Long-term COVID symptoms, work ability and fitness to work in healthcare workers hospitalized for Sars-CoV-2 infection.

BACKGROUND: COVID-19 can affect the persistence of symptoms and work ability (WA), hence the fitness to work of healthcare workers (HCW). We describe the effects of COVID-19 in hospitalized HCWs of a large Hospital in Lombardy and their implications on WA and fitness to work. METHODS: Fifty-six HCWs of Fatebenefratelli-Sacco Hospital have been hospitalized for COVID-19 since March 2020. Clinical and fitness-to-work data were acquired from Occupational Health Surveillance Program. A structured questionnaire was administered to 53/56 HCWs 18 months after infection to investigate Long-COVID symptoms and WA. RESULTS: Symptoms most reported at recovery (rhino-pharyngeal swab-NPS-negative) were exertional dyspnea (86.8%), asthenia (86.8%), arthro-myalgia (71.7%), sleep disorders (64.2%), resting dyspnea (62.3%), cough (56.6%). 69.6% underwent evaluation at out-patient clinics experienced in Long-COVID. Ten months after recovery, symptoms related to physical well-being decreased while memory and anxiety/depression were more persistent. At recovery, the WA score decreased from 10 to 8, and then an improvement from 8 to 9 was noted during the survey. At the return-to-work examination, fit-to-work judgements with restrictions increased from 31.4% to 58.7%; then, a slight decrease in the rate of judgements with restrictions was observed at the survey's time. CONCLUSION: Post-COVID-19 symptoms can persist for a long time and could impact WA and fitness-to-work of HCW. Adequate health surveillance protocols should guarantee the health protection of HCW with persistent disorders after COVID-19.

3D single cell migration driven by temporal correlation between oscillating force dipoles.

Directional cell locomotion requires symmetry breaking between the front and rear of the cell. In some cells, symmetry breaking manifests itself in a directional flow of actin from the front to the rear of the cell. Many cells, especially in physiological 3D matrices, do not show such coherent actin dynamics and present seemingly competing protrusion/retraction dynamics at their front and back. How symmetry breaking manifests itself for such cells is therefore elusive. We take inspiration from the scallop theorem proposed by Purcell for micro-swimmers in Newtonian fluids: self-propelled objects undergoing persistent motion at low Reynolds number must follow a cycle of shape changes that breaks temporal symmetry. We report similar observations for cells crawling in 3D. We quantified cell motion using a combination of 3D live cell imaging, visualization of the matrix displacement, and a minimal model with multipolar expansion. We show that our cells embedded in a 3D matrix form myosin-driven force dipoles at both sides of the nucleus, that locally and periodically pinch the matrix. The existence of a phase shift between the two dipoles is required for directed cell motion which manifests itself as cycles with finite area in the dipole-quadrupole diagram, a formal equivalence to the Purcell cycle. We confirm this mechanism by triggering local dipolar contractions with a laser. This leads to directed motion. Our study reveals that these cells control their motility by synchronizing dipolar forces distributed at front and back. This result opens new strategies to externally control cell motion as well as for the design of micro-crawlers.

Galaxy Is a Suitable Bioinformatics Platform for the Molecular Diagnosis of Human Genetic Disorders Using High-Throughput Sequencing Data Analysis: Five Years of Experience in a Clinical Laboratory.

BACKGROUND: To date, the usage of Galaxy, an open-source bioinformatics platform, has been reported primarily in research. We report 5 years' experience (2015 to 2020) with Galaxy in our hospital, as part of the "Assistance Publique-Hôpitaux de Paris" (AP-HP), to demonstrate its suitability for high-throughput sequencing (HTS) data analysis in a clinical laboratory setting. METHODS: Our Galaxy instance has been running since July 2015 and is used daily to study inherited diseases, cancer, and microbiology. For the molecular diagnosis of hereditary diseases, 6970 patients were analyzed with Galaxy (corresponding to a total of 7029 analyses). RESULTS: Using Galaxy, the time to process a batch of 23 samples-equivalent to a targeted DNA sequencing MiSeq run-from raw data to an annotated variant call file was generally less than 2 h for panels between 1 and 500 kb. Over 5 years, we only restarted the server twice for hardware maintenance and did not experience any significant troubles, demonstrating the robustness of our Galaxy installation in conjunction with HTCondor as a job scheduler and a PostgreSQL database. The quality of our targeted exome sequencing method was externally evaluated annually by the European Molecular Genetics Quality Network (EMQN). Sensitivity was mean (SD)% 99 (2)% for single nucleotide variants and 93 (9)% for small insertion-deletions. CONCLUSION: Our experience with Galaxy demonstrates it to be a suitable platform for HTS data analysis with vast potential to benefit patient care in a clinical laboratory setting.

Information and motility exchange in collectives of active particles.

We examine the interplay of motility and information exchange in a model of run-and-tumble active particles where the particle's motility is encoded as a bit of information that can be exchanged upon contact according to the rules of AND and OR logic gates in a circuit. Motile AND particles become non-motile upon contact with a non-motile particle. Conversely, motile OR particles remain motile upon collision with their non-motile counterparts. AND particles that have become non-motile additionally "reawaken", i.e., recover their motility, at a fixed rate µ, as in the SIS (susceptible, infected, susceptible) model of epidemic spreading, where an infected agent can become healthy again, but keeps no memory of the recent infection, hence it is susceptible to a renewed infection. For µ = 0, both AND and OR particles relax irreversibly to absorbing states of all non-motile or all motile particles, respectively. The relaxation kinetics is, however, faster for OR particles that remain active throughout the process. At finite µ, the AND dynamics is controlled by the interplay between reawakening and collision rates. The system evolves to a state of all motile particles (an absorbing state in the language of absorbing phase transitions) for µ > µc and to a mixed state with coexisting motile and non-motile particles (an active state in the language of absorbing phase transitions) for µ < µc. The final state exhibits a rich structure controlled by motility-induced aggregation. Our work can be relevant to biochemical signaling in motile bacteria, the spreading of epidemics and of social consensus, as well as light-controlled organization of active colloids.

[Atherosclerosis, chronic inflammation and oxidative stress in CKD].

Chronic low-grade inflammation is emerging as the pathophysiological mechanism underlying of the several chronic degenerative diseases. Atherosclerosis, inflammation and oxidative stress are some of the issues that arise from the general context of chronic inflammation. In this manuscript we analyzed the role of the immune system, metabolism and inflammation's molecular mediators in order to show an overview about only apparently different problems. Finally, we proposed some possible solutions to improve the survival and quality of life of patient with chronic kidney disease.

Defect driven shapes in nematic droplets: analogies with cell division.

Building on the striking similarity between the structure of the spindle during mitosis in living cells and nematic textures in confined liquid crystals, we use a continuum model of two-dimensional nematic liquid crystal droplets to examine the physical aspects of cell division. The model investigates the interplay between bulk elasticity of the microtubule assembly, described as a nematic liquid crystal, and surface elasticity of the cell cortex, modeled as a bounding flexible membrane, in controlling cell shape and division. The centrosomes at the spindle poles correspond to the cores of the topological defects required to accommodate nematic order in a closed geometry. We map out the progression of both healthy bipolar and faulty multi-polar division as a function of an effective parameter that incorporates active processes and controls centrosome separation. A robust prediction, independent of energetic considerations, is that the transition from a single cell to daughters cells occurs at critical value of this parameter. Our model additionally suggests that microtubule anchoring at the cell cortex may play an important role for successful bipolar division. This can be tested experimentally by regulating microtubule anchoring.

Endocytic reawakening of motility in jammed epithelia.

Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells, and ballistic motion in otherwise kinetically arrested monolayers. This is linked to increased traction forces and to the extension of cell protrusions, which align with local velocity. Molecularly, impairing endocytosis, macropinocytosis or increasing fluid efflux abrogates RAB5A-induced collective motility. A simple model based on mechanical junctional tension and an active cell reorientation mechanism for the velocity of self-propelled cells identifies regimes of monolayer dynamics that explain endocytic reawakening of locomotion in terms of a combination of large-scale directed migration and local unjamming. These changes in multicellular dynamics enable collectives to migrate under physical constraints and may be exploited by tumours for interstitial dissemination.

Hydrodynamic synchronization of colloidal oscillators.

Two colloidal spheres are maintained in oscillation by switching the position of an optical trap when a sphere reaches a limit position, leading to oscillations that are bounded in amplitude but free in phase and period. The interaction between the oscillators is only through the hydrodynamic flow induced by their motion. We prove that in the absence of stochastic noise the antiphase dynamical state is stable, and we show how the period depends on coupling strength. Both features are observed experimentally. As the natural frequencies of the oscillators are made progressively different, the coordination is quickly lost. These results help one to understand the origin of hydrodynamic synchronization and how the dynamics can be tuned. Cilia and flagella are biological systems coupled hydrodynamically, exhibiting dramatic collective motions. We propose that weakly correlated phase fluctuations, with one of the oscillators typically processing the other, are characteristic of hydrodynamically coupled systems in the presence of thermal noise.

Swimmers in thin films: from swarming to hydrodynamic instabilities.

We investigate theoretically the collective dynamics of a suspension of low Reynolds number swimmers that are confined to two dimensions by a thin fluid film. Our model swimmer is characterized by internal degrees of freedom which locally exert active stresses on the fluid. We find that hydrodynamic interactions mediated by the film can give rise to spontaneous continuous symmetry breaking (swarming), to states with either polar or nematic homogeneous order. For dipolar swimmers, the stroke averaged dynamics are enough to determine the leading contributions to the collective behavior. In contrast, for quadrupolar swimmers, details of the internal dynamics are important in determining the bulk behavior. In the broken symmetry phases, fluctuations of hydrodynamic variables destabilize order. Interestingly, this instability is not generic and depends on the length scale.

Relative digit lengths and testosterone levels in Guinea baboons.

A growing body of literature suggests that the ratio of the lengths of the second to fourth digits (2D:4D) on human hands is sexually dimorphic and associated with prenatal exposure to gonadal hormones, circulating serum testosterone, and a number of psychological and behavioral measures. Little research has investigated digit ratios in nonhuman species. In the present study, we investigated sex differences in digit ratios and their possible association with serum testosterone in a captive group of Guinea baboons (Papio papio). Contrary to the sex difference typically reported in humans, male baboons exhibited a substantially larger 2D:4D than did female baboons. Consistent with the human data, however, lower 2D:4D was associated with higher serum testosterone among the males. The present findings suggest that the relationship between digit ratios and male gonadal hormones may be phylogenetically well-conserved, although they also suggest possible species differences in the causal relationships between developmental mechanisms and sex-differentiated digit length patterns.

Herding and snaking by the harem stallion in domestic herds.

Four herds of pony mares, each consisting of a stallion and six mares, were used to characterize the nature of herding by the stallion and the factors that induced the herding behavior. Herding behaviors were compared among four successive treatments (six mares alone, stallion added, two new mares added, and entire herd moved to a new pasture). A new treatment was initiated every 7 days and behavior was studied for 5 consecutive days (Days 1-5) for each treatment. Observations were made every 10 min during a 2-h period for each day. The extent of herding was quantitated by the mean distances between mares. The extent of snaking (herding with the head and neck extended and ears held back) was scored 0, 1, 2, or 3 (nil, minimal, intermediate, and maximal, respectively). The mean distance among the original mares on Day 1 when the mares were alone was 5.0 mare lengths and was reduced (P < 0.05) to 1.9 mare lengths when the stallion was added. The mean distance among the original mares of an established stallion/mare herd (3.8 mare lengths) was reduced (P < 0.05) on the day the herd was moved to a new pasture (1.9 mare lengths), similar to the effect of the introduction of the stallion. Scores for the extent of snaking, as well as the extent of herding, were highest (P < 0.05) on Day 1 when the stallion was added or the stallion/mare herd was moved to a new pasture. The extent of herding and snaking decreased (P < 0.05) by Day 2 and was seen only occasionally on Days 3-5. The addition of new mares to the herd did not induce herding of the original mares. However, the new mares maintained mean distances of 8-12 mare lengths from the original mares, resulting primarily from chasing by the stallion. By Day 4, the distances between the new and original mares were not different (P > 0.05) from the distances among the original mares.