The rescue was substantial but incomplete, showing that ASNS is an important contributor to the disorder rather than a full explanation for every feature. Angelman syndrome results from loss of UBE3A function in the brain. UBE3A encodes an E3 ubiquitin ligase, but the study was designed around a more specific unresolved problem: which proteins affected by loss of this protein contribute to particular disease phenotypes?

The investigators combined disease-linked UBE3A mutations that gain or lose function with unbiased proteomics, then examined candidate substrates in a mouse model and in neurons derived from patient cell lines. The human cell lines included one carrying a large maternal deletion spanning UBE3A and another carrying a premature truncating mutation in the maternal UBE3A allele. ASNS emerged from the proteomic screen as a strong candidate.

The protein was more abundant in the brains of Ube3a-null mice and in human neurons with Angelman syndrome. Its expression was concentrated mainly in neurons, paralleling the neuron-specific imprinting pattern of Ube3a in the mouse. ASNS makes asparagine, a non-essential amino acid that can be obtained through the diet but must be transported across the blood–brain barrier to enter the central nervous system.

The study’s authors proposed that neurons may rely on ASNS for most or all of the asparagine they require, making changes in its abundance a potential point of vulnerability during development. Experimental manipulation linked excess ASNS to stress signalling. Overexpressing ASNS in neurons was sufficient to increase phosphorylated eIF2α and levels of HRI, the kinase encoded by Eif2ak1.

Phosphorylated eIF2α and HRI are associated with integrated stress responses, and HRI is induced in neurons during proteostatic stress. The investigators therefore examined whether altered ASNS contributed to the reduced protein synthesis observed when UBE3A was absent. The central measured defect was a global decline in neuronal protein synthesis, detected through amino-acid labelling in mouse brain and cultured neurons, together with a reduction in polysome fractions.

Monosome fractions were not reduced. The pattern of lower polysomes and unchanged monosomes is important because it distinguishes aspects of translation affected by the model. Polysomes are complexes in which several ribosomes translate the same messenger RNA, whereas previous work cited by the researchers indicates that monosomes are predominantly located in neuronal processes and can synthesize proteins from at least a subset of transcripts.

Whether monosome-dependent translation remains preserved in Ube3a-null neurons requires further study. The investigators also found elevated free amino acids in Angelman mouse brains, a result consistent with the observed reduction in protein synthesis, although the amino acid result alone does not identify the mechanism responsible. Genetic reduction of Asns expression in the mouse model restored protein synthesis, corrected microcephaly and rescued many aberrant behavioural phenotypes.

The experiments included assessments of brain weight, movement and motor performance, open-field behaviour, marble burying, hindlimb clasping, and sleep and circadian activity. The reported finding was not that every behavioural or anatomical outcome returned to normal; rather, reducing ASNS improved many of the abnormal phenotypes while leaving some pathology unresolved. That partial rescue indicates that additional UBE3A substrates probably contribute to Angelman syndrome.

It also means that the results support ASNS as a major disease-relevant target without establishing it as the sole target. It was the only integrated stress response–associated gene found to be upregulated in Angelman mice and rescued through Asns modulation. HRI is involved in mitochondrial maintenance and protein synthesis, both closely connected to the findings in this study.

The researchers did not detect activation of the amino acid response pathway that they had originally expected to accompany the increased brain amino acids. It remains unresolved whether ASNS drives stress signalling through increased asparagine production or through another, unidentified activity. The study therefore establishes a mechanistic connection among UBE3A loss, excess ASNS, altered stress signalling and reduced protein synthesis, while leaving the precise route from ASNS activity to HRI unresolved.

The direction of ASNS change in Angelman syndrome contrasts with established asparagine synthetase deficiency. Homozygous loss of ASNS causes a rare congenital condition characterized by microcephaly, global developmental delay, hypotonia, spastic quadriplegia and intractable seizures. In the Angelman model investigated here, ASNS protein abundance increased rather than decreased, and genetic correction of the overabundance improved disease-related outcomes.

This does not mean that reduced ASNS is beneficial in every context. It indicates that insufficient and excessive ASNS can be associated with different neurological problems. Gain-of-function mutations in ASNS have not yet been established as causes of neurodevelopmental disorders, so the mouse results do not establish a new human genetic condition.

Several limitations qualify the study’s scope and therapeutic implications. The main rescue was achieved by genetically reducing Asns in mice, while the human evidence came from proteomic data and neurons derived from patient cell lines rather than a clinical treatment trial. The proteomic workflow also had restricted coverage.

Affinity purification of ubiquitinated proteins can underrepresent low-abundance or rapidly degraded substrates, and the researchers could not completely exclude competition between endogenous UBE3A and overexpressed UBE3A for binding to substrate proteins. The broader landscape of UBE3A substrates relevant to Angelman syndrome therefore remains incompletely defined. The incomplete behavioural and anatomical rescue also cautions against assuming that correcting one upstream imbalance will normalize the entire disorder.

Even with those limitations, the results identify ASNS, HRI and the wider integrated stress response as possible intervention points that could complement genetically targeted approaches. The work provides a testable rationale for investigating whether reducing excess ASNS activity or modifying stress signalling can relieve part of the abnormal protein-synthesis and growth program associated with UBE3A loss. The clearest conclusion from the present study is not that a therapy has been demonstrated, but that persistent neuronal stress signalling is a central feature of the Angelman mouse model: correcting one major molecular imbalance restored protein synthesis and improved microcephaly and many behavioural deficits, while the residual phenotypes show why more than one target may be needed.

Subject of Research: Neuronal stress signalling and asparagine synthetase in Angelman syndrome

Article Title: Persistent neuronal stress signalling underlies Angelman syndrome phenotypes

Article References: Kim, K.-S., Gardner, C., Cullen, A., Stelzer, J. A., Cho, K., Sharma, A., Nemera, M. T., Law, T., Naz, H., Zhao, G., Gabel, H. W., Patti, G. J., Musiek, E. S., Ahn, T.-H., & Yi, J. J. (2026). Persistent neuronal stress signalling underlies Angelman syndrome phenotypes. Nature. https://doi.org/10.1038/s41586-026-11165-4

Image Credits: AI Generated

DOI: 10.1038/s41586-026-11165-4

Keywords: Angelman syndrome, UBE3A, asparagine synthetase, ASNS, neuronal stress, protein synthesis, neurodevelopmental disorder, mouse model, human neurons, proteostasis, Persistent, neuronal

The research, published in Discover Sustainability on 25 September 2026 as an open-access, peer-reviewed article, examined monthly data connecting the Crude Oil Volatility Index (OVX) with the Baltic Clean Tanker Index (BCTI), the Baltic Dirty Tanker Index (BDTI) and the Baltic Dry Index (BDI). By including indices for clean tankers, dirty tankers and dry-bulk shipping, the study compared how oil-price volatility related to freight-rate behavior in three representative segments of maritime transport.

The empirical framework combined econometric tests with Detrended Cross-Correlation Analysis, or DCCA, and wavelet-based analysis. Across the three freight markets, the results revealed heterogeneous but persistent relationships with the OVX. The BDTI had the strongest relationship, whereas the BDI showed comparatively weaker dependence. Wavelet analysis placed the observed dependence primarily at medium- and long-term scales. More pronounced co-movement also occurred when uncertainty in the oil market was heightened.

These results establish a statistical association, not proof that oil-price uncertainty directly causes freight rates to change. The study is limited to monthly observations from one decade and to three representative Baltic indices; it does not establish whether the same pattern holds for every route, commodity or shipping segment. Within that scope, the findings identify persistent exposure to crude oil price uncertainty as relevant to freight risk management, fuel-efficiency strategies, fleet investment and maritime financial planning. The authors also connect the results to broader implications for sustainable maritime transport and for Sustainable Development Goals 7 and 13.

Subject of Research: Scale-dependent associations between crude oil price uncertainty and Baltic maritime freight rates

Article Title: Persistent exposure to crude oil price uncertainty in maritime freight rates implications for sustainability and intergenerational justice

Article References: Mim, T. A., & Mamilla, R. (2026). Persistent exposure to crude oil price uncertainty in maritime freight rates implications for sustainability and intergenerational justice. Discover Sustainability. https://doi.org/10.1007/s43621-026-04757-7

Image Credits: AI Generated

DOI: 10.1007/s43621-026-04757-7

Keywords: crude oil volatility, maritime freight rates, Baltic indices, dirty tankers, clean tankers, dry bulk shipping, DCCA, wavelet analysis, oil-market uncertainty, maritime sustainability, Persistent, exposure

Researchers used the K/BxN serum-transfer model, in which pooled serum from arthritic mice transfers arthritis-like disease to healthy recipient animals. Twelve-week-old male C57BL/6J mice were assigned to healthy controls, untreated arthritic controls or arthritic animals given dipyridamole. Arthritis developed after two serum injections, peaked around day 15 and resolved by day 28. Treatment began only after that remission point and continued until the animals were examined on day 45. The investigators assessed paw swelling, body and tissue weights, motor performance, muscle histology, nucleotide concentrations, gene expression and intracellular signaling. Body-weight recovery was defined in advance as the primary outcome, while the other measures were secondary or exploratory outcomes.

Untreated arthritic mice retained a marked muscle deficit after their joints recovered. Their body weight remained below that of healthy controls, while the gastrocnemius and tibialis anterior muscles weighed less. White adipose tissue remained enlarged, although brown adipose tissue returned to a control-like mass. Functional testing told a similar story. Activity, forelimb grip strength and two-limb hanging endurance were reduced through much of the study, while rotarod performance recovered late in the observation period. Dipyridamole did not restore every measurement immediately, but by week 6 it had returned ambulation, grip strength and hanging endurance to levels comparable with healthy animals and further improved rotarod performance. Body weight also increased after two weeks of treatment, although it did not fully reach the sham level during the experiment.

Tissue analysis showed that untreated arthritic mice had smaller muscle fibers, an excess of type II fibers compared with the type I predominance in controls, and increased collagen deposition consistent with fibrosis. Dipyridamole attenuated fiber atrophy, shifted fiber composition back toward type I and limited collagen accumulation to the sarcolemma. It also reduced the number of fibers containing intracellular immunoglobulin, which the researchers used as an indicator of myofiber necrosis. These tissue-level changes coincided with better performance, linking structural preservation with functional recovery. The findings show that muscle abnormalities were present after joint swelling had resolved; they do not establish reduced movement during active arthritis as the cause of those abnormalities.

Chemical analysis of gastrocnemius tissue revealed a metabolic signature that persisted despite remission. Compared with healthy controls, arthritic mice had significantly less adenosine and AMP but more ATP, producing a markedly depressed AMP-to-ATP ratio. Inosine did not differ among the groups, and adenosine diphosphate was lower in arthritic muscle but was not changed by treatment. Dipyridamole reversed the principal abnormalities: muscle adenosine and AMP concentrations recovered, and the AMP-to-ATP ratio returned to a level similar to that of controls. These changes were accompanied by increased expression of the adenosine A2B receptor, or A2BR, and greater phosphorylation of AMP-activated protein kinase, or AMPK. The observed benefits therefore coincided with restoration of adenosine-related signaling, although the experiment did not establish that A2BR was required for the treatment effect.

The molecular findings also indicate that the persistent weakness involved both catabolic and anabolic pathways. Untreated arthritic muscle retained elevated myostatin, a factor associated with inhibition of muscle growth, while the Akt/mTOR anabolic pathway was suppressed. Dipyridamole reduced myostatin expression, increased insulin-like growth factor 1 receptor expression and stimulated Akt/mTOR signaling. It also reduced Murf-1, a gene related to muscle degradation, although the other measured ubiquitin-proteasome marker, Atrogin-1, did not differ between groups. The senescence-associated marker p16 was elevated in arthritic muscle and fell with treatment, whereas p21 was unchanged. No differences were detected in Pax7, myogenin or myosin heavy-chain expression, although dipyridamole increased Myf5 and reduced the elevated MyoD seen in untreated arthritic muscle. The pattern was consistent with improved muscle maintenance and anabolic capacity, but it was not a wholesale correction of every molecular marker.

The results support the concept of a “sarcopenic imprint,” in which rheumatoid arthritis leaves lasting abnormalities in muscle after visible joint inflammation has resolved. In this model, that imprint included muscle atrophy, fibrosis, abnormal fiber composition, impaired regeneration, necrosis, altered energy metabolism and reduced strength and endurance. Some abnormalities were directly reversible with post-remission dipyridamole treatment, and the temporal sequence is important: the drug was introduced only after joint swelling had subsided. The work therefore goes beyond the observation that dipyridamole can influence muscle during active disease. It shows that starting treatment after remission can still improve a persistent muscle phenotype in this experimental system.

Several limitations prevent the findings from establishing a human treatment or proving that A2BR is indispensable. The investigators did not block or genetically delete A2BR, so the receptor’s causal role remains unproven; the relationship between receptor expression, AMPK activation and muscle recovery is associative. Dipyridamole is also not a selective A2BR modulator and changes several components of the purinergic system, making it difficult to assign the benefits to one receptor. Although the experiment began at the model’s established remission point, inflammatory mediators were not directly measured at the end of the current study, so residual inflammation cannot be completely excluded. There was no conventional disease-modifying antirheumatic drug or other anti-inflammatory comparator, and the cohort was small, included only male mice and was not replicated in female animals or people. Several individual observations were excluded after identification with the ROUT method at a Q of 1%; reanalysis including them did not change the overall interpretation.

The study nevertheless provides a mechanistic lead for a problem that can be overlooked when treatment is judged by joint symptoms alone. It shows that normalization of paw swelling in experimental rheumatoid arthritis does not necessarily mean that muscle homeostasis has recovered. Dipyridamole’s capacity to improve the post-remission phenotype while adenosine, A2BR and AMPK signaling were restored makes the adenosine pathway a plausible target for further investigation. Whether the same sequence occurs in people with rheumatoid arthritis remains unknown. Addressing that gap would require larger studies in both sexes, direct measurements of residual inflammation, receptor-specific experiments and clinical validation rather than extrapolation from this mouse model alone. The results should therefore be read as evidence for a possible post-remission muscle-targeting strategy, not as proof of a clinical benefit.

Subject of Research: Experimental post-remission muscle impairment in rheumatoid arthritis and dipyridamole treatment

Article Title: Persistent sarcopenia after flare remission in experimental RA responds to dipyridamole and is associated with restoration of adenosine and A2BR signaling

Article References: Marco-Bonilla, M., Fresnadillo, M., Huete-Toral, F., Carracedo, G., Herrero-Beaumont, G., Largo, R., & Mediero, A. (2026). Persistent sarcopenia after flare remission in experimental RA responds to dipyridamole and is associated with restoration of adenosine and A2BR signaling. Frontiers in Pharmacology, 17, Article 1949677. https://doi.org/10.3389/fphar.2026.1949677

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1949677

Keywords: rheumatoid arthritis, sarcopenia, dipyridamole, adenosine, A2B receptor, skeletal muscle, AMPK, inflammation, mouse model, muscle fibrosis, Persistent, flare

The authors interpret this joint behavior as evidence that the apparent scaling is shaped by an evolving, nonequilibrium environment in the perovskite lattice, rather than solely by competition among static recombination pathways. In a common analysis, PL intensity is fitted to a power law, I PL proportional to P β , where P represents excitation power and β is the scaling exponent. Classical recombination theory links limiting values to carrier-loss processes: first-order trap or surface recombination can yield β near 2 at low excitation, direct bimolecular radiative recombination gives a slope near 1 at higher densities, and nonradiative Auger recombination can produce sublinear behavior when carrier densities become very high.

Intermediate exponents can occur when several mechanisms overlap, so superlinearity alone does not identify one uniquely defined process. That ambiguity matters because metal halide perovskites combine strong light absorption, long carrier diffusion lengths, tunable bandgaps and comparatively low nonradiative losses. Their soft lattices also support strong carrier–phonon coupling, dynamic disorder, anharmonic motion and comparatively slow vibrational dissipation.

These traits make them promising absorbers and emitters, but they also mean that photoexcited carriers relax in a material environment that may not remain static. The study therefore asks whether β can behave as an effective, condition-dependent observable rather than a direct label for recombination order. The researchers propose a phenomenological description in which energy deposited into the lattice through carrier–phonon interactions creates transient, spatially heterogeneous states that remain coupled to the evolving electronic system.

Power-dependent PL measurements on MAPbI3 films revealed intermediate superlinear scaling across the measured range, but β varied systematically with excitation conditions. At room temperature, increasing the excitation wavelength from 375 to 405 and 560 nm increased β. The corresponding optical penetration depths rose from about 22 to 31 and 67 nm, respectively.

Short-wavelength light therefore places more weight on the illuminated surface, where surface-associated losses, local defects and energetic disorder can influence relaxation, whereas longer wavelengths sample more of the film interior. This spatial shift could alter trap filling, carrier redistribution and the balance between surface and bulk losses. However, the accompanying time-resolved PL results showed that deeper excitation also lengthened delayed emission, linking the scaling behavior to the temporal recovery of carriers rather than only to where they were initially generated.

Temperature supplied another constraint. Under both 405 and 560 nm excitation, β increased as the films cooled from 293 to 180 K. The trend is compatible with a distributed-trap picture: reduced thermal escape can keep carriers in trap states longer and change the apparent PL slope under Shockley–Read–Hall statistics.

Yet cooling also changes how excitation energy moves among phonons, vibrational modes and structural degrees of freedom. The measurements remained above MAPbI3’s reported tetragonal-to-orthorhombic transition near 163 K, excluding that low-temperature phase transition as the primary origin of the observed trend. The authors’ interpretation instead allows trap-mediated carrier dynamics and temperature-dependent lattice relaxation to evolve concurrently, with changes in detrapping, vibrational redistribution and energy dissipation all affecting the environment in which radiative recombination occurs.

Prolonged illumination separated brightness from scaling even more clearly. After 10 minutes of continuous illumination, MAPbI3 emitted more light across the measured excitation range, while its fitted exponent decreased from β = 1.42 to β = 1.36. Thus, stronger absolute emission did not mean that the response had moved toward a more quadratic dependence on excitation.

The emission maximum also underwent a small systematic redshift while its linewidth changed only modestly, an observation consistent with an alteration of the energetic environment from which radiative recombination occurred. The source does not assign this behavior to a single microscopic cause; possible contributors include trap occupation, ionic redistribution, local structural relaxation, strain and carrier–lattice interactions. What the measurements establish is that prolonged excitation changes both the measured output and its dependence on excitation power.

Illumination history remained important after the excitation was removed. Measurements on FA 0.8 MA 0.2 PbI 3 showed that PL levels and normalized temporal trajectories after 30 and 60 minutes in the dark still reflected earlier illumination under 405, 520 and 620 nm excitation. The persistence far beyond the photocarrier lifetime indicates that some material degree of freedom survives electronic recombination.

The authors do not claim that a single “stored lattice energy” reservoir has been directly observed. Instead, the response may reflect coupled evolution of defects, ions, local structure and vibrational redistribution, none of which can be separated conclusively by the reported measurements. The persistence of the response after dark storage therefore provides evidence for a slowly evolving material state, while leaving its microscopic composition unresolved.

Time-resolved PL supplied the clearest link between steady-state scaling and carrier recovery. Pulsed measurements used 375 or 405 nm light, an approximately 1 MHz repetition rate, a 256 ps channel width and a 972.8 ns observation window. Biexponential fits separated a fast component from a slower emissive component, with the slow lifetime reaching roughly 100 ns in the longest fitted cases.

At room temperature under 405 nm excitation, both the slow lifetime and the ratio of slow to fast amplitude increased with excitation density. Cooling produced the same changes, while deeper 405 nm excitation generated longer-lived and more prominent delayed emission than 375 nm excitation. These trends differ from the straightforward lifetime shortening often associated with increasing bimolecular or Auger recombination at higher carrier density.

The slow component instead became longer-lived and more prominent under the same conditions that strengthened the intermediate steady-state superlinearity. The proposed framework treats the measured PL as a combination of a conventional radiative term and a second contribution associated with the evolving lattice environment. In the phenomenological expression given by the researchers, I PL ( P ) = K 1 P 2 + ε K 2 P μ , with ε representing the state-dependent contribution and μ expected between first- and second-order limits.

The coefficients are not independently measured microscopic quantities, and the authors do not use their amplitudes for quantitative comparisons among conditions. Instead, the model captures how a changing balance between ordinary free-carrier emission and delayed, lattice-conditioned recovery can produce apparent β values that do not settle at a single fixed order. The framework does not discard trap-assisted recombination; rather, it proposes that trapping, detrapping and radiative recovery can themselves occur within a photoexcited environment whose vibrational and structural degrees of freedom continue to evolve.

The interpretation remains a framework rather than a direct microscopic identification. The experiments did not image the proposed nonequilibrium regions or measure their intrinsic relaxation times, and they do not show that phonon recycling alone causes the effect. Conventional diffusion also appears too fast to account for minute-scale illumination memory: using MAPbI3’s reported thermal diffusivity of about 2.8 × 10 −7 m 2 s −1 , diffusive times for 10–100 nm structures are roughly 0.4 nanoseconds to 40 nanoseconds, much shorter than the observed history effects.

The proposal instead concerns coupled vibrational, structural and electronic degrees of freedom. Its clearest expected applicability is to soft hybrid perovskites with effectively quadratic free-carrier recombination; in strongly doped, minority-carrier-limited or exciton-dominated systems, the authors expect the mechanism to weaken or disappear. For perovskite researchers, the practical implication is that a single β value cannot safely be treated as an intrinsic measure of radiative efficiency or defect tolerance: it must be interpreted alongside excitation wavelength, temperature, illumination history, spatial generation profile and time-resolved dynamics.

Persistent superlinear PL in soft metal halide perovskites is therefore consistent with radiative recovery occurring inside a photoexcited environment that continues to evolve, making β a window onto coupled carrier–lattice relaxation rather than a fixed verdict on which recombination channel dominates.

Subject of Research: Excitation-dependent photoluminescence superlinearity and carrier–lattice relaxation in MAPbI3 perovskite thin films.

Article Title: Persistent Photoluminescence Superlinearity Beyond Static Recombination Physics in Metal Halide Perovskites

Article References: Ghasemi, M., Li, Q., Jia, B., & Wen, X. (2026). Persistent Photoluminescence Superlinearity Beyond Static Recombination Physics in Metal Halide Perovskites. Advanced Science, Article e78378. https://doi.org/10.1002/advs.78378

Image Credits: AI Generated

DOI: 10.1002/advs.78378

Keywords: metal halide perovskites, MAPbI3, photoluminescence, superlinear scaling, carrier–lattice coupling, nonequilibrium relaxation, time-resolved luminescence, trap-mediated recombination, illumination history, soft lattices, Persistent, Superlinearity

The patient had no family history of melanoma and no history of trauma to the finger, two factors that might otherwise have pointed clinicians toward a simpler explanation. In the early stages, the lesion was misdiagnosed as onychomycosis, the medical term for a fungal nail infection, at a nail salon where he received repeated manicure treatments. Unsurprisingly, these cosmetic interventions produced no improvement. When physicians eventually debrided the detached nail plate, they found pale-red proliferative tissue with erosion underneath, a finding that prompted a biopsy of the nail bed.

Histopathological examination revealed atypical melanocytes with marked cellular atypia infiltrating both the epidermis and the dermis. Immunohistochemical staining confirmed the diagnosis: the tumor cells tested positive for Melan-A, HMB45, and Prame, three markers commonly used to identify melanocytic malignancies, and the Ki-67 proliferation index was high, indicating rapid cell division. The final diagnosis was subungual amelanotic melanoma, a variant that lacks the dark pigmentation typically associated with melanoma and therefore mimics a range of benign conditions.

Staging and treatment followed established oncological protocols. Imaging studies found no evidence of metastasis, and the patient underwent wide local excision of the tumor along with a sentinel lymph node biopsy, which came back negative. He was classified as AJCC IIIC, designated T3bN1cM0, reflecting a tumor of substantial local extent with regional lymph node involvement but no distant spread. Adjuvant therapy combined interferon α1b, an immune-stimulating cytokine, with toripalimab, a checkpoint inhibitor antibody that blocks the PD-1 pathway and enhances the immune system’s ability to recognize tumor cells. At six months of follow-up, there was no local recurrence and no distant metastasis, an encouraging outcome given the aggressive staging.

The epidemiology of subungual melanoma varies dramatically across populations. In Asian and African populations, subungual tumors account for roughly 10 to 25 percent of all melanomas, whereas in Caucasian populations the figure drops to between 1 and 3 percent. This disparity is thought to relate to differences in pigmentation of the nail apparatus and surrounding skin, although the exact mechanisms remain an active area of research. The condition typically presents as pigmented streaks or masses beneath or within the nail plate, patterns that dermatologists are trained to recognize as potential warning signs.

The amelanotic variant, however, lacks pigment entirely, which strips clinicians of the most obvious visual clue. As a result, these tumors are frequently mistaken for fungal infections, viral warts, pyogenic granuloma, a benign but rapidly growing vascular lesion, or squamous cell carcinoma. Each of these misdiagnoses can delay definitive treatment by months or even years, and in melanoma, delay can be fatal. The case report emphasizes that persistent, isolated onycholysis or any non-pigmented lesion beneath the nail should prompt histopathological evaluation without delay, meaning a biopsy should be performed to obtain tissue for microscopic examination.

From a technical standpoint, the diagnostic pathway in this case illustrates the value of combining clinical observation with laboratory confirmation. The pale-red proliferative tissue visible after debridement was a subtle finding, one that could easily have been dismissed as granulation tissue from chronic irritation. Only the biopsy, followed by careful histopathological and immunohistochemical analysis, revealed the true nature of the lesion. The positivity for Melan-A and HMB45, both markers of melanocytic differentiation, together with Prame, a marker associated with malignant melanoma, and the elevated Ki-67 index, which measures the fraction of cells actively dividing, collectively ruled out benign mimics and confirmed a malignant process.

The surgical management also demonstrates current best practice for localized melanoma. Wide local excision aims to remove the tumor with a margin of healthy tissue, reducing the risk of local recurrence, while sentinel lymph node biopsy samples the first lymph node in the drainage pathway to determine whether cancer cells have begun to spread. A negative sentinel node biopsy, as in this case, is a favorable prognostic indicator. The addition of adjuvant therapy with interferon α1b and toripalimab reflects a modern approach to managing higher-risk disease, leveraging both immune stimulation and checkpoint blockade to reduce the likelihood of recurrence.

The broader lesson for the public is straightforward but important. A nail that separates from the nail bed and does not heal, particularly when it affects only one digit and there is no history of trauma or fungal infection, warrants medical evaluation rather than repeated cosmetic treatment. Nail salons are not diagnostic facilities, and manicures cannot cure an underlying malignancy. Similarly, any new growth, erosion, or discoloration under a nail, whether pigmented or not, should be examined by a healthcare professional capable of performing a biopsy. The work, titled Subungual Amelanotic Melanoma with Onycholysis as the First Manifestation, was published in Skin on August 21, 2026, and serves as a reminder that even the most mundane-seeming nail complaints can occasionally conceal a serious and life-threatening disease.

Subject of Research: Subungual amelanotic melanoma presenting as persistent nail separation

Article Title: Persistent nail separation may hide a rare melanoma

Article References: Persistent nail separation may hide a rare melanoma. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: subungual melanoma, amelanotic melanoma, onycholysis, nail cancer, misdiagnosis, biopsy, immunohistochemistry, toripalimab, wide local excision, dermatology, Persistent, nail

The patient, a long-distance lorry driver, arrived at the rheumatology department carrying a referral for a supervised exercise reconditioning programme for chronic low back pain. He had endured back discomfort for a year, but over the previous six months a far more troubling symptom had emerged: burning pain radiating down one leg, consistent with sciatica, that had grown steadily worse despite treatment with non-steroidal anti-inflammatory drugs. The pain threatened his livelihood, since prolonged driving is exactly the posture that aggravates entrapment of the sciatic nerve in the deep gluteal space.

What made his presentation unusual was the pattern of tenderness. Rather than the diffuse back pain typical of disc disease, he had exquisite point tenderness in the buttock, and the pain radiated down the leg in a distribution matching the sciatic nerve. On examination, his surgeons found no neurological deficit: muscle strength, reflexes and sensation were all intact. That combination, pain without weakness, is a hallmark of nerve entrapment rather than nerve compression by disc material, and it prompted the team to look beyond the lumbar spine.

To test the hypothesis of deep gluteal syndrome, the clinicians performed a battery of provocative manoeuvres designed to stress the piriformis and neighbouring structures. The flexion-adduction-internal rotation test, in which the hip is pushed across the body while internally rotated, reproduced the patient’s exact pain. The seated piriformis stretch test and the active hip flexion, adduction and internal rotation manoeuvre were also positive. These tests, drawn from the sports medicine literature, have increasingly been promoted as a practical bedside toolkit for distinguishing deep gluteal syndrome from lumbar radiculopathy, and in this patient they pointed decisively toward the buttock rather than the back.

Imaging then settled the question. Computed tomography of the pelvis revealed a striking asymmetry: the left piriformis muscle, measured on the original dataset, had a cross-sectional area roughly fifty per cent larger than the right. No disc herniation, spinal stenosis or nerve-root conflict was present on lumbar imaging, and blood tests showed no inflammatory activity. The muscle enlargement, in the absence of any other explanation, was judged to be the source of the nerve compression, a mechanism consistent with the anatomical studies that first described how a hypertrophied piriformis can narrow the subpiriformis space through which the sciatic nerve passes.

Deep gluteal syndrome, sometimes called piriformis syndrome in its older and narrower usage, has undergone a substantial conceptual expansion in recent years. Review articles now emphasise that the sciatic nerve can be entrapped at multiple sites within the deep gluteal space, including the piriformis muscle, the gemelli and obturator internus, the hamstring tendons and fibrous bands near the ischial tuberosity. Trauma, prolonged sitting, hip surgery and anatomical variants such as a split sciatic nerve or an anomalous piriformis have all been implicated. The authors argue that the term piriformis syndrome is too restrictive, since the piriformis is only one of several potential culprits, and that deep gluteal syndrome better reflects the true anatomy of the region.

Diagnosing the condition remains difficult, and the case report is candid about the limitations of current tools. Magnetic resonance imaging can reveal muscle asymmetry and anatomical variants, but no single measurement is definitive, and ultrasound is emerging as a dynamic alternative that can visualise the sciatic nerve during hip movement. Electrodiagnostic studies may support the diagnosis when they show prolonged H-reflex latency with normal conduction elsewhere, but they are not universally abnormal. In practice, the diagnosis is often clinical, resting on a characteristic history of buttock pain radiating down the leg, aggravated by sitting and by hip rotation, together with positive provocative tests and the exclusion of lumbar pathology.

Treatment in this case began conservatively, with analgesia and physiotherapy, but the pain proved refractory. The team therefore proceeded to a CT-guided injection of corticosteroid and local anaesthetic directly into the belly of the hypertrophied piriformis muscle, a technique that allows the needle to be placed with millimetre precision while avoiding the sciatic nerve and the gluteal vessels. The result was dramatic: the patient reported complete relief of his sciatica shortly after the injection, and at follow-up the improvement was sustained, allowing him to resume work and daily activities without restriction.

The authors place this outcome in the context of a growing evidence base for injection therapy in deep gluteal syndrome. Systematic reviews report that local anaesthetic, corticosteroid, botulinum toxin and even platelet-rich plasma have all been used with benefit, although the quality of the underlying studies varies and randomised trials remain scarce. Botulinum toxin, which relaxes the muscle rather than simply suppressing inflammation, has attracted particular interest, and some retrospective series suggest it produces longer-lasting relief than corticosteroid alone. Open surgical release of the piriformis, once the mainstay of treatment, is now reserved for refractory cases, since endoscopic and image-guided techniques offer comparable results with far less morbidity.

The case carries a broader message for clinicians and for patients with unexplained leg pain. Sciatica is a symptom, not a diagnosis, and the lumbar spine is only one of the structures capable of generating it. When back pain fails to explain the clinical picture, when neurological examination is normal, and when provocative manoeuvres of the hip reproduce the pain, the deep gluteal space deserves systematic attention. The authors conclude that deep gluteal syndrome should be considered in every patient with sciatica of uncertain origin, because a diagnosis that is missed condemns the patient to months of ineffective treatment, while a diagnosis that is made can be relieved with a single, precisely targeted injection.

Subject of Research: Deep gluteal syndrome caused by piriformis muscle hypertrophy entrapping the sciatic nerve

Article Title: Deep Gluteal Syndrome and Persistent Sciatica in a Patient With Unilateral Piriformis Muscle Hypertrophy: A Case Report

Article References: Ghani, N. (2026). Deep Gluteal Syndrome and Persistent Sciatica in a Patient With Unilateral Piriformis Muscle Hypertrophy: A Case Report. Clinical Case Reports, 14(10), Article e73730. https://doi.org/10.1002/ccr3.73730

Image Credits: AI Generated

DOI: 10.1002/ccr3.73730

Keywords: deep gluteal syndrome, piriformis syndrome, sciatic nerve entrapment, sciatica, CT-guided injection, case report, Deep, Gluteal, Syndrome, Persistent, Patient, Unilateral

In 2018, Mosetti et al. prospectively evaluated PPOP after common pediatric surgery (n = 350), defining it as intermittent or constant pain ≥4 lasting more than 3 months. Pain was assessed using age-appropriate 0–10 pain scales (FLACC scale < 3 years, Wong-Baker Faces 3–6 years, NRS >6 years). They also evaluated effects on daily activities, sleep, and other complications. Prevalence was 6% at 3 months and 4% at 6 months. No association was found between moderate- to severe acute postoperative pain (APOP) in the postanesthesia care unit (PACU) and persistent pain. Other studies have reported higher prevalences. In 2011, in a cross-sectional study, Fortier et al. conducted structured telephone interviews with children aged 2–17 years who had undergone general, urologic, or orthopedic surgery within the previous 10 months. Fifteen of 113 children (13%) reported current surgery-related pain, with a mean intensity of 4.2 on NRS, and interference with daily activities. One of the few recent prospective studies is a 2025 Spanish investigation of risk factors for PPOP after common pediatric surgery in children aged 4–7 years. Using a definition of pain ≥4 at 3 or 6 months, they reported markedly higher prevalences: 35% at 3 months and 27% at 6 months. None of these previous studies has used the ICD-11 definition of PPOP: pain persisting for more than 3 months after surgery, pain that begins or worsens after surgery, is located in the surgical area, is associated with pain-related distress, and interferes with daily activities.

A recent meta-analysis published during the completion of this study estimated the prevalence of PPOP in the pediatric population at a remarkably high 28% following major surgery. The definition of PPOP used in the included studies was pain at different levels lasting more than 3 months after surgery. None of the included studies used the ICD-11 definition of PPOP. The high prevalence of PPOP found highlights the inconsistency of current evidence, emphasizing the need for large prospective studies.

A considerable proportion of children (approximately 15% to 25%) experience persistent pain in daily life, which can lead to significant personal suffering, including school non-attendance and social isolation, and represents a serious public health concern. Among hospitalized children, 24%–27% report moderate to severe pain, most surgery-related, and as many as 80% self-report current pain during hospitalization. Pain management in children is frequently inadequate, and those who develop long-term pain appear to be at greater risk of ongoing pain-related problems than adults. Since surgery is a potential trigger for pain, PPOP is a critical issue to address in pediatric care.

Regarding risk factors for persistent pain, gender differences have been observed in childhood pain conditions such as headache and abdominal pain, with girls reporting more pain than boys. Clinical studies on postoperative pain are consistent with this pattern, suggesting that both APOP and PPOP are more common in girls. Regarding age, some studies suggest that younger children have a lower risk of PPOP, whereas other studies find no protective effect once confounders are accounted for. Psychological factors also appear influential. Children are highly affected by caregiver behavior, and elevated parental anxiety surrounding surgery has been identified as a potential risk factor. Parental catastrophizing, mental health problems, and chronic pain have similarly been associated with increased pain in children. Evidence suggests that parental influence on a child’s pain response may even increase as more time passes after surgery.

The 4P study (Persistent Postoperative Pediatric Pain) is a prospective observational multicenter study following children undergoing common pediatric surgeries in Sweden between 2023 and 2024. This predefined secondary analysis focuses specifically on PPOP with the aim of describing the prevalence, characteristics, and exploratory risk factor associations of PPOP. The primary outcome was defined as recurrent pain ≥4 lasting for over 3 months after surgery. Persistent pain was further characterized regarding its impact on various activities and whether anatomically localized at the site of surgery, and we also present prevalences based on the ICD-11 definition of PPOP. By examining in detail the small subgroup of children who develop PPOP and describing the characteristics that distinguish them, this analysis aims to improve our understanding of why some children develop PPOP while others do not.

This study was approved by the Swedish Ethics Review Authority on December 1, 2022 (Dnr 2022-04821). The research protocol was preregistered at clinicaltrials.gov under NCT06035042, and a study protocol has been published. Children aged 1–17 years scheduled for one of the ESPA-defined pediatric surgical procedures (inguinal hernia, circumcision/hypospadias/cryptorchidism, adenoidectomy/tonsillectomy/tonsillotomy, appendectomy, acute orthopedic fracture surgery) were recruited from 10 hospitals in southern Sweden in 2023–2024. As this was an observational study, the methods used for anesthesia and analgesia, as well as surgical techniques, varied according to local practice. Exclusion criteria included: repeated surgery, inability of the child or caregiver to speak/read Swedish, and inability to understand the implications of participation. Patients aged 15 years or older provided written and oral consent themselves. For younger children, caregivers provided consent after receiving written information a few days before surgery, and in-person information upon hospital arrival. For participants under 15 years, consent from both legal guardians was required, in accordance with Swedish Ethical Review Authority regulations.

PPOP was documented using the data management software Entermedic (Entergate, Halmstad, Sweden), which was programmed to send automated text-message questionnaires at the prespecified follow-up time points of 3 and 6 months after surgery, including reminders when necessary. All participants received two reminders to answer the follow-up. Thereafter, responding was not possible, as the time frame for follow-up would have been misleading, and the responses were then handled as missing values. The questionnaires answered were complete. Entermedic is certified according to the international security standard (ISO 27000:1) and is completely adapted to the European Union’s requirements of the General Data Protection Regulation. The service is also adapted to comply with Swedish law for patient data reporting, holding, and management. Furthermore, Entermedic is approved by the Swedish Medical Products Agency.

Before surgery, all legal guardians (or patients aged 15 years and older) completed a questionnaire addressing preoperative pain: recurrent pain before surgery (yes/no), pain intensity (FLACC, FPS-Revised, or NRS depending on age), duration of pain, and whether it affected normal activities. We also asked whether the child had experienced pain in the 24 h prior to surgery (yes/no) and whether analgesics had been offered. Sleep quality and anxiety were assessed similarly with a yes/no question, including duration and impact on daily activities. Self-reported parental stress (NRS 0–10) was recorded at 24 h, 3 and 6 months after surgery. The levels of stress at the time of the respective pain measurements were used for this analysis. Levels ≥4 were used when dichotomizing the stress level for logistic regression.

At 3 and 6 months postoperatively, a text-message questionnaire was sent to assess current pain using the same age-appropriate scale introduced at the hospital visit. For children aged 1–3 years, we used the FLACC (Face/Legs/Activity/Cry/Consolability Pain Scale, 0–10); for ages 4–14, the FPS-Revised (The Faces Pain Scale-Revised, 0–10); and for ages 15–17 the NRS (Numeric Rating Scale, 0–10). Higher scores indicated more pain, with zero representing

Subject of Research: Health

Article Title: Persistent postoperative pediatric pain: a secondary analysis of the 4P prospective observational multicenter study

Article References: Persson, A. K. M., & Broman, J. (2026). Persistent postoperative pediatric pain: a secondary analysis of the 4P prospective observational multicenter study. Frontiers in Pain Research, 7, Article 1930534. https://doi.org/10.3389/fpain.2026.1930534

Image Credits: AI Generated

DOI: 10.3389/fpain.2026.1930534

Keywords: chronic pain, pain after surgery, pediatric pain, persistent pain, postoperative pain, Persistent, postoperative, pediatric, pain, secondary, analysis, prospective

Imatinib has transformed the outlook for patients with advanced gastrointestinal stromal tumors, or GISTs. Before its clinical introduction in 2001, median survival in metastatic disease was only about 10 to 20 months. Early clinical studies reported complete remission in 4 percent of patients, partial remission in 67 percent, and stable disease in 18 percent, with only 11 percent progressing. With imatinib and later tyrosine kinase inhibitors such as sunitinib, regorafenib, and ripretinib, median survival in advanced disease now exceeds six years. GISTs themselves are rare, with an estimated 10 to 15 new diagnoses per million people each year, but they are the most common mesenchymal tumors of the digestive tract, arising most often from activating mutations in the KIT or PDGFRA genes.

The drug’s usual adverse effects, including anemia, periorbital edema, skin rash, fatigue, nausea, granulocytopenia, and diarrhea, are generally mild to moderate, and the fluid retention is often self-limiting. Imatinib-associated cardiotoxicity is considered uncommon and has been reported mainly in patients with pre-existing cardiovascular risk factors or underlying heart disease. Even so, new edema, dyspnea, hypertension, or heart failure-like symptoms shortly after treatment initiation should prompt cardiological assessment, particularly in patients receiving higher doses or requiring prolonged therapy.

In this case, the patient’s tumor journey began at a cardiology outpatient clinic, where she complained of easy fatigability and episodes of sweating. Initial electrocardiography and transthoracic echocardiography showed no abnormalities. Laboratory testing revealed iron-deficiency anemia, and abdominal ultrasonography demonstrated multiple rounded lesions in the small pelvis, confirmed by contrast-enhanced computed tomography. During laparoscopic surgery, an additional mass involving the small intestine was identified. Histopathological examination showed spindle-shaped cells with eosinophilic cytoplasm, moderate nuclear atypia, and a mitotic activity of 7 mitoses per 10 high-power fields. Immunohistochemical analysis showed diffuse positivity for CD117 and DOG1, supporting a spindle-cell variant GIST.

Molecular testing revealed a heterozygous six-nucleotide duplication in exon 9 of the c-KIT gene, with no mutations detected in c-KIT exon 11, PDGFRA exon 18, or BRAF exon 15. Because KIT exon 9-mutated GISTs are known to be less sensitive to standard-dose imatinib, treatment was initiated at 800 mg per day, administered in two divided doses. Approximately two months later, she developed shortness of breath, fluid retention, and elevated arterial blood pressure, with clinically evident edema predominantly involving the face and lower limbs.

Transthoracic echocardiography showed preserved left ventricular systolic function and preserved global longitudinal strain, measured at minus 21.2 percent. A small, hemodynamically insignificant pericardial effusion adjacent to the right atrium was detected during follow-up. Tissue Doppler velocities at the medial and lateral mitral annulus were preserved, and the E/e’ ratio remained below 8.8, arguing against elevated left ventricular filling pressures at the time of examination. Laboratory testing, in contrast, revealed elevated NT-proBNP levels, which fluctuated over time, while troponin values remained very low, suggesting no acute myocardial damage.

Treatment with torasemide 10 mg per day and candesartan 8 mg per day was initiated, with regular monitoring of electrolytes, particularly potassium and sodium. Imatinib was continued without dose reduction under close oncological and cardiological follow-up. One month later, the patient reported improvement in her general condition. Repeated echocardiographic examinations remained reassuring, showing preserved systolic function and strain, and the pericardial effusion resolved. NT-proBNP levels, however, remained above the reference range and continued to fluctuate, supporting ongoing cardiological follow-up.

The discussion surrounding imatinib cardiotoxicity dates to 2006, when Kerkelä and colleagues reported congestive heart failure in 10 patients treated with the drug and demonstrated left ventricular contractile dysfunction in imatinib-treated mice, suggesting a possible toxic myopathic mechanism based on mitochondrial abnormalities and membrane whorl accumulation. In response, Atallah and colleagues evaluated a large cohort of 1,276 patients and identified congestive heart failure in 22, corresponding to an incidence of 1.7 percent, occurring mainly in older patients with underlying cardiovascular risk factors or established disease. Further preclinical data published in 2010 reported that apoptosis and endoplasmic reticulum stress in cardiac myocytes and fibroblasts were observed only at cytotoxic concentrations of imatinib mesylate, whereas clinically relevant concentrations did not induce significant cardiac injury. The long-term results of the IRIS trial, following 1,106 patients with chronic myeloid leukemia for approximately 11 years, are consistent with this view, showing serious cardiac adverse events at a relatively low rate.

In this patient, the findings are most consistent with an imatinib-related fluid retention syndrome accompanied by mild cardiovascular involvement. Renal function was preserved, making renal impairment an unlikely explanation for the biomarker pattern. The patient had active malignancy, recent surgery, anemia, and repeatedly elevated D-dimer values, all of which may have influenced the clinical and laboratory picture, but no clinically overt thromboembolic event was documented during follow-up. In this context, the NT-proBNP elevation most probably reflected myocardial wall stress related to fluid retention and blood pressure elevation rather than direct myocardial damage. The authors emphasize that the findings should not be interpreted as overt systolic heart failure but as a possible early cardiovascular manifestation during imatinib therapy.

The case underlines the value of early cardiological assessment, echocardiographic follow-up with strain imaging, and cardiac biomarkers in patients who develop cardiovascular symptoms during imatinib therapy. Clinically significant cardiotoxicity during imatinib treatment remains uncommon, but new cardiovascular symptoms after treatment initiation deserve early assessment rather than routine observation alone. Serial echocardiography, including global longitudinal strain, together with cardiac biomarkers, may be useful for guiding supportive treatment in selected symptomatic patients.

Subject of Research: Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report

Article Title: Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report

Article References: Krastev, B., Megdanova-Chipeva, V., & Goudev, A. (2026). Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report. Pharmacia, 73, Article e204483. https://doi.org/10.3897/pharmacia.73.e204483

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e204483

Keywords: Imatinib-associated, fluid, retention, persistent, NT-proBNP, elevation, during, treatment, gastrointestinal, stromal, tumor, case

The historical trajectory is remarkable. In 1974, women accounted for 11 of the 87 doctorates recorded in Portugal, roughly 12.6 percent, and represented approximately 18 percent of all doctorates awarded during the 1970s. Women were therefore already present, although under-represented, among doctorate holders before the transition to democracy. What changed after 1974 was a marked increase of women in doctoral research, driven by state investment in education, European integration, and laws promoting gender equity. The Fundação para a Ciência e a Tecnologia, established in 1997, has played a key role by funding fellowships and grants that gave women independent research paths. By the early 2000s, women accounted for around half of all PhDs awarded in Portugal, and today they lead research groups all over the country, from the north to the Azores and Madeira islands.

Funding data reinforce this picture of strong participation. In FCT’s 2023 and 2021 IC&DT project competitions, women led the majority of nationally funded projects, at 58.1 percent and 55.2 percent of principal investigators respectively. In the 2023 PT2030 IC&DT call, whose results were published in 2025, women accounted for 54 percent of principal investigators among submitted applications and 58.1 percent among funded projects. This is consistent with She Figures 2024, which reports that women’s overall research-funding success rate in Portugal was 1.4 percentage points higher than men’s in 2022. Between 56 and 59 percent of FCT doctoral, postdoctoral, and research fellowships were awarded to women as of 2019. The bottleneck lies further along the pipeline: only 24 percent of Portuguese full professors are women, against 48 percent of assistant-level academic staff, and women hold just 20 percent of rectorships and university presidencies nationally.

To illustrate the depth of women-led science, the authors curated a set of studies from 2014 to 2026 where the first or last author is a woman, spanning four thematic areas. The first is the microbial ecology of traditional fermented foods. Portugal has a rich variety of PDO cheeses like Serra da Estrela, Azeitão, and Nisa, and dry-cured sausages like Paio do Alentejo and Salpicão, each with its own unique microbial community of lactic acid bacteria, coagulase negative staphylococci, yeasts, and moulds. At the Faculdade de Medicina Veterinária da Universidade de Lisboa, Teresa Semedo-Lemsaddek’s group has used conventional microbiology along with omics tools, including comparative genomics and metagenomics, to characterize enterococci and other lactic acid bacteria from Portuguese cheeses, fermented meats, and poultry production systems. Enterococcus species play a dual and often contradictory role: they contribute to cheese ripening, yet some strains carry virulence and antimicrobial resistance genes. The group characterized strains isolated from Azeitão and Nisa PDO cheeses, capturing this duality in detail, and has also examined bacterial persisters, dormant cells capable of surviving exposure to antimicrobials and sanitizers, an emerging concern for food safety.

At the Universidade Católica Portuguesa in Porto, Paula Teixeira, Full Professor in Food Microbiology and leader of the CBQF Food and Nutrition group, has built a long-running food microbiology program focused on pathogens. Her research covers the ecology, stress resistance, pathogenesis, and control of Listeria monocytogenes in food production environments, including the characterization of a cheese-related listeriosis outbreak in Portugal. The group has also studied probiotic lactobacilli from traditional Portuguese fermented foods. In the Azores, Célia Silva’s team at the Universidade dos Açores has investigated exopolysaccharide-producing lactic acid bacteria strains from local cheeses as functional starters to improve texture and water retention in low-fat cheeses, while reviewing the broader biotechnological potential and food safety relevance of these microorganisms.

The second thematic area is starter culture development and fermentation technology. At the Universidade de Évora, Marta Laranjo’s research showed that autochthonous starter cultures, strains isolated from the local meat matrix, work better than commercial ones, preserving the authentic sensory profile while improving microbiological safety. For meat sausages like Paio do Alentejo and Salpicão, the team optimized inoculation protocols that reduce biogenic amine accumulation and help beneficial microbes outcompete unwanted ones, work performed in close collaboration with Maria João Fraqueza at FMV-ULisboa, whose expertise in meat science underpinned the definition of starter culture protocols. A recent European network project has focused on mapping fermented foods across Europe and the associated fermentation technologies, as well as the health benefits these foods provide. Work on Madeira Island includes the characterization of indigenous non-Saccharomyces yeast fermentation and its impact on the chemical and phenolic composition of Madeira wine.

The third area is biofilm biology and pathogen persistence in food environments. Biofilms are one of the biggest problems in food safety because pathogens embedded in them resist sanitation and antimicrobials and can contaminate food. At the Instituto Nacional de Investigação Agrária e Veterinária, in collaboration with LEPABE at the Universidade do Porto and CEB at the Universidade do Minho, Carina Almeida built a research program at the intersection of food safety, biofilm microbiology, and molecular diagnostics, using peptide nucleic acid fluorescence in situ hybridization and related nucleic acid mimic technologies to rapidly detect foodborne pathogens in biofilm environments. At LEPABE, Luciana Gomes has worked on engineered surfaces that prevent microbial adhesion, with recent work showing that biomimetic surfaces can significantly reduce Escherichia coli attachment and retention on food contact materials. Research at CBQF on Listeria monocytogenes has documented links between antimicrobial resistance patterns and stress tolerance in strains from food processing environments, directly supporting risk assessment.

The fourth area is antimicrobial resistance surveillance under a One Health framework. The World Health Organization considers antimicrobial resistance one of the biggest threats to global public health, and the food chain is a major reservoir and transmission route for resistant bacteria and their resistance genes. At the Universidade de Trás-os-Montes e Alto Douro, Maria José Saavedra, founder and scientific coordinator of the Antimicrobials, Biocides & Biofilms Laboratory, has built an internationally recognized program studying resistance mechanisms, with particular emphasis on beta-lactam resistance and carbapenemase production, horizontal gene transfer, biofilm-associated resistance, and the molecular epidemiology of multidrug-resistant bacteria across human, veterinary, food, and environmental compartments. Datasets cover Aeromonas species, Enterobacteriaceae, Campylobacter, Enterococcus, Staphylococcus, and carbapenemase-producing Klebsiella pneumoniae from Portuguese hospitals, where genome-wide longitudinal analyses traced the predominance of KPC-2 and OXA-48 lineages in northern Portugal. A decade-long study on Campylobacter in humans and animals showed a persistent and growing prevalence of fluoroquinolone resistance, and the group has extended surveillance to rivers, freshwater mussels, and marine gastropods as reservoirs and bioindicators of resistant bacteria.

One striking methodological feature of this women-led research is how well classical microbiology is combined with advanced molecular and omics tools. Culture-based methods remain important for isolating strains and assessing safety, but they are now backed by whole genome sequencing, metagenomics, resistome profiling, and comparative genomics. Sequencing whole genomes of food isolates lets researchers identify species, count resistance and virulence genes, find mobile genetic elements, and see how strains relate to clinical and environmental ones, information directly useful for regulators and industry. Portuguese women-led groups at FMV-ULisboa, CBQF-UCP, UTAD, and INIAV were among the early adopters of whole genome sequencing in Portugal. Portugal also holds the second-highest share of women patent inventors in Europe, at 27 percent against a European average of 13.2 percent, a genuinely positive indicator that nonetheless coexists with the leadership gap and raises the question of whether patenting activity by Portuguese women microbiologists translates into leadership of commercialization or remains, like authorship, a form of participation that stops short of institutional power.

The authors close with a concrete research and policy agenda rather than broad calls for inclusion. They propose gender-disaggregated bibliometric and patent analyses specific to industrial microbiology, tracking first and last authorship, patent inventorship, and principal-investigator status over the same 2014 to 2026 period; longitudinal tracking of funding and promotion outcomes by gender within this subfield to identify where the main bottleneck occurs, whether in promotion criteria, evaluation panels, or access to leadership opportunities; systematic evaluation of whether existing initiatives such as Portugal’s Scientific Employment Stimulus and the European GENDERACTION Plus project have measurably improved retention and career progression; and qualitative research on mentoring, professional networks, and the composition of evaluation panels extended to microbiology-specific research groups and industry consortia. The argument is that closing the gender gap in industrial microbiology is not simply a matter of social justice, it is a structural requirement to improve scientific and economic competitiveness, particularly as the field faces managing antimicrobial resistance across global food systems, making fermentation processes more sustainable, and preserving traditional food heritage.

Subject of Research: Women in Portuguese industrial microbiology: a fifty-year perspective on progress and persistent barriers

Article Title: Women in Portuguese industrial microbiology: a fifty-year perspective on progress and persistent barriers

Article References: Semedo-Lemsaddek, T., Laranjo, M., & Saavedra, M. J. (2026). Women in Portuguese industrial microbiology: a fifty-year perspective on progress and persistent barriers. Frontiers in Industrial Microbiology, 4, Article 1939832. https://doi.org/10.3389/finmi.2026.1939832

Image Credits: AI Generated

DOI: 10.3389/finmi.2026.1939832

Keywords: Women, Portuguese, industrial, microbiology, fifty-year, perspective, progress, persistent, barriers, scientific research

Adolescence has long been recognized as a period of heightened risk for substance use disorders. It is the life stage when most people first experiment with drugs, and early initiation is associated with an increased lifetime risk of developing a substance use disorder. Neurobiologically, this vulnerability is thought to stem in part from the ongoing maturation of the prefrontal cortex, a region that mediates attention, decision-making, and emotional regulation. During adolescence, this region undergoes drastic structural and functional changes, including synaptic pruning and refinement of inhibitory microcircuits, and it forms an integral part of the mesocorticolimbic reward pathway. Dysfunction in the prefrontal cortex is associated with greater relapse risk, and in animal models, disruptions to the medial prefrontal cortex alter extinction learning and drug-seeking after abstinence.

At the same time, the gut microbiome is also undergoing marked developmental changes. Adolescents carry a microbial community that is distinct from both children and adults, and this difference has been proposed to modulate neuropsychiatric outcomes. Prior work from the same laboratory showed that depleting the microbiome with oral antibiotics alters cocaine and opioid reward, reinforcement, and drug-seeking after abstinence in adult animals. Intriguingly, adolescents proved more sensitive to these effects than adults: five days of antibiotic pretreatment reduced morphine conditioned place preference in adolescent mice, an effect that required fourteen days of pretreatment to achieve in adults. But whether adolescent microbiome disruption produces lasting changes in opioid-seeking behavior and brain molecular profiles that persist into early adulthood had not been investigated until now.

To address this question, researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with the Yale/NIDA Neuroproteomics Center, designed an experiment in which adolescent rats self-administered fentanyl while receiving a cocktail of oral antibiotics. Male and female Sprague-Dawley rats arrived in the colony on postnatal day 22 and were implanted with jugular catheters between days 29 and 31. Starting on day 31, half the animals received drinking water containing vancomycin, neomycin, bacitracin, and pimaricin, while the other half received plain water. After five days of pretreatment, all rats began self-administering fentanyl at a dose of 0.8 micrograms per kilogram per infusion on a fixed-ratio 1 schedule, with two 1.5-hour sessions per day across five days. This tight timeline ensured that both drug exposure and antibiotic treatment remained entirely within the adolescent period. The day after the last self-administration session, all rats were returned to plain water.

Following fourteen days of home-cage abstinence, the animals underwent a combined context-plus-cue fentanyl-seeking test in the same operant chambers where they had trained. During the context portion, both levers were extended but presses had no programmed consequence for thirty minutes. Then the light above the previously active lever was illuminated, signaling the start of the cue portion, after which every press on the active lever produced a twenty-second illumination of that light. Twenty-four hours later, the rats were euthanized and tissue from the medial prefrontal cortex and cecal contents was collected for analysis. The final sample comprised twenty water-treated rats and twenty-one antibiotic-treated rats, balanced across sex.

The behavioral results were striking and, in some respects, unexpected. Antibiotic treatment had no effect on fentanyl self-administration itself: rats on both drinks earned similar numbers of infusions and pressed the active lever at similar rates across sessions. But when tested after abstinence, rats that had received antibiotics during adolescence showed significantly reduced active lever pressing during the context portion of the seeking task, while their responding during the cue portion was unchanged. Analysis of cumulative lever presses over time confirmed a significant difference between groups during the context portion, with a shallower slope of responding in antibiotic-treated animals, but no difference during the cue portion. Further analysis of cue responsivity found no effect of prior antibiotic treatment on how rats responded to cue presentation itself, suggesting the behavioral change was specific to context-driven seeking rather than a general alteration in how the animals responded to discrete drug-predictive cues.

This reduction in context-induced seeking is notable because it runs opposite to the direction of change observed in prior work with adult animals, where microbiome depletion increased cocaine and fentanyl-seeking. The authors propose several explanations. One possibility is that the effect is genuinely adolescent-specific, consistent with their earlier finding that antibiotics reduced opioid conditioned place preference in adolescents but not adults. Because conditioned place preference relies on associative learning between contextual cues and drug effects, and the current study found altered context-induced but not cue-induced seeking, a common thread may be that adolescent antibiotic exposure impairs contextual learning. Another possibility involves a mismatch of internal states: rats experienced antibiotics during self-administration but not during seeking, and this state-dependent mismatch could have reduced context-driven responding. The authors caution that the current design cannot distinguish between these interpretations and suggest future studies comparing animals that remain on their drinks throughout abstinence with those that switch.

The microbiome analysis revealed that the effects of brief antibiotic exposure were anything but transient. Cecal contents collected two weeks after antibiotic cessation showed significantly lower microbial richness, measured with the Chao1 index, and significantly lower evenness, measured with the Simpson index, together indicating a substantial reduction in alpha diversity. Beta diversity analysis confirmed that the microbiome of former antibiotic-treated rats remained significantly distinct from that of water-treated controls. At the phylum level, antibiotic-treated animals showed a reduction in Firmicutes and an expansion of Proteobacteria and Verrucomicrobia, mirroring patterns seen in prior studies where animals remained on antibiotics for at least two weeks. The magnitude and duration of these diversity reductions were surprising, given that an earlier adolescent mouse study with a similar ten-day antibiotic regimen observed a much smaller reduction when tissue was collected immediately after treatment. The authors note that the microbiome did not return to baseline in the absence of interventions such as fecal microbiota transfer, underscoring how persistent the effects of brief adolescent antibiotic exposure can be.

The proteomic analysis of the medial prefrontal cortex, performed using data-independent acquisition mass spectrometry against a rat brain spectral library, identified 201 proteins that were significantly differentially expressed in antibiotic-treated rats, with 93 downregulated and 108 upregulated. Pathway analysis of the downregulated proteins yielded only two significant pathways, related to cellular component organization and the integrin alpha-v-beta-8 complex. In contrast, the upregulated proteins generated 255 significant pathways, of which thirteen involved metabolism, including terms related to glycolysis and gluconeogenesis, and sixteen involved neurotransmitter recycling or release, including terms related to vesicles and exocytosis. These results suggest global alterations in pathways regulating cellular metabolism and neurotransmitter release in the medial prefrontal cortex, building on prior work that identified robust changes in gene expression networks after adolescent antibiotic and morphine exposure. The authors point out that proteomic and transcriptomic pathways did not overlap between the two studies, likely reflecting technical differences in the protein libraries used and the fact that protein expression is a more reliable readout of functional change than RNA abundance, which correlates poorly with protein levels.

One limitation acknowledged by the researchers is the absence of saline-only comparison groups, which prevents determination of the effects of antibiotics or fentanyl alone on medial prefrontal cortex protein expression. It also remains unclear whether the microbiome alterations restricted to adolescence truly have enduring effects on behavior and neurobiology, since the microbiome of the two groups still differed so much by the end of testing. Nevertheless, the study demonstrates that brief oral antibiotic exposure during adolescence produces lasting alterations in drug seeking, microbiome composition, and medial prefrontal cortex neurobiology that extend at least two weeks after antibiotic cessation. These findings carry implications for understanding how early-life microbiome perturbations shape vulnerability to substance use disorders and suggest that the developing gut-brain axis may be a promising target for interventions aimed at reducing adolescent addiction risk. As antibiotic use remains common in adolescents for a variety of clinical reasons, the possibility that such treatments could interact with concurrent drug exposure to shape long-term reward circuitry is a question that will demand careful attention in future human and animal studies.

Subject of Research: Brief antibiotics exposure during adolescence produces persistent effects on the microbiome and fentanyl-seeking during adulthood in rats

Article Title: Brief antibiotics exposure during adolescence produces persistent effects on the microbiome and fentanyl-seeking during adulthood in rats

Article References: Hofford, R. S., Shipman, A. L., Wang, W., Lam, T. T., & Kiraly, D. D. (2026). Brief antibiotics exposure during adolescence produces persistent effects on the microbiome and fentanyl-seeking during adulthood in rats. Frontiers in Behavioral Neuroscience, 20, Article 1916554. https://doi.org/10.3389/fnbeh.2026.1916554

Image Credits: AI Generated

DOI: 10.3389/fnbeh.2026.1916554

Keywords: Brief, antibiotics, exposure, during, adolescence, produces, persistent, effects, microbiome, fentanyl-seeking, adulthood, rats