Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes.

Premessenger RNA splicing is catalyzed by the spliceosome, a multimegadalton RNA-protein complex that assembles in a highly regulated process on each intronic substrate. Most studies of splicing and spliceosomes have been carried out in human or S. cerevisiae model systems. There exists, however, a large diversity of spliceosomes, particularly in organisms with reduced genomes, that suggests a means of analyzing the essential elements of spliceosome assembly and regulation. In this review, we characterize changes in spliceosome composition across phyla, describing those that are most frequently observed and highlighting an analysis of the reduced spliceosome of the red alga Cyanidioschyzon merolae We used homology modeling to predict what effect splicing protein loss would have on the spliceosome, based on currently available cryo-EM structures. We observe strongly correlated loss of proteins that function in the same process, for example, in interacting with the U1 snRNP (which is absent in C. merolae), regulation of Brr2, or coupling transcription and splicing. Based on our observations, we predict splicing in C. merolae to be inefficient, inaccurate, and post-transcriptional, consistent with the apparent trend toward its elimination in this lineage. This work highlights the striking flexibility of the splicing pathway and the spliceosome when viewed in the context of eukaryotic diversity.

Mediterranean diet protects against a neuroinflammatory cortical transcriptome: Associations with brain volumetrics, peripheral inflammation, social isolation, and anxiety in nonhuman primates (Macaca fascicularis).

Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets; however, the underlying biology is poorly understood. We assessed the effects of Western versus Mediterranean-like diets on RNAseq-generated transcriptional profiles in lateral temporal cortex and their relationships with longitudinal changes in neuroanatomy, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques (Macaca fascicularis). Diet resulted in differential expression of seven transcripts (FDR < 0.05). Cyclin dependent kinase 14 (CDK14), a proinflammatory regulator, was lower in the Mediterranean group. The remaining six transcripts [i.e., "lunatic fringe" (LFNG), mannose receptor C type 2 (MRC2), solute carrier family 3 member 2 (SLCA32), butyrophilin subfamily 2 member A1 (BTN2A1), katanin regulatory subunit B1 (KATNB1), and transmembrane protein 268 (TMEM268)] were higher in cortex of the Mediterranean group and generally associated with anti-inflammatory/neuroprotective pathways. KATNB1 encodes a subcomponent of katanin, important in maintaining microtubule homeostasis. BTN2A1 is involved in immunomodulation of γδ T-cells which have anti-neuroinflammatory and neuroprotective effects. CDK14, LFNG, MRC2, and SLCA32 are associated with inflammatory pathways. The latter four differentially expressed cortex transcripts were associated with peripheral monocyte transcript levels, neuroanatomical changes determined by MRI, and with social isolation and anxiety. These results provide important insights into the potential mechanistic processes linking diet, peripheral and central inflammation, and behavior. Collectively, our results provide evidence that, relative to Western diets, Mediterranean diets confer protection against peripheral and central inflammation which is reflected in preserved brain structure and socioemotional behavior. Ultimately, such protective effects may confer resilience to the development of neuropathology and associated disease.

Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM.

Cilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs' conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryo-electron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with coarse-grained molecular dynamic simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.

Characterization of Glucokinases from Pathogenic Free-Living Amoebae.

Infection with pathogenic free-living amoebae, including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (NfGlck) as a potential target for therapeutic intervention, as glucose metabolism is critical for in vitro viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (AcGlck) and B. mandrillaris (BmGlck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, AcGlck and BmGlck have apparent Km values of 472.5 and 41.0 µM, while Homo sapiens Glck (HsGlck) has a value of 310 µM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent Km values of 45.9 µM (AcGlck) and 124 µM (BmGlck) compared to ~8 mM for HsGlck. Additionally, AcGlck and BmGlck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.

A feasibility study using time-driven activity-based costing as a management tool for provider cost estimation: lessons from the national TB control program in Zimbabwe in 2018.

BACKGROUND: Insufficient cost data and limited capacity constrains the understanding of the actual resources required for effective TB control. This study used process maps and time-driven activity-based costing to document TB service delivery processes. The analysis identified the resources required to sustain TB services in Zimbabwe, as well as several opportunities for more effective and efficient use of available resources. METHODS: A multi-disciplinary team applied time-driven activity-based costing (TDABC) to develop process maps and measure the cost of clinical pathways used for Drug Susceptible TB (DS-TB) at urban polyclinics, rural district and provincial hospitals, and community based targeted screening for TB (Tas4TB). The team performed interviews and observations to collect data on the time taken by health care worker-patient pairs at every stage of the treatment pathway. The personnel's practical capacity and capacity cost rates were calculated on five cost domains. An MS Excel model calculated diagnostic and treatment costs. FINDINGS: Twenty-five stages were identified in the TB care pathway across all health facilities except for community targeted screening for TB. Considerable variations were observed among the facilities in how health care professionals performed client registration, taking of vital signs, treatment follow-up, dispensing medicines and processing samples. The average cost per patient for the entire DS-TB care was USD324 with diagnosis costing USD69 and treatment costing USD255. The average cost for diagnosis and treatment was higher in clinics than in hospitals (USD392 versus USD256). Nurses in clinics were 1.6 time more expensive than in hospitals. The main cost components were personnel (USD130) and laboratory (USD119). Diagnostic cost in Tas4TB was twice that of health facility setting (USD153 vs USD69), with major cost drivers being demand creation (USD89) and sputum specimen transportation (USD5 vs USD3). CONCLUSION: TDABC is a feasible and effective costing and management tool in low-resource settings. The TDABC process maps and treatment costs revealed several opportunities for innovative improvements in the NTP under public health programme settings. Re-engineering laboratory testing processes and synchronising TB treatment follow-up with antiretroviral treatments could produce better and more uniform TB treatments at significantly lower cost in Zimbabwe.

A new HLA-A*03 null allele - A*03:162N caused by an exon 4 insertion and discovered during an external quality assessment exercise.

HLA-A*03:162N differs from A*03:01:01:01 by an exon 4, 664-665insCATG causing E198A and A199X.

External quality assessment of patient HLA-B*57:01 testing prior to abacavir prescription.

Hypersensitivity reactions to the drug abacavir are strongly associated with possession of HLA-B*57:01. Hence, patients with HIV/AIDS who may be prescribed abacavir should be tested for this HLA allele and the drug withheld from those that possess B*57:01. The UK National External Quality Assessment Service for Histocompatibility and Immunogenetics has operated a scheme for B*57:01 testing since 2008 which, in 2013, involved 47 participants from 12 countries. A total of 24 B*57:01-positive, 2 B*57:03-positive and 22 B*57-negative blood samples (including 2 B*58 samples) were distributed to between 28 and 47 laboratories each year over 6 years. Participants, who were unaware of the samples' HLA types, tested and reported on their B*57/B*57:01 status. A total of 1868 reports were assessed over the 6 years. Of the 880 reports on B*57:01 samples, 93.4% were correctly assigned as B*57:01, 2.8% were assigned as groups of B*57 alleles including B*57:01, and 3.3% were reported as B*57 positive only. Over the 6 years, there were four (0.46%) false B*57:01 negative reports. All the B*57:03-positive and B*57-negative samples, involving 72 and 916 assignments, respectively, were essentially reported as B*57:01 negative. Thus, there were no false B57:01 positive assignments. The reporting of B*57:01 status over the last 3 years of the scheme was 99.8% sensitive and 100% specific. Over the last year, it was 100% sensitive and 100% specific.

Unveiling the intriguing role of FAP20 in tubulin recruitment at the doublet microtubule inner junctions.

In this issue of Structure, Bangera et al. investigate the role of the inner junction protein FAP20 in doublet microtubule assembly. Using cryo-EM and microtubule dynamic assays, they demonstrate that FAP20 recruits free tubulins to existing microtubule lattices, shedding light on B-tubule closure during doublet microtubule formation.

Effect of odor treatment systems on bioaerosol microbial concentration and diversity from wastewater treatment plants.

Biofiltration, activated carbon and chemical scrubbing are technologies used for odor control in wastewater treatment plants. These systems may also influence the airborne microbial load in treated air. The study objectives were to 1) evaluate the capacity of three odor control system technologies to reduce the airborne concentration of total bacteria, Legionella, L. pneumophila, non-tuberculous mycobacteria (NTM) and Cladosporium in winter and summer seasons and 2) to describe the microbial ecology of the biofiltration system and evaluate its impact on treated air microbial diversity. A reduction of the total bacterial concentration up to 25 times was observed after odor treatment. Quantification by qPCR revealed the presence of Legionella spp. in all air samples ranging between 26 and 1140 GC/m3, while L. pneumophila was not detected except for three samples below the limit of quantification. A significant increase of up to 25-fold of Legionella spp. was noticed at the outlet of two of the three treatment systems. NTM were ubiquitously detected before air treatment (up to 2500 GC/m3) and were significantly reduced by all 3 systems (up to 13-fold). Cladosporium was measured at low concentrations for each system (< 190 GC/m3), with 68 % of the air samples below the limit of detection. Biodiversity results revealed that biofiltration system is an active process that adapts to air pollutants over time. Legionella spp. were detected in significant abundance in the air once treated in winter (up to 27 %). Nevertheless, the abundance of protozoan hosts is low and does not explain the multiplication of Legionella spp. The season remains the most influential factor shaping biodiversity. In summer only, air biofiltration caused a significant enrichment of the biodiversity. Although odor control technologies are not designed for bacterial mitigation, findings from this study suggest their potential to reduce the abundance of some genera harboring pathogenic species.

[The first steps towards advanced practice for radiation therapists]. / Les prémices de la pratique avancée pour le manipulateur en radiothérapie.

The implementation of advanced practice in RT requires evidence regarding the clinical practices of radiation therapists (RTT) in the field. In this context, the goal of this article is to report the roles assigned to RTT in order to meet the demands of patients, RT services, and/or healthcare professionals. As part of the French Society of Oncologic Radiotherapy's congress, the Radiotherapy Committee of the French Association of radiographers presented a scientific program encompassing three main themes: patient follow-up by a RTT, the expertise of an RTT in Image Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART), and the involvement of a RTT in research. This article presents an overview of five oral presentations that highlight concrete examples of roles assigned to RTTs in these specific domains. The follow-up of patients has been assigned to RTT. Research and development have been recognized as activities in which RTT play a significant role. The establishment of RTT specializing in IGRT has been reported to facilitate decision-making and is essential in ensuring professional expertise. Lastly, there is a need to enhance RTT skills in adaptive RT to support the implementation of this technique. These roles described as advanced practice meet needs and require a specific organisational framework and appropriate education and training (master type). Activities such as post-RT follow-up, validation of positioning imaging, delineation, writing research protocols, and involvement in the development of technological innovations were identified as essential tasks that can be assigned to RTT.

[Survey by SFRO, SNRO and AFPPE about the evolution of the radiation therapist profession in France]. / Enquête SFRO­SNRO­AFPPE sur l'évolution du métier de manipulateur exerçant en radiothérapie en France.

PURPOSE: As part of the multidisciplinary team, radiation therapists are in charge of elements of treatment preparation and delivery of radiotherapy to cancer patients. Helping scientific and technological improvements, more and more patients with cancer were treated with radiotherapy including hypofractionnated radiotherapy, that explain the increase of demands on services. The professional impacted by this increase of demands are radiation oncologists and medical physicists. The opportunity to push forward the radiation therapist's competencies appears with the possibility to shift them some tasks. In this context, a first work was performed with objectives to have an overview of the tasks shifted to radiation therapists in France, the tasks that they could perform but also to evaluate some criteria of job satisfaction. MATERIAL AND METHODS: The committee of "new status and value of status" including six radiation oncologists (the French society of radiation oncology [SFRO] et national union of radiation oncologists [SNRO]) and six radiation therapists committee members of the French association of radiation therapists (AFPPE), built a questionnaire including three parts: demographic characteristics, tasks shifted and job satisfaction criteria. In total, the questionnaire included 19 questions and 24 items assessed with a four point-Likert scale (ranging from "completely disagree" to "completely agree"). This survey, formatting with google form, was tested by the committee members and the final version was sent to the SFRO, AFPPE and SNRO members, before being disseminated on the social networks. RESULTS: From November 18th 2022 to December 31st 2022, 492 responses were received (response rate=18.3%): 55 % of the respondents had at least 11 years of experience in radiotherapy. The respondents worked in different type of health facilities (36 % in specialized cancer centres, 19.5 % in private centers, 17.5% in university and general hospital, 10.2% in general hospital). More than » of the respondents had a teaching lecturer activity, 20% had a management team activity and a research activity for 18%. Less than 10% of the respondents had another degree than that of radiation therapist: university degree (n=27), degree in dosimetry (n=11) and master (n=3). More than 76% would like to be trained and to have access to the advanced practice, more than 50% would like expend competencies with a university degree, 30% with a master and 67% would like to participate in research. Forty-two percent of the respondents were involved in a task shifting (excluding decree relating to acts and activities carried out by radiation therapists) and among the radiation therapists non-involved, 63% would be interested in being. Regarding job satisfaction, 53% of the respondents were satisfied with their job and their salary and 68% believed that their job occupation is in line with their professional aspirations. More than 2/3 of the respondents described a significant workload and mental load, 53% thought to have time for their patient care and 70% felt some organisational difficulties. CONCLUSION: This survey shows: (i) A significant involvement of radiation therapists in the task shifting; (ii) A very strong demand for career development, in particular with existing degrees or to be created degree such as advanced practice; and (iii) The need to reinforce a job satisfaction for almost the half of the respondents, linked to a workload, a mental load and some organisational difficulties.

[Radiation therapists shortage in France: Organizational consequences and difficulties in deploying new missions and/or tasks delegation]. / Métier de manipulateur en radiothérapie en tension en France : conséquences organisationnelles et difficultés à déployer de nouvelles missions et/ou délégation de tâches.

PURPOSE: Radiation therapists shortage has been evaluated at national level in France, specifically in oncology radiotherapy, in terms of: (i) organizational adaptations, (ii) impact on patients care, and (iii) difficulties in deploying new missions and/or tasks delegation. MATERIALS AND METHODS: French professional organisations representing radiation therapists - SFRO, SNRO and AFPPE - sent their members a national survey (ten questions on 32 items). RESULTS: From 18 November 2022 to 31 December 2022, 55 responses were received (response rate: 31%) from radiotherapy managers or department heads; 51% had a structure comprising three to five treatment rooms (receiving 500 to 1000 patients per year [36%], or 1500 to 2000 patients per year [33%]). Activities performed were intensity-modulated radiotherapy (100%), stereotaxic radiotherapy (85%), brachytherapy (40%), adaptive radiotherapy (34%). These structures described consequences in closing machine time for 25% of them (reduction of the hourly volume greater than 10% in 57%) with the following consequences in the last 6 months: (i) an extension of the period of medical care (78%), a closing of one or more accelerators (50%) and the development of moderate hypofractionation scheme or extreme hypofractionation (50%). In current functioning, linear accelerators can deliver treatments with a team of two radiation therapists per room for a short day (43%) or two to four radiation therapists per room teams for a long day (40%). During the last 6 months, there has been a 10% increase in linear accelerators operating with a single team. (ii) regarding treatment planning: 16.4% reported a decrease in the opening amplitude (less than 20% in 44% of cases, from 20 to 50% in 33 % of cases). The initial scheduling of appointments for radiotherapy sessions was carried out by radiation therapists in 84% of the departments in current functioning (0.1 to 1 FTE dedicated to this activity in 62% of the departments). Over the last 6 months, there has been a clear reduction in the number of dedicated FTEs: [FTE=0.1 to 1]=-8%; [FTE=0]=+7%. (ii) Regarding tasks delegation (excluding the decree on acts and activities carried out by the radiation therapist): organ at risk delineation is partially performed by radiation therapist in 26% of the centres; caregiver support time in 78% (56% totally or 22% partially). This activity has been reduced by 42%. Seventy-five percent of departments want to develop new techniques, patient-centered approaches (44%), implement task delegation (organ at risk delineation: 58%; weekly consultations: 67%; positioning imaging validation: 71%), and 78% of departments are interested in developing advanced radiotherapy practice. However, the number of radiation therapists is considered insufficient in their implementation in 76% of cases (one to two FTE missing for 72% of structures). CONCLUSION: This survey shows a significant impact of radiation therapist shortage in radiotherapy oncology care (treatment delays, access to caregiver support time, workload on treatment teams), and represents a major obstacle to the development of radiotherapy structures.

CEP104/FAP256 and associated cap complex maintain stability of the ciliary tip.

Cilia are essential organelles that protrude from the cell body. Cilia are made of a microtubule-based structure called the axoneme. In most types of cilia, the ciliary tip is distinct from the rest of the cilium. Here, we used cryo-electron tomography and subtomogram averaging to obtain the structure of the ciliary tip of the ciliate Tetrahymena thermophila. We show that the microtubules at the tip are highly crosslinked with each other and stabilized by luminal proteins, plugs, and cap proteins at the plus ends. In the tip region, the central pair lacks typical projections and twists significantly. By analyzing cells lacking a ciliary tip-enriched protein CEP104/FAP256 by cryo-electron tomography and proteomics, we discovered candidates for the central pair cap complex and explained the potential functions of CEP104/FAP256. These data provide new insights into the function of the ciliary tip and the mechanisms of ciliary assembly and length regulation.

Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.

Cilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, utilizing cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localized 12 DRC subunits in the N-DRC structure of Tetrahymena thermophila . We also found that the CCDC96/113 complex is in close contact with the N-DRC. In addition, we revealed that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.

The interactive effects of psychosocial stress and diet composition on health in primates.

Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implications for aging and human health. We examined the effects of social subordination stress and Mediterranean versus Western diet on multiple systems. We report that psychosocial stress and Western diet have independent and additive adverse effects on hypothalamic-pituitary-adrenal and autonomic nervous system reactivity to psychological stressors, brain structure, and ovarian function. Compared to the Mediterranean diet, the Western diet resulted in accelerated aging, nonalcoholic fatty liver disease, insulin resistance, gut microbial changes associated with increased disease risk, neuroinflammation, neuroanatomical perturbations, anxiety, and social isolation. This comprehensive, multisystem investigation lays the foundation for future investigations of the mechanistic underpinnings of psychosocial stress and diet effects on health, and advances the promise of the Mediterranean diet as a therapeutic intervention on psychosocial stress.

Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.

Cilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, using cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localize 12 DRC subunits in the N-DRC structure of Tetrahymena thermophila. We also find that the CCDC96/113 complex is in close contact with the DRC9/10 in the linker region. In addition, we reveal that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.

Native doublet microtubules from Tetrahymena thermophila reveal the importance of outer junction proteins.

Cilia are ubiquitous eukaryotic organelles responsible for cellular motility and sensory functions. The ciliary axoneme is a microtubule-based cytoskeleton consisting of two central singlets and nine outer doublet microtubules. Cryo-electron microscopy-based studies have revealed a complex network inside the lumen of both tubules composed of microtubule-inner proteins (MIPs). However, the functions of most MIPs remain unknown. Here, we present single-particle cryo-EM-based analyses of the Tetrahymena thermophila native doublet microtubule and identify 42 MIPs. These data shed light on the evolutionarily conserved and diversified roles of MIPs. In addition, we identified MIPs potentially responsible for the assembly and stability of the doublet outer junction. Knockout of the evolutionarily conserved outer junction component CFAP77 moderately diminishes Tetrahymena swimming speed and beat frequency, indicating the important role of CFAP77 and outer junction stability in cilia beating generation and/or regulation.

Mediterranean Diet Protects Against a Neuroinflammatory Cortical Transcriptome: Associations with Brain Volumetrics, Peripheral Inflammation, Social Isolation and Anxiety.

INTRODUCTION: Mediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets, however the underlying biology is poorly understood. METHODS: We assessed the effects of Western vs. Mediterranean-like diets on RNAseq generated transcriptional profiles in temporal cortex and their relationships with changes in MRI neuroimaging phenotypes, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques. RESULTS: Diet resulted in differential expression of seven transcripts (FDR<0.05). Cyclin dependent kinase 14 ( CDK14 ), a proinflammatory regulator, was lower in the Mediterranean group. The remaining six transcripts [i.e., "lunatic fringe" ( LFNG ), mannose receptor C type 2 ( MRC2 ), solute carrier family 3 member 2 ( SLCA32 ), butyrophilin subfamily 2 member A1 ( BTN2A1 ), katanin regulatory subunit B1 ( KATNB1 ), and transmembrane protein 268 ( TMEM268 )] were higher in cortex of the Mediterranean group and generally associated with anti-inflammatory/neuroprotective pathways. KATNB1 encodes a subcomponent of katanin, important in maintaining microtubule homeostasis. BTN2A1 is involved in immunomodulation of γδ T-cells which have anti-neuroinflammatory and neuroprotective effects. CDK14 , LFNG , MRC2, and SLCA32 are associated with inflammatory pathways. The latter four differentially expressed cortex transcripts were associated with monocyte transcript levels, changes in AD-relevant brain volumes determined by MRI over the course of the study, and social isolation and anxiety. CDK14 was positively correlated with monocyte inflammatory transcripts, changes in total brain, gray matter, cortical gray matter volumes, and time alone and anxious behavior, and negatively correlated with changes in total white matter and cerebrospinal fluid (CSF) volumes. In contrast, LFNG , MRC2 , and SLCA32 were negatively correlated with monocyte inflammatory transcripts and changes in total gray matter volume, and positively correlated with CSF volume changes, and SLCA32 was negatively correlated with time alone. DISCUSSION: Collectively, our results suggest that relative to Western diets, Mediterranean diets confer protection against peripheral and central inflammation which is reflected in preserved brain structure and behavior.

[Impact of a positive coronavirus diagnostic test on the radiotherapy patient journey at Gustave-Roussy institute]. / Impact d'un test de diagnostic du coronavirus positif sur le parcours du patient en radiothérapie à l'institut Gustave-Roussy.

PURPOSE: The coronavirus disease 2019 (COVID-19) epidemic continues to spread exponentially around the world. Cancer patients have a higher risk of commorbidity than the rest of the population. Radiotherapy departments are actively involved in the management of these patients, whether they have COVID or not, and it is recognized that the time taken to take charge and the continuity of treatment have a prognostic impact. The main objective was to assess the impact of the coronavirus on the treatment times of patients undergoing radiotherapy. MATERIAL AND METHODS: This retrospective study was conducted in the radiotherapy department of Gustave-Roussy institute (France) during the period from March 3, 2020 to January 12, 2021. Organizational changes, patient care times between the day of the scan and the last radiotherapy session as well as the time taken to take charge of patients between the first session and the last radiotherapy session has been studied. RESULTS: A total of 1183 patients were included, among which 60 had COVID-19. Patients were divided into four categories. Treatment times of patients who did not have COVID-19 and those of patients who did were not statistically significantly different. CONCLUSION: The organization of the radiotherapy department at the Gustave-Roussy institute is based on several points: carrying out preventive screening tests, protecting staff and patients and reorganizing the patient circuit. Thanks to the performance of diagnostic tests and the implementation of a specific workflow for patients with COVID, we ensure the continuity of patient treatment in complete safety without impacting treatment times.

Mediterranean Diet Reduces Social Isolation and Anxiety in Adult Female Nonhuman Primates.

Dietary composition is associated with the differential prevalence of psychiatric disorders; the Western diet confers increased risk, while the Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-like behaviors and social isolation have been linked to both Western diet consumption and increased inflammatory disease risk, and recent evidence suggests that diet composition may affect immune system function in part through its effects on behavior. This is particularly important in the context of the global COVID-19 pandemic in which social isolation has been associated with disease. Here, we examined the effects of Western- and Mediterranean-like diets on social behavior in a randomized, 34-month preclinical trial in middle-aged female cynomolgus macaques (Macaca fascicularis). Diet induced rapid and persistent changes in a suite of behaviors. After just three months of experimental diet consumption, a composite measure of diet-altered behavior (DAB) significantly differed between the two diets (p = 0.014) and remained different throughout the 24-month experimental observation period (p = 2.2 × 10-8). Monkeys fed the Western diet spent more time alone (FDR = 4.4 × 10-5) and displayed more anxiety behavior (FDR = 0.048), whereas monkeys fed the Mediterranean diet spent more time resting (FDR = 0.0013), attentive (FDR = 0.017), and in body contact with groupmates (FDR = 4.1 × 10-8). These differences were largely due to changes in behavior of animals fed the Mediterranean diet, while Western-diet-fed-animals exhibited similar behaviors compared to the eight-month baseline period, during which all monkeys consumed a common laboratory diet. These observations provide experimental support in a nonhuman primate model, demonstrating a potential therapeutic benefit of the Mediterranean diet consumption to reduce social isolation and anxiety and thus mitigate social isolation-associated disorders that often accompany illness and disability.