Depression is a common difficulty among adolescents with epilepsy (AWE). Compassion-focused therapy (CFT) has demonstrated potential benefits for adults with epilepsy. This study was a preliminary investigation evaluating whether an eight-session online group intervention based on CFT could reduce symptoms of depression and enhance self-compassion in AWE. Sixteen AWE aged 13-17 took part, completing measures for depression and self-compassion before the intervention (pre-CFT), immediately afterwards (post-CFT), and again six months later (follow-up). Results showed significant reductions in depression and increases in self-compassion from pre- to post-CFT, with these improvements sustained at follow-up. By both post-CFT and six-month follow-up, three-quarters of AWE were below clinical threshold for depression. Overall, these findings offer preliminary, tentative evidence that CFT may be a beneficial approach for supporting AWE who are experiencing depression, though further robust research is required to propose such recommendations.
In India, indigenous camel populations have evolved under diverse ecological conditions, leading to the emergence of several distinct breeds with specialised adaptive traits. Understanding the genomic architecture and population structure of such camel populations is essential for their conservation and sustainable utilisation. In the present study, whole-genome sequencing data were generated and analysed for Indian dromedary camels representing nine recognised breeds, along with Indian Bactrian (double-humped) and Arabian Peninsula dromedaries with the primary objective to investigate population structure and to assess the genetic distinctiveness of the geographically isolated Kharai camel, a unique breed adapted to coastal and saline environments. The sequencing depth ranged from 11.3× to 25.4× for Indian dromedaries, with high mapping efficiency to the reference genome (mCamDro1). Population structure analyses consistently revealed limited genetic differentiation among most Indian dromedary populations, reflecting shared ancestry and historical gene flow. However, the Kharai camel exhibited clear genetic distinctiveness across multiple analytical approaches. Principal component analysis separated Kharai from other dromedaries, and admixture analysis at K = 2 demonstrated near-complete clustering of Kharai individuals to a distinct ancestral component. Pairwise genetic distances (FST) further supported moderate differentiation in Kharai (0.07-0.10), compared with the low differentiation observed among other populations. Neighbour-Net and phylogenetic tree analyses corroborated these findings, showing breed-specific clustering with clear separation of Kharai. Genome-wide diversity analysis revealed a predominance of low-frequency alleles (57.7% of SNPs with MAF 0.05-0.10), indicating population subdivision and localised demographic histories. Moderate genetic diversity was observed (Hₒ = 0.303 ± 0.001; Hₑ = 0.319 ± 0.0001), with evidence of a mild heterozygote deficit likely attributable to the Wahlund effect. Linkage disequilibrium (LD) analysis showed strong short-range LD (r² = 0.783 at 0-10 kb) with gradual decay up to 10 Mb, suggesting a moderate historical effective population size. LD-based reconstruction indicated a decline in effective population size from > 2,500 ancestral individuals to approximately 167 individuals in recent generations, highlighting demographic contraction. These findings demonstrate substantial genetic homogeneity among Indian dromedary populations while highlighting the distinct genomic identity of the Kharai camel breed. The results underscore the evolutionary uniqueness of this breed and emphasise the need for targeted conservation and management strategies to preserve its genetic resources.
Data on women ageing with HIV in Australia are limited, particularly regarding those in midlife and experiencing menopause. The aim of this study is to describe the demographic characteristics of cisgender women living with HIV who attend the Alfred Hospital, Monash Medical Centre and Melbourne Sexual Health Centre for primary HIV care. In particular, we sought to identify whether documentation of menopausal status, menopausal symptoms, use of menopausal hormone therapy (MHT) and comorbidity screening had occurred in these women. Cisgender women currently in care (defined as attending the clinic between 1/7/2022 and 1/7/2024) were identified and a medical record review was conducted to identify demographic information, menopausal status, menopausal symptoms, use of MHT and documentation of related comorbidity screening results (cervical screening test [CST], mammogram, fracture risk (FRAX), bone density (DEXA), cardiovascular disease [CVD] risk). A total of 462 women were identified across the three sites. Median age was 47 years (range 20-85, interquartile range [IQR] 39-56) and the majority (342, 70%) were born overseas. Of these, 148 (32%) were pre-menopausal, 47 (10%) perimenopausal and 145 (31%) post-menopausal. Menopausal status was unable to be determined from clinical records for 122 (26%). Menopausal symptoms were documented for 70 women (age range 38-85, IQR 48-57). Cervical screening was completed in the last 3 years for 293 women (66%) aged 25-74 years, 58 (30%) over 50 years had documentation of a mammogram in the last 2 years, 105 (39%) over 45 years had CVD risk calculated and 17 (29%) over 50 years had FRAX calculated. Approximately half the women in this study were aged 40-56 years, yet menopausal status was unable to be determined for over a quarter of the cohort. Documentation of menstrual or menopausal symptoms was poor and significant gaps were identified in comorbidity screening. Further research is needed to understand the impact of menopause on women living with HIV in Australia. Clinical guidelines need updating to include gender-specific health needs of women living with HIV and to consider the impact of menopause on comorbidity management.
The rising incidence of endometrial cancer (EC) in young women presents a significant challenge in balancing oncologic safety with fertility preservation. While fertility-sparing treatment is an option for carefully selected patients with early-stage, well-differentiated EC, management of recurrence and optimization of fertility outcomes remain complex. A 33-year-old nulliparous woman was diagnosed with Grade 1 endometrioid adenocarcinoma confined to the endometrium (ER/PR positive). After multidisciplinary team (MDT) evaluation confirmed eligibility, she received first-line high-dose progestin therapy. Complete remission (CR) was achieved and confirmed by hysteroscopy at 3 months, followed by 3 months of consolidation therapy. During preparation for embryo transfer after successful oocyte retrieval via a progestin-primed ovarian stimulation (PPOS) protocol, recurrence was detected hysteroscopically. Retreatment with the same progestin regimen led to a second CR after 6 months. Subsequently, a thawed embryo transfer resulted in a successful pregnancy, culminating in the delivery of a healthy infant at term. This case suggests that successful fertility preservation and live birth may be achievable in young patients with early-stage EC when a structured approach is applied-including strict MDT selection, standardized progestin therapy with diligent surveillance, proactive management of recurrence, and well-timed assisted reproductive technology (ART). Notably, repeat conservative treatment for localized recurrence was successfully employed in this patient. Integrating weight management and comprehensive molecular profiling into future treatment paradigms could further optimize outcomes, but these observations require validation in larger cohorts.
This article is based on the results of a study analyzing the opinions and perceptions of medical students regarding their future professional activities. The objective of the study was to examine and analyze the attitudes and plans of medical students regarding their chosen profession. The object of the study was the professional attitudes of students in the Faculty of General Medicine. The theoretical methodology of the article is based on a sociological approach to professionalization, taking into account the activity-based and certification approaches. The empirical basis of the study was the results of a sociological survey conducted among 220 medical students in January 2026 (KSMU, Kursk, n = 100; RNRMU, Moscow, n = 75; PSPbSMU, St. Petersburg, n = 45). The study found that young people, typically those who have completed pre-professional school training, consciously choose medical universities. Half of the study participants expressed a willingness to remain in the state healthcare system, with minor regional differences. To create an effective healthcare system capable of adequately responding to the needs of young professionals, it is necessary to develop conditions for retaining young professionals in state healthcare, taking into account the expectations of todays students (unique experience, stability, career advancement, etc.). Статья основана на результатах исследования, посвящённого анализу мнений и представлений студентов медицинских вузов относительно будущей профессиональной деятельности. Цель исследования: изучение и анализ установок и планов студентов медицинских вузов в отношении выбранной профессии. Объект исследования — профессиональные установки студентов лечебного факультета. В основу теоретической методологии статьи положен социологический подход к профессионализации, учитывающий деятельностное и сертификационное направления. Эмпирической основой исследования стали результаты социологического исследования, проведённого среди 220 студентов медицинских вузов в январе 2026 г.: КГМУ, Курск, n = 100; РНИМУ, Москва, n = 75; ПСПбГМУ, Санкт-Петербург, n = 45). В ходе исследования установлено, что медицинский вуз выбирается осознанно молодыми людьми, как правило, прошедшими предпрофессиональное школьное обучение, остаться в системе государственной медицины выразили готовность половина участников исследования, с незначительными региональными различиями. Для формирования эффективной, способной дать адекватный ответ на запрос молодых специалистов системы организации здравоохранения необходимо формировать условия закрепления молодых специалистов в государственной медицине с учётом представлений современных студентов (уникальный опыт, стабильность, карьерный рост и т. д.).
The management of rectal adenocarcinoma requires navigation of complex, branching guideline pathways encompassing neoadjuvant sequencing, surgical approach, organ preservation, and surveillance, yet real-world guideline adherence remains as low as 60-70%. The ability of current-generation large language models (LLMs) to accurately navigate these decision points has not been fully characterized. In this cross-sectional, vignette-based study, 135 clinical questions were constructed from 45 pages of NCCN Rectal Cancer Guidelines (Version 4.2024). ChatGPT-4o was queried using standardized prompts with up to 3 clarifying questions permitted per query. Responses were independently evaluated by two physician raters on a 5-point Likert scale, with potential discrepancies adjudicated by a board-certified surgical oncologist. Primary outcomes were the proportion of responses rated Correct (score ≥ 3) and Accurate (score ≥ 4). Inter-rater reliability was assessed using Cohen's kappa, and subgroup analysis was performed across clinical domains using the Kruskal-Wallis test. Of 135 questions, 127 (94.1%; 95% CI, 88.7-97.0%) were Correct and 121 (89.6%; 95% CI, 83.3-93.7%) were Accurate. One hundred two responses (75.6%) were completely correct without additional prompting. Performance was consistent across clinical domains (Kruskal-Wallis H = 0.530, p = 0.767). Inter-rater agreement was perfect (κ = 1.0). Eight responses (5.9%) contained partially or wholly incorrect information, with errors concentrated in multi-step conditional treatment decision points. ChatGPT-4o demonstrates high concordance with NCCN rectal cancer guidelines across all evaluated clinical domains with notable improvement over prior ChatGPT iterations evaluated by our group. The concentration of errors in complex conditional treatment algorithms suggests that LLMs excel at discrete factual recall but may struggle with multi-step reasoning under clinical uncertainty. Prospective validation using real-world clinical data and comparison with multidisciplinary tumor board recommendations remain necessary prior to clinical integration.
The Intuitive Eating Scale-3 (IES-3) is a new 12-item instrument that provides an updated assessment of intuitive eating, a recognized protective factor of disordered eating. However, the IES-3's psychometric properties have not been assessed outside the parent study. Here, we assessed the psychometric properties of a novel French translation of the IES-3 in 772 French-speaking Canadian adults. Respondents completed the French IES-3 alongside additional measures selected to provide assessments of validity. Exploratory factor analysis with a first split-half subsample showed that a 4-factor model fit the data well. In a second split-half subsample, a bifactor-exploratory structural equation model (B-ESEM) with a G-factor and four S-factors best fit the data. Across subsamples, the 4-factor and B-ESEM models demonstrated gender invariance, and did not show measurement bias in terms of age and body mass index (BMI). Additional analyses showed some variation in intuitive eating as a function of age, BMI, and gender identity. Finally, results supported the composite reliability and convergent and concurrent validity. In sum, the French IES-3 demonstrates strong psychometric properties.
Neural substrates of cancer-related cognitive impairment (CRCI) remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions. Breast cancer survivors aged ≥60 years (n = 64) and non-cancer controls (n = 62) completed structural MRI and neuropsychological testing and self-reported cognition and health information at pretreatment baseline and 12- and 24-month follow-ups. Regional gray matter volume and brain age were evaluated using FreeSurfer and brainageR. Longitudinal linear mixed models tested effects of group, time, and group-by-time interactions on volume. Secondary analyses examined relationships between group, comorbidities, age, gray matter volume, and cognition. Survivors exhibited frontal (p = 0.025, q = 0.058), thalamic (p = 0.008, q = 0.052), and limbic (p = 0.015, q = 0.052) gray matter decline relative to controls over 24 months, with smaller effects in parietal (p = 0.055, q = 0.097) and temporal (p = 0.091, q = 0.127) regions. Survivors showed average yearly frontal and thalamic volume loss at twice the rate of controls (p < 0.05). Survivors with a high comorbidity burden (≥3 comorbidities) exhibited the lowest frontal gray matter volume at all timepoints. A trend-level group-by-time interaction for brain age (p = 0.093) suggested accelerated brain aging in survivors. Survivors failed to show practice effects in the attention, processing speed, and executive functioning neuropsychological domain, whereas controls improved significantly over time (group-by-time interaction p = 0.030). Older breast cancer survivors tended to demonstrate gray matter decline and accelerated brain aging throughout the first two years of survivorship, with comorbidity burden amplifying frontal vulnerability. Findings highlight the need for longitudinal cognitive monitoring and targeted intervention, particularly for older survivors with high comorbidity burden.
Understanding how 24-h movement behaviors (i.e., physical activity, sedentary behavior, sleep) differ among children with developmental disabilities (e.g., delays, disorders, disabilities) is crucial, with evidence indicating that variations seen in older children may begin to emerge in early childhood. However, reviews have not acknowledged such developmental considerations in young participants. Therefore, a scoping review of the growing body of research focused on preschool-aged children is essential for gaining deeper insights into how these behaviors evolve and differ during this critical period. This scoping review aimed to (1) identify 24-h movement behavior levels in preschool-aged children with developmental disabilities, (2) determine whether 24-h movement behaviors differed between children with and without developmental disabilities, and (3) determine if 24-h movement behaviors varied by the domain of developmental difference. We conducted a systematic search in nine databases. Inclusion criteria were: (1) children between 33 and 72 months, (2) inclusion of children with developmental disabilities in the sample, (3) measures of at least two movement behaviors, (4) written in English, and (5) empirical, original research designs. The date of publication was unrestrained. Title/abstract and full text screening were completed by two independent reviewers. The date of publication was unrestrained. Twenty predominantly cross-sectional articles published between 2004 and 2024 were included. Studies examined movement behaviors across various developmental domains such as autism spectrum disorder, cerebral palsy, and developmental coordination disorder. Findings on sleep, sedentary behavior, and physical activity were mixed, with some studies reporting significant group differences while others found no or inconsistent group differences. This review highlights the variability and gaps in current research on movement behaviors among children with developmental disabilities, underscoring the need for more comprehensive and consistent measurements that consider all 24-h movement behaviors to better inform targeted interventions.
Assessing fall risk is essential for older adults as well as for specific patient populations, including those with neurological or musculoskeletal disorders. The Activities-specific Balance Confidence Scale is a widely used instrument for evaluating perceived balance confidence, and its Hungarian version has already been validated. However, administering the original 16-item scale can be time-consuming. The aim of this study was to develop and validate the 6-item short version of the Hungarian Activities-specific Balance Confidence Scale among individuals with neurological and musculoskeletal conditions. Our investigation was conducted in two phases. In the first phase, 167 participants completed the full 16-item version of the Hungarian Activities-specific Balance Confidence Scale, data for the 6 selected items were extracted and analyzed. Convergent validity was tested against the Berg Balance Scale here. In the second phase, 63 participants completed the 6-item Hungarian short version of the scale along with other patient-reported surveys. Data on falls in the previous year and perceived pain levels were also collected. Internal consistency was evaluated using Cronbach's alpha and McDonald's omega, while test-retest reliability was assessed via the intraclass correlation coefficient. We also calculated floor and ceiling effects and minimal detectable change. Convergent validity was evaluated using the Hungarian version of the Falls Efficacy Scale - International. Discriminative validity was examined comparing the scores of patients with or without falls. The effect of perceived pain on scale results was also evaluated. The 6-item Hungarian short version of the Activities-specific Balance Confidence Scale demonstrated high reliability with no floor or ceiling effect. Strong to moderate correlations were found with the physical test and the Falls Efficacy Scale - International. The scale effectively discriminated between individuals with and without a history of falls. Perceived pain did not significantly influence the scores. The average completion time was under 4 minutes. The 6-item Hungarian version of the Activities-specific Balance Confidence Scale is a brief, reliable, and valid instrument for assessing balance confidence in patients with neurological and musculoskeletal conditions. Due to its sensitivity and short completion time, it is highly suitable for both clinical practice and research. Orv Hetil. 2026; 167(27): 1068-1078. Bevezetés: Az eleséskockázat felmérése alapvető jelentőségű mind idősek, mind speciális betegcsoportok, így a neurológiai és mozgásszervi betegek körében. A Tevékenységfüggő Egyensúlybiztonsági Skála (Activities-specific Balance Confidence Scale) a szubjektív egyensúlybiztonság értékelésére szolgál, magyarul is elérhető, azonban a teljes, 16 kérdéses változat kitöltése időigényes lehet. Célkitűzés: Tanulmányunk célja a Tevékenységfüggő Egyensúlybiztonsági Skála rövidített, 6 kérdéses magyar változatának létrehozása és pszichometriai jellemzőinek vizsgálata volt, neurológiai és mozgásszervi betegek körében. Módszer: Vizsgálatunk két fázisban zajlott. Az első fázisban 167 beteg töltötte ki a teljes, 16 kérdéses skálát, jelen tanulmányunkban a kiválasztott 6 kérdés értékeit vettük figyelembe. Ebben a fázisban a konvergens validitást fizikális teszttel, a Berg Egyensúlybiztonsági Skálával összehasonlítva vizsgáltuk. A második fázisban 63 beteg a skála rövid, 6 kérdéses változatát és más önkitöltős skálákat kapott. Itt rákérdeztünk az előző évben elszenvedett esésekre, illetve a megélt fájdalomra. A megbízhatósági vizsgálatok során a belső konzisztenciát Cronbach-alfa és McDonald-ómega, a teszt-reteszt megbízhatóságot osztályon belüli korrelációs együttható segítségével vizsgáltuk. Emellett plafon- és padlóhatást, illetve minimálisan kimutatható változást is számoltunk. A konvergens validitás vizsgálatához a Falls Efficacy Scale – International magyar változatát használtuk. A diszkriminatív validitás vizsgálata céljából összehasonlítottuk az esést szenvedett és nem szenvedett betegek eredményeit, és elemeztük a megélt fájdalom hatását a skála eredményére. Eredmények: A rövidített Tevékenységfüggő Egyensúlybiztonsági Skála megbízhatóságát jónak találtuk. Plafon- és padlóhatás nem jelentkezett. Erős vagy mérsékelt korrelációt találtunk a fizikális teszttel és más egyensúlybiztonsági skálákkal való összehasonlítás során. Ez a skála megfelelően különbséget tett az eleső és nem eleső betegek között, míg a fájdalom nem befolyásolta az eredményeket. A kitöltés átlagos ideje 4 percnél kevesebb volt. Következtetés: A 6 kérdéses Tevékenységfüggő Egyensúlybiztonsági Skála rövid, jól értelmezhető és megbízható eszköz a szubjektív egyensúlybiztonság mérésére neurológiai és mozgásszervi betegek körében. Rövid kitöltési ideje és érzékenysége alapján alkalmas a mindennapi klinikai gyakorlatban és kutatásokban való alkalmazásra. Orv Hetil. 2026; 167(27): 1068–1078.
Understanding the organization of afferent and efferent spinal cord pathways can be challenging for students due to their complex spatial relationships. This study aimed to develop a three-dimensional (3D) educational model demonstrating these pathways and to compare student learning outcomes between model-based instruction and conventional slide-based teaching. A pre-test/post-test educational study was conducted with second-year dental students (n = 60). Transverse sections of the C4 and T7 vertebrae were designed and 3D-printed at four times their anatomical size. A spinal cord model made of modeling clay was placed within the vertebral canal, and afferent and efferent pathways were represented using color-coded cables. Students completed a 15-item multiple-choice pre-test assessing baseline knowledge of spinal cord pathways and were allocated into two groups. Group 1 (n = 30) received conventional slide-based instruction, while Group 2 (n = 30) was taught using the 3D model. After the instructional sessions, students completed the same test as a post-test. Within-group and between-group comparisons were analyzed using paired-sample and independent-sample t-tests. Both instructional approaches resulted in significant improvements in post-test scores. In the slide-based instruction group, mean scores increased from 5.00 ± 1.98 to 8.47 ± 2.54 (p < 0.001). In the 3D model group, mean scores increased from 4.77 ± 2.39 to 10.27 ± 2.29 (p < 0.001). The mean improvement was significantly greater in the 3D model group (5.50 ± 3.07) compared with the slide-based group (3.47 ± 2.70) (p = 0.007). The effect size for the difference between groups was moderate to large (Cohen's d ≈ 0.70). Both instructional methods improved short-term knowledge of spinal cord pathways; however, model-based instruction was associated with greater learning gains. These findings suggest that three-dimensional models may serve as a useful supplementary tool in neuroanatomy education. Further studies using validated assessment tools and evaluating long-term knowledge retention are needed to confirm these findings.
Family environments play a critical role in shaping children's lifestyle behaviours that influence obesity risk. However, culturally validated instruments to assess these behaviours are lacking in Portuguese primary care. This study aims to translate and culturally adapt the Family Nutrition and Physical Activity (FNPA) screening tool for use in Portugal (FNPA-PT) and to evaluate its face and content validity through cognitive interviews with parents attending well-child visits. An exploratory, descriptive study followed internationally endorsed guidelines (Beaton; MAPI) for translation and cross-cultural adaptation. The process comprised seven stages: forward translations, synthesis, back translations, comparisons of back translations, expert committee review, cognitive debriefing and final proofreading. Ten parents of five-year-old children attending a public primary care centre in Lisbon completed the FNPA-PT while participating in individual cognitive interviews. Data were analysed using Content Analysis, guided by Tourangeau's four-stage response model. Semantic equivalence between forward and back translations was high (85% of items with satisfactory or perfect equivalence). Minor linguistic and cultural adaptations were introduced to improve clarity and contextual relevance. Cognitive interviews indicated that the FNPA-PT was well understood, acceptable to parents, and feasible to complete during well-child visits. Parents valued the questionnaire's comprehensiveness and its potential to enhance awareness and stimulate discussion about family health behaviours. Minor revisions addressed comprehension issues in three items related to milk consumption, screen time and sleep. The FNPA-PT demonstrated strong face and content validity and high acceptability among Portuguese parents. It provides a culturally appropriate, family-centred tool for health professionals to support early identification of obesogenic environments and to guide preventive counselling in primary care. The study also offers a transparent methodological pathway for translating and adapting behavioural measures across languages and settings.
STAT3 is a promising therapeutic target for human cancers and other diseases. Herein, we report our development of novel STAT3 proteolysis-targeting chimera degraders using high-affinity STAT3 and Von Hippel-Lindau 1 ligands, which led to the discovery of SD-2301 as a highly potent, selective, and efficacious STAT3 degrader. SD-2301 achieved DC50 = 4 nM and Dmax of >95% and is >100 times more potent than SD-36 and SD-91. SD-2301 is highly selective for inducing STAT3 degradation over other Signal Transducer and Activator of Transcription members. SD-2301 inhibited cell growth with IC50 = 5-11 nM in the SU-DHL-1 and SUP-M2 lymphoma cell lines. SD-2301 displayed an excellent pharmacokinetic profile in mice and achieved rapid and persistent depletion of STAT3 protein in native and xenograft tumor tissues in mice. SD-2301 was capable of achieving complete and long-lasting tumor regression in vivo and is a promising STAT3 degrader for the treatment of human cancers and other human diseases.
Magnesium oxide nanoparticles (MgONPs) demonstrate size-influenced antibacterial activity against Ralstonia solanacearum, with physical disruption mechanisms appearing to play a more prominent role than reactive oxygen species (ROS) effects under the tested conditions. While 30 nm particles generated maximum ROS levels, 20 nm MgONPs exhibited superior bactericidal efficacy, reducing survival to 36% at 300 mg/L versus 46% for 30 nm particles-a superiority consistently supported by motility, membrane, and transcriptomic assessments even at the complete-killing concentration (500 mg/L). This size-dependent efficacy was further validated in vivo. ROS scavenging tests and transcriptomics suggested that oxidative stress may not be the primary driver of antimicrobial action, though a potential synergistic role cannot be entirely excluded. The primary mechanisms involved size-specific physical membrane damage, DNA integrity changes, and metabolic interference. Smaller particles (20 nm) caused significant membrane destabilization and uniquely disrupted acetyl-CoA metabolism and oxidoreductase activity through downregulation of ribosome biogenesis, oxidative phosphorylation, and amino acid degradation pathways. Transcriptomic profiling revealed that particle size modulates catabolic gene expression and redox-related processes, with 20 nm particles inducing distinct metabolic suppression patterns. This study provides insights into the ongoing debate regarding ROS versus physical mechanisms, suggesting that nanoscale precision combined with surface properties governs antibacterial efficiency. The findings position MgONPs as a tunable antimicrobial platform where optimized particle dimensions and formulation strategies enhance pathogen control through targeted physical disruption and metabolic interference. These mechanistic insights offer a basis for engineering nanomaterials with improved bactericidal performance via optimization of multiple physicochemical properties.
The use of peptide receptor radionuclide therapy (PRRT) is well established in the treatment of advanced or unresectable neuroendocrine tumours (NETs) after progression on somatostatin analogues (SSA), with randomised clinical trials such as NETTER-1 and NETTER-2 showing improvement in progression free survival (PFS) as well as tumour response [12, 13]. Current landmark trials only considered patients suitable for PRRT if all known lesions displayed SSTR expression, via avidity on planar scintigraphy or Gallium-68 DOTATATE PET/CT. However, there is a select group of patients with oligodiscordant disease (3 or less lesions which are FDG avid but not DOTATATE avid) on dual DOTATATE/FDG PET imaging who may benefit from PRRT in combination with additional therapies such as liver directed therapy (LDT) or chemotherapy. There is currently no data regarding the efficacy and outcomes of PRRT in oligodiscordant disease. This study is the first to describe the treatment patterns and outcomes of patients with oligodiscordant disease receiving PRRT. A single-centre retrospective review was performed in patients with advanced gastroenteropancreatic NETs with oligodiscordant disease who received at least one cycle of PRRT with [177Lu]Lu-DOTA-TATE from 2020 to 2024. Safety was assessed by renal and haematological parameters (CTCAE v5.0) during PRRT, and at 3 months post completion of treatment. Response to treatment was evaluated on molecular imaging with Gallium-68 DOTATATE PET/CT. Kaplan-Meier method was used to perform median progression free survival (PFS), overall survival (OS), and time to next treatment (TTNT) analyses. Thirteen patients met the inclusion criteria, the median age was 66 years, and 54% were male. Primary site: small bowel (7), pancreas (4), colorectal (2). WHO grade: none had grade 1 disease, ten grade 2 and three had grade 3 disease. Median OS was 27.3 months (95% CI 19.7 - not reached), median PFS 15.1 months (95% CI 7.1-20.1), and median TTNT 15.0 months (95% CI 6.7-39.6). One of 15 patients developed treatment related myeloid neoplasm on long term follow-up, confirmed by bone marrow biopsy. No patients developed significant renal toxicity on follow-up. In patients with advanced NETs with oligodiscordant disease identified on dual PET imaging, the combination of PRRT with systemic therapy or other therapies (surgery, liver directed therapy, radiotherapy) can be effective with acceptable toxicity and should be considered as a possible option for treatment in selected patients. The sequencing of treatment modalities and exact strategy employed is best decided at an experienced NET centre with multi-disciplinary input.
Transcutaneous cervical electrical stimulation (TCES) offers a noninvasive approach to modulate the autonomic nervous system (ANS), but optimal stimulation parameters remain undefined. This pilot study aimed to identify optimal TCES parameters by evaluating autonomic and neural responses across varying frequencies, current intensities, electrode montages, and durations, using heart rate variability (HRV) and electroencephalography (EEG) alpha-band power as biomarkers of parasympathetic activity. Twenty healthy adults completed four testing sessions, each examining one stimulation parameter. Autonomic data were collected including electrocardiography, non-invasive blood pressure, pupillometry, photoplethysmography, and dry-electrode EEG. Four frequencies (10, 25, 40, 150 Hz), three current intensities (sub-sensation threshold, sensation threshold, supra-sensation threshold), three electrode montages (bilateral, left-only, right-only), and two durations (4, 20 min) were tested. Root mean square of successive differences (RMSSD) and global EEG alpha-band power were primary outcomes. Parameters were sequentially optimized across visits based on individual RMSSD responses. No single frequency produced a significantly higher RMSSD or alpha-band power response. However, each participant exhibited a personalized preferred frequency yielding a mean 41% RMSSD increase in visit 1. This individualized frequency was selected for further visits varying current intensity and electrode montage. Supra-sensation threshold intensity was most effective, with 60% of participants responding strongest at this level. Left-sided stimulation resulted in a decrease in both RMSSD and alpha-band power, while right-sided and bilateral montages resulted in similar increases for these biomarkers. Due to decreasing cardiac vagal response in successive sessions, the preferred frequency was reevaluated before testing duration. The mean RMSSD response increased 54% upon recalibration in visit 4, though the preferred frequency shifted in 75% of participants. Autonomic vitals did not significantly modulate more with longer stimulation duration; pulse rate variability during 20-min stimulation revealed oscillatory autonomic dynamics with peak parasympathetic responses emerging around 4 min. TCES can modulate cardiac vagal and cortical responses as measured by RMSSD and EEG alpha-band power, respectively, and a personalized, biomarker-guided approach to TCES parameter optimization is essential for future clinical applications targeting autonomic dysfunction. This study was registered with Clinicaltrials.gov, identifier NCT04100486, on September 16, 2019.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are systemic autoimmune disorders affecting small- and medium-sized vessels. Cutaneous involvement is common, but diagnosis can be challenging when inflammatory lesions mimic infectious processes, particularly fungal infections such as cryptococcosis. We describe two female patients with ANCA-associated vasculitis who developed widespread cutaneous lesions with histopathological features resembling Cryptococcus. The first patient, a 57-year-old woman with p-ANCA MPO-positive vasculitis, presented with bullous and purpuric lesions along with pulmonary hemorrhage. Despite corticosteroids and cyclophosphamide, her disease course was complicated by multiorgan involvement and fatal outcome. The second patient, a 73-year-old woman with multiple comorbidities, developed vesicular and necrotic skin lesions initially misdiagnosed as disseminated herpes zoster. Histology demonstrated vasculitis with Cryptococcus-like changes, and after exclusion of fungal infection, immunosuppressive therapy led to complete resolution. Cryptococcus-like histopathological changes have been reported in neutrophilic dermatoses, described as cryptococcoid Sweet syndrome. These yeast-like structures are thought to represent degenerating neutrophils rather than fungal organisms. Awareness of this rare finding is essential to avoid unnecessary antifungal therapy and ensure prompt initiation of immunosuppression. Cutaneous Cryptococcus-like changes in ANCA vasculitis are rare but clinically significant. Accurate diagnosis requires integration of clinical context, microbiological testing, and histopathology. Early recognition is critical to guide appropriate management and improve patient outcomes.
Cognitive decline is common after cancer, but little is known regarding the etiology of this adverse effect, especially in terms of molecular mechanisms. This prospective study obtained brain imaging and cognitive testing from 50 newly diagnosed women with primary breast cancer prior to any cancer treatment and 53 female controls. Participants completed up to seven assessments for a total time span of 9.7 ± 0.92 years. Imaging transcriptomics was used to measure the expression of genes in the brain involved in N-methyl-D-aspartate (NMDA) and calcium-mediated neurotransmission. GRIN2A, GRIN2B, and CACNA1C were significantly expressed in gray matter in both groups (R2 ≥ 0.092, p ≤ 0.015). GRIN2A (t = -2.72, p = 0.018) was significantly lower in the cancer group compared to controls across timepoints. GRIN2A declined over time in patients, and this was significantly different compared to controls (χ2 = 9.73, p = 0.005). Cognitive scores were significantly lower in patients compared to controls (p ≤ 0.004). In patients, GRIN2A was significantly associated with cognitive performance over time (p ≤ 0.009). These findings suggest that gene expression involved in neurotransmission is disrupted in the brain among patients with breast cancer and may contribute to cognitive changes. Our results provide novel molecular insights regarding the roles of non-CNS cancer pathology and treatments in the brain related to NMDA signaling and pro-survival/plasticity-related pathways. Our findings also point to potential treatments for cognitive effects of cancer.
Primary mediastinal large B-cell lymphoma (PMBCL) during pregnancy is rare and presents therapeutic challenges due to fetal safety concerns. We report the case of a 29-year-old woman diagnosed with PMBCL at 19 weeks of gestation who wished to continue her pregnancy despite her diagnosis. She received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy with multidisciplinary management and delivered a healthy infant at term. Although the tumor partially responded, residual disease persisted after eight cycles of treatment. She subsequently underwent chimeric antigen receptor T-cell therapy and achieved a complete response. This case highlights the importance of individualized treatment decisions and multidisciplinary collaboration in managing PMBCL during pregnancy.
Cerebral amyloid angiopathy (CAA) is associated with transient focal neurological episodes (TFNEs), which are brief, stereotyped symptoms. As these may occur regularly, pharmacological treatment of TFNEs is needed but remains poorly investigated. To systematically evaluate the available evidence on the use of pharmacological treatment to reduce the frequency, severity, or duration of TFNEs in patients with CAA. A systematic literature search of PubMed and Embase was conducted. Eligible studies included observational studies, interventional trials, and case reports or series that assessed pharmacological interventions for TFNEs in patients with confirmed CAA. Nine case reports/series involving 13 patients met the inclusion criteria. The mean age was 75.15 years, with a predominance of sensory and motor TFNE symptoms. One EEG recording out of nine reported paroxysmal activity whereas the rest showed no epileptiform activity. Antiseizure medications (levetiracetam) were the most common treatment. Eleven patients experienced complete remission, and two had partial improvement. Most patients exhibited convexity subarachnoid hemorrhage or cortical superficial siderosis on imaging. Although symptomatic improvement following pharmacological treatment was commonly reported, the current evidence is limited to descriptive case reports without control groups. The unpredictable course of TFNEs and absence of long-term follow-up complicate treatment evaluation. Larger, controlled studies or observational studies are needed to establish effective and evidence-based treatment strategies for TFNEs in CAA.