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Wetlands are an important feature for our society that provides versatile benefits, such as habitat for diverse wildlife, shoreline erosion protection, flood control, and mitigation of climate change through capture and storage of carbon. The aim of this work was to assess the application of nanotechnologies for the restoration of the water quality in the Cascajo Wetlands, Peru, where the water quality was deteriorated. Ceramic-based bio-filters (CBBFs) were used to reduce and buffer the contamination rates of pollutants, whereas micro-nano bubbles (MNBs) were applied to increase the dissolved oxygen and release free radicals in water. Additionally, bio-fence was implemented to prevent water intrusion from the ocean. Remote sensing data through the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) was used to monitor the water surface condition. With treatment of CBBFs and MNBs for 13 months, we observed reduction in the chemical oxygen demand (COD), biological oxygen demand (BOD), total nitrogen (TN), and total phosphate (TP) in the water body, showing removal percentages of 98.5%, 97.5%, 98.1%, 98.5%, and 94.6%, respectively, in comparison with values before starting the implementation. The trends of NDVI and EVI over seasons are not completely aligned with the results taken from the wetlands treated with MNBs, CBBFs and bio-fence. While TN was highly correlated with the empirical value of TN based on remote sensing, no correlation was observed between COD and empirical COD. The use of eco-friendly techniques has performed efficiently to remove the pollutant.

Background Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration ClinicalTrails.gov, NCT03589014 . Retrospectively registered on 17 July 2018.

Background:International guidelines recommend combining pharmacological and non-pharmacological treatments for axSpA patients. Physiotherapists often rely on personalized exercise programs and self-management strategies (home-based exercises) to complement standard care and enhance patient outcomes [1]. Poor adherence to these programs can negatively impact results and increase healthcare costs. Digital Therapeutics (DTx) is a subset of digital health that encompasses various healthcare technologies used independently or alongside medications and therapies to optimize patient care and outcomes. DTx are emerging as a new form of therapeutic interventions but data on axSPa are scarce.Objectives:The primary aim was to evaluate the satisfaction of physiotherapists and axSpA patients using a DTx-based home rehabilitation program. Secondary objectives included assessing adherence, pain levels, depression, activities of daily living, and joint tenderness.Methods:A non-randomized, uncontrolled clinical trial was conducted with an intervention group comprising 20 patients and 10 physiotherapists recruited between June and July 2023 from Hospital S. Anna e S. Sebastiano, Rheumatology department in Caserta. Patients inclusion criteria were: age between 20 and 75 years, axSpa in remission status, basic technological proficiency, and ownership of an Android or iOS smartphone. The DTx used in the study allowed the physiotherapists to customize the rehabilitation programmes by selecting the frequency and type of exercises. Patients received home exercises programs on their devices and were guided by a virtual instructor providing real-time feedback. The technology, accessible to all, used the front camera of the patient’s personal smartphone or tablet to detect movements and offer real-time corrections and guidance. At T0, patients were trained to use the app and were assessed using various scales (Zung Self-Rating Depression Scale, Modified Health Assessment Questionnaire, Modified Ritchie Articular Scales Index, Numeric Rating Scale). After 3 months, the patients were reassessed and the User Satisfaction Evaluation Questionnaire (USEQ) was administered to both patients and physiotherapists. The patients’ average adherence to the exercise programme was monitored by the Dtx app.Figure 1.DTx app usedResults:The study included 11 males and 9 females with an average age of 55. After 3 months of DTx use, both physiotherapists (25.6 ± 1.2) and patients (21.7 ± 3.5) rated DTx as above-average in satisfaction according to USEQ. From T0 to T1, improvements were observed in ZSDS values (46.6 ± 14 to 39.5 ± 14.1; p < 0.05), MHAQ values (1.12 ± 0.4 to 0.8 ± 0.34; p < 0.05), MRAI values (11.75 ± 10.6 to 8.85 ± 8.67; p < 0.05), and NRS values (66 ± 13.3 to 40 ± 12). The average patient adherence to the exercise program was 41.55% ± 19.4. No adverse effects were recorded.Figure 1.Result of the USEQ questionnaire patients and physiotherapistsConclusion:The use of DTx in home exercises for axSpA patients is satisfactory for both patients and physiotherapists. Preliminary data indicate positive effects on depression, activities of daily living, pain levels, and adherence. A future randomized controlled trial (RCT) is necessary to validate these preliminary findings.REFERENCES:[1] Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, et al. Asas-EULAR recommendations for the management of Axial Spondyloarthritis: 2022 update. Annals of the Rheumatic Diseases. 2022;82(1):19–34. doi:10.1136/ard-2022-223296.Acknowledgements:We thank all the physical therapists, physicians, and people who performed this clinical study with professionalism and dedication.Disclosure of Interests:None declared.

A prospective, one-armed, safety non-inferiority trial with historical controls was performed at a single-center, quaternary, children’s hospital. Inclusion criteria were children aged 3 months–18 years after pediatric cardiac surgery resulting in a two-ventricle repair between 7/2020 and 7/2021. Eligible patients were compared with patients from a 5-year historical period (selected using a database search). The intervention was that “regular risk” patients received no diuretics and pre-specified “high risk” patients received 5 days of twice per day furosemide at discharge. 61 Subjects received the intervention. None were readmitted for pleural effusions, though 1 subject was treated for a symptomatic pleural effusion with outpatient furosemide. The study was halted after an interim analysis demonstrated that 4 subjects were readmitted with pericardial effusion during the study period versus 2 during the historical control (2.9% versus 0.2%, P  = 0.003). We found no evidence that limited post-discharge diuretics results in an increase in readmissions for pleural effusions. This conclusion is limited as not enough subjects were enrolled to definitively show that this strategy is not inferior to the historical practice. There was a statistically significant increase in readmissions for pericardial effusions after implementation of this study protocol which can lead to serious complications and requires further study before conclusions can be drawn regarding optimal diuretic regimens.

Colorectal cancer, the third most common cancer worldwide, affects 40–45% of patients on the right side. Surgery, especially minimally invasive methods such as laparoscopic and robotic procedures, is the preferred treatment. However, these techniques present technical complications. The anatomical complexity and variations in vessel branching patterns pose challenges, particularly for less experienced surgeons. The CoDIG 2 is a nationwide observational study involving 76 specialized Italian general surgery departments focused on colorectal surgery. The centres were directed to maintain their standard surgical and clinical practices. The aim of this study was to analyse the intraoperative vascular anatomy of Italian patients who underwent laparoscopic right colectomy and explore the ligature techniques used by Italian surgeons. Surgeons reported information about vascularization of the right colon for 616 patients and about surgical anatomy of RCA for 368 patients. Fifty-three patients (10.8%) showed no RCA intraoperatively. The right colic artery (RCA) was categorized according to the Yada classification (types 1–4) during evaluation, and intraoperative assessments revealed that Yada type 1 was the most common type (55.2%), while radiologic evaluations revealed a higher prevalence of type 2. Furthermore, compared with the superior mesenteric vein (SMV), the RCA is more often located anteriorly according to intraoperative and contrast-enhanced CT examination; 59.9% were found in the anterior position during intraoperative examination, while 40.1% were found in the same position on preoperative contrast-enhanced CT. Vascularization of the right colon, including missing branches, additional branches, shared trunks, and retro-superior courses of the mesenteric vein, exhibited notable variations. To understand vascular variations, a preoperative radiological study is necessary; although there was no concordance between the intraoperative and radiological evaluations, this is a limitation of preinterventional radiological evaluation (PII) because it is always needed for oncological staging. This approach is especially critical for inexperienced surgeons to avoid potential complications, such as problematic bleeding.

Purpose The aim of our prospective randomised trial was to demonstrate the efficacy and improvement in surgical skills of inexperienced surgeons in the balloon kyphoplasty procedures trained with virtual reality (VR) compared to untrained inexperienced surgeons. Methods Six orthopaedic residents were randomized to group VR1 (trained) and group VR0 (untrained, control group). At the beginning, all participants, after a theoretical lesson, performed a virtual kyphoplasty. Each resident of the Group VR1 did four training sessions in 1 month (2 h per week) and at the end of training was re-evaluated performing a virtual kyphoplasty. Residents were evaluated with global task completion time and rates subtask ability according to Global Rating Scale of Operative Performance adaptation (both in VR simulation and during the surgery). A percutaneous vertebral augmentation with balloon kyphoplasty was performed by all residents. Intraoperative parameters, complications and cumulative transfer effectiveness ratio (CTER) were analysed. Results Intraoperative scores revealed an improvement in the group VR1 between the first VR trial and the intraoperative phase (2.85 ± 0.65 vs. 4.09 ± 0.62, P  < 0.05), which was not seen in the group VR0 (2.71 ± 0.71 vs. 2.85 ± 0.75). Statistical analyses indicated significant differences in intraoperative scores between the two groups. The CTER was 0.85 and suggests that 10 training sessions could reduce the procedure time by approximately 8 min in a 15 min of surgery. Conclusion Our study about the balloon kyphoplasy reaffirms the potential of VR as an effective and cost-efficient training tool, bridging the gap between theoretical knowledge and practical execution.

• Background and Aims The extreme complexity of asclepiad flowers (Asclepiadoideae-Apocynaceae) has generated particular interest in the pollination biology of this group of plants especially in the mechanisms involved in the pollination processes. This study compares two South American species, Morrenia odorata and Morrenia brachystephana, with respect to morphology and anatomy of flower structures, dynamic aspects of the pollination mechanism, diversity of visitors and effectiveness of pollinators. • Methods Floral structure was studied with fresh and fixed flowers following classical techniques. The pollination mechanism was studied by visiting fresh flowers in the laboratory with artificial pollinator body parts created with an eyelash. Morphometric and nectar measurements were also taken. Pollen transfer efficiency in the flowers was calculated by recording the frequency of removed and inserted pollinia. Visitor activity was recorded in the field, and floral visitors were captured for subsequent analysis of pollen loads. Finally, pollinator effectiveness was calculated with an index. • Key Results The detailed structure of the flowers revealed a complex system of guide rails and chambers precisely arranged in order to achieve effective pollinaria transport. Morrenia odorata is functionally specialized for wasp pollination, and M. brachystephana for wasp and bee pollination. Pollinators transport chains of pollinaria adhered to their mouthparts. • Conclusions Morrenia odorata and M. brachystephana present differences in the morphology and size of their corona, gynostegium and pollinaria, which explain the differences in details of the functioning of the general pollination mechanism. Pollination is performed by different groups of highly effective pollinators. Morrenia species are specialized for pollination mainly by several species of wasps, a specialized pollination which has been poorly studied. In particular, pompilid wasps are reported as important pollinators in other regions outside South Africa. A putative new function of nectar in asclepiads is presented, as it would be contributing to the pollination mechanism.

Lung cancer maintains a relatively small survival rate (~19%) over a 5-year period and up to 80–85% of all lung cancer diagnoses are Non-Small Cell Lung Cancer (NSCLC). To determine whether metformin reduces non-small cell lung cancer (NSCLC) LL/2 cell growth, cells were grown in vitro and treated with metformin for 48 h. qPCR was used to assess genes related to cell cycle regulation and pro-apoptotic markers, namely Cyclin D, CDK4, p27, p21, and HES1. Treatment with 10 mM metformin significantly reduced HES1 expression (p = 0.011). Furthermore, 10 mM metformin treatment significantly decreased REDD1 (p = 0.0082) and increased p-mTOR Ser2448 (p = 0.003) protein expression. Control cells showed significant reductions in phosphorylated p53 protein expression (p = 0.0367), whereas metformin treated cells exhibited reduced total p53 protein expression (p = 0.0078). There were no significant reductions in AMPK, PKB/AKT, or STAT3. In addition, NSCLC cells were treated for 48 h. with 10 mM metformin, 4 µM gamma-secretase inhibitor (GSI), or the combination of metformin (10 mM) and GSI (4 µM) to determine the contribution of respective signaling pathways. Metformin treatment significantly reduced total nucleus expression of the proliferation maker Ki-67 with an above 65% reduction in Ki-67 expression between control and metformin-treated cells (p = 0.0021). GSI (4 µM) treatment significantly reduced Ki-67 expression by ~20% over 48 h (p = 0.0028). Combination treatment (10 mM metformin and 4 µM GSI) significantly reduced Ki-67 expression by more than 50% over 48 h (p = 0.0245). As such, direct administration of metformin (10 mM for 48 h) proved to be an effective pharmaceutical agent in reducing the proliferation of cultured non-small cell cancer cells. These intriguing in vitro results, therefore, support the further study of metformin in appropriate in vivo models as an anti-oncogenic agent and/or an adjunctive therapy.

Cells with stem cell properties have been isolated from various areas of the postnatal mammalian brain, most recently from the postnatal mouse cerebellum. We show here that inactivation of the tumor suppressor genes Rb and p53 in these endogenous neural stem cells induced deregulated proliferation and resistance to apoptosis in vitro. Moreover, injection of these cells into mice formed medulloblastomas. Medulloblastomas are the most common malignant brain tumors of childhood, and despite recent advances in treatment they are associated with high morbidity and mortality. They are highly heterogeneous tumors characterized by a diverse genetic make-up and expression profile as well as variable prognosis. Here, we describe a novel ontogenetic pathway of medulloblastoma that significantly contributes to understanding their heterogeneity. Experimental medulloblastomas originating from neural stem cells preferentially expressed stem cell markers Nestin, Sox2 and Sox9, which were not expressed in medulloblastomas originating from granule-cell-restricted progenitors. Furthermore, the expression of these markers identified a subset of human medulloblastomas associated with a poorer clinical outcome.

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06–1.53; P =0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37–0.80; P =0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.