BACKGROUND: This study aims to implement a set of wearable technologies to record and analyze the surgeon’s physiological and ergonomic parameters during the performance of conventional and ...robotic-assisted laparoscopic surgery, comparing the ergonomics and stress levels of surgeons during surgical procedures. METHODS: This study was organized in two different settings: simulator tasks and experimental model surgical procedures. The participating surgeons performed the tasks and surgical procedures in both laparoscopic and robotic-assisted surgery in a randomized fashion. Different wearable technologies were used to record the surgeons’ posture, muscle activity, electrodermal activity and electrocardiography signal during the surgical practice. RESULTS: The simulator study involved six surgeons: three experienced (>100 laparoscopic procedures performed; 36.33 ± 13.65 years old) and three novices (<100 laparoscopic procedures; 29.33 ± 8.39 years old). Three surgeons of different surgical specialties with experience in laparoscopic surgery (>100 laparoscopic procedures performed; 37.00 ± 5.29 years old), but without experience in surgical robotics, participated in the experimental model study. The participating surgeons showed an increased level of stress during the robotic-assisted surgical procedures. Overall, improved surgeon posture was obtained during robotic-assisted surgery, with a reduction in localized muscle fatigue. CONCLUSIONS: A set of wearable technologies was implemented to measure and analyze surgeon physiological and ergonomic parameters. Robotic-assisted procedures showed better ergonomic outcomes for the surgeon compared to conventional laparoscopic surgery. Ergonomic analysis allows us to optimize surgeon performance and improve surgical training.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel ...cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown. We explored the presence and role of SF3B1 in PDAC and interrogated its potential as an actionable target.
SF3B1 was analyzed in PDAC tissues, an RNA-seq dataset, and publicly available databases, examining associations with splicing alterations and key features/genes. Functional assays in PDAC cell lines and PDX-derived CSCs served to test Pladienolide-B treatment effects in vitro, and in vivo in zebrafish and mice.
SF3B1 was overexpressed in human PDAC and associated with tumor grade and lymph-node involvement. SF3B1 levels closely associated with distinct splicing event profiles and expression of key PDAC players (KRAS, TP53). In PDAC cells, Pladienolide-B increased apoptosis and decreased multiple tumor-related features, including cell proliferation, migration, and colony/sphere formation, altering AKT and JNK signaling, and favoring proapoptotic splicing variants (BCL-XS/BCL-XL, KRASa/KRAS, Δ133TP53/TP53). Importantly, Pladienolide-B similarly impaired CSCs, reducing their stemness capacity and increasing their sensitivity to chemotherapy. Pladienolide-B also reduced PDAC/CSCs xenograft tumor growth in vivo in zebrafish and in mice.
SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer.
The coral microbiome conforms a proxy to study effects of changing environmental conditions. However, scarce information exists regarding microbiome dynamics and host acclimation in response to ...environmental changes associated to global-scale disturbances. We assessed El Niño Southern Oscillation (ENSO)-derived thermal anomalies shifts in the bacterial microbiome of Pacifigorgia cairnsi (Gorgoniidae: Octocorallia) from the remote island of Malpelo in the Tropical Eastern Pacific. Malpelo is a hot spot of biodiversity and lacks direct coastal anthropogenic impacts. We evaluated the community composition and predicted functional profiles of the microbiome during 2015, 2017 and 2018, including different phases of ENSO cycle. The bacterial community diversity and composition between the warming and cooling phase were similar, but differed from the neutral phase. Relative abundances of different microbiome core members such as Endozoicomonas and Mycoplasma mainly drove these differences. An acclimated coral holobiont is suggested not just to warm but also to cold stress by embracing similar microbiome shifts and functional redundancy that allow maintaining coral's viability under thermal stress. Responses of the microbiome of unperturbed sea fans such as P. cairnsi in Malpelo could be acting as an extended phenotype facilitating the acclimation at the holobiont level.
The therapeutic relationship (TR) is essential in mental health nursing care and plays a fundamental role in the understanding and treatment of the patient's health status. Despite being a ...bidirectional construct, limited evidence is available to shed light on this issue in mental health units and even less so in the first days of admission. This study aimed to examine the association and differences between nurses' and patients' perspectives on the establishment of the therapeutic relationship in acute mental health units during the first days of hospitalization. A cross-sectional study was carried out in 12 Spanish mental health units. Data were collected from patients and nurses using the Working Alliance Inventory-Short (WAI-S) questionnaire. A total of 234 cases were analysed, including 234 patients and 58 nurses. The results showed a positive association between nurses' and patients' perspectives on the therapeutic relationship, but also revealed significant differences on each WAI-S dimension. Nurses assigned higher scores compared to patients on the perception of the quality of the therapeutic relationship. The dimensions with the greatest weight from the patients' perspective regarding the quality of the therapeutic relationship were the perception of greater agreement on goals and tasks among nurses. This study demonstrates the importance of establishing shared goals and tasks with nurses from the first days of hospitalization to improve the quality of the therapeutic relationship as perceived by patients. These findings underline the need to consider the different perspectives of both parties to promote a high-quality therapeutic relationship.
Background
Recent proposals of high dose rate plans in protontherapy as well as very short proton bunches may pose problems to current beam monitor systems. There is an increasing demand for ...real‐time proton beam monitoring with high temporal resolution, extended dynamic range and radiation hardness. Plastic scintillators coupled to optical fiber sensors have great potential in this context to become a practical solution towards clinical implementation.
Purpose
In this work, we evaluate the capabilities of a very compact fast plastic scintillator with an optical fiber readout by a SiPM and electronics sensor which has been used to provide information on the time structure at the nanosecond level of a clinical proton beam.
Materials and methods
A 3 × 3 × 3 mm3 plastic scintillator (EJ‐232Q Eljen Technology) coupled to a 3 × 3 mm2 SiPM (MicroFJ‐SMA‐30035, Onsemi) has been characterized with a 70 MeV clinical proton beam accelerated in a Proteus One synchrocyclotron. The signal was read out by a high sampling rate oscilloscope (5 GS/s). By exposing the sensor directly to the proton beam, the time beam profile of individual spots was recorded.
Results
Measurements of detector signal have been obtained with a time sampling period of 0.8 ns. Proton bunch period (16 ns), spot (10 μs) and interspot (1 ms) time structures could be observed in the time profile of the detector signal amplitude. From this, the RF frequency of the accelerator has been extracted, which is found to be 64 MHz.
Conclusions
The proposed system was able to measure the fine time structure of a clinical proton accelerator online and with ns time resolution.
Coordinated intra- and inter-organ growth during animal development is essential to ensure a correctly proportioned individual. The Drosophila wing has been a valuable model system to reveal the ...existence of a stress response mechanism involved in the coordination of growth between adjacent cell populations and to identify a role of the fly orthologue of p53 (Dmp53) in this process. Here we identify the molecular mechanisms used by Dmp53 to regulate growth and proliferation in a non-autonomous manner. First, Dmp53-mediated transcriptional induction of Eiger, the fly orthologue of TNFα ligand, leads to the cell-autonomous activation of JNK. Second, two distinct signaling events downstream of the Eiger/JNK axis are induced in order to independently regulate tissue size and cell number in adjacent cell populations. Whereas expression of the hormone dILP8 acts systemically to reduce growth rates and tissue size of adjacent cell populations, the production of Reactive Oxygen Species-downstream of Eiger/JNK and as a consequence of apoptosis induction-acts in a non-cell-autonomous manner to reduce proliferation rates. Our results unravel how local and systemic signals act concertedly within a tissue to coordinate growth and proliferation, thereby generating well-proportioned organs and functionally integrated adults.
Partial isomorphic substitution of Zn in IRMOF metal clusters by cobalt ions is described for the first time. Specifically, different numbers of Co2+ ions have been incorporated during solvothermal ...crystallization into the Zn-based MOF-5 (IRMOF-1) framework, which is one of the most studied MOF materials. The amount of Zn that can be substituted seems to be limited, being no more than 25% of total metal content, that is, no more than one Co atom inside every metal cluster formed by four transition-metal ions, on average. Several characterization techniques, including X-ray diffraction, DR UV−visible spectroscopy, N2 adsorption isotherms, and thermogravimetrical analysis, strongly support the effective incorporation of Co into the material framework. As-synthesized CoMOF-5 has cobalt ions in octahedral coordination, changing to tetrahedral by simple evacuation, presumably by the removal of two diethylformamide molecules per Co ion. Moreover, the H2, CH4, and CO2 uptake of MOF-5 materials systematically increases with the Co content, particularly at high pressure. Such an increase is moderate anyway, considering that Co is incorporated into unexposed metal sites that are less accessible to gas molecules.
DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the ...interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells γH2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of γH2AX-only cells increases after caspase inhibition while the relative number of TUNEL-only cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration.
The main goal of this study was to investigate the neural substrates of fluid reasoning and visuospatial working memory in adolescents with precocious mathematical ability. The study population ...comprised two groups of adolescents: 13 math-gifted adolescents and 14 controls with average mathematical skills. Patterns of activation specific to reasoning tasks in math-gifted subjects were examined using functional magnetic resonance images acquired while the subjects were performing Raven's Advanced Progressive Matrices (RAPM) and the Tower of London (TOL) tasks.
During the tasks, both groups showed significant activations in the frontoparietal network. In the math-gifted group, clusters of activation were always bilateral and more regions were recruited, especially in the right hemisphere. In the TOL task, math-gifted adolescents showed significant hyper-activations relative to controls in the precuneus, superior occipital lobe (BA 19), and medial temporal lobe (BA 39). The maximum differences between the groups were detected during RAPM tasks at the highest level of difficulty, where math-gifted subjects showed significant activations relative to controls in the right inferior parietal lobule (BA 40), anterior cingulated gyrus (BA 32), and frontal (BA 9, and BA 6) areas. Our results support the hypothesis that greater ability for complex mathematical reasoning may be related to more bilateral patterns of activation and that increased activation in the parietal and frontal regions of math-gifted adolescents is associated with enhanced skills in visuospatial processing and logical reasoning.
► Math-gifted (MG) subjects show higher recruitment of right hemisphere and more bilateralism. ► Frontoparietal network in MG is used to resolve complex visuospatial and analytical tasks. ► Only during difficult tasks MG show different activation than controls.
The anthozoan sub-class Octocorallia, comprising approximately 3000 species of soft corals, gorgonians, and sea pens, remains one of the most poorly understood groups of the phylum Cnidaria. Efforts ...to classify the soft corals and gorgonians at the suprafamilial level have long thwarted taxonomists, and the subordinal groups in current use are widely recognized to represent grades of colony forms rather than clades. Molecular phylogenetic analyses of the sub-class do not support either the current morphologically based subordinal or familial-level taxonomy. To date, however, the resolution necessary to propose an alternative, phylogenetic classification of Octocorallia or to elucidate patterns of morphological evolution within the group is lacking. Attempts to understand boundaries between species and interspecific or intraspecific phylogenetic relationships have been hampered by the very slow rate of mitochondrial gene evolution in Octocorallia, and a consequent dearth of molecular markers with variation sufficient to distinguish species (or sometimes genera). A review of the available ITS2 sequence data for octocorals, however, reveals a yet-unexplored phylogenetic signal both at sequence and secondary-structure levels. In addition, incongruence between mitochondrial and nuclear gene trees suggests that hybrid speciation and reticulate evolution may be an important mechanism of diversification in some genera. Emerging next-generation genomic-sequencing technologies offer the best hope for a breakthrough in our understanding of phylogenetic relationships and of evolution of morphological traits in Octocorallia. Genome and transcriptome sequencing may provide enough characters to resolve relationships at the deepest levels of the octocoral tree, while simultaneously offering an efficient means to screen for new genetic markers variable enough to distinguish species and populations.
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