CEOs, psychedelics investors, and podcasters in active addiction — it is a travesty and injustice to the American people of unprecedented proportions. The marijuana industry is the new Big Tobacco, and President Trump is welcoming them to the homes of families across this country with open arms.”

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STAT+: Legislatures in Colorado and Virginia resist moves to constrain drug affordability boards

Legislators in two states have resisted efforts to restrict prescription drug affordability boards, the controversial panels that are designed to function as rate-setting authorities and place limits on the cost of prescription medicines.

In Virginia, the General Assembly unanimously rejected a move by Gov. Abigail Spanberger (D) to delay a key provision of two bills that would create a board and allow it to place price caps that mirror the negotiated prices paid by Medicare. Spanberger must now either accept or veto the legislation as originally intended.

In Colorado, the House Health and Human Services Committee postponed consideration of a bill that would exempt orphan drugs, which are used to treat rare diseases, from pricing caps that might be pursued by the state board. By delaying action until the end of the legislative session, the bill is effectively dead.

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<![CDATA[How do estrogen, testosterone, and aromatase shape binge eating and bulimia risk? Let’s explore brain biomarkers and future hormone-aware treatments.]]>

Transcutaneous auricular vagus nerve stimulation for paroxysmal sympathetic hyperactivity syndrome after intracerebral hemorrhage: a hypothesis-generating case report

ObjectiveTo observe the clinical effect of transcutaneous auricular vagus nerve stimulation (taVNS) in drug-refractory paroxysmal sympathetic hyperactivity (PSH).MethodsThis case report describes the clinical course of a 63-year-old male with PSH following intracerebral hemorrhage. PSH episodes were characterized by tachypnea, tachycardia, hypertension, and increased muscle tone. After 2 weeks of combination pharmacotherapy (propranolol, baclofen, gabapentin), blood pressure, heart rate, and muscle tone improved, but tachypnea remained inadequately controlled. Although sedative agents alleviated tachypnea, they led to decreased consciousness level and could not be continued. Subsequently, taVNS was added to the ongoing pharmacotherapy.ResultsAfter 4 weeks of taVNS treatment, PSH episode frequency and tachypnea improved. Baclofen and gabapentin were discontinued, propranolol dosage was reduced, and the patient’s consciousness level showed improvement. After another 4 weeks of continued treatment, only mild tachypnea occurred occasionally under strong stimulation, without other sympathetic symptoms. Consciousness level further improved.ConclusionThis case suggests that taVNS may be a safe adjunctive intervention option for drug-refractory PSH. The symptom relief and consciousness improvement observed during treatment may be related to the application of taVNS.

Functional methods for evaluating the efficacy of retinal optogenetic therapy for vision restoration

Optogenetic therapy is a promising strategy for vision restoration. Functional assays have an important role in assessing the modulation of neural activity in response to light stimulation. Each functional assay needs to be carefully considered and evaluated for the preclinical development of optogenetic approaches to work toward meaningful vision restoration. Each strategy contributes to understanding the efficacy of vision restoration and the physiology of retinal optogenetic therapy. At a molecular level, bioluminescence resonance energy-transfer based and G protein coupling assays can be used. Calcium imaging provides measurements with useful spatial and temporal resolution using fluorescent calcium indicators at the cellular level. Electrophysiological tests can include ex vivo recordings by patch-clamping at single-cell resolution, multielectrode array recordings at the network level, and in vivo recordings at the lateral geniculate nucleus and cortical levels. Behavioural tests such as light avoidance, optomotor response and visual discrimination assess functional restoration in vivo. In this review, each functional assay is discussed in the context of retinal optogenetic therapy with notable examples that have demonstrated vision restoration. The advantages, disadvantages, and limitations of each assay are critically compared to highlight their relative scientific value and applicability across different stages of development. This provides insight into how these methods can be integrated within a translational framework, from molecular validation to behavioural outcomes, to better inform the design of preclinical studies. As clinical trials in optogenetic therapy continue to expand, improved alignment between preclinical functional assays and clinically meaningful endpoints will be essential to maximise translational success.

Speech recognition performance with dual-microphone audio processors in mandarin-speaking cochlear implant users

BackgroundCochlear implant (CI) audio processor upgrades have demonstrated speech recognition benefits in non-tonal language populations, but high-level evidence for native Mandarin-speaking CI users (a tonal language with unique signal processing requirements) remains critically limited. This study aimed to assess the speech perception performance of the SONNET 2 and RONDO 3 dual-microphone audio processors in native Mandarin-speaking CI users.MethodsThis prospective single-subject repeated-measures study enrolled 51 native Mandarin-speaking CI users. Speech recognition performance was tested across five processor configurations: the legacy baseline processor, SONNET 2 (S2) in omnidirectional (S2.OMNI) and adaptive intelligence (S2.Adaptive) modes, and RONDO 3 (R3) in omnidirectional (R3.OMNI) and adaptive intelligence (R3.Adaptive) modes. Outcome measures included monosyllabic words, disyllabic words, and sentence recognition in quiet, and sentence recognition in co-located speech-shaped noise (S0N0 paradigm). The pre-specified primary endpoint was sentence recognition in noise for S2.OMNI vs. the legacy processor; confirmatory linear mixed-effects models (LMMs) and subgroup analyses were exclusively performed for the primary endpoint, with pairwise comparisons for all secondary exploratory endpoints.ResultsIn quiet, all four upgraded configurations yielded significantly higher monosyllabic word recognition scores vs. the legacy baseline (all p < 0.05, FDR-adjusted); all configurations except R3. Adaptive showed significant improvements in disyllabic word recognition (all p < 0.05, FDR-adjusted). In the S0N0 noise condition, S2.OMNI and R3.OMNI significantly enhanced sentence recognition vs. the legacy processor (p < 0.001 and p = 0.011, respectively, FDR-adjusted), while no significant benefit was detected for either adaptive mode after FDR correction. LMM analysis confirmed that upgrading to the S2.OMNI configuration was an independent positive predictor of noise sentence recognition (F = 9.885, p = 0.003), with consistent significant benefits across pediatric/adult and unilateral/bilateral users in pre-specified subgroup analyses.ConclusionThis study provides confirmatory evidence that upgrading to the S2.OMNI configuration significantly improves sentence recognition in noise in native Mandarin-speaking CI users, with consistent benefits across key clinical subgroups. Exploratory analyses show that the S2 and R3 processors also deliver significant improvements in word recognition in quiet, These results fill a critical evidence gap for tonal language CI populations and may help guide clinical device selection.

Intracerebroventricular diphtheria toxin causes off-target toxicity in CD11b-DTR and wild-type mice, revealing limitations of DTR-based depletion studies

Diphtheria toxin receptor (DTR)–based depletion models are widely used to study microglial and macrophage function, yet the extent to which diphtheria toxin (DT) produces off-target effects remains incompletely defined. Here, we examined tolerability, behavioural outcomes, and cellular responses following intracerebroventricular (i.c.v.) DT administration in wild-type (WT) and CD11b-DTR mice. Mice received bilateral i.c.v. infusions of DT or vehicle over a 10-day period and were assessed for survival, motor and cognitive behaviour, myeloid cell changes, and neuropathology. Unexpectedly, DT induced dose-dependent mortality in WT mice, demonstrating that toxicity can occur independently of DTR expression. CD11b-DTR mice exhibited greater susceptibility, with reduced survival and the emergence of illness at lower DT doses. Behavioural testing revealed significant dose-dependent impairments in rotarod performance and Y-maze spontaneous alternation in both genotypes, while open-field mobility was largely preserved among animals. Region-specific analysis of myeloid cells in CD11b-DTR mice showed robust depletion in the midbrain at higher DT doses, whereas hippocampal cell numbers remained unchanged with marked morphological signs of activation. These findings indicate that DT-mediated myeloid cell responses vary across brain regions, potentially reflecting differential toxin exposure following ventricular delivery. Consistent with this, focal abnormalities in the brain—including ventriculitis, meningoencephalitis and spongiotic changes—were observed in a subset of clinically affected DT-treated animals, whereas peripheral organs were largely unremarkable and haematological changes were infrequent. Together, these data demonstrate that i.c.v. DT administration can induce mortality, behavioural dysfunction, and focal CNS pathology in both WT and CD11b-DTR mice, with transgene expression amplifying susceptibility. Our findings highlight the need for careful dose optimisation, appropriate DT-treated controls, and cautious interpretation of behavioural phenotypes when employing this model.

Cortical activity during cognitive and walking tasks in individuals with chronic nonspecific low back pain: a functional near-infrared spectroscopy study

IntroductionPrevious research demonstrates that individuals with chronic nonspecific low back pain (CNSLBP) exhibit changes of gait patterns. However, the neural mechanisms responsible for these adverse events remain unelucidated. In this study, we used functional near-infrared spectroscopy (fNIRS) to investigate cortical activities during cognitive and walking tasks to provide evidence of the central mechanisms responsible for changes of gait patterns in individuals with CNSLBP.MethodsIn this cross-sectional study, we evaluated 18 individuals with CNSLBP (the CNSLBP group) and 18 healthy controls (the HC group) under three specific conditions: Task 1 (a single walking task), Task 2 (a single cognitive task) and Task 3 (a cognitive-walking dual task). Cortical activities were measured using fNIRS, including the bilateral premotor cortex and supplementary motor area (PMC/SMA), primary motor cortex (M1), somatosensory association cortex (SAC), and primary somatosensory cortex (S1). Gait parameters, including step duration, step length, stride length, velocity, cadence, swing power, and cycle, were measured using a three-dimensional gait analysis system.ResultsIn Task 1, the CNSLBP group exhibited a significantly lower velocity (p = 0.029) and higher activation in the left SAC (p = 0.001) and right S1 (p = 0.018) than that of the HC group. In Task 2, the CNSLBP group exhibited higher activation in the left SAC (p = 0.028), right SAC (p = 0.033), and left S1 (p = 0.032). In Task 3, the CNSLBP group exhibited significantly lower step length (p = 0.031), stride length (p = 0.041), velocity (p = 0.016), and swing power (p = 0.047). Correlation analysis in Task 1 revealed stronger associations between parameters in the CNSLBP group.ConclusionOur findings suggest that individuals with CNSLBP exhibit distinct patterns of cortical activities and gait performance. The SAC and S1 were involved in walking, and central sensitization was observed in individuals with CNSLBP in daily cognitive and walking tasks. These findings could contribute to the recovery and rehabilitation of CNSLBP.

Psychiatric comorbidities and sexual health risks in HIV-serodiscordant heterosexual couples involving women with borderline personality disorder: a mixed-method study and theoretical modeling

BackgroundHIV-serodiscordant heterosexual couples consist of one partner who is HIV-positive and the other who is HIV-negative. Our previous studies found that the HIV-negative female partner in no-prevention couples (NPC) may be affected by borderline personality disorder (BPD) and might have a history of child abuse, trauma, and neglect. These couples provide valuable insights into public health, particularly regarding health behaviors and psychosocial factors that influence the relationship between psychopathology, illness behaviors related to borderline personality disorder, and the transmission of sexually transmitted diseases.Population and methodsThis study was conducted in three sequential phases. Phase One involved a cross-sectional, multicenter, anonymous survey of 175 HIV-serodiscordant couples, aimed at assessing preventive sexual behaviors. Participants reported sexual protection use during at-risk sexual encounters on a scale ranging from 0% (‘never’) to 100% (‘always’). Phase Two, which constitutes the core of the present investigation, employed qualitative, unstructured interviews and narrative analysis with HIV-negative female partners in serodiscordant relationships. The analytic focus was on identifying patterns of psychopathological comorbidity and health-related behaviors. Through iterative narrative synthesis and thematic coding, the presence of Borderline Personality Disorder (BPD) emerged consistently across cases. The confirmation of BPD as a clinical diagnosis was thus an outcome of this phase, derived from converging narrative indicators and psychopathological profiles rather than a pre-established inclusion criterion. Phase Three, drawing on the findings from both preceding phases, involved developing a theoretical model of the observed behavioral patterns. Integrating quantitative trends from Phase One with the qualitative insights from Phase Two, we developed a conceptual framework to explain the interaction between BPD-related psychopathology, relational dynamics, and HIV (or other sexually transmitted diseases) risk behaviors. This model aims to guide future healthcare strategies for HIV-negative women with BPD in serodiscordant relationships, a group identified as particularly vulnerable to sexually transmitted HIV due to compromised primary prevention.ResultsSpecific health belief models and behaviors related to health emerged among HIV-negative female partners with BPD who decline prevention during behaviors that put them at risk for HIV sexual transmission in stable relationships with HIV-positive males. Results illustrate that women with BPD who have a history of child abuse and trauma often exhibit comorbid self-defeating personality disorder (SDPD), dependent personality disorder (DPD), and complex post-traumatic stress disorder (CPTSD). We could not replicate similar findings in HIV negative males.ConclusionsThe current study confirms that health behaviors and women’s health may be influenced by underlying personality, behavioral, and psychosocial factors, which public health policymakers must address to improve primary prevention of transmissible diseases. We suggest that child abuse, neglect, and trauma may be connected to overlooked health behaviors across a person’s entire life span.