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Jhoes Naylin R Plaza-Ccuno,1 Cristabel Vasquez Puri,1 Yaquelin E Calizaya-Milla,1 Wilter C Morales-García,2 Salomon Huancahuire-Vega,2 Anderson N Soriano-Moreno,2,* Jacksaint Saintila3,* 1School of Human Nutrition, Universidad Peruana Unión, Lima, Perú; 2Clinical and Epidemiological Research Unit, School of Medicine, Universidad Peruana Unión, Lima, Perú; 3School of Medicine, Señor de Sipán University, Chiclayo, Perú*These authors contributed equally to this workCorrespondence: Anderson N Soriano-Moreno, Clinical and Epidemiological Research Unit, School of Medicine, Universidad Peruana Union, Lima, Peru, Email andsor19@gmail.com Jacksaint Saintila, School of Medicine, Señor de Sipán University, Km 5, Carretera a Pimentel, Chiclayo, Lambayeque, 14001, Perú, Email jacksaintsaintila@gmail.comBackground: The pandemic has drastically impacted lifestyles, including the frequency, duration, and intensity of physical activity, which, in turn, leads to negative effects on job burnout among healthcare workers.Objective: This study evaluated the association between the level of physical activity and job burnout in a sample of health professionals during health emergency.Methods: In this cross-sectional study, 300 workers working in a public hospital, located in the city of Rioja, Department of San Martin, Peru, were considered. Data were collected through an online and face-to-face survey. Job burnout was assessed using a validated questionnaire adapted to the Peruvian population and physical activity was assessed based on a single item. Crude and adjusted linear regression models were created to assess the association between the frequency of physical activity performed weekly and the level of job burnout.Results: In the crude models, it was observed that participants who performed physical activity 1– 2 times, 3– 4 times, or more than 4 times per week had, respectively, 6.29 (95% CI, 11.00– 1.59), 14.28 (95% CI, 21.70– 6.85), and 14.95 (95% CI, 25.17– 4.72) lower job burnout points compared to those who never performed physical activity. In the model adjusted for confounding variables, the association of this result was maintained, showing a dose-response effect.Conclusion: These findings suggest the need for the implementation of health education programs that include physical activity to minimize the negative effects of job burnout and ensure better medical care by health professionals for the benefit of patients.Keywords: health care workers, physical activity, COVID-19, occupational stress, job burnout, Peru

Age-associated changes in T-cell function play a central role in immunosenescence. The role of aging in the decreased T-cell repertoire, primarily because of thymic involution, has been extensively studied. However, increasing evidence indicates that aging also modulates the mechanical properties of cells and the internal ordering of diverse cell components. Cellular functions are generally dictated by the biophysical phenotype of cells, which itself is also tightly regulated at the molecular level. Based on previous evidence suggesting that the relative nuclear size contributes to variations of T-cell stiffness, here we examined whether age-associated changes in T-cell migration are dictated by biophysical parameters, in part through nuclear cytoskeleton organization and cell deformability. In this study, we first performed longitudinal analyses of a repertoire of 111 functional, biophysical and biomolecular features of the nucleus and cytoskeleton of mice CD4

The mechanical properties of the extracellular matrix (ECM) determine cell differentiation, proliferation and migration through mechanoresponsive proteins including YAP. However, how different mechanical signals cooperate, synergize or compete to steer cell behavior remains poorly understood. Here, we have examined competition between the two major ECM mechanical cues, i.e. rigidity, which activates cell mechanosensing, and viscous energy dissipation, which reduces stiffness blunting cell mechanotransduction. To trigger competition, we have engineered protein hydrogels allowing concomitant modulation of stiffness and viscosity by mechanisms characteristic of native ECM. Culturing cells on these hydrogels, we have found that substrate energy dissipation attenuates YAP mechanosensing prevailing over stiffness cues. Hampered YAP activation on more dissipative substrates correlates with faster actin flow and smaller focal adhesions. Mechanistically, inhibition of actomyosin contractility reverses the outcome of the competition between rigidity and energy dissipation. Our results highlight the dominating contribution of substrate viscosity to the biology of the cell.

Ageing is interrelated with the development of immunosenescence. This article focuses on one of the cell sets of the adaptive immune system, T cells, and provides a review of the known changes in T cells associated with ageing. Such fundamental changes affect both cell molecular content and internal ordering. However, acquiring a complete description of the changes at these levels would require extensive measurements of parameters and, furthermore, important fine details of the internal ordering that may be difficult to detect. Therefore, an alternative approach for the characterisation of cells consists of the performance of physical measurements of the whole cell, such as deformability measurements or migration measurements: the physical parameters, complementing the commonly used chemical biomarkers, may contribute to a better understanding of the evolution of T-cell states during ageing. Mechanical measurements, among other biophysical measurements, have the advantage of their relative simplicity: one single parameter agglutinates the complex effects of the variety of changes that gradually appear in cells during ageing.

Background Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease affecting skin that bears apocrine glands and is characterised by painful, deep-seated, inflamed lesions. Treatment includes antibiotics, steroids, surgery, and adalimumab as the only approved biological agent. An association between inflammatory bowel disease (IBD) and HS has been reported, but very limited evidence exists on the efficacy of non-anti-TNF biological agents for the treatment of HS in IBD patients. Methods This multicenter case series was performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project by ECCO. Cases of patients with HS and IBD treated with non-anti-TNF biological agents were retrospectively collected through a standardised collection form. Efficacy measures were reported by the local gastroenterologist/dermatologist using physician global assessment (PGA). Results Fifty-five patients (65.5% women, median [IQR] age 40.0 [33.1-47.6] years, 50.9% active smokers) were identified (Table 1), all with HS diagnosis confirmed by a dermatologist. We observed a strong CD predominance (90.9%) in the current cohort. HS affected mainly the inguinal (82.0%) and axillary (76.0%) regions, followed by the anogenital region (46.0%). In 42 patients, HS was diagnosed a median of 10.0 [4.3-16.4] years after the IBD diagnosis, whereas in 13 HS preceded the IBD diagnosis by 4.1 [2.2-5.4] years. Prior to initiating a non-anti-TNF biological agent, all patients had been exposed to at least 1 anti-TNF agent, including (high dose) adalimumab in 83.2% of the cases. In 20% of patients, HS developed while being treated with an anti-TNF agent. After anti-TNF failure (for either IBD and/or HS), physicians opted for ustekinumab (83.6%), vedolizumab (14.5%), or risankizumab (1.8%) as the preferred first non-anti-TNF agent. During ustekinumab treatment (n=46, median time on therapy 2.1 [0.8-3.3] years)), 76.1% showed a clinically relevant HS improvement (including 50.0% complete remission), whereas 23.9% did not experience any benefit. With vedolizumab (n=8), 37.5% experienced some benefit (including 25.0% with complete remission), while 62.5% did not report any improvement. The single patient on risankizumab had complete remission. Finally, 6 out of 8 vedolizumab-treated patients were ultimately treated with ustekinumab, reporting a clinical benefit in 5 out of 6. Conclusion Ustekinumab is the preferred biological agent after anti-TNF failure in IBD patients with concomitant HS. Although placebo-controlled trials are lacking and ustekinumab is not approved for the treatment of HS, the current multi-centre case series demonstrates a substantial benefit in 78.4% of patients.

Background There are limited data available on the course of IBD in patients with solid organ transplantation. The aim of this ECCO CONFER study was to evaluate the trend of IBD before and after solid organ transplantation but liver. Methods This was a retrospective observational multicentre study that collected cases through the CONFER project. Patients with an established IBD diagnosis who underwent a solid organ transplantation (with the exception of liver) were eligible candidates. Results 33 patients with solid organ transplantation (67% male; 55% CD) were collected from 12 referral centres in five different countries. Mean age was 53 ± 16 years. 34 organs were transplanted in 33 patients. Most of the patients underwent kidney transplantation (n=27, 82%). 4 (12%) received a heart and 1 (3%) underwent lung transplantation; 1 (3%) underwent a combined heart and kidney transplant. The mean duration of IBD was 18.4 ± 14.7 months. Clinical characteristics are summarized in Table 1. The median follow-up after transplantation was 4.3 years (IQR 3.25 – 10.7). 7/33 patients (21.2%) experienced organ rejection, with 1 kidney retransplant. Regarding immunosuppressive therapy, 29/33 patients (88%) were treated with tacrolimus, 25 (76%) with systemic steroids, 22 (67%) with mycophenolate mofetil, 11 (33%) with everolimus, 6 with cyclosporine (18%), 3 (9%) with thiopurines. Regarding biologics, 1 patient was treated with infliximab, 2 with adalimumab, 2 with vedolizumab, 1 with ustekinumab. Defining a severe IBD course the need for biologic therapy or bowel resection or hospitalization, 4 patients (11.7%) had a severe disease course after transplantation versus 3 patients (9.3%) in the first 51 months of disease before transplantation (p = 0.26). Univariate analysis is reported in Table 2. 1 case of low-grade dysplasia was found 10 years after the transplantation. 1 case of colorectal cancer was found in a patient affected by CD five years after kidney transplantation. The other cases of tumours after transplantation are reported in Table 3. The first serious infectious episode after transplantation is shown in Table 4: 17 of 33 patients (51.5%) reported at least 1 episode of serious infection. In total 29 different serious infectious episodes after transplantation were recorded, compared to 28 episodes in the pre-transplantation period. At the last follow-up visit, 6/33 (18.2%) patients had died: 1 due to cholangiocarcinoma, 1 amyloidosis, 1 heart failure, 1 myocardial infection (2 not available). Conclusion Solid organ transplantation appears to have a satisfactory course for both the transplanted organ and IBD, in terms of organ survival and IBD severity; furthermore, the use of biologics in these patients does not appear to be linked to a worse outcome.

Total lymphoid irradiation (TLI) is used in the management of pediatric allogeneic hematopoietic stem cell transplantation (HSCT. This work aims to simplify the treatment planning process for TLI via a proposed template using the volumetric modulated arc therapy (VMAT) technique. Fifteen pediatric patients were planned, prescribed to 8 Gy in 4 fractions. Cost functions included in the template were the ones for the planning target volume (PTV), and conformality cost function (CCF) for the rest of the patient's volume. Conformity index (CI), homogeneity index (HI), conformation number (CN), gradient index (GI), integral dose, and doses to the organs at risk achieved with the template were reported. Cost function influence over various indexes was studied by Wilcoxon signed ranks test. Same 15 patients were planned with 3-dimensional conventional radiotherapy (3D-CRT) technique for comparison. Mean CI and HI were 1.33 and 0.13, respectively, which indicates good dose conformation and homogeneity. Mean CN and GI values were 0.69 and 4.51, respectively. Mean PTV coverage was reached (V100% > 95%). No correlation between the CCF and indexes values was found (p > 0.05). Doses to organs at risk (OARs) were as low as possible without losing PTV coverage. VMAT plan showed higher levels of conformation and similar homogeneity as 3D-CRT plans. Doses to OARs were inferior with VMAT except for the right kidney. The proposed template simplifies the planning of TLI treatments, and it is able to create acceptable plans with little modification in order to reduce doses to certain organs like the kidneys or the heart. VMAT technique showed higher conformation and lower doses to OAR compared to 3D-CRT.

Deformability and internal ordering are key features related to cell function, particularly critical for cells that routinely undergo large deformations, like T cells during extravasation and migration. In the measurement of cell deformability, a considerable variability is typically obtained, masking the identification of possible interrelationships between deformability, internal ordering and cell function. We report the development of a single-cell methodology that combines measurements of living-cell deformability, using micropipette aspiration, and three-dimensional confocal analysis of the nucleus and cytoskeleton. We show that this single-cell approach can serve as a powerful tool to identify appropriate parameters that characterize deformability within a population of cells, not readably discernable in population-averaged data. By applying this single-cell methodology to mouse CD4+ T cells, our results demonstrate that the relative size of the nucleus, better than other geometrical or cytoskeletal features, effectively determines the overall deformability of the cells within the population.

Mitochondrial DNA sequences were found inserted in the nuclear genome of mouse peritoneal T lymphocytes that increased progressively with aging. These insertions were preferentially located at the pericentromeric heterochromatin. In the same individuals, binucleated T-cells with micronuclei showed a significantly increased frequency associated with age. Most of them were positive for centromere sequences, reflecting the loss of chromatids or whole chromosomes. The proliferative capacity of T lymphocytes decreased with age as well as the glutathione reductase activity, whereas the oxidized glutathione and malondialdehyde concentrations exhibited a significant increase. These results may point to a common process that provides insights for a new approach to understanding immunosenescence. We propose a novel mechanism in which mitochondrial fragments, originated by the increased oxidative stress status during aging, accumulate inside the nuclear genome of T lymphocytes in a time-dependent way. The primary entrance of mitochondrial fragments at the pericentromeric regions may compromise chromosome segregation, causing genetic loss that leads to micronuclei formation, rendering aneuploid cells with reduced proliferation capacity, one of the hallmark of immunosenescence. Future experiments deciphering the mechanistic basis of this phenomenon are needed.

Background The use of biological drugs for the treatment of IBD in elderly patients is becoming more frequent in our environment. However, given the greater risk of these patients to develop related adverse effects, the profile of the patients in whom it is applied and the type of drug to choose, has not been established. Methods Patients have been retrospectively included with established diagnosis of IBD UC, CD or indeterminate colitis (IC) by usual criteria (clinical, laboratory, endoscopic, radiological and / or histological) 65 years at the time of initiating biological treatment (Infliximab, Adalimumab, Golimumab, Ustekinumab or Vedolizumab) and that they have received at least the induction doses. Variables corresponding to the baseline characteristics of the patients have been collected, as well as data referring to the characteristics of IBD that have been considered relevant for the study. We calculated the comorbidity of the patients using the Charlston index The statistical analysis was completed using Stata 15.0. For continuous variables, after checking the normality of the distribution, were compared using t Student and categorical variables chi2 test for proportions Results 1090 biological treatments started in patients aged 65 years or older have been retrospectively included. The baseline characteristics are summarized in TABLE 1 and those related to his IBD in TABLE 2.most used treatments in order of frequency were: Infliximab (377, 34.8%), Adalimumab(311, 28.7%),Golimumab (28, 2.6%), Ustekinumab (157, 14.5%) and Vedolizumab (209, 19.3%). It should be noted that most of the patients had monotherapy treatment, finding only 27.7% (299 patients) combined with immunosuppressants (IMS) (thiopurines in 72.9% of cases). Identify 705 patients (64.8%) had a Charlston score = 3 points (high comorbidity). It was objective that the choice of the type of biological could be conditioned by the presence of comorbidity, presenting 22% of the patients (66 cases) who opted for Ustekinumab / vedolizumab high comorbidity versus 15% of patients with antiTNF (98 cases) with high comorbidity. (p = 0.012). It was investigated whether the antecedent of neoplasia influenced the choice of biological treatment, finding that 47% of the cases (72 patients) opted for antiTNF and in 53% (80 patients) by ustekinumab / vedolizumab, these differences being statistically significant(p Conclusion In our experience, biological drugs with different therapeutic targets are used in elderly patients, generally in non-frail patients.The use of more specific treatments(ustekinumab, vedolizumab)is preferred in those with greater associated comorbidity

Background The most feared adverse events related to biological treatment in patients with inflammatory bowel disease (IBD) are the development of tumors and / or serious infections. These events are generally more frequent in elderly patients, so the increased use of biological drugs in these patients today makes it necessary to assess the safety of these drugs in this population. Methods Patients have been retrospectively included with established diagnosis of IBD at age, 65 at the time of initiating biological treatment(Infliximab, Adalimumab, Golimumab, Ustekinumab or Vedolizumab).Data regarding the development of oncological events during treatment have been collected. Variables related to infectious processes during biological treatment have also been included, documented by microbiological analysis and requiring systemic treatment and / or hospitalization(excluding bowel infection by CMV). Statistical analysis was performed with Stata, 15.0,categorical variables were compared with the chi2 test for proportions Results 1090 patients have been retrospectively included. Regarding the development of tumors, we observed an oncological event in, 74 (6.9%). They developed in, 30 patients (8%) with infliximab, 23 patients (7.1%) with adalimumab, 3 patients(11.1%) with golimumab, 10 patients (6.4%) with ustekinumab, and, 8 (3, 8%) vedolizumab. It was significantly lower(p = 0.04) for the vedolizumab group compared to other treatments, however, statistical significance was not reached for the ustekinumab group (p = 0.5)., 31% (23 patients) had an oncological history prior to the start of the biological treatment under study. The most frequently developed tumors were cutaneous, not melanocytic in, 10 patients, lung in, 10 patients and hematological tumors (7 non-Hodgkin lymphoma, 3 acute leukemias and, 2 intestinal lymphomas), 7 bladder tumors, 5 prostate and, 4 colorectal carcinoma.Regarding the development of infections, these occurred in, 160 patients during biological treatment(14.9%), without differences between the different biological drugs used (p = 0.61): infliximab, 61,(19.4%), adalimumab, 39 (12.5%), golimumab, 5(17.8%), ustekinumab, 22(14.1%), and vedolizumab, 34 (16.5%).Likewise, 85 (53.1%) require hospitalization due to the infectious process and in, 51(31.9%), it is permanently suspended due to the infection.Until the end of the follow-up, 158 patients (36.4%) suspended the biological drug due to an adverse effect, with the time until suspension:, 1.47 years(mean); SD:1.6 Conclusion In our experience, the development of tumors is more frequent in patients who use anti-TNF compared to other targets, although its incidence is generally low. However, there are no differences in the development of infections between the different biological treatments.

The prominence of spider silk as a hallmark in biomimetics relies not only on its unrivalled mechanical properties, but also on how these properties are the result of a set of original design principles. In this sense, the study of spider silk summarizes most of the main topics relevant to the field and, consequently, offers a nice example on how these topics could be considered in other biomimetic systems. This review is intended to present a selection of some of the essential design principles that underlie the singular microstructure of major ampullate gland silk, as well as to show how the interplay between them leads to the outstanding tensile behavior of spider silk. Following this rationale, the mechanical behavior of the material is analyzed in detail and connected with its main microstructural features, specifically with those derived from the semicrystalline organization of the fibers. Establishing the relationship between mechanical properties and microstructure in spider silk not only offers a vivid image of the paths explored by nature in the search for high performance materials, but is also a valuable guide for the development of new artificial fibers inspired in their natural counterparts.

Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep‐tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical‐thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto‐based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto‐triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment., A magnetomechanical thermal induction therapy (MTIT) strategy is developed based on a single platform of assembly of magnetic nanocubes coupled with alternating magnetic fields. There is a synergistic effect between mechanical responses and thermal properties, which is highly efficient both in vitro and in vivo. The mechanisms of the synergistic effect are investigated, which can be attributed to the manipulation of biochemical reactive oxygen species (ROS) signal level. This MTIT strategy holds potential for precise treatment of deep‐seated tumors in a spatiotemporal controllability.

Polyacrylamide hydrogels are interesting materials for studying cells and cell&ndash, material interactions, thanks to the possibility of precisely adjusting their stiffness, shear modulus and porosity during synthesis, and to the feasibility of processing and manufacturing them towards structures and devices with controlled morphology and topography. In this study a novel approach, related to the processing of polyacrylamide hydrogels using soft-lithography and employing microstructured templates, is presented. The main novelty relies on the design and manufacturing processes used for achieving the microstructured templates, which are transferred by soft-lithography, with remarkable level of detail, to the polyacrylamide hydrogels. The conceived process is demonstrated by patterning polyacrylamide substrates with a set of vascular-like and parenchymal-like textures, for controlling cell populations. Final culture of amoeboid cells, whose dynamics is affected by the polyacrylamide patterns, provides a preliminary validation of the described strategy and helps to discuss its potentials.

Background Biological drugs are being increasingly used for the treatment of inflammatory bowel diseases (IBD) in elderly patients. Despite the particular characteristics of this population subgroup, the efficacy and safety of these treatments in real clinical practice is poorly evaluated. Methods Retrospective and multicenter study of GETECCU, carried out in 28 Spanish hospitals. Patients with IBD who started biological treatment (Infliximab, Adalimumab, Golimumab, Ustekinumab or Vedolizumab) aged 65 years or older were included. Efficacy (clinical- at the criteria of the responsible physician-, biochemical and endoscopic) was assessed at 12-14 weeks and at 52 weeks of treatment. Adverse effects such as tumors or serious infections were also recorded. Results A total of 570 patients were included, baseline characteristics are shown in Table 1. Biologics used were: Infliximab (214, 37.5%), Adalimumab (167, 29.3%), Golimumab (16, 2.8%), Ustekinumab (73, 12.8%) and Vedolizumab (100, 17.5%). After 12-14 weeks of treatment, in 38.7% (220) of the cases clinical remission had been achieved and in 47.7% (270) there was clinical response without remission. However, 80 patients (13.9%) had no response, resulting in treatment discontinuation due to primary failure. At week 52, only 379 patients (66.5%) continued on biological treatment: 216 (57%) were in clinical remission (216, 57.0%) while 129 (34%) had response without remission and 34 (9%)had no response. In addition, 119 patients (21%) had an endoscopic study performed: 47 (39,5%) presented with endoscopic remission, 38 (31,9%) with mild activity, 28 (23,5%) with moderate activity and 6, (5.1%) with severe activity. At the end of the follow-up, only 60% of the patients continued on biological treatment, being the reason for withdraw lack of efficacy or due to the report of adverse side effects. Regarding treatment safety in this population, 12.1% (68 patients) suffered an infectious complication with a microbiological diagnosis, requiring hospitalization in 62.1% of the cases. In addition, 39 patients (6.9%) were diagnosed with a tumor until the end of the follow-up, noting that 34.2% of the cases continued on biological therapy after the diagnosis. Likewise, in 25 patients (36.8%) this infection forced discontinuation of biological treatment. Finally, 10 patients stopped biological treatment due to a serious adverse reaction to it Conclusion Response rates to biological treatment in elderly patients are similar to those described in the general population, with approximately one third of failures happening during the first year. However, a remarkable proportion of patients developed a serious adverse effect that could be related to treatment

Background Patients with colon Inflammatory Bowel Disease (IBD) have a higher risk of colorectal cancer (CRC) than general population. Current guidelines establish endoscopic surveillance recommendations; however, epidemiological studies show poor compliance. The main aim of our study was to analyse adherence to endoscopic surveillance guidelines. Secondary aim was to evaluate the prevalence and time-to advanced lesions or CRC. Methods Retrospective multicentre study of patients with IBD followed-up in the participating centres between 2005 and 2020, who were diagnosed of IBD between 2005 and 2008, with criteria for CRC surveillance. Patients with CRC before IBD diagnosis were excluded. The ECCO 2013–2017 guidelines were used to evaluate adherence. Adenomatous lesions with >25% of villous component, >1cm or with high-grade dysplasia or serrated lesions >1cm or with any degree of dysplasia were considered advanced lesions. Software used for all analysis was R in its 3.6.1 version. Normality was checked with the Shapiro-Wilks test. Mean comparison was carried out using t-Student test while normality assumptions held true, otherwise, Mann-Whitney test. Time-to advanced lesions or CRC event between patients that had adherence to ECCO guidelines versus those who did not was performed through Kaplan-Meier and Log-rank test. P-values below 0.05 were considered significant. Results A total of 1004 (713 Ulcerative Colitis, 252 Crohn’s disease and 39 Indeterminate Colitis; 52% male) patients from 25 centres were recruited with a median age of 36 (26–47) years. 87% of all patients were included in the endoscopic surveillance programme. The main reasons for non-inclusion were the absence of indication by the physician (38%) and the presence of inflammatory activity (37%). Adherence to the first or subsequent surveillance colonoscopies was 45% and 61%, respectively, with a total adherence rate of 32%. Prevalence of advanced lesions or CRC was 4% and 7 cases of CRC were detected. Time-to-detection of these lesions since IBD diagnosis was significantly longer in non-adherent patients (13.4 + 1.3 vs13.04 + 1.7; p Conclusion Adherence to ECCO guidelines for endoscopic surveillance is low in this Southern European population. A higher and earlier detection of advanced lesions or CRC was identified in the adherent group. The results of this study highlight the need to improve compliance with the recommendations to obtain better outcomes.

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).

Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.

As spun silkworm (Bombyx mori) silk fibers were compared in terms of their tensile behavior and microstructure with fibers subjected to different degumming treatments. Fibers were initially retrieved by forced silking directly from the worms and, either characterized in the as spun condition, or subjected to one of the following treatments: immersion in water, conventional degumming or degumming under longitudinally constrained conditions. Microstructure was assessed by X-ray diffraction and Raman spectroscopy. In addition, polyacrylamide gel electrophoresis was used to determine the influence of degumming on silk at a molecular level. Our study not only shows that degumming represents a major contribution to the accepted idea of silkworm silk as a highly variable material, but also provides new insights in the relationship between microstructure and tensile behavior in these fibers. In particular, it is shown that the arrangement of the hydrogen bond network in fibers subjected to different treatments plays a critical role in determining the mechanical behavior of silkworm silk., The work was funded by Ministerio de Economía y Competitividad (Spain) through projects MAT2012-38412-C02-01 and DPI2013-46485, by the Comunidad de Madrid (Spain) (Grant S2011/BMD-2460) and by Fundación Marcelino Botín and by Banco Santander through its Santander Universities Global Division. MINECO/ICTI2013-2016/DPI2013-46485

The need to quantify the uptake of 131I in the thyroid of the exposed population or workers is one of the main concerns to take into account in case of nuclear or radiological emergencies. In such scenarios, due to the high volatility and rapid intake by inhalation of 131I, it is very important a rapid identification of the exposed individuals to know their level of internal contamination in order to establish action protocols and countermeasures. In vivo measurements of 131I in the thyroid by gamma spectrometry at Whole Body Counters (WBC) is the recommended technique, but it is difficult to manage in case of a large number of individuals potentially exposed. It is known that gamma cameras located in the nuclear medicine services are available at most hospitals and could be used as an alternative method in order to provide support in the emergency response. Thus, this work describes a methodology to calibrate this kind of equipment with anthropometric phantoms to carry out direct measurement of 131I in thyroid for the quantification of internal contamination of the exposed population. A Gamma Camera (GC) of a public hospital from Madrid, H.U. La Paz, was calibrated for such purpose taking into account that a realistic geometry (10 cm distance from GC to phantom) and a rapid screening (counting time of 300 s with collimators removed) of internally contaminated individuals is necessary at early stage response. The calibration factors obtained for 131I vary with thyroid size being in the range of 0.0459 to 0.0541 cps·Bq-1. The minimum detectable activity (MDA) also varies with the thyroid size of the phantoms being in the range of 67 Bq to 79 Bq. An estimation of minimum detectable effective dose for children (E(70)) and adults (E(50)) has been carried out, taking into account such MDA values. Results show that, assuming a scenario of acute inhalation of 131I by members of the public, this methodology allows estimating doses far below 1 mSv three days after the intake. Moreover, the validation of the methodology has been carried out by participating in an international intercomparison exercise (CATHYMARA project, EC-OPERRA 2016–2017) for the in vivo measurement of 131I in thyroid to the exposed population in emergencies.

With five decades of sustained application, micropipette aspiration has enabled a wide range of biomechanical studies in the field of cell mechanics. Here, we provide an update on the use of the technique, with a focus on recent developments in the analysis of the experiments, innovative microaspiration-based approaches, and applications in a broad variety of cell types. We first recapitulate experimental variations of the technique. We then discuss analysis models focusing on important limitations of widely used biomechanical models, which underpin the urge to adopt the appropriate ones to avoid misleading conclusions. The possibilities of performing different studies on the same cell are also considered.

The possibility of spinning regenerated silkworm (Bombyx mori) fibers from a range of aqueous dopes by using a biomimetic approach based on straining flow spinning is explored in this work. It is found that spinning conditions can be established that allow fibers to be produced from environmentally friendly dopes with fibroin concentrations even one order of magnitude lower than that of the natural system. However, it is also found that the spinning process is favored and that the mechanical properties of the fibers are improved when dopes with higher fibroin concentration are employed. Since highly concentrated fibroin solutions in water are unstable, a stabilizing agent is required in order to obtain a spinnable dope at such large protein concentrations. CaCl2 is found to be an adequate stabilizing agent compatible with the straining flow spinning process. The optimization of the spinning parameters leads to the production of high-performance fibers with a work to fracture comparable to that of the natural material. Ministerio de Economía y Competitividad en España MAT2016-75544-C2- 1-R, MAT2016-79832-R y DPI2016-78887-C3-1-R

Background Approximately one half of the patients with Crohn’s disease (CD) develop intestinal strictures during their lifetime. The effectiveness of currently approved drugs in fibrosis-predominant lesions is very limited. Our aim was to determine the effectiveness of anti-TNF therapy in CD complicated by symptomatic intestinal strictures in a real-world setting. Methods We included adult patients with symptomatic stricturing CD receiving their first-line anti-TNF therapy. Strictures were defined as constant luminal narrowing with pre-stenotic dilatation. We excluded those patients with previous anti-TNF exposure, surgery or endoscopic therapy of the stenosis. The effectiveness of the anti-TNF was defined as a composite outcome combining the persistence of the treatment and without dose or frequency intensification, with no new immunomodulators, surgery or endoscopic therapy during follow-up. A multivariate Cox regression was performed and the final multivariate model was determined using a backward procedure. Results A total of 262 patients from 32 sites were included (141 received infliximab and 121 adalimumab). The median number of stenosis per patient was 1 (range 1–9). The treatment was effective in 81% and 59% of patients after 6 and 12 months, respectively, while this outcome was fulfilled by 21% after a median of 40 months (IQR, 19–85). During follow-up, anti-TNF therapy required a dose or frequency adjustment in 39% of patients, 12% required a new immunomodulator or endoscopic therapy in 4%. The proportion of subjects requiring surgery was 15% and 21% after 1 and 2 years, respectively, with an overall rate of surgery of 32%. Infliximab was associated with a higher rate of surgery as compared with adalimumab (OR 1.78; 95% CI, 1,025-3,09). A shorter time since the diagnosis of CD or the stricture and the initiation of anti-TNF therapy was associated with a greater effectiveness at 6 and 12 months (HR 0.99 95% CI 0.99–1, p = 0.045; HR 0.99 95% CI 0.99–0.99, p = 0.015; HR 0.98 95% CI 0.96–0.99, p = 0.024; HR 0.99 95% CI 0.98–1.0, p = 0.046; respectively). In the survival analysis, younger age, lower albumin levels at baseline, strictures being located in the descending colon, concomitant use of mesalamine and the presence of ulcers or lymphadenopathy at the stricture were associated with lower effectiveness. The anti-TNF agent was discontinued in 131 patients (50%), and 88 subjects (34%) required a switch to a new biologic. Conclusion Anti-TNF agents are effective in approximately 20% of patients with CD complicated with symptomatic strictures. Early introduction of anti-TNF therapy improves the effectiveness in the short term in these patients. Some clinical and radiological predictors can identify patients with a lower probability of response.

A comparative analysis of T-lymphocyte mechanical data obtained from Micropipette Aspiration (MPA) and Atomic Force Microscopy (AFM) is presented. Results obtained by fitting the experimental data to simple Hertz and Theret models led to non-Gaussian distributions and significantly different values of the elastic moduli obtained by both techniques. The use of more refined models, taking into account the finite size of cells (simplified double contact and Zhou models) reduces the differences in the values calculated for the elastic moduli. Several possible sources for the discrepancy between the techniques are considered. The analysis suggests that the local nature of AFM measurements compared with the more general character of MPA measurements probably contributed to the differences observed. pre-print 1,18 MB

Straining Flow Spinning is a versatile and robust spinning technique for the production of regenerated silkworm silk fibers using mild chemistries. However, reaching high values of tensile strength and strain at breaking requires a step of wet-stretching in water, which limits scalability and the practical usage of the technique. Here, we show that adding a post-spinning drawing step to the procedure improves the performance of the fibers, and allows the development of a scalable process. It is also shown that the properties of the fiber can be tuned by varying the parameters of the post-spinning step. Finally, equivalence is established between the discrete wet-stretching process and the continuous post-spinning drawing step.

Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5′-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of β1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy. SAF 2010 3.111 JCR (2015) Q2, 42/124 Medicine, research & experimental; Q3, 14/21 Cell & tissue engineering, 97/187 Cell biology UEM

This work aims to study the effect on surface dose and dose distribution caused by the Elekta Fraxion cranial immobilization system. The effect of Fraxion inclusion in Elekta Monaco treatment planning system and its calculation accuracy is also checked. To study the dose attenuation, a cylindrical phantom was located over the Elekta Fraxion with an IBA CC13 ionization chamber placed in the central insert at the linac isocenter. Dose measurements at multiple gantry angles were performed for three open fields, 10 × 10 cm, 5 × 5 cm and other smaller 2 × 2 cm. Measured doses were compared with the ones calculated by Monaco. Surface dose and dose distribution in the buildup region were measured placing several Gafchromic Films EBT3 at linac CAX between the slabs of a RW3 phantom located over Fraxion and read using FilmQA Pro software. Measures were performed for two open field sizes and results were compared with Monaco calculations. Measurements show a 1% attenuation for 180° gantry angle but it can be as high as 3.4% (5 × 5 open field) for 150°/210° gantry angle, as with these angles the beam goes through the Fraxion's headrest twice. If Fraxion is not included in the calculation Monaco calculation can result in a 3% difference between measured and calculated doses, while with Fraxion in the calculation, the maximum difference is 0.9%. Fraxion increases 3.7 times the surface dose, which can be calculated by Monaco with a difference lower than 2%. Monaco also calculated correctly the PDD for both open fields (2%) when Fraxion is included in the calculation. This work shows that the attenuation varies with gantry angle. The inclusion of Fraxion in Monaco improves the calculation from 3% difference to 1% in the worst case. Furthermore, the surface dose increment and the dose in the buildup region are correctly calculated.

This work summarizes the main principles and some of the most significant results of straining flow spinning (SFS), a technology developed originally by the authors of this work. The principles on which the technology is based, inspired by the natural spinning system of silkworms and spiders, are presented, as well as some of the main achievements of the technique. Among these achievements, spinning under environmentally friendly conditions, obtaining high-performance fibers, and imparting the fibers with emerging properties such as supercontraction are discussed. Consequently, SFS appears as an efficient process that may represent one of the first realizations of a biomimetic technology with a significant impact at the production level. Ministerio de Economía y Competitividad MAT2016-75544-C2-1-R Ministerio de Economía y Competitividad MAT2016-79832-R Ministerio de Economía y Competitividad CPI2016-78887-C3-1-R Comunidad de Madrid NEUROCENTRO-B2017 Comunidad de Madrid BMD-3760

Silk fibers from Argiope trifasciata and Nephila inaurata orb-web weaving spiders were UV irradiated to modify the molecular weight of the constituent proteins. Fibers were characterized either as forcibly silked or after being subjected to maximum supercontraction. The effect of irradiation on supercontraction was also studied, both in terms of the percentage of supercontraction and the tensile properties exhibited by irradiated and subsequently supercontracted fibers. The effects of UV exposure at the molecular level were assessed by polyacrylamide gel electrophoresis and mass spectrometry. It is shown that UV-irradiated fibers show a steady decrease in their main tensile parameters, most notably, tensile strength and strain. The combination of the mechanical and biochemical data suggests that the restricted conformational freedom of the proteins after UV irradiation is critical in the reduction of these properties. Consequently, an adequate topological organization of the protein chains emerges as a critical design principle in the performance of spider silk.

High performance silk fibers were produced directly from the silk glands of silkworms ("Bombyx mori") following an alternative route to natural spinning. This route is based on a traditional procedure that consists of soaking the silk glands in a vinegar solution and stretching them by hand leading to the so called silkworm guts. Here we present, to the authors’ best knowledge, the first comprehensive study on the formation, properties and microstructure of silkworm gut fibers. Comparison of the tensile properties and microstructural organization of the silkworm guts with those of naturally spun fibers allows gain of a deeper insight into the mechanisms that lead to the formation of the fiber, as well as the relationship between the microstructure and properties of these materials. In this regard, it is proved that an acidic environment and subsequent application of tensile stress in the range of 1000 kPa are sufficient conditions for the formation of a silk fiber.

The actin cytoskeleton plays a key role in the deformability of the cell and in mechanosensing. Here we analyze the contributions of three major actin cross-linking proteins, myosin II, α-actinin and filamin, to cell deformability, by using micropipette aspiration of Dictyostelium cells. We examine the applicability of three simple mechanical models: for small deformation, linear viscoelasticity and drop of liquid with a tense cortex; and for large deformation, a Newtonian viscous fluid. For these models, we have derived linearized equations and we provide a novel, straightforward methodology to analyze the experiments. This methodology allowed us to differentiate the effects of the cross-linking proteins in the different regimes of deformation. Our results confirm some previous observations and suggest important relations between the molecular characteristics of the actin-binding proteins and the cell behavior: the effect of myosin is explained in terms of the relation between the lifetime of the bond to actin and the resistive force; the presence of α-actinin obstructs the deformation of the cytoskeleton, presumably mainly due to the higher molecular stiffness and to the lower dissociation rate constants; and filamin contributes critically to the global connectivity of the network, possibly by rapidly turning over cross-links during the remodeling of the cytoskeletal network, thanks to the higher rate constants, flexibility and larger size. The results suggest a sophisticated relationship between the expression levels of actin-binding proteins, deformability and mechanosensing.

The use of magnetic nanoparticles (MNPs) is a promising technique for future advances in biomedical applications. This idea is supported by the availability of MNPs that can target specific cell components, the variety of shapes of MNPs and the possibility of finely controlling the applied magnetic forces. To examine this opportunity, here we review the current developments in the use of MNPs to mechanically stimulate cells and, specifically, the cell mechanotransduction systems. We analyze the cell components that may act as mechanosensors and their effect on cell fate and we focus on the promising possibilities of controlling stem-cell differentiation, inducing cancer-cell death and treating nervous-system diseases.

The study of fungal cells is of great interest due to their importance as pathogens and as fermenting fungi and for their appropriateness as model organisms. The differential pressure between the hyphal cytoplasm and the bordering medium is essential for the growth process, because the pressure is correlated with the growth rate. Notably, during the invasion of tissues, the external pressure at the tip of the hypha may be different from the pressure in the surrounding medium. We report the use of a method, based on the micropipette-aspiration technique, to study the influence of this external pressure at the hyphal tip. Moreover, this technique makes it possible to study hyphal growth mechanics in the case of very thin hyphae, not accessible to turgor pressure probes.We found a correlation between the local pressure at the tip and the growth rate for the species Arpergillus nidulans. Importantly, the proposed method allows one to measure the pressure at the tip required to arrest the hyphal growth. Determining that pressure could be useful to develop newmedical treatments for fungal infections.Finally, we provide a mechanical model for these experiments, taking into account the cytoplasm flow and the wall deformation., The authors received support from the Ministerio de Economía y Competitividad, Spain, througth Projects No. MAT2016-76847-R, No. BIO2015-30695R, and No.MAT2016-79832-R.

Resumen Objetivos El tratamiento de fracturas pertrocantereas con clavo DHS (Dynamic Hip Screw) mediante tecnica minimamente invasiva (MIDHS) ha mostrado resultados superiores a la tecnica convencional (CDHS) en estudios previos. El presente estudio pretende determinar si existen diferencias en requerimientos transfusionales, morbilidad, estancia hospitalaria y en el coste asociado, a partir de un analisis retrospectivo de 2 cohortes. Material y metodo Estudio de cohortes en 80 pacientes con fracturas intertrocantereas de femur (31-A1 y 31-A2.1) tratados con implante DHS entre julio de 2005 y septiembre de 2007: 40 de ellos con la tecnica convencional y 40 de ellos con tecnica MIDHS. Resultados No se observaron diferencias estadisticamente significativas ni en la perdida sanguinea, ni en requerimientos transfusionales, ni en morbilidad. La estancia hospitalaria en el grupo MIDHS fue 1,3 dias menor, con un coste directo de 306,3 € por caso, inferior al grupo CDHS, aunque sin significacion estadistica (p = 0,3). La duracion de la intervencion fue menor en el grupo MIDHS: 49,3 versus 78,8 min (p = 0,0001). Discusion Contrariamente a lo publicado en estudios previos, en el presente estudio la tecnica MIDHS no ha mostrado ventajas excepto por requerir un menor tiempo para realizar la tecnica. Consideramos que la tecnica MIDHS podria ayudar en mejorar la productividad y eficiencia en el uso de quirofanos.

Resumen Objetivos Se presenta un metodo de segmentacion automatico para imagenes de tomografia por emision de positrones (PET) basado en una aproximacion iterativa mediante valor umbral, que incluye la influencia tanto del tamano de la lesion como del fondo presente durante la adquisicion. Material y metodos A partir de un estudio de imagen PET de un maniqui que contiene esferas de diversos tamanos y en diferentes entornos radiactivos conocidos, se determinan los valores umbral optimos que suponen una correcta segmentacion de volumenes. Estos valores optimos son normalizados al fondo y ajustados, mediante tecnicas de regresion, a una funcion de 2 variables: volumen de la lesion y relacion senal-fondo (RSF). Esta funcion de ajuste es usada para construir un metodo de segmentacion iterativo, y, basandose en el, se propone un procedimiento de contorneo automatico. Se valida dicho procedimiento sobre estudios en maniqui y se comprueba su viabilidad aplicandose, de manera retrospectiva, sobre 2 pacientes oncologicos. Resultados La funcion de ajuste obtenida presenta una dependencia lineal con la RSF e inversamente proporcional y negativa con el volumen. Durante la validacion del metodo iterativo propuesto se encuentra que las desviaciones de volumen respecto al valor real y al volumen TC estan por debajo del 10 y del 9%, respectivamente, excepto para lesiones con un volumen por debajo de 0,6 ml. Conclusiones El metodo automatico de segmentacion propuesto puede ser aplicado en la practica clinica para la planificacion de tratamientos de lesiones tumorales en radioterapia de manera sencilla y fiable con una precision cercana a la resolucion de la imagen PET.

Objectives An automatic segmentation method is presented for PET images based on an iterative approximation by threshold value that includes the influence of both lesion size and background present during the acquisition. Material and methods Optimal threshold values that represent a correct segmentation of volumes were determined based on a PET phantom study that contained different sizes of spheres and different known radiation environments. These optimal values were normalized to background and adjusted by regression techniques to a two-variable function: lesion volume and signal-to-background ratio (SBR). This adjustment function was used to build an iterative segmentation method. Based on this method, a procedure of automatic delineation was proposed. This procedure was validated on phantom images and its viability was confirmed by retrospectively applying it on two oncology patients. Results The resulting adjustment function obtained had a linear dependence with the SBR and was inversely proportional and negative with the volume. During the validation of the proposed method, it was found that the volume deviations with respect to its real value and CT volume were below 10% and 9%, respectively, except for lesions with a volume below 0.6 ml. Conclusions The automatic segmentation method proposed can be applied in clinical practice to tumor radiotherapy treatment planning in a simple and reliable way with a precision close to the resolution of PET images.

Aim The treatment of intertrochanteric fractures using a minimally invasive dynamic hip screw (MIDHS) technique has been reported to provide better results than the conventional technique (CDHS). The present study aims to determine whether there are any differences in terms of transfusion needs, morbidity, length of hospital stay, and economical costs, based on a study of two retrospective cohorts. Materials and methods Cohorts study of 80 patients with intertrochanteric femoral fractures (31-A1 and 31-A2.1) who underwent DHS procedure from July 2005 to September 2007; 40 of them were treated using the traditional technique (CDHS), and the other 40 using the minimally invasive technique (MIDHS). Results No differences were found in terms of blood loss, transfusion requirements or morbidity. Mean hospital stay for MIDHS group was 1.3 days lower, reducing the costs regarding the CDHS group by €306.3, but this difference was not statistically significant ( P = .3). The time required to perform the surgery was shorter for the MIDHS group: 49.3 versus 78.8 minutes ( p = 0.0001). Discussion Contrary to previous studies published, the present study did not show any advantage for the MIDHS technique, except for a shorter surgical time to perform the procedure. We consider that the MIDHS could help in improving operating room productivity and efficiency.

In cells, mechanical forces play a key role in impacting cell behaviors, including adhesion, differentiation, migration, and death. Herein, a 20 nm mitochondria-targeted zinc-doped iron oxide nanocube is designed as a nanospinner to exert mechanical forces under a rotating magnetic field (RMF) at 15 Hz and 40 mT to fight against cancer. The nanospinners can efficiently target the mitochondria of cancer cells. By means of the RMF, the nanocubes assemble in alignment with the external field and produce a localized mechanical force to impair the cancer cells. Both in vitro and in vivo studies show that the nanospinners can damage the cancer cells and reduce the brain tumor growth rate after the application of the RMF. This nanoplatform provides an effective magnetomechanical approach to treat deep-seated tumors in a spatiotemporal fashion.