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Luigi Mangione will assert psychiatric defense in murder case in UnitedHealthcare CEO’s killing

NEW YORK — Luigi Mangione plans to assert a psychiatric defense at his state murder trial, claiming he was suffering from extreme emotional disturbance when he gunned down UnitedHealthcare CEO Brian Thompson, a judge said Wednesday. It wouldn’t absolve him of the Dec. 4, 2024, killing, but could free him from prison sooner.

If a jury accepts that defense, the panel would convict Mangione of manslaughter and he would face up to 25 years in prison. Alternatively, the jury could reject the extreme emotional disturbance defense and convict him of murder, which carries a potential life sentence. That defense isn’t available in his federal case.

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<![CDATA[Midlife sleep trouble predicts poorer well-being 9 years later, especially for women. Here’s why clinicians should ask about sleep and menopause triggers.]]>
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Vibrating Pill Predicts Anorexia Relapse

A vibrating capsule that assesses how nerve signals from the stomach are registered by the brain could help identify patients with anorexia at risk of relapse, a clinical trial suggests.

The findings, in JAMA Psychiatry, offers an insight into how the eating disorder affects the nervous system as well as a way to personalize and assess the success of treatment.

The results suggest that disruptions in gastrointestinal (GI) interoception—involving the detection, transmission, and processing of signals in the digestive tract—can increase the risk of anorexia returning, even if weight has normalized.

Gastric signals could therefore act as scalable biomarkers to identify who is at increased risk of relapse and track whether treatment is improving gut-brain signaling.

“People with anorexia nervosa do not simply ignore signals from the body,” explained researcher Sahib Khalsa, PhD, at the University of California, Los Angeles.

“Rather, their nervous system may process gut sensations differently, making those signals harder to detect, trust and learn from. Over time, that may contribute to the persistence of symptoms even after weight is restored.”

Khalsa and co-workers asked 62 girls and women with anorexia nervosa whose weight had been restored to healthy levels to swallow the vibrating capsule in their crossover trial.

The capsule could be remotely controlled by the researchers to produce mechanosensory stimulation of different intensities in the stomach.

Participants were asked to press a button upon sensing a vibration, with 54 patients followed up at six months after discharge from hospital and their results compared with 57 healthy control individuals.

Computational modeling was used to estimate how strongly participants anticipated feeling sensations in their stomachs, how heavily their brains depended on body signals, and how quickly they adjusted their expectations as to the presence or absence of signals.

The researchers found that participants with anorexia had abnormal GI interoception across behavioral and computational domains compared with healthy participants, despite having intact neural and physiological responses.

Participants with anorexia were less able to detect subtle stomach sensations and were more likely than others to believe there were no sensations when the pill was vibrating. They were also less likely to update those expectations when gastric signals occurred.

Patients who were more likely to ignore the stomach signals were also at increased likelihood of relapsing to the eating disorder.

“One of the most striking findings was that these differences persisted even after weight restoration,” said Khalsa.

“Recovery from anorexia nervosa isn’t just about restoring body weight. The underlying brain–body communication problems may remain and could contribute to relapse.”

The researchers conclude that their results support the use of ingestible mechanosensory probes and computer modeling as scalable tools to monitor treatment response and guide relapse prevention in eating disorders.

The post Vibrating Pill Predicts Anorexia Relapse appeared first on Inside Precision Medicine.

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Analytics Map Purification Optimization Tradeoffs

Speed or quality? When it comes to two-step chromatography purification, biopharmaceutical manufacturers want both, despite knowing, realistically, that each choice involves tradeoffs.

With purity, stability, toxicity, processing times, and costs hanging in the balance, the key optimization questions, therefore, are which purification efforts deliver the greatest return and how they can be combined to achieve the ultimate, optimal balance.

A small multinational team of researchers is among the first to address that question with an analytical model “to jointly manage speed-quality tradeoffs and stage-specific lead-time constraints in purification operations,” Yasemin Limon, PhD, assistant professor, Bilkent University, tells GEN. This method guides optimization decisions, helping biomanufacturers decide how aggressively to intervene at each purification step of a serial, two-step chromatographic purification process based upon the costs of the intervention and the time constraints of the purification steps.

The model, based on queueing network theory, captures what the authors call “practically relevant” tradeoffs, correlating intervention efforts, their effects on stability timeframes, and the probability of quality enhancement. It was developed by Limon and colleagues, Tugce Martagan, PhD, associate professor, Northeastern University, and Ananth Krishnamurthy, PhD, professor, Indian Institute of Management Bangalore.

“Understanding how much and at which stations interventions should be applied allows biomanufacturers to optimize system performance without compromising on manufacturing lead times,” the team reports. Thus, the risk of long wait times between steps that may cause product deterioration is reduced.

They divided purification optimization steps into two categories: Type I—those that improve batch quality without increasing purification processing time (such as selecting better resins or reagents)—and Type II—those that increase both batch purity and purification processing times (such as reducing flow rates).

For each category, they evaluated how each optimization affected stage-specific lead-time constraints and how those constraints varied between the two categories of interventions.

Choices are interrelated

“Optimal intervention efforts change with costs,” they acknowledge. Here are the key takeaways:

  • Under-investing in upstream purification pushes purification downstream, where increasing the polishing time may risk product stability
  • For Type I interventions, put maximum effort into the least expensive options until product stability becomes a constraint
  • For Type II interventions, each decision affects both quality and processing times. Characterize process times at each chromatography step and document stability-based time windows to create a reference chart that can be used repeatedly
  • Shortening the stability window for step two necessitates more aggressive purification at step one. Fresh time constraints—related to new molecular stability data, for example—should not be evaluated in isolation
  • Create a reference map for the range of operating conditions typically encountered in your facilities, along with possible interventions, their costs, and stability-based time effects. Use this as a real-time reference on the manufacturing floor

“The optimal policy depends on costs, processing times, and lead-time constraints,” Limon says. “Decisions at the first and second chromatography steps are interdependent.” Map those effects early to guide decisions in real time.

She recommends turning the model into a decision map. “A manufacturer can estimate its own process parameters (batch arrival rates, processing times at each purification step, stability-based time limits, intervention costs, and the effect of each intervention on quality and processing time) and use the model to identify which intervention policy is optimal under those conditions.

“Distinguish carefully between interventions that improve quality without increasing processing time and interventions that improve quality but slow the process,” Limon continues. “The first type affects lead time mainly through congestion at the downstream step, while the second type directly affects processing time and can make stage-specific lead-time constraints restrictive. Therefore, firms should quantify how interventions change processing time, congestion, and feasibility with respect to stability-based time windows.”

The post Analytics Map Purification Optimization Tradeoffs appeared first on GEN – Genetic Engineering and Biotechnology News.

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Continuous Production Platform Offers New Gene Therapy Options

A new continuous bioprocessing platform for advanced therapy medicinal products (ATMPs) could help manufacturers increase yields and improve productivity, allowing them to treat larger groups of patients.

The platform, developed by an independent U.K. innovation center, the Cell and Gene Therapy (CGT) Catapult, aims to provide an additional option for manufacturing gene therapies.

“We’re not going to get rid of batch processing, but it is another tool for people to use when developing and manufacturing gene therapies and other ATMPs that could tackle some [existing] bottlenecks,” explains Bilal Ozdoganoglu, an associate senior scientist at the CGT Catapult.

Ozdoganoglu spoke at the Bioprocessing Summit Europe in March about the downstream capture and polishing step of the continuous bioprocessing platform earlier this year.

According to Ozdoganoglu, the platform aims to use continuous bioprocessing to overcome the problems of low yields and productivity, allowing ATMPs to cater to larger groups of patients while taking advantage of economies of scale.

The platform uses perfusion technology in the upstream, followed by, in the downstream, a clarification step and multi-column chromatography.

“Multi-column chromatography is almost bread and butter of more traditional biologics, but it’s relatively new in the gene therapy space,” he says.

“As such, we had quite a few challenges to overcome to allow a system originally built for mAbs to cater for gene therapies.”

For the polishing step, Ozdoganoglu explains that they heavily relied on digital modeling to generate parameters they could take into the laboratory.

According to Ozdoganoglu, the recovery rates and overall performance of the continuous system were slightly better than, or comparable to, traditional batch processing.

The next step, he explains, is to develop the platform further so it becomes an alternative to batch processing.

As such, he says, the CGT Catapult is looking for collaborators, including therapy developers as well as vendors, automation suppliers, and contract development and manufacturing organizations (CDMOs).

The post Continuous Production Platform Offers New Gene Therapy Options appeared first on GEN – Genetic Engineering and Biotechnology News.

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Bacterial Expression Tech Prompts NorthX and enGenes Collaboration

Bacterial expression systems are becoming more versatile, say Swedish contractor NorthX Biologics and Austrian technology firm enGenes Biotech, who have teamed up to create an integrated, E.coli-based protein production platform.

E.coli-based protein expression systems are not a new idea. They have been around since the 1970s and used to make everything from recombinant human insulin to treatments for growth hormone deficiency.

They are generally cheaper than expression systems that use mammalian cells, primarily due to lower reagent costs. They also tend to be faster to set up, easier to scale, and have a reduced risk of viral contamination.

Typically, E.coli-based systems are selected for the manufacture of simple proteins that do not require human-like post-translational modifications such as glycosylation. However, recent advances in strain engineering are starting to expand their scope.

As a result, more biopharmaceutical firms are considering them for commercial-scale protein production, says Ola Tuvesson, CTO at NorthX, who cites this demand as a driver for the enGenes partnership.

“The biggest growth vectors are biosimilar manufacturing, peptide therapeutics, and antibody fragments, including ADC components. Advances in glycosylation engineering are also expanding what the platform can address at the higher end of biologics complexity.

“Several trends are reinforcing this direction: sustained pricing pressure pushing biopharma away from higher-cost production systems for this segment of the pipeline, growing investment in CRISPR-based strain engineering that extends microbial platforms into more complex program types, and a manufacturing infrastructure that needs to keep pace with industry demand,” Tuvesson tells GEN.

Integrated pathway

NorthX Biologics and enGenes’ strategy is to offer an integrated service that covers everything from strain design through manufacture.

Tuvesson says, “The E. coli development to GMP manufacturing pathway typically covers expression system development, process development, scale-up, and transfer into GMP production. While the technical steps are well established, the challenge in many programs is that these stages are often handled by different providers, leading to delays, rework, and increased scale-up risk.

“The pathway we are establishing addresses this fragmentation by integrating expression development and GMP manufacturing into a single, aligned workflow. This reduces handovers, improves data continuity, and helps ensure that the expression system is optimized from the start for manufacturing at scale,” he adds.

The new pathway will combine high-throughput screening platforms, multi‑fermenter systems, and multivariate experimental design with advanced analytical support and scale-up engineering.

According to NorthX Biologics and enGenes Biotech, the idea is to enable rapid iteration and the generation of decision-grade data early in development, supporting more robust and scalable processes.

There is an option to extend the partnership, according to Tuvesson, who says, “The collaboration may also open up opportunities to implement more continuous manufacturing approaches over time.”

The firms plan to monetize the platform by providing it to biopharma customers as a manufacturing service, rather than out-licensing, as Tuvesson explains.

“Expression systems and processes developed for a specific protein can be transferred under standard commercial terms. However, the pathway itself is not a standalone licensable product.

“The focus is instead on integrating expression development and manufacturing into a single workflow, reducing handovers and enabling faster development timelines,” he says.

The post Bacterial Expression Tech Prompts NorthX and enGenes Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.

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Solvent Recovery Gains Ground in Bioprocessing

In addition to making products, a bioprocessor should be thinking more about solvents. “Solvent recovery is becoming a critical part of operational resilience and fiscal strategy for bioprocessing companies,” says Rudy Morin, engineering and modular solutions manager at Koch Modular. “It provides three primary benefits: operating expense reductions, supply-chain independence, and corporate sustainability.”

The financial case is especially compelling for bioprocessors that rely on high-purity HPLC- or USP-grade solvents, which are costly to procure and expensive to dispose of properly. By recovering and reusing solvents from waste streams, companies can meaningfully cut virgin-solvent purchases while reducing hazardous waste disposal costs. Morin notes that the economics tend to work in a bioprocessor’s favor. “The payback periods are often attractive given quantities and solvent costs, and the recovery system quickly becomes a predictable long-term asset,” he says.

Supply-chain reliability has become an equally pressing concern. Geopolitical tensions, severe weather, and transportation disruptions have laid bare the vulnerabilities in chemical sourcing. Solvent recovery addresses this by creating a closed-loop supply within the facility itself. “A solvent-recovery system gives bioprocessing facilities total control over their solvent supply and business continuity,” Morin says.

Implementation, however, is rarely straightforward. Bioprocessing waste streams typically contain multiple solvents, water, and solids. Such mixtures often demand sophisticated separation technologies, such as pressure-swing distillation, extractive distillation, vacuum distillation, or liquid-liquid extraction. “Each additional unit operation adds intricate controls and operational variables, making the initial design phase absolutely critical,” Morin says.

Capital costs present another barrier. Automated systems generally start in the low seven-figure range, with complexity driving costs higher. To manage risk, Morin recommends combining pilot testing, process simulation, and modular construction. Pilot testing clarifies feed characteristics and yields critical process data; simulation software optimizes designs before a dollar is spent on construction; and modular fabrication reduces project risk by moving work off-site, compressing schedules, and tightening quality control.

Looking ahead, Morin sees meaningful opportunities in advanced extraction technologies and modular deployment. Liquid-liquid extraction, for instance, can recover products directly from fermentation broths while enabling downstream solvent recycling. For facilities considering the leap, his advice is practical: start with a clear design basis, conduct a rigorous economic analysis, and engage experienced process-engineering partners early. “Any solvent-recovery stream is worth a conversation with an experienced process engineering company, given the multiple potential benefits,” he says.

As cost pressures and sustainability commitments converge, solvent recovery is increasingly positioned not as a compliance measure but as a strategic investment—one capable of delivering measurable value across operations, supply chains, and environmental performance.

The post Solvent Recovery Gains Ground in Bioprocessing appeared first on GEN – Genetic Engineering and Biotechnology News.

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<![CDATA[Learn a multidimensional approach to suicide prevention in schizophrenia—screening, insight paradox, cannabis, cognition, trauma, and ethical AI monitoring.]]>
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Age-Related Inflammation Linked to R-Loop Nucleic Acids, Opens Therapies

In a new study published in Nature Aging titled, “Nuclear export of R-loop by the DDX1 and XPO1 complex promotes senescence-associated secretory phenotype and inflammaging,” researchers from the University of Texas (UT) MD Anderson Cancer Center have uncovered a previously unknown connection between R-loop nucleic acid structures and age-related inflammation or inflammaging. The results support new intervention options for chronic inflammation and subsequent health conditions.  

In preclinical models, the administration of KPT-330 (selinexor) prevented export of R-loops and led to significant improvement in inflammation, liver damage, fat gain, muscle loss and overall lifespan.   

“Chronic, widespread inflammation is a driving factor in many age-related diseases, including cancer, and our research has discovered one reason why this happens,” said Rugang Zhang, PhD, professor and chair of Experimental Therapeutics at UT MD Anderson and corresponding author on the study. “Understanding the cause is the first step toward developing treatments. We saw encouraging results using a drug that has already been tested in humans, paving the way for potential clinical use to alleviate age-related conditions.”

Cells begin releasing signals that contribute to chronic inflammation once they enter senescence and stop dividing. Researchers have now pinpointed R-loops as a key component to modulating these inflammatory signals.

An R-loop is a temporary cellular structure created during transcription, when a double strand of RNA and DNA becomes tangled with a third displaced single strand of DNA. While R-loops are traditionally confined to the cell nucleus, the study found that cells in senescence increasingly export R-loops into the cytoplasm. These R-loops attach to fragments of DNA debris to trigger chronic inflammation.

This study identified the two proteins involved in exporting R-loops, DDX1 and XPO1. DDX1 attaches to the R-loop inside the nucleus to facilitate export. XPO1 allows the R-loops to be transported into the cytoplasm by forming a complex with DDX1.

Researchers administered KPT-330, a FDA-approved drug for treating multiple myeloma that blocks nuclear export. The R-loops remain trapped inside the nucleus and could not trigger an inflammatory response.

The study showed that shutting down nuclear export by blocking XPO1 in preclinical mouse models suppressed inflammaging, reduced liver fibrosis, lowered systemic inflammatory markers, and reversed age-related body composition changes.

In a separate experiment, the same inflammatory alarm enabled the immune system to find and eliminate precancerous cells. The authors state that future studies could explore blocking DDX1 specifically, instead of shutting down all nuclear export, to mitigate side effects.

The post Age-Related Inflammation Linked to R-Loop Nucleic Acids, Opens Therapies appeared first on GEN – Genetic Engineering and Biotechnology News.