Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

In-House Virtual Planning and 3D Printed Surgical Guides for Reconstructive Rhinoplasty.

BACKGROUND: Performing rhinoplasty in patients with craniofacial malformations remains a challenge, even for experienced surgeons. Advances in 3D technology and its application in surgical planning and printing of cutting guides and splints have become important tools to improve aesthetic and functional results. OBJECTIVES: To describe an in-house workflow for surgical planning and printing of cutting guides and splints for complex rhinoplasty cases. METHODS: This article describes an in-house workflow for complex rhinoplasty, as used in the maxillofacial department of a children's hospital specialized in the treatment of cleft and craniofacial malformations. RESULTS: Customized surgical guides help the surgeon to harvest and mold potential septal and costochondral grafts more accurately, to reduce surgical time and to verify the dimensions of the sculpted nasal shape following surgical planning templates. Patient satisfaction degree according to Rhinoplasty Outcome Evaluation questionnaire was 18/24. CONCLUSIONS: The presented workflow represents a potential asset in obtaining more accurate and satisfactory results in complex rhinoplasties.

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer.

The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC.

Albumin-based nanostructures for uveal melanoma treatment.

Uveal melanoma (UM) is an intraocular tumor which is almost lethal at the metastatic stage due to the lack of effective treatments. In this regard, we have developed an albumin-based nanostructure (ABN) containing AZD8055 (ABN-AZD), which is a potent mTOR kinase inhibitor, for its efficient delivery to the tumors. The drug has been conjugated to ABN using tailored linkers that have a disulfide moiety, allowing its release selectively and effectively in the presence of an elevated concentration of glutathione, such as inside the tumoral cells. Our therapeutic approach induced significant cellular toxicity in uveal melanoma cells, but not in non-tumoral keratinocytes, highlighting the excellent selectivity of the system. In addition, these nanostructures showed excellent activity in vivo, decreasing the tumor surface compared to the free AZD8055 in mice models. Remarkably, the results obtained were achieved employing a dose 23 times lower than those used in previous reports.

A randomized clinical trial comparing the initial vascular approach to the inferior mesenteric vein versus the inferior mesenteric artery in laparoscopic surgery of rectal cancer and sigmoid colon cancer.

BACKGROUND: The inferior mesenteric artery approach with a selective lateral splenic flexure mobilization is the most widely used initial step in laparoscopic rectal and left colon surgery. Surgery started through the inferior mesenteric vein (IMV) with systematic medial mobilization (MM) has some theoretical advantages that have never been analyzed in a clinical trial. The aim of this study was to compare the two techniques with regards to surgical technique variables (conversion, surgical time, bleeding, morbidity, and mortality) and pathological outcomes. METHODS: A single-blinded, randomized, controlled trial of patients operated electively by laparoscopic with curative intention for rectal or sigmoid cancer was performed at a single, specialized colorectal surgery department from April 2016 to October 2017. RESULTS: 49 patients were included in each group. There were no statistical differences in patient demographics between the two approaches. Pathological outcomes did not differ between the two groups. Intra-operative characteristics showed a higher conversion rate in patients in which the inferior mesenteric artery was dissected first (p = 0.031). The artery approach also increased intra-operative bleeding (p = 0.049), but there were no differences regarding operative time. On multivariate analysis, the artery approach was associated with a higher risk of conversion (OR 8.68; p = 0.050). Post-operatory complications did not differ between artery and vein dissection. CONCLUSIONS: In our study, the initial approach by the IMV with a systematic MM of the splenic flexure has allowed us to reduce the conversion rate without increasing complications or the surgical time. No differences were observed in the pathological results. Both approaches seem to be safe and effective and well-trained laparoscopic surgeons should have the two techniques available to them for use as needed.

Is Seasonal Households' Consumption Good for the Nexus Carbon/Water Footprint? The Spanish Fruits and Vegetables Case.

Proximity and in-season consumption criteria have been suggested as solutions for fruits and vegetables consumers to drive the economy to a more sustainable development. Using a new concept, seasonal avoided footprint by imports, we disentangle the role of period and country of origin. Although, as a general rule, consumers could reduce the footprint by choosing domestic produce, this is not always the case. Due to the high efficiency of Spanish domestic production in terms of both CO2e and water use (except for scarce water), imports from some regions, like Africa (green beans, peppers, tomatoes, bananas, strawberries, oranges), contribute to significantly increasing both water and carbon impacts. However, a monthly basis analysis shows unsustainable hotspots for domestic production. Importing from France (apples, potatoes) or Portugal (tomatoes, strawberries) reduces both footprints, so Spanish local consumption would be bad for the environment. Hotspots are mainly concentrated in scarce water and, especially, for out-of-season vegetables during 11 months a year (savings up to 389%), nine months for out-of-season fruits, and five months for in-season fruits. The results suggest the difficulty to generalize an easy environmental recommendation based on buying local fruits and vegetables: consumption must be analyzed on monthly/seasonal, product, and country bases.

Are patients with bipolar disorder and comorbid attention-deficit hyperactivity disorder more neurocognitively impaired?

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

[How do Sick People and Their Caregivers Live Non-Invasive Ventilation? Systematic Literature Review of Qualitative Research]. / ¿Cómo viven la ventilación no invasiva los enfermos y sus cuidadores?.

Introduction: W know that non-invasive ventilation (NIV) is a basic ventilator support, but sometimes it fails, because of intolerance, lack of adherence, breach, etc. How can we anticipate that failure? We intend to explore the qualitative evidence on the experiences of people with this treatment and their formal and informal caregivers. Method: Systematic literature review of original articles indexed from 2005 to 2015, which study the NIV in adult population with qualitative methodology in six databases. Peer review of scientific quality with tool of the CASPe Program. Qualitative metasynthesis of the findings. Results: 15 articles met selection criteria, based on Grounded Theory and Phenomenology, which use interviews, observation and focus group, directed both patients, and families and health professionals. Its studies emphasize the feeling of anxiety and loss of control, although the NIV relieves them dyspnea (ambivalence). Search daily well-being through routines and active participation. Interaction dependence/autonomy, especially in decision-making, finding differences that make complex the process information and advance directives. Practical wisdom of nursing care 24 hours with patients id described basic, and difficulties being narrated: lack of time, overload of work, technocentrism, inexperience. Conclulsions: The qualitative evidence of treatment with VNI is varied although scarce; different plots (acute situations, chronic, terminals) are explored, from different points of view. The integration of these findings in our practice will help us to increase adherence and become the treatment successful, but especially to improve the quality of life of ventilated patients and their families.

Improved Protoplast Production Protocol for Fungal Transformations Mediated by CRISPR/Cas9 in Botrytis cinerea Non-Sporulating Isolates.

Botrytis cinerea is a necrotrophic fungus that causes considerable economic losses in commercial crops. Fungi of the genus Botrytis exhibit great morphological and genetic variability, ranging from non-sporogenic and non-infective isolates to highly virulent sporogenic ones. There is growing interest in the different isolates in terms of their methodological applications aimed at gaining a deeper understanding of the biology of these fungal species for more efficient control of the infections they cause. This article describes an improvement in the protoplast production protocol from non-sporogenic isolates, resulting in viable protoplasts with regenerating capacity. The method improvements consist of a two-day incubation period with mycelium plugs and orbital shaking. Special mention is made of our preference for the VinoTaste Pro enzyme in the KC buffer as a replacement for Glucanex, as it enhances the efficacy of protoplast isolation in B459 and B371 isolates. The methodology described here has proven to be very useful for biotechnological applications such as genetic transformations mediated by the CRISPR/Cas9 tool.

Multicore iron oxide nanoparticles for magnetic hyperthermia and combination therapy against cancer cells.

HYPOTHESIS: Multicore flower-like iron oxide nanoparticles (IONPs) are among the best candidates for magnetic hyperthermia applications against cancers. However, they are rarely investigated in physiological environments and their efficacy against cancer cells has been even less studied. The combination of magnetic hyperthermia, using multicore IONPs, with selected bioactive molecules should lead to an enhanced activity against cancer cells. EXPERIMENTS: Multicore IONPs were synthesized by a seeded-growth thermal decomposition approach. Then, the cytotoxicity, cell uptake, and efficacy of the magnetic hyperthermia approach were studied with six cancer cell lines: PANC1 (pancreatic carcinoma), Mel202 (uveal melanoma), MCF7 (breast adenocarcinoma), MB231 (triple-negative breast cancer line), A549 (lung cancer), and HCT116 (colon cancer). Finally, IONPs were modified with a chemotherapeutic drug (SN38) and tumor suppressor microRNAs (miR-34a, miR-182, let-7b, and miR-137), to study their activity against cancer cells with and without combination with magnetic hyperthermia. FINDINGS: Two types of multicore IONPs with very good heating abilities under magnetic stimulation have been prepared. Their concentration-dependent cytotoxicity and internalization have been established, showing a strong dependence on the cell line and the nanoparticle type. Magnetic hyperthermia causes significant cell death that is dramatically enhanced in combination with the bioactive molecules.

Analysis of the implementation of a circuit for intra-operative superposition and comparison of the surgical outcomes using ICBCT in maxillofacial surgery.

PURPOSE: This paper describes a novel circuit for intraoperative analysis with ICBCT in maxillofacial surgery. The aim is to establish guidelines, define indications, and conduct an analysis of the implementation of the circuit for intraoperative comparison of surgical outcomes in relation to 3D virtual planning in maxillofacial surgery. METHODS: The study included 150 maxillofacial surgical procedures. Intraoperative actions involved fluoroscopy localization, intraoperative CBCT acquisition, segmentation, and superimposition, among other steps. Surgical times due to intraoperative superposition were measured, including time required for ICBCT positioning and acquisition, image segmentation, and comparison of 3D surfaces from the surgical planning. RESULTS: Successful intraoperative comparison was achieved in all 150 cases, enabling surgeons to detect and address modifications before concluding the surgery. Out of the total, 26 patients (17.33%) required intraoperative revisions, with 11 cases (7.33%) needing major surgical revisions. On average, the additional surgical time with this circuit implementation was 10.66 ± 3.03 min (n = 22). CONCLUSION: The results of our research demonstrate the potential for performing intraoperative surgical revision, allowing for immediate evaluation, enhancing surgical outcomes, and reducing the need for re-interventions.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Exploring the Potential of Three-Dimensional Imaging, Printing, and Modeling in Pediatric Surgical Oncology: A New Era of Precision Surgery.

Pediatric surgical oncology is a technically challenging field that relies on CT and MRI as the primary imaging tools for surgical planning. However, recent advances in 3D reconstructions, including Cinematic Rendering, Volume Rendering, 3D modeling, Virtual Reality, Augmented Reality, and 3D printing, are increasingly being used to plan complex cases bringing new insights into pediatric tumors to guide therapeutic decisions and prognosis in different pediatric surgical oncology areas and locations including thoracic, brain, urology, and abdominal surgery. Despite this, challenges to their adoption remain, especially in soft tissue-based specialties such as pediatric surgical oncology. This work explores the main innovative imaging reconstruction techniques, 3D modeling technologies (CAD, VR, AR), and 3D printing applications through the analysis of three real cases of the most common and surgically challenging pediatric tumors: abdominal neuroblastoma, thoracic inlet neuroblastoma, and a bilateral Wilms tumor candidate for nephron-sparing surgery. The results demonstrate that these new imaging and modeling techniques offer a promising alternative for planning complex pediatric oncological cases. A comprehensive analysis of the advantages and limitations of each technique has been carried out to assist in choosing the optimal approach.

Multifunctional magnetic nanoparticles elicit anti-tumor immunity in a mouse melanoma model.

Immunotherapy has emerged as a promising strategy to eradicate cancer cells. Particularly, the development of cancer vaccines to induce a potent and sustained antigen-specific T cell response has become a center of attention. Herein, we describe a novel immunotherapy based on magnetic nanoparticles (MNP) covalently modified with the OVA254-267 antigen and a CpG oligonucleotide via disulfide bonds. The MNP-CpG-COVA significantly enhances dendritic cell activation and CD8+ T cell antitumoral response against B16-OVA melanoma cells in vitro. Notably, the immune response induced by the covalently modified MNP is more potent and sustained over time than that triggered by the free components, highlighting the advantage of nanoformulations in immunotherapies. What is more, the nanoparticles are stable in the blood after in vivo administration and induce potent levels of systemic tumor-specific effector CD8 + T cells. Overall, our findings highlight the potential of covalently functionalized MNP to induce robust immune responses against mouse melanoma.

A state-of-the-art guide about the effects of sterilization processes on 3D-printed materials for surgical planning and medical applications: A comparative study.

Surgeons use different medical devices in the surgery, such as patient-specific anatomical models, cutting and positioning guides, or implants. These devices must be sterilized before being used in the operation room. There are many sterilization processes available, with autoclave, hydrogen peroxide, and ethylene oxide being the most common in hospital settings. Each method has both advantages and disadvantages in terms of mechanics, chemical interaction, and post-treatment accuracy. The aim of the present study is to evaluate the dimensional and mechanical effect of the most commonly used sterilization techniques available in clinical settings, i.e., Autoclave 121, Autoclave 134, and hydrogen peroxide (HPO), on 11 of the most used 3D-printed materials fabricated using additive manufacturing technologies. The results showed that the temperature (depending on the sterilization method) and the exposure time to that temperature influence not only the mechanical behavior but also the original dimensioning planned on the 3D model. Therefore, HPO is a better overall option for most of the materials evaluated. Finally, based on the results of the study, a recommendation guide on sterilization methods per material, technology, and clinical application is presented.

Advanced Strategies for the Fabrication of Multi-Material Anatomical Models of Complex Pediatric Oncologic Cases.

The printing and manufacturing of anatomical 3D models has gained popularity in complex surgical cases for surgical planning, simulation and training, the evaluation of anatomical relations, medical device testing and patient-professional communication. 3D models provide the haptic feedback that Virtual or Augmented Reality (VR/AR) cannot provide. However, there are many technologies and strategies for the production of 3D models. Therefore, the aim of the present study is to show and compare eight different strategies for the manufacture of surgical planning and training prototypes. The eight strategies for creating complex abdominal oncological anatomical models, based on eight common pediatric oncological cases, were developed using four common technologies (stereolithography (SLA), selectie laser sinterning (SLS), fused filament fabrication (FFF) and material jetting (MJ)) along with indirect and hybrid 3D printing methods. Nine materials were selected for their properties, with the final models assessed for application suitability, production time, viscoelastic mechanical properties (shore hardness and elastic modulus) and cost. The manufacturing and post-processing of each strategy is assessed, with times ranging from 12 h (FFF) to 61 h (hybridization of FFF and SLS), as labor times differ significantly. Cost per model variation is also significant, ranging from EUR 80 (FFF) to EUR 600 (MJ). The main limitation is the mimicry of physiological properties. Viscoelastic properties and the combination of materials, colors and textures are also substantially different according to the strategy and the intended use. It was concluded that MJ is the best overall option, although its use in hospitals is limited due to its cost. Consequently, indirect 3D printing could be a solid and cheaper alternative.

Comparison between epidural technique and mid-axillary ultrasound-guided TAP block for postoperative analgesia of laparoscopic radical prostatectomy: a quasi-randomized clinical trial.

BACKGROUND: Our goal was to evaluate whether TAP block offers the same analgesic pain control compared to epidural technique in laparoscopic radical prostatectomy surgery through the morphine consumption in the first 48 hours. METHODS: In this study, 45 patients were recruited and assigned to either TAP or epidural. The main study outcome was morphine consumption during the first 48 hours after surgery. Other data recorded were pain at rest and upon movement, technique-related complications and adverse effects, surgical and postoperative complications, length of surgery, need for rescue analgesia, postoperative nausea and vomiting, start of intake, sitting and perambulation, first flatus, and length of in-hospital stay. RESULTS: From a total of 45 patients, two were excluded due to reconversion to open surgery (TAP group = 20; epidural group = 23). There were no differences in morphine consumption (0.96 vs. 0.8 mg; p = 0.78); mean postoperative VAS pain scores at rest (0.7 vs. 0.5; p = 0.72); or upon movement (1.6 vs. 1.6; p = 0.32); in the TAP vs. epidural group, respectively. Sitting and perambulation began sooner in TAP group (19 vs. 22 hours, p = 0.03; 23 vs. 32 hours, p = 0.01; respectively). The epidural group had more technique-related adverse effects. CONCLUSION: TAP blocks provide the same analgesic quality with optimal pain control than epidural technique, with less adverse effects.

Iron oxide-manganese oxide nanoparticles with tunable morphology and switchable MRI contrast mode triggered by intracellular conditions.

Stimuli-responsive nanomaterials are very attractive for biomedical applications. They can be activated through external stimuli or by the physico-chemical conditions present in cells or tissues. Here, we describe the preparation of hybrid iron oxide-manganese oxide core-satellite shell nanostructures that change their contrast mode in magnetic resonance imaging (MRI) from T2 to T1, after being internalized by cells. This occurs by the dissolution of the MnO2 of the shell, preserving intact the iron oxide at the core. First, we study the seeded-growth synthesis of iron oxide-manganese oxide nanoparticles studying the effect of varying the core size of the magnetic seeds and the concentration of the surfactant. This allows tuning the size and shape of the final hybrid nanostructure. Then, we show that the shell can be removed by a redox reaction with glutathione, which is naturally present inside the cells at much higher concentrations than outside the cells. Finally, the dissolution of the MnO2 shell and the change in the contrast mode is confirmed in cell cultures. After this process, the iron oxide nanoparticles at the core remain intact and are still active as heating mediators when an alternating magnetic field is applied.