Category: 8. Health

Sepsis remains a critical health challenge globally, with 48.9 million cases annually, contributing to significant morbidity and mortality. Despite being a preventable, treatable disease – due in part to advancements in therapeutics – sepsis claims the lives of 11 million individuals each year (20% of all global deaths), making it a leading cause of mortality worldwide.

Nearly half (20 million) of all cases occur in children under five years of age. The highest incidence rates are seen in low- and middle-income countries (LMICs). Sepsis drives hospital mortality and incident disability; patients who survive hospitalisation develop an increased risk for negative health outcomes, including new morbidity, deterioration, hospital readmission and death. The World Health Organization (WHO) Global Antimicrobial Surveillance System report underscores the serious global impact of antimicrobial resistance (AMR), which exacerbates the substantial burden that sepsis poses on patients, the health community and health systems.

Globally, 4.95 million and 1.27 million deaths are, respectively, associated or attributed to AMR. Projections estimate ten million deaths by 2050 with cost of care compounding the burden: a UK report calculated a $100trn global economic impact, particularly due to AMR. These factors focus our lens on modern sepsis management strategies like rapid early diagnosis and intervention, for better health outcomes, and benefit to the medical community, health systems and governments.

Impetus for early recognition and treatment
Given its frequency, high morbidity and mortality, timely sepsis management at the point of care (POC) is a globally recognised public health priority – the urgent need underscored by the World Health Assembly resolution (2017) towards improving the prevention, diagnosis, rehabilitation from, and management of, sepsis. Regional disparities exacerbate the burden; sepsis is common in high-income countries (HICs) – 1.7 million and 48,000 deaths annually, for the US and the UK, respectively. LMICs face a heavier burden due to limited access to healthcare services, few qualified healthcare providers (HCPs), and inadequate diagnostics and lab services. Mitigating the burden, particularly in low-resource settings, requires the adoption of easy-to-use low-cost diagnostic instruments, alongside provider education, to enhance sepsis management. Clinical decisioning support tools, including biomarker diagnostics like C-reactive protein (CRP) and procalcitonin (PCT), widely used in HICs, are also potentially efficacious in LMIC populations to avert antibiotic overuse and improve patient outcomes.

Challenges in point-of-care management
Significant challenges persist in managing sepsis in POC settings across diverse healthcare systems and resource settings. Late presentation and delayed or missed diagnosis, which occur in HICs and are more pronounced in LMICs, result in negative health outcomes. Clinical symptoms of sepsis often present like other conditions. There is no single definitive diagnostic test, which can lead to variable triage and recognition. Furthermore, diversity in patient populations from varying health conditions and immune responses, and the prevalence of healthcare-associated infections (HAIs) are major factors in treatment failure and rapid progression to sepsis and septic shock.

Collaborative international initiatives, like the Surviving Sepsis Campaign (2021) and National Institute for Health and Care Excellence (NICE) updates to the NG51 guideline (2024) have focused on evidence-based guidelines and practices to address high sepsis mortality rates stemming from persistent delays in recognition, diagnosis and treatment. Given that 918,000 patients are hospitalised each year in the UK with ‘suspicion of sepsis’, and that 80-87% of sepsis hospitalisations in the US present from the healthcare community setting, there are opportunities for early identification and response from patient-provider encounters in the time frame before sepsis hospitalisation. Recognising sepsis early in the disease continuum, when clinical symptoms first manifest – rapid heart rate, fever, abnormal white blood cell count in response to infection – is essential to timely therapy to halt the cascade to multi-organ dysfunction and failure. This narrow window of opportunity also presents challenges. Treatment delays dramatically worsen outcomes; one analysis shows patients admitted to intensive care units (ICUs) with severe sepsis have a 39.8% risk of death, each hour of delay in antibiotic administration contributes up to a 9% increase in mortality.

Read the article in full here.

What if there was a drug that could treat addiction, reduce your risk of cardiovascular disease and colorectal cancer, mitigate symptoms of polycystic ovary syndrome (PCOS), lower your blood sugar, and more? Semaglutides like Ozempic might be the answer—and now, there’s a growing body of research which suggests the medication could also reduce your risk of developing Alzheimer’s disease and dementia.

Whether you’re taking the medication, are considering going on it, or are simply following all the hype, it’s understandable to be curious.

Here’s what the latest study found about the link between Ozempic use and Alzheimer’s disease, plus what this means for treatment going forward.

Meet the expert: Verna Porter, MD, a neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California.

What did the study find?

For the study, which was published in the journal Alzheimer’s & Dementia, researchers analyzed three years of electronic records of nearly 1 million Americans with type 2 diabetes. The researchers then used a statistical approach that mimicked a randomized clinical trial.

They discovered that patients who were prescribed semaglutide (the active ingredient in Ozempic and Wegovy) had a “significantly” lower risk of developing Alzheimer’s disease compared to people who had taken any one of seven other anti-diabetic medications.

The exact numbers depended on the type of medication patients took, but the risk of developing Alzheimer’s was up to 70 percent lower in patients who took semaglutide compared to those who took insulin.

What’s the relationship between Type 2 diabetes and Alzheimer’s?

There’s a link between type 2 diabetes and dementia, with research suggesting that people with type 2 diabetes have a 50 percent higher risk of developing dementia. The link is strongest with vascular dementia, which is a form of cognitive decline that causes “changes to memory, thinking, and behavior resulting from conditions that affect the blood vessels in the brain,” according to the National Institute on Aging (NIA).

“The overlap between type 2 diabetes and Alzheimer’s disease stems from shared risk factors such as insulin resistance, inflammation, and increased risk for vascular damage,” says Verna Porter, MD, a neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California.

Why did semaglutide users have a significantly lower risk of developing Alzheimer’s?

It’s not entirely clear at this point. However, semaglutide tamps down inflammation, lowering the risk of obesity and heart disease—which are risk factors for developing dementia and Alzheimer’s disease, Dr. Porter says.

Why did semaglutide seem to work better than other anti-diabetic medications?

That’s also not clear yet. But the findings “add to the growing body of evidence suggesting that GLP-1 receptor agonists may have neuroprotective properties, which could benefit patients beyond glucose control,” Dr. Porter says.

Semaglutide is in a class of medications known as GLP-1 receptor agonists. Others include Wegovy, Mounjaro, and more.

Can taking semaglutide drugs like Ozempic reduce my risk of Alzheimer’s?

It’s important to point out that this particular study simply found a link between taking semaglutide and having a lower risk of Alzheimer’s disease in people with type 2 diabetes. It didn’t find that taking semaglutide caused the difference.

Also, this study wasn’t an actual randomized, controlled clinical trial—it merely mimicked it. But it definitely raises some questions.

Ultimately, doctors need way more data before they begin prescribing semaglutide for Alzheimer’s prevention. “As a clinician, I’m aware of the need for further research—including longer-term studies and randomized controlled trials—to better understand the mechanisms and validate these findings before making changes to my treatment approach,” Dr. Porter says.

How can I reduce my risk of Alzheimer’s?

There are a lot of aspects of Alzheimer’s disease that remain a mystery, but the Alzheimer’s Association says there are a few things you can do to lower your risk:

• Try to manage your blood pressure, diabetes, and high cholesterol
• Get regular physical exercise
• Eat a heart-healthy diet with limited sugar and saturated fats, making sure to load up on fruits, vegetables, and whole grains
• Try to stay socially connected
• Aim to regularly stimulate your brain
• Try to lower your risk of head trauma by wearing a seat belt and using a helmet when biking

Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Men’s Health, Women’s Health, Self, Glamour, and more. She has a master’s degree from American University, lives by the beach, and hopes to own a teacup pig and taco truck one day.

Co-Infection dynamics between Mpox and COVID-19

Mpox is a zoonotic disease caused by the monkeypox virus [21]. The current outbreak of Mpox in July 2022 was declared a global health emergency as it spread to over 100 non-endemic countries [22]. Co-infection of Mpox with COVID-19 has been reported, with patients showing symptoms of both infections. One of the first reported cases of COVID-19 and Mpox confection was from Florida in the United States of America (USA). The patient was immunosuppressed with a history of intravenous drugs on current HAART (highly active antiretroviral therapy and coinfected with Mpox, COVID-19 and herpes [23]. Another case report, published in Barcelona, Spain, revealed a 56-year-old man to have both Mpox and COVID-19 and syphilis simultaneously [24]. According to a review done in 2022, it was found that 3 patients who had sex with men were found co-infected with Mpox and COVID-19 [25]. A 38-year-old from the USA was found to be COVID-19 and Mpox positive by PCR [25]. One more case was reported from Italy about a 36-year-old male who was coinfected and diagnosed by PCR and tested positive for Mpox and COVID-19 at the same time [25].

Epidemiological characteristics of Mpox and COVID-19 co-infections

Between 2001 and 2021, no significant data were found about the co-infection of Mpox and COVID-19, despite the COVID-19-caused pandemic in 2020. On the contrary, significant cases were found in 2022 co-infection of MpOX and COVID-19 [26].In the post-COVID-19 era around March 2022, most countries removed their travel restrictions and returned to their pre-pandemic policies, which further provided a favourable environment for co-infections [26]. Additionally, three cases of co-infection reported were of men who had engaged in sex with men before their infections. This suggests a potential risk factor for transmission of viral infections and sexual health [25]. However, it is still too early to form any definitive epidemiological trends due to a lack of data.

Outcomes of co-infection

According to one study published, 3 patients with co-infection of Mpox and COVID-19 were diagnosed through PCR and were subsequently admitted to the hospital. Their hospital stays lasted between 4 and 9 days, indicating a need for medical intervention and monitoring during their co-infection [26]. Upon admission, two patients exhibited multiple vesicular lesions on various body sites, along with tonsillar inflammation. The third patient presented with genital ulcers and inguinal lymph node enlargement. These symptoms highlight the diverse clinical manifestations that can arise from co-infection, which may complicate diagnosis and treatment [26]. However one of the reported cases of a patient with HIV co-infected with monkeypox and COVID-19, the clinical course was relatively uncomplicated despite the presence of multiple infections [26].

Shared risk factors

The symptoms of co-infection can overlap, making diagnosis challenging. A patient exhibited symptoms common to both Mpox and COVID-19, such as fever, sore throat, and lymphadenopathy [27]. This overlap can complicate clinical assessments and necessitates thorough anamnestic collection and consideration of sexual habits for accurate diagnosis [27]. Both COVID-19 and Mpox require close contact for transmission. Mpox is primarily spread through direct contact with infected skin lesions or bodily fluids, while COVID-19 spreads through respiratory droplets during close interactions [28]. This overlap in transmission dynamics increases the risk of co-infection in settings where close contact is common, such as households or social gatherings [28].

Immune response interactions

Due to limited research studies on the co-infections of COVID-19 with Mpox, there is currently a significant gap in understanding the immune response interactions each disease has concurrently or sequentially. Comprehending these interactions is crucial, especially since both viruses are known to provoke strong immune responses that may interact in intricate ways. The innate and adaptive immune response systems both play a hand in viral clearance. In the case of orthopoxvirus infections, including Mpox, bypassing the immune system is a major factor in the progression of the disease. Through the generation of proteins, the virus impedes the host’s natural antiviral defenses, including nuclear factor kappa B (NF-kB) signalling and cytokine production [29, 30]. Mpox has also been studied to repress the cytotoxicity and migration of natural killer (NK) cells, as well as the complement system [31]. A powerful type 2 immune response is set off by Mpox infection with high levels of Th2-associated cytokines. Type 1 associated cytokines, however, remain at baseline levels. This displays the complicated immune dysfunction seen in Mpox infections [32,33,34]. Adding to the list of proteins released by the Mpox virus is a protein named orthopoxvirus MHC class I-like protein (OMCP), which helps evade the immune system by avoiding the NK response and also deflecting recognition by T cells [35]. Taking into consideration the role of adaptive immunity, especially the antibody response, the presence of Mpox-specific immunoglobulin G and immunoglobulin M antibodies is generally found in infected patients and is thus also used as a diagnostic markers [31].

On the other hand, in COVID-19, which is brought about by the novel coronavirus SARS-CoV2, the innate system can occasionally produce inadvertent effects. In particular, an inflated surge in cytokine output, which is also known as a “cytokine storm”, often leads to the unfavourable aggravation of immune-mediated tissue damage [36, 37]. Monocytes especially play a vital role in cytokine storm formation because they release pro-inflammatory cytokines such as IL-6 and TNF-⍺ [38]. Eosinophils have also been studied to be involved in the immune response by releasing cytokines associated with homeostasis and type 2 immune responses [39]. Following infection with SARS-CoV-2, there have been reports of low blood eosinophil levels, which were strongly associated with poor disease prognosis and mortality [40,41,42,43,44,45]. In a study done by Ranjbar et al., they reported an increase in levels of type 2 cytokines in their patients with COVID-19. On the other hand, no notable elevations were seen in type 1 cytokine levels [38]. This coincides with the pattern of cytokines observed in Mpox infections, however, there is reliable research yet to be done on an official link in the pattern between the two.

A common factor linking the two diseases was recently studied and involves the endoglycosidase named Heparanase (HPSE). HPSE, which cleaves heparan sulfate (HS), is produced by both SARS-CoV-2 and Mpox, and the interplay between the two molecules leads to the release of pro-inflammatory cytokines and thus the evolution of a cytokine storm, endothelial dysfunction and thrombotic events [46]. Furthermore, activated HPSE increases the polarization of macrophages, T cells and NK cells through the expression of TLR4 [47]. HPSE can initiate NK cells through natural cytotoxic receptors and simultaneously can get rid of HS, which antagonizes NK cell activation [48]. As a result of these findings, treatments targeting HPSE with specific inhibitors like low molecular weight heparin (LMWH) could lower the risk of complications in coinfection with Mpox and Covid 19 [46]. Additionally, HS mimetic compounds like pixatimod may serve as important therapeutic tools by inhibiting HPSE and reducing its induced inflammation and blood clotting issues [49] (Table 1 shows a summary of all studies).

Disease severity and complications

Mpox, previously endemic to the African region, commonly presents with a prodromal stage manifesting as fever, body ache, back pain, sore throat, chills, cough, and fatigue. Following that, is the emergence of the characteristic Mpox rash, starting typically on the face. As the infection progresses, the rash becomes generalized and typically spreads centrally. It starts with the involvement of the oral mucosa, eyes, and then prominently in the genital area. The vesiculopapular skin lesions can range from a few to thousands and are typically elevated and filled with clear/yellowish fluid [50,51,52]. The lesions undergo gradual desquamation and completely resolve 4 weeks after initial symptoms [52].

In contrast, the current global outbreak of Mpox since 2022 has been labelled as atypical as it has proved to be mostly a mild version of its previous type. The clinical presentation varies occasionally, manifesting with the absence of the classic prodromal symptoms before the rash, while the observed skin lesions are most commonly found and primarily limited to the genital and perianal region. Nonetheless, lymphadenopathy presenting as painful and enlarged lymph nodes in the maxillary, cervical, or inguinal region continues to be a distinctive sign even in the current atypical presentation [52, 53]. The interleukin-1 receptor antagonist-like protein pathway is a shared link, leading to a sustained immune response in Mpox while causing a rapid remission of COVID-19 [14, 54]. This indicates that while both these infections may co-exist, it is unlikely to find any severe instances of COVID-19 cases in monkeypox infections, and any co-infection will most likely follow the pattern of decreased clinical severity [14]. The re-emergence of Mpox is still relatively new, and the reported cases in the literature of its co-infection with COVID-19 are rare, with a small sample size to conclude from. A systematic review summarized the effects of co-infection of Mpox and COVID-19 as reported in three different case reports. It is to be noted that all patients also had multiple co-morbid illnesses (such as HIV, herpes, syphilis, type 2 diabetes mellitus, depression, and bipolar disorder) before co-infection and in some cases tri-infection with other viruses [25].

It is to be considered that all 3 patients observed in a study25 were male and most often presented with minor systemic symptoms of fever, lymphadenopathy, headache, sore throat, and fatigue, which are common overlapping symptoms of both Mpox and COVID-19. However, due to these non-specific symptoms mostly being attributed to COVID-19, the presence of vesicular and ulcerative lesions, especially in the genital area, is what confirmed the Mpox diagnosis [25]. The systematic review outlined that all 3 of the cases were hospitalized for the provision of proper care and further monitoring. The hospital stay was uncomplicated, lasting for around 4–9 days, and no severe outcomes were observed [25]. Another reported case of co-infection had an asymptomatic presentation of COVID-19, further confirming that concurrent infection does not mean more severe symptoms or complications [55]. Complications of Mpox vary in intensity and include, but are not limited to, keratitis, bronchopneumonia, altered levels of consciousness, secondary bacterial infections of the skin lesions, and eye infection with corneal scarring so severe that it leads to vision loss [56, 57]. Previously reported co-morbidities that exacerbated COVID-19 outcomes now had no such severe effect during the co-infection [58]. The current atypical Mpox outbreak has followed a mild clinical course, with estimated mortality in non-endemic regions being 0.01% [25].

Mpox cases have not had any intensive care unit admissions, and co-infection with COVID-19 did not alter the favourable outcome [23]. So far, no documented cases of co-infection have reported any complications, and all patients made a recovery and were swiftly discharged [25]. It can be inferred, from all the evidence provided in the limited research available, that Mpox does not lead to drastic patient outcomes whether it manifests alone or in concurrence witCOVID-1919. However, further research and documentation of cases are required to fully understand co-infection, as it can vary from person to person [25].

Impact on transmission dynamics

A study done to correlate cell culture infectivity with viral load in an Mpox clinical sample showed that viral load was increased in skin lesions in comparison to those in throat or nasopharyngeal samples [59]. Additionally, samples from the anal region showed a high viral load in comparison to the throat or nasopharyngeal samples [59]. Similarly, another study done to evaluate the relationship between viral load and the course of COVID-19 showed that 5 days after the symptom onset, the viral load was significantly higher in the fatal cases in comparison to those cases which were symptomatic or asymptomatic [60]. Additionally, people who had a worse prognosis were older in comparison to those in the symptomatic or asymptomatic groups [60]. A cohort study done to see pre-symptomatic viral shedding in high-risk Mpox individuals [61] showed that presymptomatic Mpox DNA was seen as early as 4 days before the symptom onset [61]. Another study done to understand temporal dynamics in viral shedding and transmissibility of COVID-19 showed that viral shedding might begin 5–6 days before the appearance of first symptoms [62].

Another study on the estimation of Mpox spread in non-endemic countries with contact tracing showed delay in contact tracing led to a higher number of cases [63]. When the primary affected individual self-reports, the number of infections only rises by 11%; however, if the primary affected individual does not self-report, the average number of infections would rise by 40%. Similarly, an increase in the number of cases was seen if an unreported individual had contact with more people [63]. Another study showed the impact of delay on effective contact tracing strategies for COVID-19 [64]. With a 0-day tracing delay, prevention can reach up to 79.9%, but if a 3-day tracing delay occurs, the figure drops to 41.8 and similarly decreases to 4.9% with a 7-day treatment delay [64]. A study showed that all 20 patients who tested positive for SARS-COV2 had positive respiratory samples; similarly, among 20 stool samples, the SARS-COV-2 genome was found to be positive in 10 stool samples. In most patients, the ability to diagnose SARS-COV2 in the respiratory tract disappears after 2–3 weeks, but it can still be detected in stool samples for more than 4 weeks, thereby showing that stool can be used as an additional source of diagnosis [65].

Increased compliance with facemask usage can reduce the transmission of both COVID-19 and Mpox by limiting the spread of respiratory droplets. Vaccination provides immunity against both diseases, thereby reducing the number of susceptible individuals in the population. Similarly, practicing social distancing among infected individuals can prevent the incidence of coinfection. The use of personal protective equipment (PPE) can reduce the occurrence of healthcare-associated transmissions and the incidence of Mpox cases. Additionally, the use of rodenticides which target the vector of Mpox can help in reducing the overall reservoir population of the vectors, thereby decreasing the likelihood of spillover events [66].

There is no data available which shows whether infection with one virus affects the transmissibility of the other hence, further research should be done on this to understand the dynamics between these two viruses. (Table 2 shows the summary of all the studies).

Vaccine efficacy and cross-reactivity

The rising co-infection of COVID-19 and increased Mpox infection rate has led to the development of only the approved third-generation smallpox/monkeypox vaccine JYNNEOS, which is based on the highly attenuated modified vaccinia Ankara (MVA) vector [67]. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine, JYNNEOS [68]. The immune responses elicited by COH04S1 were compared to those from individuals vaccinated with JYNNEOS, the only FDA-approved smallpox/mpox vaccine. The results showed that the MPXV cross-reactive humoral responses from COH04S1 were comparable to those from JYNNEOS-vaccinated subjects. This indicates that COH04S1 could serve as an effective alternative or complement to existing mpox vaccines [68].

In a Phase 1 clinical trial, healthy adults who received COH04S1 exhibited substantial humoral and cellular immune responses. Notably, 45% of these subjects developed MPXV cross-neutralizing antibodies, indicating a significant level of cross-reactivity. This suggests that vaccination with COH04S1 not only protects against COVID-19 but may also confer some level of immunity against MPXV [68]. (Table 3 shows all the listed vaccines). While the above studies primarily focus on the immune response to MPXV and COVID-19 vaccines, the findings imply that vaccination against one virus may influence the immune response to the other. The presence of cross-reactive antibodies could potentially alter disease outcomes in individuals co-infected with both viruses. Dual-purpose vaccines like COH04S1 could streamline vaccination efforts by reducing the number of vaccines needed, thus conserving resources and simplifying logistics. The ability to provide immunity against multiple pathogens could be particularly beneficial in endemic regions or during concurrent outbreaks, enhancing public health responses [67].

However, further research is needed to fully understand the implications of such co-infections and the role of vaccination in modulating immune responses.

Open Access Government sits down with a researcher from the Department of Human Health and Nutritional Sciences to discuss their groundbreaking work on nonalcoholic steatohepatitis (NASH) and insulin resistance. Their research delves into the molecular underpinnings of these increasingly prevalent conditions, offering new avenues for understanding, prevention, and treatment

Given your research focuses on nonalcoholic steatohepatitis (NASH) and insulin resistance, what do you believe are the most critical public health implications of these conditions today?

NASH and insulin resistance are increasing public health problems with widespread social and economic consequences. Public health efforts must shift toward early detection, improved education, and targeted interventions that address the metabolic origins of the disease.

By addressing obesity and promoting lifestyle changes, healthcare systems can help mitigate the growing impact of these interrelated chronic conditions.

How do you envision your research findings translating into practical strategies for improving human health and nutrition at a population level? Are there any immediate applications you foresee?

Our studies expand the fundamental knowledge of liver health by integrating the regulation of lipid metabolism, epigenetics, and therapeutic interventions into a unified framework for better understanding and treating non-alcoholic steatohepatitis (NASH).

They reinforce the importance of membrane phospholipid homeostasis in preventing fat accumulation and the development of insulin resistance and introduce epigenetic modulations as a promising avenue for reversing disease progression.

Examining: Pcyt2 deficiency causes age-dependent development of nonalcoholic steatohepatitis and insulin resistance, that could be attenuated with phosphoethanolamine.

Your work identifies Pcyt2 deficiency as a causative factor in NASH and insulin resistance. Could you elaborate on the significance of this specific molecular pathway in the context of metabolic disease development?

The study elucidates the pivotal role of the Kennedy pathway for phosphatidylethanolamine (PE) synthesis in maintaining metabolic homeostasis. In this pathway, the enzyme Pcyt2 catalyzes the rate-limiting step, and in conditions of Pcyt2 deficiency, as shown in the heterozygous mouse model (Pcyt2+/-), the reduced flux through this pathway sets off a cascade of metabolic dysfunctions that affect gene expression and signal transduction, contributing to altered glucose and lipid metabolism. Importantly, even before overt liver disease is detectable, young mice with Pcyt2 deficiency exhibit altered expression of the key metabolic regulators. As they age, mice develop NASH characterized by insulin resistance, liver fibrosis, and inflammation. The supplementation with phosphonoethanolamine (PEA), an artificial substrate for Pcyt2, can reverse the metabolic derangements caused by its deficiency.

This suggests that in scenarios where the Kennedy pathway is compromised, restoring or bypassing its rate-limiting step could ameliorate liver steatosis, inflammation, and insulin resistance. Immediate applications could involve developing pharmacological agents or nutritional supplements that enhance or mimic Pcyt2 activity, which might be especially beneficial in high-risk populations predisposed to NASH and related metabolic disorders.

Your study highlights the age-dependent development of these conditions. What implications does this age dependency have for preventative or therapeutic strategies, particularly for an ageing population?

The study showed that early defence mechanisms may buffer against the full-blown development of NASH. As the body ages, the cumulative impact of altered membrane dynamics, reduced energy metabolism, and increased oxidative stress overturns the balance, leading to liver pathology and systemic metabolic dysfunction. The gradual, age-dependent disease progression indicates a critical window for early intervention before compensatory mechanisms begin to fail. Screening for the subtle metabolic changes or biomarker shifts in individuals at risk could enable preventative measures before irreversible damage occurs.

Therapeutic regimens tailored for older individuals might require a combination approach that not only incorporates nutrition modulation but also addresses inflammation and oxidative stress. Stratifying individuals based on their metabolic profile and age could help in fine-tuning intervention strategies. For instance, older patients demonstrating early biochemical signs of membrane dysfunction might be prioritized for targeted therapies, whereas younger at-risk individuals might focus primarily on preventive lifestyle changes.

Beyond the molecular findings, how might the insights from this paper influence our understanding of dietary recommendations or nutritional interventions for individuals at risk of NASH?

The impairments in the Kennedy pathway for phospholipid PE synthesis result in a dramatic imbalance in membrane composition and play a significant role in NASH development. Individuals at risk of NASH, especially those whose metabolic profiles indicate impaired phospholipid profiles, might benefit from diets that optimize not only macronutrients but also specific bioactive compounds that ensure proper phospholipid metabolism. The demonstration that supplementation with PEA can mitigate the progression of NASH in an animal model paves the way for considering similar strategies in humans. However, further research is necessary to confirm the safety and efficacy of PEA in clinical settings.

Examining: Epigenome-wide methylation analysis shows phosphonoethylamine alleviates aberrant DNA methylation in NASH caused by Pcyt2 deficiency.

This publication delves into epigenome-wide methylation changes. How does the concept of epigenetics, and specifically DNA methylation, offer a new lens through which to understand the progression and potential treatment of NASH?

In the context of NASH, the discovery of widespread shifts in methylation patterns suggests that the progression of liver pathology is not solely driven by permanent genetic mutations but also by reversible epigenetic changes. Unlike genetic alterations, these modifications can potentially be corrected or even re-programmed with appropriate interventions.

Pcyt2 deficiency is associated with widespread aberrant epigenetic reprogramming in genes crucial for energy metabolism and cellular homeostasis. As such, epigenetic changes compound the metabolic dysfunction by further altering gene expression, potentially leading to inflammation, fibrosis, and insulin resistance seen in NASH.

Treatment with PEA dramatically attenuates abnormal DNA methylation, suggesting that targeted nutritional or pharmacological interventions can not only ameliorate metabolic disturbances but also reverse detrimental epigenetic modifications. In practical terms, developing treatments that modulate DNA methylation could improve gene expression patterns associated with lipid metabolism and inflammation, thereby halting or even reversing the progression of liver disease.

The finding that phosphonoethylamine alleviates aberrant DNA methylation is significant. Could you explain the practical implications of targeting epigenetic modifications for the treatment of NASH?

The proof-of-concept that PEA can mitigate abnormal DNA methylation opens an avenue for the development of new drugs targeting epigenetic modifiers. Future agents could be designed to either mimic the action of PEA or directly inhibit aberrant methylation processes, offering another therapeutic tactic to manage or reverse NASH. This not only broadens the therapeutic arsenal but also allows for continuous innovation in the field of metabolic disease treatments.

The field of epigenetic modifications offers a promising and multifaceted strategy for treating NASH. It provides the possibility to reverse pathological gene expression, create early diagnostic tools, and implement personalized therapies, all of which could dramatically impact patient outcomes. This approach signifies a shift from merely managing symptoms towards addressing the root molecular disturbances that drive liver disease.

How might the insights from your epigenome-wide methylation analysis contribute to the development of personalized nutrition or precision medicine approaches for individuals with NASH?

Aberrant DNA methylation is an early indicator of NASH progression.

By mapping these changes, especially in genes regulating insulin signaling, inflammation, and lipid metabolism, researchers can identify which individuals are at heightened risk even before clinical symptoms become apparent. This opens the possibility of developing blood-based epigenetic biomarkers that enable clinicians to monitor disease progression and therapeutic efficacy in real-time, tailoring interventions to each patient’s molecular profile.

Dietary interventions could be designed not only to focus on nutrient balance but also to provide the right substrates to correct or prevent deleterious changes affecting liver metabolism. This precision approach could, for instance, target those with a predisposition to altered methylation in pathways critical for insulin signaling and energy metabolism, thereby mitigating the risk of full-blown NASH. Treating epigenetic modifications as dynamic biomarkers and therapeutic targets not only enriches our understanding of NASH pathophysiology but also offers a blueprint for precision medicine.

The potential to adjust dietary interventions based on an individual’s unique methylation profile represents a significant leap forward in personalized healthcare for metabolic diseases.

How do you see the research in the two publications contributing to the broader scientific dialogue surrounding liver health and metabolic disorders?

These two publications contribute to the broader knowledge surrounding liver health and metabolic disorders. The studies integrate lipid metabolism, epigenetics, and therapeutic interventions into a unified framework for understanding and treating NASH. They reinforce the importance of phospholipid homeostasis and epigenetic modulations as a promising avenue for reversing disease progression. These insights could reshape clinical approaches, leading to more effective, personalized treatments for metabolic liver disorders. Key contributions include:

1. the establishment of Pcyt2 deficiency as a novel mechanism in age- dependent metabolic dysfunction, which links impaired membrane phospholipid metabolism to the progression of NASH, reinforcing the idea that lipid composition plays a fundamental role in liver disease beyond simple fat accumulation.
2. evidence that PEA supplementation can reverse metabolic and inflammatory damage caused by Pcyt2 deficiency and that targeting phospholipid biosynthesis could be a viable therapeutic strategy for NASH.
3. advancing the epigenetic perspective in metabolic disorders by revealing that aberrant DNA methylation plays a significant role in NASH pathogenesis.
4. demonstrating the reversibility of DNA methylation by PEA showing that epigenetic interventions, whether through diet, supplements, or pharmacological agents, could be used to restore normal gene function and prevent disease progression.

Final messages and the power of the liver

If I had to distill the key message from these research publications into something accessible to the public, it would be this:

Your Liver’s Hidden Protector: How Molecular Balance Could Be the Key to Better Health.

Did you know that liver disease isn’t just about sugar and fat? Recent research reveals a surprising connection between your liver’s health and crucial molecular processes of phospholipid metabolism and epigenetic regulation. Scientists have uncovered that when this balance is disrupted, it can lead to nonalcoholic steatohepatitis (NASH), a serious liver condition linked to insulin resistance and metabolic disorders. But here’s the most exciting finding: this damage might not be permanent. A new discovery reveals that PEA supplementation can reverse harmful changes in DNA methylation, thereby restoring normal liver function at the cellular level.

Produced on 9 July 2025 based on data submitted up to 2 July 2025

Epidemiological summary

In 2025, and as of 2 July 2025, no countries in Europe reported any locally acquired[1] human cases of WNV infection with known place of infection. In the previous five years, the first locally acquired cases of the WNV transmission season usually had symptom onset in June. However, the absence of notification of locally acquired cases of WNV in the EU/EEA and EU-neighbouring countries is not unexpected at this time of the year. This could either be due to the absence of WNV infections in humans or due to a delay in diagnosis and reporting of cases of WNV infection. Furthermore, a majority of WNV infections in humans remain asymptomatic or pauci-symptomatic. From the veterinary perspective, 2 WNV outbreaks among equids and 3 outbreaks among birds have been reported in Europe in 2025. The earliest start date of an outbreak among equids and birds was on 15 January 2025 in Germany and 16 February 2025 in Italy, while the latest onset of an outbreak among equids and birds was, respectively, on 12 June 2025 in Hungary and 11 June 2025 in Italy. The number of outbreaks in birds and equids reported during this first period of 2025 is below the mean monthly outbreak count for the same time frame (calculated from 2015–2024). During the same period in 2024, 16 outbreaks were reported. In 2025, as of 2 July, this is the lowest number of outbreaks in birds and equids reported during the same period since 2022. All three countries (and their associated regions) reported WNV outbreaks in birds and/or equids in 2024 and in prior years, indicating endemic WNV activity in these regions. In temperate regions like Europe, WNV transmission typically occurs from mid-June to mid-November, when mosquito activity is highest. Off-season reports of WNV outbreaks in birds and equids should be carefully evaluated as they raise questions about the timing of infection. The two early-season WNV outbreak reports (Germany’s equid case in January and Italy’s bird case in February) require cautious interpretation, as they may reflect residual detection (e.g. lingering antibodies or viral RNA from prior infections) rather than active transmission in 2025. The absence of reported human West Nile virus infections in Europe as of 2 July 2025, alongside a notably lower number of outbreaks in birds and equids compared to 2024, suggests a reduced level of viral circulation in the environment during the early transmission season in 2025. Natural fluctuations in virus prevalence can occur year to year, influenced by immunity levels in bird populations and ecological conditions. Human cases are expected to occur in the coming weeks.

[1] Locally acquired cases refer to cases acquired within the reporting country

Hi, it’s Michelle in New York. You may have heard of “Ozempic blindness,” when obesity drugs are linked to rare vision loss. Does this discovery change the risk-benefit analysis for the drugs? More in a moment, but first …

In June, EU regulators said that people with type 2 diabetes taking semaglutide, the active ingredient in Novo Nordisk’s Ozempic and Wegovy, are at risk of developing a rare eye condition that can cause vision loss. This could possibly affect as many as 1 in 10,000 people taking the medicine.

Research has identified key mechanisms driving aging and actionable targets for promoting longevity. A promising strategy is to preserve the cell’s ability to produce energy, repair DNA, and stress resilience, with nicotinamide adenine dinucleotide (NAD+) playing a central role. Here, Dr. Rebecca Crews presents a multi-target approach to support healthy aging

Decades of research have uncovered key mechanisms driving the aging process, identifying actionable targets to support longevity. One of the most promising strategies is preserving the cell’s capacity for energy production, DNA repair, and stress resilience. Central to all of these processes is nicotinamide adenine dinucleotide (NAD+), a coenzyme that fuels hundreds of metabolic reactions, including mitochondrial ATP production and sirtuin-mediated cellular maintenance.

It is known that NAD+ levels significantly diminish with age. This decline is tightly linked to the hallmarks of aging, contributing to mitochondrial dysfunction, impaired repair, cellular senescence, and age-related damage. Restoring NAD+ levels closer to youthful norms has, therefore, become a major focus within longevity science.

However, simply boosting NAD+ with precursors addresses only one aspect of a complex issue. A truly effective strategy tackles the root causes of NAD+ decline and maximizes outcomes. Therefore, a thoughtful strategy involves a multi-pronged approach: slowing NAD+ degradation, supporting its synthesis, and improving how NAD+-dependent pathways function (Sharma et al., 2023).

The foundation: NAD+ precursors

The most straightforward way to boost NAD+ levels is by supplying the body with its molecular precursors.

The two most widely used options are:

• Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN): Both convert efficiently into NAD+ via the salvage pathway. Human trials consistently report 40–60% increases in blood NAD+ at daily doses of 250–1,000 mg (Conlon & Ford, 2022).

Choosing between NR, NMN, or using both typically depends on individual goals and cost. Consistent, daily dosing is key to maintaining elevated NAD+ levels.

Enhancing efficiency: Sirtuin activators

Many of NAD+’s health benefits stem from its role in fueling sirtuins, a family of NAD+-dependent enzymes that drive DNA repair, metabolic balance, stress resilience, and inflammation control. Sirtuin Activating Compounds (STACs) amplify these protective functions:

• Resveratrol:
  • A grape polyphenol that directly stimulates SIRT1. Its poor bioavailability is improved when taken with dietary fat or via advanced delivery systems (e.g., liposomal encapsulation, and solid-lipid nanoparticles).
• Pterostilbene:
  • A blueberry-derived analog of resveratrol that achieves higher plasma levels and may exert stronger SIRT1 activation.

Combining NAD+ precursors with STACs ensures both ample substrate and maximized sirtuin function (Sharma et al., 2023).

Protecting the pool: CD38 Inhibitors

CD38 is a major NADase whose activity increases with age and chronic inflammation, accelerating NAD+ depletion. Inhibiting CD38 conserves existing NAD+, keeping it available for beneficial pathways like sirtuin mediated repair.

Natural flavonoids have emerged as promising CD38 inhibitors:

• Apigenin:
  • Abundant in chamomile, parsley, and celery, apigenin blocks CD38 in preclinical models, elevating NAD+ and downstream sirtuin activity. It also delivers anti-inflammatory and antioxidant benefits (Kramer & Johnson, 2024).
• Quercetin:
  • A common flavonoid found in onions, apples, and berries, quercetin inhibits CD38 and offers potent antioxidant, anti-inflammatory, and senolytic benefits (Chini et al., 2018).

Flavonoid CD38 inhibitors offer multiple benefits: they simultaneously preserve NAD+, reduce oxidative stress, and curb inflammatory signaling.

Clearing the way: Senolytics

Senescent cells accumulate with age, acting as cellular “zombies” that resist death while secreting pro-inflammatory factors (SASP). This SASP, in turn, boosts CD38 in nearby cells, leading to faster NAD+ depletion.

Key senolytics (compounds that selectively eliminate these “zombie” cells) include:

• Fisetin: Found in strawberries and apples, this flavonoid has demonstrated the ability to reduce senescent cell burden, enhance health span, and extend lifespan in aged mice (Yousefzadeh et al., 2018).
• Spermidine: This polyamine, present in fermented foods and legumes, induces autophagy and may support the clearance of senescent cells. It’s associated with improved cardiovascular health and lifespan in mice (Hofer et al., 2022).

Calming the storm: Anti-inflammatory support

Chronic inflammation, a hallmark of aging, further depletes NAD+ by increasing CD38 activity. Resolving this inflammation is key to preserving the NAD+ pool and creating a healthier cellular environment:

• Curcumin: The active compound in turmeric, suppresses NF-κB and COX-2 signaling and may indirectly support sirtuins. Due to poor absorption, high-bioavailability formulations are essential (Hegde et al., 2023).
• Omega-3 Fatty Acids (EPA & DHA): These fish oil–derived fats integrate into cell membranes to reduce inflammatory signals and serve as building blocks for specialized pro resolving mediators (SPMs) that actively shut down inflammation (Kavani et al., 2022).

Synergistic anti-inflammatory effects have been observed when curcumin and omega-3 fatty acids are administered together (Saw et al., 2010).

Integrating the stack: Synergy and practical considerations

This multi-component stack represents a strategic and comprehensive approach to NAD+ metabolism. NAD+ precursors ensure ample substrate supply, STACs optimize its efficient use, CD38 inhibitors protect against its premature breakdown, senolytics reduce the detrimental burden of senescent ‘zombie’ cells, and targeted anti-inflammatory compounds re- establish cellular homeostasis. The goal is a synergistic effect that promotes overall cellular resilience.

However, implementation requires attention:

• Lifestyle first: Supplements cannot replace a foundation of a healthy diet, regular exercise, quality sleep, social connection, and stress management.
• Gradual introduction: Start supplements one by one (“start low, go slow”) to gauge individual tolerance.
• Quality is key: Opt for reputable brands that provide third-party testing for purity and potency.
• Personalization: Monitor biomarkers and subjective well being.

Conclusion: A balanced perspective on NAD+ optimization

Supporting NAD+ levels is a promising strategy in the effort to maintain cellular function and health with age. The approach outlined here – boosting NAD+ production, reducing its breakdown, improving how it’s used, and supporting the broader cellular environment – reflects the current understanding of NAD+ as a dynamic and interconnected system.

NAD+ boosting strategies should be seen as a flexible starting point, not a one-size-fits-all solution. As research advances, more personalized strategies will likely become available, guided by individual health data and deeper insights into NAD+ biology.

Importantly, NAD+support works best as part of a bigger picture. Lasting health and longevity depend just as much on diet, exercise, sleep, stress management, and social connection. Keeping these foundations strong while staying informed about new science is the most practical way to approach NAD+ optimization today.

Elinzanetant offers a new, non-hormonal treatment option for menopausal hot flushes and night sweats. Now approved by the MHRA, it provides symptom relief for women seeking alternatives to hormone therapy

The MHRA has become the first medical regulator in the world to approve elinzanetant, a novel non-hormonal oral agent, for the treatment of moderate to severe vasomotor symptoms associated with menopause. This approval introduces a new therapeutic option targeting neurokinin receptor pathways, expanding treatment possibilities beyond hormone replacement therapy.

The new marketing authorisation was granted on 8 July 2025 to Bayer plc. 

Elinzanetant significantly reduced the number and intensity of hot flushes

Approximately 13 million women in the UK are going through perimenopause or menopause, with up to 80% expected to experience hot flushes during the menopause transition, and many remaining untreated.

When oestrogen levels drop during menopause, specific brain cells become overactive and interrupt the body’s ability to control temperature, which leads to hot flushes and night sweats. 

Elinzanetant works by calming these signals in the brain, helping to bring the body’s temperature back to a normal level. The medication can also help alleviate sleep problems and is administered in tablet form.

Julian Beach, MHRA Interim Executive Director of Healthcare Quality and Access, said:  “Hot flushes and night sweats associated with menopause can have a significant negative impact on quality of life.  

“We are therefore pleased to announce our approval of elinzanetant, which has met the MHRA’s standards for safety, quality, and effectiveness. 

Elinzanetant offers a non-hormonal alternative for those who may not be able to, or prefer not to, take hormone-based therapies. As with all licensed medicines, we will continue to monitor its safety closely as it becomes more widely used.” 

Successful in-human clinical trial

Elinzanetant’s approval is based on results from the OASIS clinical trials, which involved over 1,400 women aged 40 to 65 across several countries.

The Phase III OASIS 1 and 2 clinical trials were randomised, double-blind, placebo-controlled studies evaluating the efficacy and safety of elinzanetant in menopausal women experiencing moderate to severe vasomotor symptoms, such as hot flushes and night sweats. Participants received a daily oral dose of 120 mg elinzanetant or placebo for 12 weeks. Results showed that elinzanetant significantly reduced both the frequency and severity of hot flushes compared to placebo, with improvements observed early in the treatment course. Secondary outcomes also demonstrated enhancements in sleep quality and overall menopause-related quality of life.

“Menopausal symptoms are frequent side effects of endocrine therapy for breast cancer, often leading to treatment discontinuation, which is why management of these symptoms can play an important role in breast cancer treatment,” said Dr. Fatima Cardoso, Principal Investigator of OASIS-4, from Lisbon, Portugal. “With no currently approved treatments for this indication, there is an unmet medical need for therapeutic options.”

“The robust efficacy and favourable safety profile of elinzanetant reinforces its potential as a non-hormonal treatment for women experiencing menopause,” said Dr. Christian Rommel, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. “We look forward to submitting applications to health authorities for marketing authorisations of elinzanetant to treat moderate to severe VMS associated with menopause in women, building upon our extensive legacy and commitment to women’s healthcare.”