Fasciola gigantica: Ultrastructural localisation of neoblast recruitment in somatic tissues during growth and development in the hepatic parenchyma of experimentally infected mice.

Application of 'omics' technology, and advances in in vitro methods for studying the growth of Fasciola hepatica, have highlighted the central role of migrating neoblasts in driving forward development and differentiation towards the adult-like form. Neoblast populations present molecular heterogeneity, morphological variation and changes associated with recruitment of these stem cells into their final tissue locations. However, terminal differentiation towards function, has received much less attention than has been the case for the free-living Platyhelminths. An actively replicating neoblast population, comprising cells with heterochromatic nuclei consistent with regulation of gene expression, has been identified in the parenchyma of juvenile Fasciola gigantica migrating in the liver of experimentally infected mice. In some of these cells, early cytoplasmic differentiation towards myocyte function was noted. Neoblasts have also been identified close to, and incorporated in, the subtegumental zone, the gastrodermis and the excretory ducts. In these locations, progressive morphological differentiation towards terminal function has been described. This includes the appearance of specific progenitors of type-1, type-2 and type-3 tegumental cells, the latter possibly contributing to tegumental spine development. 'Cryptic' surface molecular differentiation is postulated to account for recognition and 'docking' of migrating neoblasts with their final site for terminal differentiation.

Practicing Interoceptive Sensitivity as a Couple: A Mixed-Methods Acceptance Analysis of a Dyadic vs. Single Pilot Randomized Controlled Trial.

Training interoceptive sensitivity (IS) might be a first step in effectively promoting intuitive eating (IE). A dyadic interoception-based pilot randomized controlled trial was conducted to increase IE among couples aged 50+. The training consisted of three exercises, a Body Scan (BS), a hunger exercise (HU), and a satiety (SA) exercise. This study explored how spouses accepted the (dyadic vs. single) training. In a mixed-methods convergence design, the findings of a survey (n = 68 couples) and focus groups (n = 4) were synthesized. Moderate general acceptance (e.g., regarding feasibility and low burden) and a hierarchical gradient in favor of the BS (e.g., pleasantness and improved sleep quality) emerged. Barriers concerned a perceived lack of the exercises' usefulness and a limited understanding of the training purpose. A wish for regular feedback and exchange with the study stuff and other participants was expressed. Spousal training involvement was experienced as being rather beneficial. Previously harmonized dietary practices and daily routines appeared as constructive pre-conditions for the joint training. This study highlights the potential and implications of training couples in IS. Future interventions should involve a regular exchange and closer guidance by study staff to promote a better understanding of the processes and goals of IS and IE.

Oral Hypoxia-Inducible Factor 2α Inhibitor Belzutifan in Ocular von Hippel-Lindau Disease: Subgroup Analysis of the Single-Arm Phase 2 LITESPARK-004 Study.

PURPOSE: To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. METHODS: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%-100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 µm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cervicothoracic ventral-dorsal rhizotomy for bilateral upper-extremity hypertonia in cerebral palsy: illustrative case.

BACKGROUND: Management of medically refractory limb-specific hypertonia is challenging. Neurosurgical options include deep brain stimulation, intrathecal baclofen, thalamotomy, pallidotomy, or rhizotomy. Cervical dorsal rhizotomy has been successful in the treatment of upper-extremity spasticity. Cervical ventral and cervical ventral-dorsal rhizotomy (VDR) has been used in the treatment or torticollis and traumatic hypertonia; however, the use of cervicothoracic VDR for the treatment of upper-extremity mixed hypertonia is not well described. OBSERVATIONS: A 9-year-old girl with severe quadriplegic mixed hypertonia secondary to cerebral palsy (CP) underwent cervicothoracic VDR. Modified Ashworth Scale scores, provision of caregiving, and examination improved. Treatment was well tolerated. LESSONS: Cervicothoracic VDR can afford symptomatic and quality of life improvement in patients with medically refractory limb hypertonia. Intraoperative positioning and nuances in surgical techniques are particularly important based on spinal cord position as modified by scoliosis. Here, the first successful use of cervicothoracic VDR for the treatment of medically refractory upper-limb hypertonia in a pediatric patient with CP is described.

Effect of floating treatment wetland coverage ratio and operating parameters on nitrogen removal: toward design optimization.

Floating treatment wetlands (FTWs) have the potential to improve the quality of wastewater discharges, yet design basics are unavailable to size these systems. This study investigates the effect of FTWs' coverage ratio and hydraulic retention time on agri-food wastewater treatment. This was studied in a pilot-scale experiment comprising four lagoons (6.5 m3 each) fed with real effluent from an existing tertiary treatment lagoon. An evaluation of FTW of different sizes (L24, L48, and L72 representing 24, 48, and 72% of pilot lagoons surface areas) and a control, L0 (without FTW), was performed over 16 months. Overall, L72 and L48 moderately improved total nitrogen (TN) mass removal compared to L0 (p < 0.05), while L24 exhibited similar TN mass removal (p = 0.196). The highest improvement was observed for L72, exhibiting up to 55% (mean of 13%) greater N mass removal than the control. The net increase in TN removal by FTWs was mainly related to denitrification, promoted by decreasing dissolved oxygen for increasing FTW coverage ratio. Residence time, temperature, and dissolved oxygen were the main parameters driving TN removal by FTWs. Retrofitting existing lagoons with FTW can facilitate N retrieval through plant harvesting, thereby reducing N remobilization from sediment (common in conventional lagoons).

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4).

INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

Exploring neonicotinoid effects on Drosophila: insights into olfactory memory, neurotransmission, and synaptic connectivity.

Neonicotinoid insecticides, the fastest-growing class in recent decades, interfere with cholinergic neurotransmission by binding to the nicotinic acetylcholine receptor. This disruption affects both targeted and non-targeted insects, impairing cognitive functions such as olfaction and related behaviors, with a particular emphasis on olfactory memory due to its ecological impact. Despite the persistent presence of these chemicals in the environment, significant research gaps remain in understanding the intricate interplay between cognitive function, development, neuronal activity, and neonicotinoid-induced toxicity. This study focuses on the fruit fly Drosophila melanogaster, chosen for its genetic tractability, well-characterized neural circuitry, and remarkable parallels with bees in neurotransmitter systems and brain structures. Our aim is to establish the fruit fly as a valuable model organism for studying the effects of neonicotinoids on behavior and neuronal circuitry, with particular attention to olfactory memory and associated brain circuitries. To achieve this aim, we conducted experiments to investigate the effects of short-term exposure to sublethal doses of the neonicotinoid imidacloprid, mimicking realistic environmental insecticide exposure, on the formation of odor memories. Additionally, we evaluated synaptic contacts and cholinergic neurotransmission within the mushroom body, the primary memory network of insects. Our results showed significant impairments in odor memory formation in flies exposed to imidacloprid, with exposure during the adult stage showing more pronounced effects than exposure during the larval stage. Additionally, functional studies revealed a decrease in synaptic contacts within the intrinsic olfactory projection neurons and the mushroom body. Furthermore, another experiment showed an odor-dependent reduction in cholinergic neurotransmission within this network. In summary, employing Drosophila as a model organism provides a robust framework for investigating neonicotinoid effects and understanding their diverse impacts on insect physiology and behavior. Our study initiates the establishment of the fruit fly as a pivotal model for exploring neonicotinoid influences, shedding light on their effects on olfactory memory, neuronal integrity, and synaptic transmission.

"If I want to be able to keep going, I must be active." Exploring older adults' perspectives of remote physical activity supports: a mixed-methods study.

Introduction: Pandemic-related public health restrictions limited older adults' physical activity programs and opportunities. Physical activity supports shifted to remote options, however, information on their adoption and effectiveness is limited. This study aims to describe the remote supports received by older adults and their perceived effectiveness. Additionally, it aims to describe facilitators and barriers to remote supports for physical activity among older adults, particularly those reliant on technology. Methods: This study used an explanatory, sequential, mixed-methods design. Community-dwelling older adults (≥ 60 years) were recruited to partake in a web-based survey and an optional semi-structured follow-up interview informed by the COM-B model. Participant characteristics, perceived effectiveness of remote supports, and the presence and severity of barriers were described. Changes in physical activity levels before and during the pandemic were analyzed using the Wilcoxon signed-rank test. Qualitative data underwent inductive thematic analysis. Results: Fifty seven older adults (68.3 ± 7.1 years, 43 Female) completed the survey, of which 15 participants (67.4 ± 5.8 years, 12 Female) participated in interviews. The majority were Caucasian, highly educated, and resided in Canada. Total physical activity levels showed no statistically significant change from before to during the pandemic (p = 0.74); however, at-home exercise participation and technology usage increased. Pre-recorded and real-time virtual exercise supports were perceived as most effective. Main barriers included limited contact with exercise professionals, limited access to exercise equipment or space, and decreased mental wellness. Thematic analysis identified five main themes: (i) Enabled by knowledge and resources; (ii) Diverse motivations for physical activity; (iii) Fostering participation through social connection; (iv) Supervision and safety: enabling adherence; and (v) Virtual exercise: a sustainable option with technological considerations. Conclusion: Virtual platforms show promise in supporting older adults' physical activity at home, especially for those with limited in-person access. Our study suggests that both real-time and pre-recorded virtual exercise supports are feasible, depending on technological capacity and support. While interactive real-time virtual programs allow interaction with professionals and peers, pre-recorded programs provide timing flexibility. Further research is needed to establish best practices for safe and effective virtual exercise programming, promoting its long-term adoption for supporting a wider range of older adults.

Imaging Update for Hereditary Abdominopelvic Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms have shown a linear increase in incidence and prevalence in recent decades, primarily due to improved cross-sectional imaging, expanded use of endoscopic procedures, and advanced genetic analysis. However, diagnosis of hereditary neuroendocrine tumors is still challenging because of heterogeneity in their presentation, the variety of tumor locations, and multiple associated syndromes. Radiologists should be familiar with the spectrum of these tumors and associated hereditary syndromes. Furthermore, as the assessment of multiple tumor elements such as morphology, biochemical markers, and presence of metastatic disease are essential for the treatment plan, conventional anatomic and functional imaging methods are fundamental in managing and surveilling these cases. Our article illustrates the role of different cross-sectional imaging modalities in diagnosing and managing various hereditary abdominopelvic neuroendocrine tumors.

Correlation of Ocular Plane-Wave Doppler With Optical Coherence Tomography Angiography in Preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a severe complication of pregnancy characterized by hypertension, proteinuria and compromised fetal blood supply. The eye, like other end organs, is affected by this systemic condition, but unlike in other organs, ocular media transparency allows high-resolution optical visualization of the vascular structure of the retina. Our aim was to assess how ultrasound-determined ocular blood-flow correlates with vascular structure of the retina and choriocapillaris determined by optical coherence tomography angiography (OCTA). METHODS: Plane-wave ultrasound and OCTA were performed on both eyes of 40 consecutive subjects consisting of normal controls (n = 11), mild PE (n = 5), severe PE (n = 17) and chronic or gestational hypertension (n = 7) within 72 hours following delivery. From ultrasound, we measured pulsatile flow velocity and resistance indices in the central retinal artery (CRA) and vein, the short posterior ciliary arteries (SPCAs) and choroid. From OCTA, we measured vascular density (VD) in the superficial, deep retina and choriocapillaris. We determined differences in Doppler and OCTA parameters among groups and correlations between ultrasound and OCTA. RESULTS: In severe PE, flow resistance was reduced with respect to controls. Flow velocity and resistance in the and SPCA were moderately correlated with VD in the choriocapillaris and peripapillary retina, but VD in PE did not differ significantly from controls. CONCLUSIONS: Although OCTA parameters were moderately correlated with Doppler ultrasound, OCTA did not demonstrate significant differences between PE and controls postpartum.

Stability and longitudinal association between Body Mass Index and maladaptive eating behaviors in older adults: Results from the NutriAct Family Study (NFS).

PURPOSE: Due to the increasing prevalence of overweight and obesity with age and associated health risks, older adults are an important target group to promote healthy weight. Evidence indicates that maladaptive eating behaviors are associated with higher BMI. However, older adults are often neglected in this research field. This prospective study aims to clarify the temporal relationship between BMI and maladaptive eating behaviors among older adults. METHODS: In total, 964 participants of the NutriAct Family Study (Mage = 63.34 years) completed web-based questionnaires two times (M = 3.33 years apart). BMI was assessed via self-reported height and weight, and maladaptive eating behaviors with the Dutch Eating Behavior Questionnaire (DEBQ). The stability and longitudinal associations were analyzed using cross-lagged models. RESULTS: Cross-sectional analysis showed positive correlations between BMI and emotional (r = 0.218), external (r = 0.101), as well as restrictive eating (r = 0.160). All maladaptive eating behaviors (ß > 0.684) and BMI (ß > 0.922) were longitudinally stable. No significant bidirectional relationships were found between BMI and maladaptive eating behaviors over time, except for BMI predicting restrictive eating (ß = 0.133). CONCLUSION: The observed cross-sectional, but not longitudinal associations between BMI and maladaptive eating behaviors underline the need for prospective study designs to deepen the understanding of the role of maladaptive eating behaviors in weight management among the general population. Maladaptive eating behaviors among older adults may have already consolidated and play a smaller role in explaining weight course, compared to early life like childhood.

An old foe on peculiar paths: severe falciparum malaria in a Syrian refugee, possibly infected during migrant smuggling from Türkiye to Germany.

Infectious diseases and their imperative awareness gain major relevance through global warming and multi-continent refugee crises. Here, we demonstrate the challenges of malaria diagnosis, disease course, and treatment, including post-artesunate hemolysis in a Syrian refugee with severe falciparum malaria, most probably infected during migrant smuggling from Türkiye to Germany.

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe.

BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

Exploring the Longitudinal Stability of Food Neophilia and Dietary Quality and Their Prospective Relationship in Older Adults: A Cross-Lagged Panel Analysis.

Poor dietary quality is a major cause of morbidity, making the promotion of healthy eating a societal priority. Older adults are a critical target group for promoting healthy eating to enable healthy aging. One factor suggested to promote healthy eating is the willingness to try unfamiliar foods, referred to as food neophilia. This two-wave longitudinal study explored the stability of food neophilia and dietary quality and their prospective relationship over three years, analyzing self-reported data from N = 960 older adults (MT1 = 63.4, range = 50-84) participating in the NutriAct Family Study (NFS) in a cross-lagged panel design. Dietary quality was rated using the NutriAct diet score, based on the current evidence for chronic disease prevention. Food neophilia was measured using the Variety Seeking Tendency Scale. The analyses revealed high a longitudinal stability of both constructs and a small positive cross-sectional correlation between them. Food neophilia had no prospective effect on dietary quality, whereas a very small positive prospective effect of dietary quality on food neophilia was found. Our findings give initial insights into the positive relation of food neophilia and a health-promoting diet in aging and underscore the need for more in-depth research, e.g., on the constructs' developmental trajectories and potential critical windows of opportunity for promoting food neophilia.

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience.

BACKGROUND: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment. MATERIALS AND METHODS: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019. RESULTS: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities. CONCLUSION: ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease.

Rapid Education Event: A Streamlined Approach to Ultrasound Guided Nerve Block Procedural Training.

In the Emergency Medicine Residency setting, procedural ultrasound education often takes place at the bedside when the procedure becomes clinically necessary. As ultrasound technology and its applications continue to gain more importance, there is a greater need for effective and standardized educational models for teaching ultrasound-guided procedures. This pilot program aimed to demonstrate that residents and attending physicians can achieve procedural competence in fascia iliaca nerve block following a rapid and compact procedural education event. Our curriculum covered anatomy identification, procedural knowledge, and technical skills of probe manipulation. After completing our new curriculum, more than 90% of participants demonstrated adequate learning through the pre- and post-assessments and direct observation of procedural performance on a gel phantom model.

An experimental approach to training interoceptive sensitivity: study protocol for a pilot randomized controlled trial.

BACKGROUND: Eating in absence of hunger is quite common and often associated with an increased energy intake co-existent with a poorer food choice. Intuitive eating (IE), i.e., eating in accordance with internal hunger and satiety cues, may protect from overeating. IE, however, requires accurate perception and processing of one's own bodily signals, also referred to as interoceptive sensitivity. Training interoceptive sensitivity might therefore be an effective method to promote IE and prevent overeating. As most studies on eating behavior are conducted in younger adults and close social relationships influence health-related behavior, this study focuses on middle-aged and older couples. METHODS: The present pilot randomized intervention study aims at investigating the feasibility and effectiveness of a 21-day mindfulness-based training program designed to increase interoceptive sensitivity. A total of N = 60 couples participating in the NutriAct Family Study, aged 50-80 years, will be recruited. This randomized-controlled intervention study comprises three measurement points (pre-intervention, post-intervention, 4-week follow-up) and a 21-day training that consists of daily mindfulness-based guided audio exercises (e.g., body scan). A three-arm intervention study design is applied to compare two intervention groups (training together as a couple vs. training alone) with a control group (no training). Each measurement point includes the assessment of self-reported and objective indicators of interoceptive sensitivity (primary outcome), self-reported indicators of intuitive and maladaptive eating (secondary outcomes), and additional variables. A training evaluation applying focus group discussions will be conducted to assess participants' overall acceptance of the training and its feasibility. DISCUSSION: By investigating the feasibility and effectiveness of a mindfulness-based training program to increase interoceptive sensitivity, the present study will contribute to a deeper understanding of how to promote healthy eating in older age. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00024903. Retrospectively registered on April 21, 2021.