T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.

Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.

Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G>A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23-27 (SE23-27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and restored protein expression. However, bystander editing at the adjacent adenine (c.3847A>G), caused an amino acid change (R1283G) that affects CFTR maturation and ablates ion channel activity. In primary human nasal epithelial cells homozygous for W1282X, ABE corrected 27% of alleles, but with a notably lower level of bystander editing, and CFTR channel function was restored to 16% of wild-type levels. Using the HITI approach, correct integration of a SE23-27 in intron 22 of the CFTR locus in 16HBEge W1282X cells was detected in 5.8% of alleles, resulting in 7.8% of CFTR transcripts containing the SE23-27 sequence. Analysis of a clonal line homozygous for the HITI-SE23-27 produced full-length mature protein and restored CFTR anion channel activity to 10% of wild-type levels, which could be increased three-fold upon treatment with the triple combination of CF modulators. Overall, these data demonstrate two different editing strategies can successfully correct W1282X, the second most common class I variant, with a concomitant restoration of CFTR function.

Quorum sensing in bacteria: in silico protein analysis, ecophysiology, and reconstruction of their evolutionary history.

BACKGROUND: Quorum sensing (QS) is a sophisticated cell-to-cell signalling mechanism that allows the coordination of important processes in microbial populations. The AI-1 and AI-2 autoinducer systems are among the best characterized bacterial QS systems at the genetic level. RESULTS: In this study, we present data derived from in silico screening of QS proteins from bacterial genomes available in public databases. Sequence analyses allowed identifying candidate sequences of known QS systems that were used to build phylogenetic trees. Eight categories were established according to the number of genes from the two major QS systems present in each genome, revealing a correlation with specific taxa, lifestyles or metabolic traits. Many species had incomplete QS systems, encoding the receptor protein but not the biosynthesis of the quorum sensing molecule (QSMs). Reconstruction of the evolutionary history of the LuxR family and prediction of the 3D structure of the ancestral protein suggested their monomeric configuration in the absence of the signal molecule and the presence of a cavity for its binding. CONCLUSIONS: Here we correlate the taxonomic affiliation and lifestyle of bacteria from different genera with the QS systems encoded in their genomes. Moreover, we present the first ancestral reconstruction of the LuxR QS receptors, providing further insight in their evolutionary history.

Genetic underpinnings of arthropod community distributions in Populus trichocarpa.

Community genetics seeks to understand the mechanisms by which natural genetic variation in heritable host phenotypes can encompass assemblages of organisms such as bacteria, fungi, and many animals including arthropods. Prior studies that focused on plant genotypes have been unable to identify genes controlling community composition, a necessary step to predict ecosystem structure and function as underlying genes shift within plant populations. We surveyed arthropods within an association population of Populus trichocarpa in three common gardens to discover plant genes that contributed to arthropod community composition. We analyzed our surveys with traditional single-trait genome-wide association analysis (GWAS), multitrait GWAS, and functional networks built from a diverse set of plant phenotypes. Plant genotype was influential in structuring arthropod community composition among several garden sites. Candidate genes important for higher level organization of arthropod communities had broadly applicable functions, such as terpenoid biosynthesis and production of dsRNA binding proteins and protein kinases, which may be capable of targeting multiple arthropod species. We have demonstrated the ability to detect, in an uncontrolled environment, individual genes that are associated with the community assemblage of arthropods on a host plant, further enhancing our understanding of genetic mechanisms that impact ecosystem structure.

When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology.

Changes in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old. Our findings unveil complex, non-linear power trajectories that defy the traditional linear paradigm, with notable cortical region variations. Interestingly, slow wave activity increases correlate with improved cognitive performance throughout life and larger gray matter volume in the elderly. Conversely, fast wave activity diminishes in adulthood. Elevated low-frequency activity during aging, traditionally seen as compensatory, may also signify neural deterioration. This dual interpretation, highlighted by our study, reveals the intricate dynamics between brain oscillations, cognitive performance, and aging. It advances our understanding of neurodevelopment and aging by emphasizing the regional specificity and complexity of brain rhythm changes, with implications for cognitive and structural integrity.

Artificial-intelligence-model to optimize biocide dosing in seawater-cooled industrial process applications considering environmental, technical, energetic, and economic aspects.

This research introduces an Artificial Intelligence (AI) based model designed to concurrently optimize energy supply management, biocide dosing, and maintenance scheduling for heat exchangers. This optimization considers energetic, technical, economic, and environmental considerations. The impact of biofilm on heat exchangers is assessed, revealing a 41% reduction in thermal efficiency and a 113% increase in flow frictional resistance of the fluid compared to the initial state. Consequently, the pump's power consumption, required to maintain hydraulic conditions, rises by 9%. The newly developed AI model detects the point at which the heat exchanger's performance begins to decline due to accumulating dirt, marking day 44 of experimentation as the threshold to commence the antifouling biocide dosing. Leveraging this AI model to monitor heat exchanger efficiency represents an innovative approach to optimizing antifouling biocide dosing and reduce the environmental impact stemming from industrial plants.

Sex Differences in Chronic Postsurgical Pain after Open Thoracotomy.

STUDY OBJECTIVE: To determine the incidence of chronic postsurgical pain (CPSP) in women after open thoracotomy. Secondary objectives were to compare relevant patient and procedural variables between women and men. DESIGN: Observational cohort study. SETTING: Ten university-affiliated hospitals. SUBJECTS: Ninety-six women and 137 men. INTERVENTIONS: Scheduled open thoracotomy. MEASUREMENTS: Pain histories, psychological measures, and perceived health status and catastrophizing scores were obtained. The diagnosis of chronic postsurgical pain was by physical examination at 4 months. Standard preoperative, intraoperative, and postoperative data were also recorded. MAIN RESULTS: The chronic postsurgical pain incidence was significantly higher in women (53.1%) than in men (38.0%) (p = 0.023). At baseline, women had significantly worse scores on psychological measures (perception of mental state [p = 0.01], depression [p = 0.006], and catastrophizing [p < 0.001]). Women also reported more preoperative pain in the operative area (p = 0.011) and other areas (p = 0.030). CONCLUSION: These findings show that the incidence of physician-diagnosed chronic postsurgical pain is higher in women than in men after surgeries involving thoracotomy. Sex and gender should be included in future clinical research on pain in surgical settings.

F-Chin/Feminizing the Chin: A Genioplasty Technique with Virtual Planning for Male-to-Female Transgender Patients.

The chin is an essential structure in facial harmony and an important gender marker. Advancing a receding chin is fundamental to improve the facial appearance, particularly in male-to-female transgender patients. However, in patients with microgenia and/or retrognathia, desiring a more feminine appearance, a chin advancement can result in a wider, square shape; an undesirable effect. Genioplasty is a versatile procedure used in facial feminization surgery that allows modifying the natural anatomy of the chin in all three spatial dimensions. The technique herein described proposes a simple genioplasty procedure for feminizing the chin (F-chin genioplasty) in transgender patients where anteroposterior advance is required. Virtual planning was used to establish the landmarks for an anteroposterior advancement with transverse reduction in the chin. A perpendicular line to the Frankfurt plane passing through the incisal edge of the upper central incisor was used to plan the anteroposterior movement, and two vertical lines on the outer wall of the nasal cavity  for the chin transverse measurement. The authors present three case reports with the F-chin genioplasty transgender technique with satisfactory results, ensuring a more feminine facial appearance.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of a respiratory and neurological rehabilitation treatment plan in post Covid-19 affected university students. Randomized clinical study.

BACKGROUND: COVID-19 demonstrated the possibility of neurological complications such as loss of sense of smell and taste, together with respiratory problems. Respiratory training and rehabilitation of neurological sequelae are essential to improve respiratory function and thus quality of life, and the aim of this study is to evaluate the efficacy of a pulmonary and neurological rehabilitation program. OBJECTIVES: To apply a treatment to reduce dyspnea, increase exertional capacity, increase vital capacity and respiratory muscle strength, together with an increase in olfactory and gustatory sensitivity in post-SARS-CoV-2 patients. METHODS: A randomised controlled experimental study was conducted in 220 patients with a medical diagnosis of COVID-19 and more than 5 months of evolution, dyspnoea or perceived fatigue, including olfactory and gustatory perception problems, of whom 200 patients completed the study. 100 patients were randomly assigned to the intervention group, consisting of an inspiratory training treatment plan (Powerbreathe Plus®) combined with aerobic exercise and olfactory gustatory treatment for 31 days, and 100 patients to the control group, for 31 days without any type of therapy. RESULTS: The study was conducted in post-Covid-19 patients for 5 months. Two hundred patients were divided into an intervention group (n = 100) and a control group (n = 100). The comparison between the groups showed significant differences in spirometric variables; forced vital capacity (p < .001; Eta2 (0.439); Mean: 0,6135), the ratio between both FEV1/FVC (p < 0.01; Eta2 (0.728); Mean:9,313), peak inspiratory pressure (p < 0.01; Eta2 (0.906); Mean:4,526); changes were observed in dyspnoea measured with the modified Borg scale (p < 0.01; Eta2 (0.811); Mean:1,481) and the modified Medical Research Council scale (p < 0.01; Eta2 (0.881); Mean: 0.777); finally, changes were found in neurological variables, in the questions of the Singapore Smell and Taste Questionnaire, How was your sense of smell after treatment? (p < 0.01; Eta2 (0.813); Mean: 1,721) and How is your sense of taste after treatment? (p < 0.01; Eta2 (0.898); Mean: 1,088). CONCLUSION: The implementation of a respiratory rehabilitation treatment plan with the Powerbreathe Plus® device, aerobic exercise and neurorehabilitation with olfactory and gustatory training, is a therapeutic option against respiratory and neurological sequelae in patients who have suffered such sequelae due to the SARS-CoV-2 virus. Clinicaltrials.gov: NCT05195099. First posted 18/01/2022; Last Update Posted 29/06/2022.

Dry needling of the flexor digitorum brevis muscle reduces postural control in standing: A pre-post stabilometric study.

There are studies that show the better balance after dry needling in lumbar pain. However, the postural control effects after foot dry needling are unknown. Our objective was to check if dry needling reduces postural control. Eighteen subjects with flexor digitorum brevis (FDB) muscle Myofascial trigger point were evaluated pre- and post-deep dry needling. We measured stabilometric variables in a pre-post study. We have found significant differences in three stabilometric variables: surface with eyes closed (29.36-53.21 mm2 ) (p = 0.000), medium speed of the laterolateral displacement with eyes closed (1.42-1.64 mm/s) (p = 0.004), and medium speed of the anteroposterior displacement with eyes closed (1.30-1.53 mm/s) (p = 0.025). Dry needling therapy application in FDB muscle reduces standing postural control with eyes closed.

Prediction of biological development effects on drag forces of ceramic hull coating using Reynolds-averaged Navier-Stokes-based solver.

Ships in service feature surfaces that exhibit biofouling, which alters the hydrodynamics of the vessels, thus affecting their normal displacement and significantly increasing their fuel consumption. The application of three types of ceramic coatings as ecological, effective and durable alternatives to commercial silicone-based marine coatings is investigated in this study. Three different ceramic glazes and two control commercial paints are analysed in an actual environment during 20 months of exposure to simulate the navigation conditions such that growth and roughness data can be obtained and then applied to computational fluid dynamics (CFD) software using an open-source Reynolds-averaged Navier-Stokes solver. The CFD results are validated under smooth hull conditions with a full-scale Kriso Container Ship (KCS) model and with different levels of hull roughness. The developed approach shows that the drag in hulls coated with conventional paint is 19% greater than that in hulls with ceramic coating.

Bilateral arthroscopy of the temporomandibular joint: clinical outcomes and the role of a second intervention-a prospective study.

OBJECTIVE: Evaluate the efficacy of bilateral temporomandibular joint (TMJ) arthroscopy in patients with different categories of severity based on Dimitroulis classification (categories 2-4) and the role of a second TMJ intervention in primary failure. METHODS: A 3-year prospective study was designed, including patients submitted to bilateral TMJ arthroscopy. The primary outcome was TMJ pain (VAS, 0-10) and the secondary outcomes were the maximum mouth opening (MMO) and masticatory myalgia degree (0-3). In cases of symptomatic relapse, a second TMJ intervention was performed (TMJ arthrocentesis or TMJ open surgery). RESULTS: Eighty patients (93.4% women) were enrolled, with a mean age of 32.40 ± 11.41 years. With an average follow-up of 523.7 days (34-1606), a statistically significant improvement in TMJ pain, MMO, and myalgia degree was observed (P < 0.0001). The overall successful outcome of one-single bilateral arthroscopy was ~ 69%. Twenty-two patients relapsed: (1) arthralgia (n = 15, 68.18%); (2) arthralgia + myalgia (n = 4, 18.18%); (3) dislocated disc without reduction (DDwoR) (n = 2, 9.09%); (4) DDwoR + osteoarthrosis (OA) (n = 1, 4.55%). Arthralgia was re-managed with TMJ arthrocentesis with local anesthesia (n = 19, 86.36%). New DDwoR with or without OA was re-treated with TMJ open surgery (n = 3, 13.64%). After the second intervention, the success rate increased to 85%. CONCLUSIONS: Bilateral TMJ arthroscopy presented overall benefit in all parameters evaluated. CLINICAL RELEVANCE: This study highlights the importance of TMJ arthroscopy as the first line of treatment for moderate-severe temporomandibular disorders cases contributing to the reduction of TMJ open surgeries. In cases of arthroscopy unsuccess, TMJ arthrocentesis under local anesthesia was an effective and safe intervention for patients with recurrent TMJ arthralgia.

Comparison between virtual and hybrid education for psychological factors and academic stress in freshman nursing students: a case-control study.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has prompted several changes in the learning methods of students. The purpose of this study was to establish whether a relationship between levels of resilience, self-esteem, anxiety, depression, and academic stress in both hybrid and virtual learning education exist. METHODS: A descriptive and observational case-control study was carried out in universities that offer nursing designation. A total sample of 140 freshman nursing students was recruited. Concretely, 70 participants were recruited from an university receiving hybrid education and 70 participants were recruited from another university receiving virtual learning education. Nursing students self-reported the following questionnaires: the Rosenberg Self-Esteem scale, the 10 CD-Risk Connor-Davidson Risk Resilience Scale, the Beck Anxiety Inventory, the Beck Depression Inventory and the Academic Stress Coping Scale. RESULTS: Significant differences (P = 0.001) showed higher depression levels for students who received virtual education versus received hybrid education. Differences in Rosenberg test for self-esteem and Beck Anxiety Inventory for anxiety (P > 0.05) were not found. CONCLUSION: Students who received online education presented higher depression levels which could be due to they had not face-to-face relationships with teachers or classmates, whereas the hybrid education group received a different type of direct interaction with teachers and peers.

Impact of the selective A2AR and A2BR dual antagonist AB928/etrumadenant on CAR T cell function.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has been successfully translated to clinical practice for the treatment of B cell malignancies. The suppressive microenvironment of many malignancies is a bottleneck preventing treatment success of CAR T cells in a broader range of tumours. Among others, the immunosuppressive metabolite adenosine is present in high concentrations within many tumours and dampens anti-tumour function of immune cells and consequently therapeutic response. METHODS: Here, we present the impact of the selective adenosine A2A and A2B receptor antagonist AB928/etrumadenant on CAR T cell cytokine secretion, proliferation, and cytotoxicity. Using phosphorylation-specific flow cytometry, we evaluated the capability of AB928 to shield CAR T cells from adenosine-mediated signalling. The effect of orally administered AB928 on CAR T cells was assessed in a syngeneic mouse model of colon carcinoma. RESULTS: We found that immunosuppressive signalling in CAR T cells in response to adenosine was fully blocked by the small molecule inhibitor. AB928 treatment enhanced CAR T cell cytokine secretion and proliferation, granted efficient cytolysis of tumour cells in vitro and augmented CAR T cell activation in vivo. CONCLUSIONS: Together our results suggest that combination therapy with AB928 represents a promising approach to improve adoptive cell therapy.

Genetic characterization of the cyclohexane carboxylate degradation pathway in the denitrifying bacterium Aromatoleum sp. CIB.

The alicyclic compound cyclohexane carboxylate (CHC) is anaerobically degraded through a peripheral pathway that converges with the central benzoyl-CoA degradation pathway of aromatic compounds in Rhodopseudomonas palustris (bad pathway) and some strictly anaerobic bacteria. Here we show that in denitrifying bacteria, e.g. Aromatoleum sp. CIB strain, CHC is degraded through a bad-ali pathway similar to that reported in R. palustris but that does not share common intermediates with the benzoyl-CoA degradation pathway (bzd pathway) of this bacterium. The bad-ali genes are also involved in the aerobic degradation of CHC in strain CIB, and orthologous bad-ali clusters have been identified in the genomes of a wide variety of bacteria. Expression of bad-ali genes in strain CIB is under control of the BadR transcriptional repressor, which was shown to recognize CHC-CoA, the first intermediate of the pathway, as effector, and whose operator region (CAAN4 TTG) was conserved in bad-ali clusters from Gram-negative bacteria. The bad-ali and bzd pathways generate pimelyl-CoA and 3-hydroxypimelyl-CoA, respectively, that are metabolized through a common aab pathway whose genetic determinants form a supraoperonic clustering with the bad-ali genes. A synthetic bad-ali-aab catabolic module was engineered and it was shown to confer CHC degradation abilities to different bacterial hosts.

Exercise Physiology at "Conversational Level" Is Not Impaired in Healthy Young Subjects Wearing Masks or Respirators.

OBJECTIVE: The aim of this study was to evaluate the effects of the use of both surgical masks and FFP2 respirators on the inspiratory muscle strength, metabolic parameters, heart rate, subjective perceived exertion, and dyspnea perception, before and during 30 min stable load exercise at "conversational level". METHODS: A randomized cross-over study was carried out. Nineteen healthy adults completed 3 conditions (without a mask, with a surgical mask or an FFP2 respirator) during a 30-min steady-state test at the lactate threshold intensity. Inspiratory muscle strength was measured before and after the test, and metabolic parameters, heart rate, subjective perceived exertion, and dyspnea perception were collected at baseline, during, and after the test. RESULTS: There was a significant reduction in inspiratory muscle strength after the 30-min test in all conditions (control: 6.26 mm Hg, p < 0.5; surgical mask: 8.55 mm Hg, p < 0.01; FFP2 respirator: 12.42 mm Hg, p < 0.001), but without significant differences between them (p = 0.283). Data showed a statistically significant effect for time, but did not show a statistically significant interaction between condition and time for heart rate (p = 0.674), oxygen saturation (p = 0.297), blood lactate level (p = 0.991), rating perceived exertion (p = 0.734) and dyspnea (p = 0.532) comparisons. CONCLUSIONS: The present study findings suggested that inspiratory muscle strength and physiological parameters during "conversational level" exercise were not impaired under wearing masks in healthy, nonsmoking young adults.

Predicting tubular heat exchanger efficiency reduction caused by marine biofilm adhesion using CFD simulations.

A novel efficiency reduction model to tubular heat exchanger based on heat transfer losses by biofilm adhesion is proposed, which included a modified equation based on the real data-dependent time, seawater, hydrodynamics and heat transfer resistance using computational fluid dynamics (CFD). The biofilm growth model based on Verhulst model and experimental data has been obtained and simulated in a CFD software tool to analyze the tubular heat exchanger performance prediction cooled by seawater. The biofilm CFD model with appropriate fit, and the correlation coefficient (R2) values are between 0.97 and 0.99, was validated by experimental data obtained at different flow velocity. The final results of in/outlet difference temperatures were from 3.9 °C to 2.2 °C for different flow velocity with R2 > 0.97. The simulation results demonstrate that the novel CFD model is capable of predicting the efficiency losses during the development period of biofilm growth in in open-loop cooling seawater systems.

Influence on Depression, Anxiety, and Satisfaction of the Relatives' Visit to Intensive Care Units prior to Hospital Admission for Elective Cardiac Surgery: A Randomized Clinical Trial.

Background: Intensive care units (ICUs) may produce stress on the relatives of patients that have long-term physiological and psychological implications. Objectives: This study aimed to evaluate the effects of the relatives´ visit prior to hospital admission(s) on the patient's scheduled cardiac surgery regarding depression, anxiety, and satisfaction of the patient's family in an ICU. Methods: A randomized clinical trial [NCT03605420] was carried out according to the CONSORT criteria. Thirty-eight relatives of ICU patients were recruited at an ICU and randomized into study groups. Experimental group participants (n = 19) consisted of relatives who received 1 ICU visit prior to the patient's admission. Control group participants (n = 19) consisted of patients' relatives who received standard care alone. A self-report test battery, including the Impact of Event Scale-Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), was completed by the patient's relative prior to the patient's ICU admission and again three and 90 days after ICU discharge. Furthermore, the Family Satisfaction with Care in the Intensive Care Unit (FS-ICU) and Critical Care Family Needs Inventory (CCFNI) were administered to help determine the respondents' satisfaction three days after the patient's ICU discharge. Results: Statistically significant differences in FS-ICU results were found between control and experimental groups; no statistically significant differences were found in IES-R, HADS, and CCFNI results. Thus, members in the control group were more satisfied with the time elapsed to raise their concerns (p=0.005), emotional support provided (p=0.020), quality of care (p=0.035), opportunities to express concerns and ask questions (p=0.005), and general satisfaction with the ICU's decision-making (p=0.003). Conclusions: Relatives' satisfaction during patients' ICU admission may be impaired after their prior visit to the hospital admission. Relative's anxiety and depression scores did not seem to be significantly affected. Relatives´ visit prior to elective cardiac surgery hospital admission impaired their satisfaction in an ICU and may not be advisable for healthcare practice.

CRISPR/Cas9-Directed Gene Trap Constitutes a Selection System for Corrected BCR/ABL Leukemic Cells in CML.

Chronic myeloid leukaemia (CML) is a haematological neoplasm driven by the BCR/ABL fusion oncogene. The monogenic aspect of the disease and the feasibility of ex vivo therapies in haematological disorders make CML an excellent candidate for gene therapy strategies. The ability to abolish any coding sequence by CRISPR-Cas9 nucleases offers a powerful therapeutic opportunity to CML patients. However, a definitive cure can only be achieved when only CRISPR-edited cells are selected. A gene-trapping approach combined with CRISPR technology would be an ideal approach to ensure this. Here, we developed a CRISPR-Trap strategy that efficiently inserts a donor gene trap (SA-CMV-Venus) cassette into the BCR/ABL-specific fusion point in the CML K562 human cell line. The trapping cassette interrupts the oncogene coding sequence and expresses a reporter gene that enables the selection of edited cells. Quantitative mRNA expression analyses showed significantly higher level of expression of the BCR/Venus allele coupled with a drastically lower level of BCR/ABL expression in Venus+ cell fractions. Functional in vitro experiments showed cell proliferation arrest and apoptosis in selected Venus+ cells. Finally, xenograft experiments with the selected Venus+ cells showed a large reduction in tumour growth, thereby demonstrating a therapeutic benefit in vivo. This study represents proof of concept for the therapeutic potential of a CRISPR-Trap system as a novel strategy for gene elimination in haematological neoplasms.

Fit factor compliance of masks and FFP3 respirators in nurses: A case-control gender study.

AIMS: To determine the fit factor and compliance with American Industrial Hygiene Association (AIHA) and Occupational Safety and Health Administration (OSHA) requirements of surgical masks and filtering respirators in male versus female nurses. DESIGN: A case-control gender study performed from 2016 to 2019. METHODS: A gender and age matched-paired sample of 74 nurses was recruited and divided into men (n = 37) and women (n = 37). FFP3 filtering respirators and surgical masks fit factors were compared between male and female nurses by Mann-Whitney U tests. These measurements were tested to pass or fail according to the OSHA (≥100) and AIHA (≥50) criteria by Fisher exact tests for a 95% confidence interval. RESULTS: Global fit factor mean (standard deviation) was 2.86 (2.73) and 3.55 (6.34) for male and female nurses wearing surgical masks (p = .180), respectively, and nobody passed neither OSHA nor AIHA criteria (p = 1.00). Nevertheless, global fit factor were 30.82 (28.42) and 49.65 (43.04) for male and female nurses wearing FFP3 respirators, respectively, being significantly lower and worse in male nurses (p = .037). According to OSHA criteria, only 2.70% and 13.51% of male and females nurses, respectively, passed with non-significant difference (p = .199), meanwhile 21.62% and 48.64% of male and female nurses, respectively, passed AIHA criteria showing significant differences (p = .027) wearing FFP3 respirators. CONCLUSIONS: All male and female nurses wearing surgical masks failed to pass OSHA and AIHA criteria. Global fit factor of the proposed FFP3 filtering respirators was decreased and worse in male than female nurses. IMPACT: Our recommendation is to avoid surgical masks use for protective purposes and use the proposed FFP3 filtering respirators among nurses. Each nurse should be fit tested for its own respirator with special caution in male nurses due to their lower fit factor achieved and most of them failed to pass OSHA and AIHA criteria, especially during COVID-19 pandemic.