Category: 8. Health

Search and screening results

A total of 485 studies were retrieved after the initial search across three databases, including 183 from PubMed, 243 from Scopus, and 59 from Web of Science. After 335 duplicate studies were detected and resolved, titles and abstracts of 293 articles were screened based on the eligibility criteria. A total of 212 studies which were initially considered eligible and were subjected to full-text evaluation. After full-text examination, 38 articles were eligible for inclusion [humans (n = 21), animals (n = 7), environment (n = 2), Interdisciplinary studies (n = 8)] (Fig. 1).

Characteristics of included studies

All included studies were published between 2011 and 2024, with most of them (63.2%) having been conducted between 2015 and 2019. Studies that met the inclusion criteria were from only 9  out of 16 countries in West Africa. Nigeria had the highest number of individual studies (n = 17), followed by Ghana (n = 13), Senegal (n = 3), and Burkina Faso (n = 2). The remaining countries, Guinea-Bissau, Guinea, Niger, Gambia, and Benin, had one study each (Fig. 2) (Supplementary data 1; Table 3).

The number of confirmed ESBL-positive isolates across the studies ranged from 1 to 1937 and comprised 25 different bacterial isolates across the nine West African countries, encompassing various populations, settings, and sample types (Fig. 3) (Supplementary data 2; Table 1).

A majority of the studies were conducted on humans (76.3%, n = 29), followed by animals (34.3%, n = 13) and the environment (15.6%, n = 6) (Supplementary data 1; Table 3). Most studies isolated ESBL-positive bacteria from hospital-based settings (68.2%, n = 24), followed by communities (15.8%, n = 6), farms (10.5%, n = 4), and markets (2.6%, n = 1). Some isolated the bacteria from a combination of sources, such as markets and farms (7.9%, n = 3) and communities and hospitals (5.3%, n = 2). Most studies isolated the bacteria from two major sample types: clinical specimens (39.5%, n = 15) and faeces (31.6%, n = 12) (Supplementary data 1; Table 3).

Among the 25 ESBL-positive isolates, 18 were identified as Enterobacteriaceae and 7 were classified as non-Enterobacteriaceae (Supplementary data 2; Table 1).

The most commonly used ESBL diagnostic methods were EUCAST disk diffusion (18 studies), Double-Disk Synergy Test (DDST) (18 studies), Whole Genome Sequencing (WGS) (30 studies), and Multilocus Sequence Typing (MLST) (34 studies) (Supplementary data 1; Table 3).

ESBL-producing bacterial species across human, animal, and environmental sources in West Africa

E. coli and K. pneumoniae accounted for 64% and 31% of the ESBL-positive isolates, respectively. Other Enterobacteriaceae species collectively comprised 4% of the isolates, whereas non-Enterobacteriaceae constituted 1% of the total isolates (Supplementary data 2; Table 1A).

ESBL genes and clones

A total of 171 ESBL genes were identified, with blaCTX-M being the most predominant gene (70.8%) across humans, animals, and the environment. The most frequent variant, blaCTX-M-15 (31.6%), was detected in all three sources, with greater occurrence in humans (21.1%) than in animals (7.6%) or the environment (2.9%) (Fig. 4) (Supplementary data 2; Table 2–10).

Multilocus sequence typing (MLST) was performed on 7 of 25 isolates, identifying 153 unique sequence types (STs) (Supplementary data 2; Table 14). Among these, Nigeria accounted for 133 clones from 5 isolates, with ST10, ST131, and ST410 being the most frequently observed. Ghana contributed 139 clones from 3 isolates, predominantly featuring ST131 and ST617, whereas 64 clones were identified from 4 isolates in other countries (Supplementary data 2; Table 11–13).

In terms of species-specific observations, E. coli exhibited considerable differences in sequence types among the different sources. In humans, ST131, ST10, ST410, and ST617 were prominent, whereas animals predominantly exhibited ST48, ST10, and ST38. Environmental samples were marked by the prevalence of ST10, ST58, and ST155. For K. pneumoniae, the predominant human STs were ST17, ST36, ST530, ST15, and ST14. In animals, ST307 was observed, and ST152 was most frequently observed in the environment. Non-Enterobacteriaceae displayed notable source-specific trends, with Pseudomonas aeruginosa ST1469 and ST235 linked to human samples and Acinetobacter baumannii ST109, ST1, ST78, ST132, and ST1136 linked to environmental samples (Supplementary data 2; Table 11–13).

Clonal distribution analysis showed that 71 clones were unique to humans, 27 to animals, and 14 to the environment. The number of shared clones between humans and animals was 25, between humans and the environment was 4, and between animals and the environment was 5. Notably, seven clones including ST10, ST410, ST58, ST155, ST4684, ST2178, and ST37 were detected predominantly in E.coli across all three sources. ST37 was also observed in K. pneumoniae (Fig. 5) (Supplementary data 2; Tables  11–14; Fig. 1).

Potential transmission routes of ESBL clones

Data from 7 of 38 studies (18.4%) were analysed for possible transmission routes of ESBL clones across human, animal and environmental sources. These studies used a combination of sources to detect the prevalence of ESBL-producing bacteria in hospitals, markets, and farms (Supplementary data 1; Table 3). These studies included Humans-Animals, Humans-Environment, and Humans-Animals-Environment studies (Table 1). Although the studies did not clearly state the transmission routes, they acknowledged that because of the common ESBL clones detected, the transmission routes were possible.

Antimicrobial resistance patterns

An analysis of 24 studies covering 1215/1937 ESBL-producing bacterial isolates revealed significant resistance patterns against non-beta-lactam antibiotics (Supplementary data 1; Table 4) (Supplementary data 2; Table 15–15A). The results show that bacteria from humans are much more resistant than those from animals and the environment. Phenotypically, the bacteria were particularly resistant to commonly prescribed antibiotics such as ciprofloxacin (71%), gentamicin (58%), and trimethoprim-sulfamethoxazole (53%). Resistance to tobramycin (39%) and tetracycline/doxycycline (28%) was moderate, whereas nalidixic acid (17%), imipenem/meropenem (16.7%), and chloramphenicol (14.1%) showed lower resistance (Fig. 6).

Co-resistance genes

The ESBL-producing bacterial isolates also exhibited the genotypic presence of co-resistance genes. Aminoglycoside and fluoroquinolone/quinolone resistance genes were the most frequently reported, each appearing in 15 studies, with aac(6′)-Ib-cr identified as the predominant resistance gene. Folate pathway antagonists’ resistance genes were reported in 12 studies, where dfrA14 was the most common resistance gene. This was followed by sulfonamides (11 studies), where sul2 was the most common gene, and tetracyclines (10 studies), with tet(A) as the predominant resistance gene. Phenicols were reported in 9 studies, with catA1 being the most prevalent gene. Finally, carbapenem resistance genes were documented in 8 studies, with blaNDM, blaOXA-48, and blaOXA-181 identified as the predominant resistance genes. Additionally, five studies reported mutations within the quinolone resistance-determining regions (QRDR) of gyrA, parC, parE, and parcE (Table 2). (Other reported co-resistance genes are present in the supplementary data 2; Table 16).

Mobile genetic elements

A total of 22 studies performed mobilome analyses to identify the plasmid types carrying ESBL and other co-resistance genes. IncF plasmids emerged as the most prevalent, found across human, animal, and environmental sources, with an overall prevalence of 50.0%. Col plasmids were the second most common, accounting for 16.4%. Other plasmid types, including IncH, IncQ, and IncI, were detected at lower frequencies, with prevalence rates ranging from ~ 4.0% to ~ 7.0%. (Fig. 7) (Supplementary data 2; Table 17–17A).

Meta-analysis

Prevalence of ESBL

The overall pooled prevalence of ESBL in West Africa was 16.8% (95% CI [12.1; 22.1]. Nigeria and Ghana reported the highest prevalence at 18.3% and 17.3%, respectively, while Burkina Faso and Senegal had low prevalences at 6.0% and 1.2%, respectively (Fig. 8).

Humans had the highest prevalence at 20.4%, followed by animals at 12.8% and the environment at 9.3% (Fig. 9). Among settings, market-based environments recorded the highest prevalence at 23.6%, followed by hospitals at 21.8% and community-based settings at 7.5% (Supplementary data 1; Fig. 1).

Prevalence of ESBL-producing E. coli and K. pneumoniae

The study explored ESBL-producing E. coli and K. pneumoniae in 34 of 38 and 20 of 38 studies, respectively, across humans, animals, and the environment (Supplementary data 2; Tables 18-23). The prevalence of ESBL E. coli was 15.9% (95% CI: [9.8; 23.1], 26 studies) in humans, 15.0% (95% CI: [6.5; 26.0], 11 studies) in animals, and 6.1% (95% CI: [1.8; 12.4], 5 studies) in the environment (Table 3). The prevalence of ESBL K. pneumoniae was 8.2% (95% CI: [3.9; 13.8], 16 studies) in humans, 2.0% (95% CI: [0.4; 4.3], 4 studies) in animals, and 6.6% (95% CI: [4.4; 9.2], 2 studies) in the environment (Table 4).

Subgroup analysis

The subgroup analysis of pooled prevalence estimates for ESBL-positive E. coli and K. pneumoniae across humans, animals, and the environment revealed distinct patterns based on settings and sample types.

For E. coli, human studies showed the highest prevalence in hospital-based settings (17.6%) and faecal samples (23.2%). Among animals, faecal samples have the highest prevalence (27.0%), and farm-based settings (21.7%) were particularly affected. In environmental studies, the abattoir environment has the highest rate (22.4%), whereas hospital-based environments have much lower rates (1.7%) (Table 3).

Clinical specimens: urine, ear swab, sputum, blood culture, eye swab, wound swab, urethral swab, endocervical swab, stool, high vaginal swab, nasal swab, gastric lavage, pus, tracheal aspirates, semen, axilla, groin, perianal region, cerebrospinal fluid, lower respiratory tracts, urinary tract infections (UTIs), ascitic fluid.

Patient environment: swabs of high- and low-touch areas, beds, taps, and drip stand.

NICU environment: swabs of incubator doors, cots, nurse trolley handle, weighing scales, tables, and desks.

For K. pneumoniae, human studies revealed a dominance of hospital-based settings (10.4%) and clinical specimens (9.5%) prevalence, with wound swabs reporting the highest prevalence in individual samples (57.1%). In animals (4 studies, 2.0%), community-based settings (2.5%), and rectal swabs (10.3%) showed higher prevalence rates. Environmental studies for K. pneumoniae (6.6% prevalence) indicated that patient environments (7.4%) had a slightly higher prevalence than NICU environments (5.8%) (Table 4).

Heterogeneity was significant in human studies on both isolates (I² ~99%), indicating variability across settings and sample types, whereas environmental studies on K. pneumoniae showed minimal variability (I² = 0%). This subgroup analysis indicated significant differences in the prevalence of ESBL E. coli and K. pneumoniae depending on the host/source, settings, and sample type.

Heterogeneity and publication bias

The funnel plot illustrates a publication bias, which was confirmed by Egger’s regression test (p = < 0.0001) (Supplementary data 1; Fig. 2). Estimated prevalences were significantly heterogeneous across countries, populations, and settings (H > 1 and I² ≥ 75%). The overall prevalence also showed significant heterogeneity (H = 8.98 [8.51; 9.49] and I = 98.8% [98.6%; 98.9%]).

Sensitivity analysis and meta-regression

The impact of each study on the pooled prevalence of ESBL-producing bacteria was assessed using a leave-one-out sensitivity analysis. The sensitivity analysis revealed that excluding individual studies had a minimal impact on the pooled prevalence of 16.8%, with most exclusions resulting in prevalence values ranging from 16.0 to 17.4%. Only one study reported a slightly lower prevalence of 15.8%. These findings indicate that the pooled prevalence was stable and not overly influenced by any single study, demonstrating the robustness of the meta-analysis results (Supplementary data 1; Table 5).

A random effects meta-regression analysis was used to assess the effect of the three study characteristics on the observed wide variations in effect sizes in this study. Country, population, and settings were used as covariates. Gambia had a minimally significant negative association with heterogeneity. The remaining covariates did not significantly affect heterogeneity (Table 5).

Researchers at the Optics and Photonics Research Center (CePOF) have succeeded in increasing the susceptibility of the fungus Candida albicans to drug treatment through light-activated therapy. The results of the study offer a promising alternative in the fight against antimicrobial resistance, a growing global problem that occurs when bacteria, viruses, fungi, and other parasites develop genetic mutations that render them resistant to drugs.

In the study, published in the journal Photochemistry and Photobiology, the researchers evaluated photodynamic inactivation (PDI) combined with the antifungal amphotericin B (AmB) to control the growth of the fungus, particularly its yeast (single-celled) and hyphae (filamentous colony) forms.

The results showed that combining the two treatments reduced the C. albicans growth by 75% in the yeast form and by 87.5% in the hyphae form. In addition, two sessions of PDI further increased antifungal efficacy, particularly against hyphae, which were more sensitive to the treatment.

“It’s a technique that consists of using a molecule [in this case curcumin] and activating it with blue light. Activation, in the presence of oxygen, causes the molecule to produce free radicals, thereby inducing oxidative stress, killing or weakening the pathogen,” explains Vanderlei Bagnato, coordinator of CePOF, a FAPESP Research, Innovation, and Dissemination Center (RIDC) based at the São Carlos Institute of Physics of the University of São Paulo (IFSC-USP) in Brazil. “In the case of C. albicans, mainly in the hyphae, which form a biofilm that’s almost impenetrable to drugs, photodynamic therapy was able to ‘break’ these colonies, resulting in the potentiation of the antifungal effect.”

The study involved photodynamic inactivation using 2.5 μM (micrometers) curcumin, which was activated by 450 nm (nanometers) LED light and different concentrations of the antifungal AmB.

An imminent danger

C. albicans is naturally present in the human body and is usually harmless. However, it can cause skin manifestations such as thrush or vaginal candidiasis. In more serious cases, the fungus can cause systemic candidiasis, an invasive blood infection. This serious condition is being diagnosed more frequently in intensive care units (ICUs) due to the growing number of immunocompromised patients and increased microbial resistance.

There’s growing resistance to fungi, and C. albicans is no exception. It’s a very common fungus, but there are already cases of patients who have died from resistant systemic infections. Therefore, it’s very important to anticipate the problem and present an alternative that allows for more effective combat against the fungus without side effects or the need for excessive medication use.”

Gabriela Gomes Guimarães, researcher at CePOF and first author of the study

Guimarães explains that the decision to begin photodynamic inactivation tests on fungi using C. albicans was motivated by the two morphologies of the species. “The fungus forms both yeasts and hyphae, which form biofilms. Therefore, the fact that it worked so well for C. albicans gives us confidence to conduct new tests on other species, such as C. auris, an emerging fungus that’s causing concern, has shown resistance to treatment, and can be fatal,” says the researcher.

Applications in food

In addition to testing the effects of photodynamic therapy on other fungal species that pose a threat to human health, the researchers will conduct studies focused on food safety. “The proof of principle we’ve just published on C. albicans allows us to conduct studies on the application of photodynamic therapy in food decontamination. Fungi are also a problem in grain contamination, for example. Therefore, our next step is to test the application of this technique in storage silos, for example,” Bagnato anticipates.

CePOF has been conducting various laser research projects aimed at advancing treatments for bacteria, viruses, and other diseases, including cancer and fibromyalgia (read more at: agencia.fapesp.br/50500). 

“The principle is always the same: activate a molecule with a laser so that it oxidizes. What varies in each case is the application, the amount of light, color temperature, amount of drug, and how much of the pathogen is eliminated or inactivated,” Bagnato summarizes.

Jennifer Soares, a member of CePOF and a FAPESP scholarship recipient, explains that the researchers are also concerned with using molecules that are compatible with human health and the environment.

“Curcumin, for example, is a compound found in curry and has already been approved for use in humans. But there’s also concern about how to apply the light. Our studies have shown that blue light, due to its wavelength, is ideal for treating superficial infections such as in the throat. That’s why we’re developing devices capable of illuminating the tonsils, for example. Red or infrared light, on the other hand, is more suitable for treating deep infections, such as pneumonia, which requires devices adapted to illuminate the chest area,” she explains.

CePOF also conducts studies focused on treating cervical cancer by applying medication and photosensitizing molecules through specific routes, such as the intravaginal canal.

A new UC Berkeley study shows that the so-called love hormone, oxytocin, is also critical for the formation of friendships.

Oxytocin is released in the brain during sex, childbirth, breastfeeding and social interactions and contributes to feelings of attachment, closeness and trust. Never mind that it’s also associated with aggression; the hormone is commonly referred to as the “cuddle” or “happy” hormone, and people are encouraged to boost their oxytocin levels for better well-being by touching friends and loved ones, listening to music and exercising.

But recent studies involving the prairie vole have called this love association into question. They’ve shown that oxytocin, which in the brain acts as a neuromodulator, is not essential for long-term mate bonding, or “social monogamy,” or for parenting behavior, though without it, voles take longer to form such bonds.

Scientists focus on prairie voles because, like humans, they form stable and selective relationships. While most studies focus on mate bonds, the Beery lab at UC Berkeley is particularly interested in selective peer relationships, analogous to human friendships. Such studies could shed light on human psychiatric conditions, such as autism and schizophrenia, that interfere with a person’s ability to form or maintain social bonds.

Prairie voles are special because they allow us to get at the neurobiology of friendship and how it’s similar to and different from other types of relationships.”

Annaliese Beery, a UC Berkeley associate professor of integrative biology and neuroscience and senior author of the study

Beery and integrative biology graduate student Alexis Black, one of two first authors of the study, found that prairie voles that lack oxytocin receptors take longer than normal voles to form peer relationships. Prairie voles that are close friends typically huddle side by side, groom and even sit on one another.

“Oxytocin seems to be particularly important in the early formation phase of relationships and especially in the selectivity of those relationships: ‘I prefer you to this stranger,’ for example,” Beery said. “The animals that didn’t have intact oxytocin signaling took longer to form relationships. And then when we challenged those relationships by making new groups, they lost track of their original partners right away.”

The voles, genetically modified in the UC San Francisco laboratory of collaborator and co-author Dr. Devanand Manoli, also lacked the social rewards that normally come from selective attachments – they didn’t work very hard to snuggle up with their friends and were less avoidant of and less aggressive towards strangers.

“In other words, oxytocin is playing a crucial role not so much in how social they are, but more in who they are social with, their selectivity,” she said.

Lacking oxytocin receptors also changed the regulation of oxytocin availability and release in the brain, which the group documented using a novel oxytocin nanosensor in collaboration with postdoctoral fellow Natsumi Komatsu and Markita Landry, a UC Berkeley professor of chemical and biomolecular engineering.

“That helped us understand the feedback consequences of lacking this receptor, and how oxytocin signaling was altered in the brain,” said Beery.

The study was published Aug. 8 in the journal Current Biology.

What social voles tell us about social humans

Beery has long been interested in social relationships in rodents, focusing primarily on the animals’ seldom-studied peer or friendship relationships. While voles are her main focus, she believes studying similar behaviors across multiple species is key to determining what’s species-specific versus generalizable across species.

To complement her laboratory research, she has conducted field studies comparing social behavior and oxytocin receptor distribution in the brain within and across species in a group of South American rodents and North American Belding’s ground squirrels, which vary in whether or not they live in groups. She also recently began field tests of multiple vole species – there are about 50 worldwide – to compare their social behavior.

She suspects that in rodents such as voles, and perhaps in other mammals, the formation of peer relationships may have preceded the evolution of monogamous mating relationships.

“While most rodents prefer to interact with unfamiliar individuals, it turns out that the majority of vole species we’ve tested in our early trials form peer-partner preferences, which is what we call these selective friendships. So there seems to be this widespread tendency to bond,” Beery said. “But only a couple of those species are also monogamous. Someday, I hope to be able to tell you, ‘Do selective peer relationships precede the development of monogamy? Is that why monogamy has evolved so many times in this genus?’ I think this familiarity preference is deeply rooted.”

Beery was a co-author of a 2023 study led by Manoli that threw into question the association of oxytocin with sex and parenting. That study showed that prairie voles unable to respond to oxytocin exhibit the same monogamous mating, attachment and parenting behaviors as regular voles. Those voles had been genetically engineered to have no cellular receptors for oxytocin, and were the same voles used in the current study.

But while oxytocin isn’t essential for eventual bond formation, additional studies by the same group published in 2024 showed that these receptor-deficient (or “null mutant”) prairie voles took about twice as long as normal voles to establish a relationship with a potential mate.

Interested in how the lack of an oxytocin receptor affects voles’ friendship bonds, as opposed to mating bonds, Beery and Black conducted three sets of experiments. In one, they tested how long it took for voles to establish a preference for a partner. Whereas normal voles take about 24 hours of close proximity to form a relationship that makes them choose that partner over a stranger, oxytocin receptor-deficient voles showed no preference in that amount of time, and took up to a week to establish a peer preference.

“Wild-type animals form this incredibly robust preference within one day of co-housing, but the null mutants have no sign of a relationship after 24 hours. After a week, they mostly get there, and the lifetime partners look no different from each other,” Beery said. “Our conclusion from that experiment is that oxytocin isn’t required to have a relationship, but it’s really important in those early phases of a relationship to facilitate it happening quickly and efficiently.”

They then put long-term pair-bonded voles in a party-like, mixed-group situation: an enclosure with other voles and many rooms connected by tubes. In such a situation, normal voles would hang out with known friends until they eventually started to socialize with strangers.

“They can all separate, they can all come together, or they can hang out in any combinations that they want,” she said. “The wild-type animals keep track of who they know. It’s like if I went to a party with a friend, I would stand near that friend for the first part of the party and then I might start to mingle. The voles that lack oxytocin receptors just mixed. It was as if they didn’t even have a partner in there with them.”

In the third experiment, they tested the strength of both peer and mate bonding by having the voles press levers to get access to either a friend/mate or a stranger.

“Female wild-type voles typically press more to get their partner than to get a stranger, in both peer and mate relationships. The oxytocin receptor deficient mutants also press more to get to their mating partner, but not for peer relationships,” Beery said. “That makes sense at some level because we think mate relationships are more rewarding than peer relationships, or at least they depend more on reward-signaling pathways.”

Lack of oxytocin signaling thus not only delays the formation of relationships, but also creates deficits in long-term peer relationships.

On the flip side, voles lacking oxytocin receptors were also less aggressive toward strangers and less avoidant of them. 

“You can see contributions of oxytocin signaling to both sides of selectivity,” Beery said. “On the prosocial side, it’s involved in wanting to be with a known friend or peer, while on the antisocial side, it’s aiding in rejecting an unfamiliar animal. We’ve seen effects of oxytocin on both affiliation and aggression in our other studies in prairie voles, and it parallels human findings on a role of oxytocin in in-group/out-group dynamics.”

Oxytocin nanosensors

The researchers used a new oxytocin sensor developed in Landry’s UC Berkeley lab to determine whether lack of an oxytocin receptor caused increases or decreases in oxytocin release. If oxytocin release increased in these voles, it could potentially interact with a receptor for a similar neuropeptide that is also involved in formation of social relationships, compensating for the absence of oxytocin receptors.

Landry, an associate professor in the departments of chemical and biomolecular engineering, neuroscience, and molecular and cell biology and a co-corresponding author of the paper, created these sensors from carbon nanotubes joined with specific single-stranded DNA sequences selected because they latch onto the oxytocin molecule and fluoresce. Komatsu and Landry found no excess of oxytocin in the voles’ brains. In fact, oxytocin was being released in lower amounts from fewer sites in the nucleus accumbens, a key brain region for social reward across species.

Co-authors with Black, Komatsu, Beery, Landry and Manoli are Jiaxuan Zhao, Scarlet Taskey and Nicole Serrano of UC Berkeley, and Ruchira Sharma of UCSF. Beery’s work was supported by the National Science Foundation (CAREER award 2239635) and the National Institutes of Health (R01MH132908). Komatsu is now an assistant professor at the University of Illinois.

In Western Finland, the longest-lived region thrives without following classic Blue Zone habits, while another community shows promising lifestyle patterns, challenging the idea that there’s only one path to a long and healthy life.

Study: Searching for a Potential Blue Zone in the Nordics: A Study on Differences in Lifestyle and Health in Regions Varying in Longevity in Western Finland. Image Credit: Trygve Finkelsen / Shutterstock

Since their description in 1999 by Poulain and colleagues, “Blue Zones”, geographical regions characterized by the unusual longevity of their inhabitants, have been identified worldwide. However, the Blue Zone framework has never explicitly investigated the Nordic areas. In a recent study published in the Journal of Aging Research, researchers evaluated four regions within Western Finland to see if any have the lifestyle principles typically associated with Blue Zones.

Study findings revealed an unexpected paradox – the most long-lived region, the Åland Islands, demonstrated the best health outcomes but did not adhere closely to the Blue Zone lifestyle. Conversely, areas demonstrating stronger adherence to these principles did not have uniformly high longevity. Finnish-speaking Ostrobothnia deviated most significantly from Blue Zone principles. The findings suggest that in a Nordic welfare state context, factors beyond the classic Blue Zone lifestyle,  like environmental agreeableness, genetics, and socioeconomic resources, may be critical drivers of healthy aging, guiding public health policy in these regions that are gradually aging.

Background

“Blue Zones” are geographical areas where people live significantly longer (measured through rigorous demographic validation like extreme longevity indexes) and healthier lives. First identified in Ogliastra, Italy (1999), these longevity hotspots, which now also include Nicoya, Costa Rica, and Okinawa, Japan, famously share common lifestyle traits, popularly distilled into principles like “move naturally,” “eat wisely,” and “avoid stress and get plenty of sleep” (combined as one principle).

The Blue Zone framework’s social and public health benefits cannot be understated, as the concept has inspired several global public health initiatives to leverage its principles to promote healthy aging. Critics, however, question whether the Blue Zone framework, derived from specific cultural contexts, can be universally applied, especially in regions such as Nordic welfare states with unique social and environmental landscapes that radically differ from those of validated Blue Zones.

About the Study

The present study addresses this knowledge gap by searching for a potential Blue Zone in Western Finland, a region known for its linguistic diversity with previously reported notable differences in health and longevity between its Swedish-speaking and Finnish-speaking populations. This research additionally aims to validate whether the region with the highest longevity also shows the best health and the strongest adherence to established Blue Zone lifestyle principles.

The study leveraged data from four distinct populations in Western Finland that differ in language (ethnolinguistically) and longevity: 1. The Åland Islands (Swedish), 2. Ostrobothnia (bilingual), split into Swedish- and Finnish-speaking subgroups for analysis, and 3. South Ostrobothnia (Finnish). Official (government) statistics comprised the study’s longevity data and were used to rank the regions on the longevity of their inhabitants. However, these statistics could not differentiate between language groups within Ostrobothnia.

Regions’ health and lifestyle data were obtained from surveys collected from older adults (aged 66-91) in these regions as part of the Gerontological Regional Database (GERDA) in 2021-2022. However, the GERDA survey’s self-response format may overrepresent healthier individuals, especially in Finnish-speaking regions with lower response rates.

Adherence to Blue Zone principles was assessed across seven core metrics plus an environmental supplement: 1. Move naturally, 2. Eat wisely, 3. Avoid stress and get plenty of sleep, 4. Strong family ties and community support, 5. Respect the planet, 6. A purpose in life, and 7. Environmental features (added as a supplementary principle). Health variables with known longevity associations (e.g., medical conditions and instrumental activities of daily living [IADL]) were used to measure healthy aging. Scoring was composite, with each principle awarded fractional points based on multiple sub-variables. Participants’ sociodemographic data (age, sex, education status, etc.) were accounted for in statistical models (Analysis of Variance [ANOVAs]).

Åland Islands. Image Credit: Heikki Wichmann / Shutterstock

Study Findings

Longevity data confirmed that the Åland Islands were the most long-lived region, with a life expectancy at birth of 83.47 years (2020-2022), closely followed by Ostrobothnia (83.10 years), while South Ostrobothnia had the lowest (81.83 years). Åland also showed the highest rates of nonagenarians and centenarians.

Unexpectedly, however, health and lifestyle data analysis revealed that while Åland demonstrated the best overall health scores (e.g., lowest medication use, best dental health, and least pain), its inhabitants did not follow the core Blue Zone lifestyle closely, scoring only 1.23 out of a possible 7+ principles. Its main strength was “environmental agreeableness” (0.8/1), a measure of living in a pleasant, activity-promoting natural environment linked to its archipelago setting. Researchers attribute Åland’s longevity to potential genetic advantages and higher socioeconomic status (education/income) alongside environmental factors.

In contrast, Swedish-speaking Ostrobothnia and South Ostrobothnia showed the strongest adherence to the core Blue Zone lifestyle principles, both scoring 1.73. They demonstrated the highest adherence in principles related to “strong family ties,” “community support,” and “purpose in life.” Both regions are part of Finland’s religious “Bible Belt,” with high rates of religious activity potentially contributing to purpose-driven living. South Ostrobothnia additionally showed notable strength in “respect for the planet.” Despite this, Swedish-speaking Ostrobothnia had slightly lower longevity than Åland, and South Ostrobothnia had the poorest health and the lowest longevity of the studied regions. Critically, Finnish-speaking Ostrobothnia scored 0, showing the weakest alignment with Blue Zone principles, yet had better health than South Ostrobothnia.

Conclusions

The present study challenges the universality of the Blue Zone framework and highlights that the pathways to a long and healthy life are not one-size-fits-all. In Nordic welfare states, longevity may stem from context-specific factors like environmental assets (Åland) or social-religious cohesion (Swedish-speaking Ostrobothnia) rather than universal lifestyle principles. The researchers suggest Swedish-speaking Ostrobothnia warrants further investigation as a potential Blue Zone candidate due to its balance of longevity, health, and lifestyle adherence.

In recent years, there has been growing concern over the H5N1 influenza virus. It was first identified in birds three decades ago and has now gradually found its way to humans. H5N1 is a strain of the influenza virus harboring type 5 hemagglutinin (H5) and type 1 neuraminidase (N1) surface proteins, which help in viral entry and spread, respectively.

Researchers led by Kesavardhana Sannula, Assistant Professor in the Department of Biochemistry, Indian Institute of Science (IISc) have now discovered that the currently circulating 2.3.4.4b clade of H5N1 has specific mutations in its genome that increase its human adaptive potential. Clade represents a group of organisms having a common ancestor.

The 2.3.4.4b clade has infected many mammalian species and is adapting to [non-human] mammals, which is a concern for human adaptation. The clade is panzootic, causing unprecedented mortality in birds and mammals, along with several sporadic human infections.”

Kesavardhana Sannula, Assistant Professor, Department of Biochemistry, Indian Institute of Science 

When the influenza virus enters a new organism, it can develop genetic mutations. This helps the virus adapt to the new host. The researchers were trying to decode whether the 2.3.4.4b clade was evolving to produce crucial adaptations in its proteins that allow it to infect humans. They also wanted to decipher which host animals can potentially accelerate this adaptation, giving the virus a leg up in scaling the evolutionary ladder.

Kesavardhana’s team took a computational approach and analysed 7,000 protein sequences of 2.3.4.4b H5N1 found in birds, 820 sequences from non-human mammals, and 35,000 human H1N1 and H3N2 sequences, in order to identify which amino acids are under selection pressure – rapidly changing. They used multiple sequence alignment (a tool to identify similar regions in multiple proteins), constructed phylogenetic trees (which represent how species have diverged from their common ancestor over time) and annotated specific variations in all the proteins of H5N1 infecting non-human mammals and humans. 

The team found an increased number of mutations specifically in the viral polymerase complex (PA, PB2), nucleoproteins, and hemagglutinin (HA) proteins. Once they identified these mutations, the team classified them depending on whether the mutations can help the virus spread from non-human mammals to humans (adaptive) or simply survive in the non-human host (barrier). Finally, they developed a simple mathematical approach and estimated the human adaptive potential for the 2.3.4.4b clade.

The team was also able to pinpoint animals that would be likely to harbor virus strains with the highest human adaptive potential. Interestingly, viruses that can adapt to fox hosts seemed to have higher adaptive potential than cattle-adapted strains. “It is very surprising,” Kesavardhana says. 

Based on their findings, the researchers suggest that enhanced and proactive surveillance measures need to be implemented.

“This clade is acquiring the same key mutations that pandemic human influenza strains possess, which could be a growing risk,” says Ranjana Nataraj, Project Associate at the Department of Biochemistry and the study’s first author.

In a recently published study, researchers at Fox Chase Cancer Center revealed for the first time that cancer cells can evade anti-cancer drugs by entering and surviving within bone marrow fibroblasts, a phenomenon they describe as “cell-in-cell.”

The results of this five-year study, led by Y. Lynn Wang, MD, PhD, FCAP, a Professor and physician-scientist in the Department of Pathology and the Cell Signaling and Microenvironment Research Program at Fox Chase, could mark a major change in the treatment of chronic lymphocytic leukemia (CLL) and related diseases. CLL is the most common hematological cancer in western countries.

Our discovery that tumor cells can actually get inside bone marrow fibroblast cells, which support the tumor cells in their microenvironment, has never been reported before as a live phenomenon.”

Y. Lynn Wang, MD, PhD, FCAP, Professor and physician-scientist, Department of Pathology and the Cell Signaling and Microenvironment Research Program at Fox Chase

“This finding helps to explain why, even when CLL patients initially respond to treatment, many of them carry residual disease and later relapse. We are hopeful that our discovery will lead to treatments that better eliminate residual disease and move toward a cure for cancer,” added Wang, who conducted the study with researchers at Fox Chase and other institutions.

BTK inhibitors, a class of anti-cancer drugs, are the current standard of care for CLL. Over 90% of patients who are treated with these drugs show an initial response – they feel better and their tumors shrink – but only 8% to 11% achieve complete remission in which clinically patients show no evidence of disease. This means that a high number of patients carry residual disease that leaves them vulnerable to relapse. Wang and her team wanted to understand how the disease manages to persist in spite of good initial response to the drugs.

Using confocal microscopy and other techniques, the researchers analyzed bone marrow samples from patients. They witnessed live CLL cells entering bone marrow fibroblasts in response to BTK exposure, and by recording continued independent movement of those subsumed cells, they were able to confirm that the cancer cells stayed alive inside the fibroblasts. Wang’s team then demonstrated that the cancer cells hiding inside the fibroblasts had higher survival rates compared to the cells that remained outside the fibroblasts exposed to the drug.

“It’s like the tumor cells are retreating off the street into a house where they’re safer from the street bullies, i.e., the drugs,” Wang said.

The way CLL cells do this, her team found, is by increasing the expression of CXCR4, a receptor protein on the surface of the tumor cells, in response to exposure to BTK inhibitors. The expression of this protein makes tumor cells sense a chemical gradient that draws the tumor cells closer to the fibroblasts that secrete the ligands for the receptor, allowing the former to enter the latter.

Once Wang and her team understood the mechanism by which tumor cells got inside their “safe houses,” they were able to demonstrate how clinicians might alter treatment to stop this from happening. By blocking CXCR4 with drugs approved for other clinical indications, the researchers prevented CLL cells from entering fibroblasts, potentially making the cancer more vulnerable to treatment.

“If we can block CXCR4, it’s like locking the door of the house where tumor cells wanted to retreat and hide,” said Wang. “This could potentially increase complete response rates through combination therapy using both BTK inhibitors and CXCR4 blockers.”

The discovery may also have applications beyond CLL. The researchers found similar “cell-in-cell” hiding behavior in follicular lymphoma and suspect the mechanism could apply to many different cancer types. Wang is encouraged about the potential of her team’s discovery.

“We want the larger scientific community to know about this mechanism so other researchers can build on these findings. If we can understand what makes cancer cells persist as residual disease, we can better treat cancer and move toward the ultimate goal of cancer elimination.”

University of Oklahoma researchers are conducting a first-of-its-kind study to determine whether cannabis use affects recovery from the wounds associated with head and neck cancer surgery. The outcomes may have implications for other types of surgery and conditions.

Lurdes Queimado, M.D., Ph.D., and Mark Mims, M.D., have been funded by the Presbyterian Health Foundation in Oklahoma City to lead the research, which will include 220 adult patients undergoing surgery for head and neck cancer and reconstruction after the tumor removal. Many such surgeries compromise both appearance and physiological functions such as swallowing and breathing.

The research is unique in that it is prospective – patients will be followed for six months from the time of their treatment – rather than retrospectively looking at patient data. In addition, patients’ self-reporting of cannabis use will be biochemically verified through blood tests, which adds strength to the study.

Research has shown that there is a high rate of cannabis use among cancer patients – more than 50% in some studies, and up to 80% among those who also use tobacco. But there is very little in the medical literature about how cannabis use affects the healing of wounds. Importantly, there are no prospective studies on this topic. We believe the data that we gather will advance our understanding of how the diverse modes of cannabis use affect wound healing and establish a framework for related studies.”

Lurdes Queimado, M.D., Ph.D., lead principal investigator and Professor of Otolaryngology

Queimado also directs the Tobacco Regulatory Science Lab at the TSET Health Promotion Research Center, a program of OU Health Stephenson Cancer Center.

Based on her preliminary research, Queimado hypothesizes that cannabis smoking negatively affects wound healing. Her initial studies, though limited, show that non-cancer patients who smoke cannabis have more inflammation and a decrease in immune system function, both of which could reduce wound healing and increase complications.

However, there are many factors to take into consideration, such as the mode in which patients consume cannabis and how often they use it. Queimado’s trial is designed with four groups of patients – those who use cannabis, those who use cannabis and tobacco, those who use tobacco only, and those who use neither.

“We will monitor each group of patients for infections, bleeding, medical complications and scar healing,” she said, “and we will assess how they are using cannabis, whether it’s smoking, vaping or edibles, because they are very different in the effects they have. The ultimate goal is to have information to guide the patient.”

Facial plastic and reconstructive surgeon Mark Mims, M.D., an assistant professor of otolaryngology and surgery, said this study is both relevant and timely.

“Patients come to my office and ask if using cannabis will affect their reconstructive surgery outcome, and we just don’t have enough data to counsel them with confidence,” Mims said.

While the main purpose of the study is to understand the effects of cannabis on wound healing in head and neck cancer patients, Queimado and her team will also gather information about patients’ responses to any treatment in addition to surgery, such as chemotherapy and radiation.

“I think this study has the potential to have major implications for other types of cancer and surgeries, but also for chronic diseases because inflammation and immunity play a significant role in many conditions, such as autoimmune diseases,” Queimado said. “I think there will be many opportunities for growth into other areas once we have established the framework of this study.”

For many breast cancer survivors, fatigue may linger long after treatment ends, which can have a significant impact on cognitive function, ability to work, and overall quality of life. A new study from George Mason University’s College of Public Health suggests that this is not just a subjective feeling but a measurable reality. 

Ali Weinstein, professor of global and community health and senior scholar at the Center for the Advancement of Well-Being studied how breast cancer survivors respond to physically and mentally tiring tasks. Researchers measured changes in both inflammation and participants’ self-reported fatigue, two common symptoms among breast cancer survivors that are believed to be connected, impact quality of life, and may also play a role in cancer recurrence. 

The researchers found that women who reported higher levels of fatigue at the beginning of the study experienced more inflammation after the tasks, particularly in levels of TGF-β and eotaxin (indicators of inflammation that are linked to immune function, stress, and mood). 

Even women in the control group (who watched a nature video) with high baseline fatigue showed signs of increased inflammation and fatigue, suggesting reactivity even to this relatively innocuous stimulus. 

Surprisingly, most inflammation markers and fatigue levels did not change following mentally or physically fatiguing tasks, suggesting that these short tasks do not affect inflammation or fatigue among most breast cancer survivors. 

This study, published in BMC Women’s Health, explores three previously unstudied areas among breast cancer survivors: 1) how mental fatigue may be connected to inflammation, 2) responses in the short term to tasks that may induce fatigue, and 3) the effects of physically versus mentally fatiguing tasks. 

Studying inflammation in breast cancer survivors is important because past research has shown a link between inflammation and cancer progression or recurrence. Fatigue can also strongly influence survivors’ daily quality of life, and we suspect it may be connected to inflammation. We’re working to better understand that connection, particularly with short-term exposures that may accumulate-and increase inflammation-over time.” 

Ali Weinstein, professor of global and community health and senior scholar at the Center for the Advancement of Well-Being

The team worked with female breast cancer survivors, each randomly assigned to one of three short activities: a physically demanding walk/run, a mentally challenging computer test, or simply watching a nature video (used as a control). Blood samples and fatigue ratings were collected before the task, immediately after, and again after a 30-minute recovery period. 

The researchers highlight the need for more personalized approaches to fatigue management for breast cancer survivors, particularly strategies that consider existing levels of fatigue and the body’s inflammatory response to everyday physical and cognitive demands. 

This work was supported by a grant from the PNC Charitable Trust (Grant #112881). 

Irritable bowel syndrome with diarrhea (IBS-D) is an unpleasant condition to live with, affecting millions of people worldwide. Now a new study has identified what could be a key trigger for the condition – a trigger which could be targeted by future treatments.

An investigation on 108 people with and without IBS-D and related conditions has revealed a hormone called insulin-like peptide 5 (INSL5) is released when bile acids that aid digestion find themselves further along the digestive tract than usual, in the large intestine.

This shouldn’t happen, but when it does – due to certain conditions and gut malfunctions – more INSL5 gets produced, which causes diarrhea-like symptoms.

This is potentially responsible for around two out of every five cases of IBS-D, the researchers say, and may explain why a lot of existing drugs and strategies to combat IBS-D are ineffective.

Related: Surprising ‘Nocebo Effect’ Shows Gluten May Not Be The Problem in IBS

“When you go to the doctor with chronic diarrhea, they’ll likely test for food intolerances, rule out an infection or look for signs of inflammation,” says Chris Bannon, an endocrinologist at the University of Cambridge in the UK. “There has been significant research interest in the microbiome, but gut hormones have been neglected.”

“It’s becoming increasingly clear that gut hormones play an important role in things like gut health and weight management.”

The study included participants with bile acid diarrhea (BAD) as well as IBS-D, helping the researchers identify a link between these conditions, the differences between them, and the triggers responsible for them.

At the moment, BAD is difficult to diagnose and is often classed as IBS, and the researchers hope that being better able to spot it will lead to treatments that can more effectively target the underlying causes.

It’s also important to note that INSL5 is naturally produced by the body. Although it brings on diarrhea, it’s actually a sign of the body trying to protect itself: it detects that bile acids shouldn’t be in the colon, and flushes them out.

“It makes sense that you would have something that detects toxins and helps the body rid itself of them,” says Bannon. “But a problem develops if it’s always being triggered by bile acid, causing very dramatic symptoms.”

Studies using mouse models had found that INSL5 could cause diarrhea, but this is the first time researchers have been able to show the same processes in people, and in ways that are connected to two recognized conditions.

The next steps are to look at potential treatments targeting INSL5. Some IBS-D patients in previous studies showed improved symptoms when given the anti-sickness medicine ondansetron – a known INSL5 blocker – which may indicate one route forward, although it’s not yet clear why ondansetron works so well.

“This was a very exciting finding because it showed us that this hormone could be playing a big part in symptoms of this misunderstood condition,” says Bannon.

“It also meant it might allow us to develop a blood test to help diagnose bile acid diarrhea if INSL5 levels are only high in these individuals.”

The research has been published in Gut.

During Australia’s National Science Week in August, Hort Innovation has announced a new research project developing “plant vaccines” to protect Australia’s vegetables from viral diseases.  

The project, which is funded by the organisation and led by The University of Queensland (UQ), is a five-year initiative exploring how peptides – which are tiny biological molecules – can be used to prime plants to defend themselves against viruses, much like vaccines do in humans.  

The research team will use advanced plant molecular biology tools to identify promising peptide candidates and assess their ability to trigger broad immune responses in vegetable crops. In parallel, the project will also investigate beneficial bacteria from vegetable root systems that may act as natural defence primers.  

Brett Fifield, Hort Innovation CEO said the cutting-edge initiative is set to solve “real-world problems”. 

“The project is using advanced plant molecular biology to develop eco-friendly, scalable solutions for growers across the country,” he said. “We’re combining cutting-edge science with practical farming needs to create virus-resistant crops that don’t rely on chemicals. This is science in action, using biology to solve real-world problems, which is exactly the kind of innovation we celebrate during National Science Week.”  

UQ’s Mark Jackson added: “Just like people might get a flu shot to prepare their immune systems, we’re helping plants get ready for viral attacks using peptides. These molecules can prime the plant’s natural defences, so when a real virus shows up, the plant knows how to fight back”.  

However, unlike traditional vaccines that use weakened or dead viruses, this project is investigating peptide elicitors – molecules that simulate the presence of a virus without introducing any actual pathogen. These peptides trigger a “teaching effect,” helping plants build immunity before infection occurs.  

“Peptides are like keys that fit into the plant’s immune system locks,” Jackson said. “But finding the right key is complex, as there are many peptides and receptors, and only a perfect match will trigger the defence response. Our goal is to find generalist peptides that can protect against a wide range of viruses, offering a more holistic and scalable solution for growers.”  

The project will be focused on Queensland growing regions, where viruses like papaya ringspot virus and zucchini yellow mosaic virus are spread rapidly by insect carriers.   

“Importantly, this research will support reduced reliance on chemical treatments by offering growers practical, eco-friendly virus control options,” added Fifield. It will also enhance crop resilience and productivity, helping to future-proof farming systems against emerging viral threats.”