Multidisciplinary analysis of cancer-related fatigue at the time of diagnosis: preliminary results of the BIOCARE FActory cohort.

PURPOSE: Cancer-related fatigue (CRF) is a common side effect of cancer and cancer treatment that significantly impairs the quality of life and can persist for years after treatment completion. Although fatigue is often associated with cancer treatment, it is also a result of the disease itself, even before intervention. CRF at the time of diagnosis may affect treatment timing or completion and is a consistent predictor of post-treatment fatigue at any time. The mechanisms underlying CRF are multidimensional and not well understood, particularly at the time of diagnosis. METHODS: Sixty-five breast cancer patients at the time of diagnosis were included. The participants completed self-assessment questionnaires about CRF, sleep disturbances, and emotional symptoms and wore an accelerometer to assess levels of spontaneous physical activity and sleep quality. During the experimental session, the participants underwent cognitive, neuromuscular, and exercise metabolism evaluations. RESULTS: Using augmented backward elimination regression, this study found that emotional symptoms and perceived sleep disturbances were the strongest predictors of CRF (adjusted r2 = 0.51). Neuromuscular fatigability and sleep disturbance were also associated with physical dimensions, whereas cognitive performance was associated with cognitive dimensions. CONCLUSION: At the time of diagnosis, emotional and cognitive dimensions are over-represented compared to the general population, and specific subdimensions have specific predictors that support the idea of distinct mechanisms. Evaluating CRF subdimensions and their potential mechanisms at the time of diagnosis would be particularly relevant for identifying high-risk patients and offering them appropriate interventions. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT04391543) in May, 2020.

Comparison of neuromuscular fatigability amplitude and etiologies between fatigued and non-fatigued cancer patients.

PURPOSE: Cancer-related fatigue (CRF) is the most reported side effect of cancer and its treatments. Mechanisms of CRF are multidimensional, including neuromuscular alterations leading to decreased muscle strength and endurance (i.e., fatigability). Recently, exercise fatigability and CRF have been related, while fatigability mechanisms remain unclear. Traditionally, fatigability is assessed from maximal voluntary contractions (MVC) decrease, but some authors hypothesized that the rate of force development (RFD) determined during a rapid contraction could also be an interesting indicator of functional alterations. However, to our knowledge, no study investigated RFD in cancer patients. The purpose of this study was to determine whether RFD, fatigability amplitude, and etiology are different between fatigued and non-fatigued cancer patients. METHODS: Eighteen participants with cancer, divided in fatigued or non-fatigued groups according their CRF level, completed a 5-min all-out exercise in ankle plantar flexor muscles composed of 62 isometric MVC of 4 s with 1 s rest, to assess fatigability amplitude as the force-time relationship asymptote (FA). Before and after exercise, fatigability etiologies (i.e., voluntary activation (VA) and evoked forces by electrical stimulation (Db100)) were assessed as well as RFD in 50 and 100 ms (RFD50 and RFD100, respectively) during rapid contractions. RESULTS: FA is significantly lower in fatigued group. Significant differences were found between pre- and post-exercise VA, Db100, RFD50, and RFD100 for both groups, with no statistical difference between groups. CONCLUSION: During treatments, fatigability is higher in fatigued patients; however, the mechanisms of fatigability and RFD alterations are similar in both groups. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04391543, May 2020.

Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. METHODS: BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. DISCUSSION: This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

Microfluidic synthesis of retinoic acid-loaded nanoparticles for neural differentiation of trabecular meshwork mesenchymal stem cell.

OBJECTIVES: This study aimed to fabricate the PCL-nanoparticles (NPs) loaded retinoic acid (RA) using the microfluidic system for successful cellular uptake and induction of neuronal differentiation of trabecular meshwork mesenchymal stem cells (TMMSCs). METHODS: A microfluidic system used to synthesize RA-loaded NPs, DLS, FTIR, TEM, and UV-spectroscopy was recruited to characterize and study the release of RA. Also, the toxicity, cellular uptake, and neuronal differential of TMMSCs have been assessed. RESULTS: According to the obtained results, the spherical NPs (117.6±0.35 nm, ‒19.4±5.3) and RA-loaded NPs (121.6±0.75 nm, ‒23.6±1.3) were synthesized successfully by microfluidic system. 7.8±2.04 % of RA was loaded in NPs, and 25 % was released in the first four hours. Thus, the NPs have been successfully internalized into the stem cells, leading to a significant increase in neural genes and protein (ß Tubulin III and Map-2) expression. CONCLUSION: Our study's harvested results have represented valid data for practical use of microfluidic systems in the term of NPs loaded RA synthesis and its successful function to cellular internalization and euronal differentiation of TMMSCs (Tab. 2, Fig. 10, Ref. 46).

External pH modulation during the growth of Vibrio tapetis, the aetiological agent of brown ring disease.

AIMS: Brown ring disease (BRD) is an infection of the Manila clam Ruditapes philippinarum due to the pathogen Vibrio tapetis. During BRD, clams are facing immunodepression and shell biomineralization alteration. In this paper, we studied the role of pH on the growth of the pathogen and formulated hypothesis on the establishment of BRD by V. tapetis. METHODS AND RESULTS: In this study, we monitored the evolution of pH during the growth of V. tapetis in a range of pH and temperatures. We also measured the pH of Manila clam haemolymph and extrapallial fluids (EPFs) during infection by V. tapetis. We highlighted that V. tapetis modulates the external pH during its growth, to a value of 7·70. During the development of BRD, V. tapetis also influences EPFs and haemolymph pH in vitro in the first hours of exposure and in vivo after 3 days of infection. CONCLUSIONS: Our experiments have shown a close interaction between V. tapetis CECT4600, a pathogen of Manila clam that induces BRD, and the pH of different compartments of the animals during infection. These results indicate that the bacterium, through a direct mechanism or as a consequence of physiological changes encountered in the animal during infection, is able to interfere with the pH of Manila clam fluids. This pH modification might promote the infection process or at least create an imbalance within the animal that would favour its persistence. This last hypothesis should be tested in future experiment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first observation of pH modifications in the context of BRD and might orient future research on the fine mechanisms of pH modulation associated with BRD.

Nonresonant Polarized Raman Spectra Calculations of Nitrogen-Doped Single-Walled Carbon Nanotubes: Diameter, Chirality, and Doping Concentration Effects.

Raman spectra of nitrogen-doped single-walled carbon nanotubes are calculated using the spectral moment's method combined with the bond polarizability model. The influence of the nanotube diameter and chirality is investigated. We also address the important question of the effect of the N-doping concentration, and we propose an equation to estimate the doping concentration from the knowledge of the tube diameter and the frequency of the radial breathing mode.

Handgrip fatiguing exercise can provide objective assessment of cancer-related fatigue: a pilot study.

PURPOSE: As a subjective symptom, cancer-related fatigue is assessed via patient-reported outcomes. Due to the inherent bias of such evaluation, screening and treatment for cancer-related fatigue remains suboptimal. The purpose is to evaluate whether objective cancer patients' hand muscle mechanical parameters (maximal force, critical force, force variability) extracted from a fatiguing handgrip exercise may be correlated to the different dimensions (physical, emotional, and cognitive) of cancer-related fatigue. METHODS: Fourteen women with advanced breast cancer, still under or having previously received chemotherapy within the preceding 3 months, and 11 healthy women participated to the present study. Cancer-related fatigue was first assessed through the EORTC QLQ-30 and its fatigue module. Fatigability was then measured during 60 maximal repeated handgrip contractions. The maximum force, critical force (asymptote of the force-time evolution), and force variability (root mean square of the successive differences) were extracted. Multiple regression models were performed to investigate the influence of the force parameters on cancer-related fatigue's dimensions. RESULTS: The multiple linear regression analysis evidenced that physical fatigue was best explained by maximum force and critical force (r = 0.81; p = 0.029). The emotional fatigue was best explained by maximum force, critical force, and force variability (r = 0.83; p = 0.008). The cognitive fatigue was best explained by critical force and force variability (r = 0.62; p = 0.035). CONCLUSION: The handgrip maximal force, critical force, and force variability may offer objective measures of the different dimensions of cancer-related fatigue and could provide a complementary approach to the patient reported outcomes.

High-precision gigahertz-to-terahertz spectroscopy of aqueous salt solutions as a probe of the femtosecond-to-picosecond dynamics of liquid water.

Because it is sensitive to fluctuations occurring over femtoseconds to picoseconds, gigahertz-to-terahertz dielectric relaxation spectroscopy can provide a valuable window into water's most rapid intermolecular motions. In response, we have built a vector network analyzer dielectric spectrometer capable of measuring absorbance and index of refraction in this frequency regime with unprecedented precision. Using this to determine the complex dielectric response of water and aqueous salt solutions from 5.9 GHz to 1.12 THz (which we provide in the supplementary material), we have obtained strong new constraints on theories of water's collective dynamics. For example, while the salt-dependencies we observe for water's two slower relaxations (8 and 1 ps) are easily reconciled with suggestions that they arise due to rotations of fully and partially hydrogen bonded molecules, respectively, the salt-dependence of the fastest relaxation (180 fs) appears difficult to reconcile with its prior assignment to liberations of single hydrogen bonds.

A feasible approach to measure metal concentrations in drill hole waters on site for mineral exploration.

The new technologies used in the green transition towards carbon-free societies typically demand extensive use of metals. This leads to a heavily growing need for exploration and extraction of ore deposits. Exploration can be facilitated by measuring metal concentrations in ground and surface waters carrying trace concentrations of metals leached from nearby deposits. Currently, measuring metal concentrations in water is slow and expensive and it cannot be done on-site, which hinders the discovery of new ore deposits. To address this challenge, we have developed a method to collect and concentrate the dissolved metals in a solid filter and measure the metal concentrations directly from the filter with a portable X-ray fluorescence spectrometer. The permeable filter is made of mesoporous silicon modified with bisphosphonates. Two types of adsorbing materials for the filters were prepared based on scalable production methods: i) regenerative etching of metallurgical grade silicon powder, and ii) magnesiothermic reduction of silica from barley husks. Empirical calibrations were prepared in a concentration range of 10-200 µg/L for Mn, Co, Ni, Cu, Zn, and Pb using water samples prepared by spiking well water with standard metal solutions. Both filter types were tested for their ability to adsorb metals from the real water samples taken from drill holes. The developed system was able to detect metal concentrations down to 12 µg/L (ppb) showing its potential for on-site measurements of dissolved metals in water samples, which could be feasible in the discovery of new mineral deposits. This innovation enables smart sampling during exploration and provides real-time information on metal concentrations in water.

Oleuropein, a phenolic component of Olea europaea L. ameliorates CCl4-induced liver injury in rats through the regulation of oxidative stress and inflammation.

OBJECTIVE: This study aimed to assess the hepatoprotective role of oleuropein (Olp), a phenolic compound found in olive, against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The research involved male albino rats, which received intraperitoneal injections of 100 mg/kg b.w. of oleuropein for 8 consecutive weeks before being subjected to carbon tetrachloride (CCl4) at a dosage of 1.0 ml/kg b.w. Changes induced by CCl4 in antioxidant and inflammatory marker levels were assessed using ELISA assay kits. Moreover, CCl4-induced liver tissue architecture alteration, fibrosis, and expression pattern of protein were evaluated by performing H&E, Sirius red, Masson trichrome, and immunohistochemistry staining. RESULTS: Increased serum transaminases and massive hepatic damage were observed by this liver toxicant. The hepatic injury was further evidenced by a significant decrease in antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione (GSH) and Total Antioxidant Capacity (T-AOC)]. The administration of CCl4 resulted in an increased inflammatory response, which was measured by C-reactive protein, interleukin-6, as well as tumor necrosis factor-alpha. Olp as a curative regimen led to significant attenuation in the inflammatory response and oxidative/nitrosative stress. This polyphenol treatment improved the hepatic tissue architecture and decreased fibrosis. In the CCl4 treatment group, the expression pattern of IL-6 protein was high, whereas expression was decreased after Olp, as evidenced by immunohistochemistry staining. CONCLUSIONS: The study suggests that oleuropein treatment has the potential to reduce liver damage caused by CCl4 induction by inhibiting oxidative stress and inflammation and maintaining liver tissue architecture. This could make it a promising treatment option for liver pathogenesis.

Potential of Marine Strains of Pseudoalteromonas to Improve Resistance of Juvenile Sea Bass to Pathogens and Limit Biofilm Development.

The European sea bass (Dicentrarchus labrax), one of the most produced marine fish species in Europe, is acutely vulnerable to multiple infectious hazards. In this study, we investigated the potential probiotic effect of some marine Pseudoalteromonas bacterial strains against two major pathogens of this species, Vibrio harveyi and the nervous necrosis virus (NNV), and examined their antibiofilm effect. Impregnation phase was done by repeated immersion of juvenile's sea bass during 8 to 12 weeks in seawater containing the probiotic candidates at a concentration of 106 CFU/mL. Four candidates were tested: (1) a combination of two strains producing antimicrobial compounds, hCg-42 and hOe-125; (2) strain 3J6, with known antibiofilm properties; (3) strain RA15, from the same genus, but with no identified probiotic effect; and (4) a control group without probiotics. At the end of the impregnation phase, fish underwent an infection challenge with V. harveyi or with a pathogenic strain of NNV and mortality was monitored. For the V. harveyi challenge, improved survival rates of 10 and 25% were obtained for the RA15 and the mix hCg-42 + hOe-125-impregnated groups, respectively. For the NNV challenge, no significant benefic effect of the probiotics on infection kinetics or cumulative mortality was observed. At the end of the impregnation phase, the maximal thickness of biofilm was significantly lower in the 3J6, double strain, and RA15 groups, compared with the non-impregnated control group. This study highlights the interesting probiotic potential of marine bacteria to limit mortalities induced by bacterial pathogens as well as biofilm development.

Near-field probing of slow Bloch modes on photonic crystals with a nanoantenna.

We study the near-field probing of the slow Bloch laser mode of a photonic crystal by a bowtie nano-aperture (BNA) positioned at the end of a metal-coated fiber probe. We show that the BNA acts as a polarizing nanoprobe allowing us to extract information about the polarization of the near-field of the slow-light mode, without causing any significant perturbation of the lasing process. Near-field experiments reveal a spatial resolution better than λ/20 and a polarization ratio as strong as 110. We also demonstrate that the collection efficiency is two orders of magnitude larger for the BNA than for a 200 nm large circular aperture opened at the apex of the same metal-coated fiber tip. The BNA allows for overcoming one of the main limitations of SNOM linked to the well-known trade off between resolution and signal-to-noise ratio.

Does Alzheimer's disease with early onset progress faster than with late onset? A case-control study of clinical progression and cerebrospinal fluid biomarkers.

BACKGROUND: Early-onset Alzheimer's disease (EOAD) is generally thought to have a more rapid course compared to late-onset Alzheimer's disease (LOAD). The faster progression of EOAD observed in some studies has also been thought to correlate with cerebrospinal fluid (CSF) biomarkers. Our clinical experience has not been suggestive of any difference in disease progression; therefore, we decided to investigate whether differences in clinical progression and CSF biomarkers between EOAD and LOAD could be demonstrated. METHODS: Case-control study with 42 patients, 21 EOAD and 21 matched LOAD patients. Rates of progression were calculated and these, as well as CSF biomarker levels, were statistically compared. RESULTS: There were no statistically significant differences in clinical progression between the EOAD group and the LOAD group. There was no significant difference in the absolute values of CSF biomarkers, but a tendency towards lower levels of ß-amyloid in patients with EOAD was observed. CONCLUSIONS: Our findings did not converge with results from the majority of previous studies, which have been suggestive of a faster clinical progression in EOAD. Possibly, the very strict algorithm by which our patients were matched explains our findings. However, the findings should be repeated in a larger study population.

Screening for neonatal hearing loss in the Eastern region of United Arab Emirates.

The incidence of sensorineural hearing loss among infants in the neonatal intensive unit (NICU) is higher than in normal infants. This study determined the rate of hearing loss in healthy newborns and in NICU patients before hospital discharge at a single institution in the Eastern region of the United Arab Emirates; 96.5% of all eligible infants were screened. Hearing deficit was diagnosed in 25/13 854 healthy newborns (0.18%; 95% CI: 0.12%-0.27%) and 14/826 infants in the NICU (1.7%; 95% CI: 0.9%-2.8%). Although hearing impairment was significantly more common in those admitted to the NICU (RR = 9.4; 95% CI: 4.9-17.9), healthy newborns accounted for 25 of the 39 cases with hearing loss. The rate of congenital hearing deficit was comparable to international data. Universal screening is recommended since selective screening of high-risk infants missed two-thirds of newborns with hearing loss.

Delayed cervical cancer diagnosis: a systematic review.

OBJECTIVE: Cervical cancer (CC) is a preventable women's cancer. Vaccination and routine Pap smear screening have reduced cervical cancer-related mortality by 70-80% in the world. The eradication of CC depends on identifying the disease early and removing barriers to its timely detection. This review study was designed to determine diagnostic delay and factors related to delayed CC diagnosis in the world. MATERIALS AND METHODS: A comprehensive search was carried out in databases including Medline, Web of Science, Core Collection (Indexes = SCI-EXPANDED, SSCI, A & HCI Timespan), and Scopus for articles published up to December 2021. Publications were included if they reported data on the delayed CC, and factors related to diagnosis of CC in women. There was no time restriction in this review. RESULTS: In total, 45 articles were entered into the study. In studies, advanced stages of CC (IIB to IV) varied from 10.2% to 87.9% due to delayed diagnosis. A delayed CC diagnosis was reported in 4.3%-89.1% of patients. The median and mean days of delayed diagnosis were 59-210 days and 2.92-10.5 months, respectively. Factors related to delayed CC diagnosis were categorized into three components including patient, medical history, and health system delay. Patient delay included socio-demographic, husband/ partner, and knowledge. Medical history included medical issues, obstetrics, and family history. Health system delays included health facilities and levels of accessibility. CONCLUSIONS: There is an urgent need to shorten the diagnostic journey of CC patients by addressing all the components of diagnostic delay and developing strategies to modify the factors associated with these delays.

Design and investigation of surface addressable photonic crystal cavity confined band edge modes for quantum photonic devices.

We propose to use a localized Γ-point slow Bloch mode in a 2D-Photonic Crystal (PC) membrane to realize an efficient surface emitting source. This device can be used as a quantum photonic device, e.g. a single photon source. The physical mechanisms to increase the Q/V factor and to improve the directivity of the PC microcavity rely on a fine tuning of the geometry in the three directions of space. The PC lateral mirrors are first engineered in order to optimize photons confinement. Then, the effect of a Bragg mirror below the 2DPC membrane is investigated in terms of out-of-plane leakages and far field emission pattern. This photonic heterostructure allows for a strong lateral confinement of photons, with a modal volume of a few (λ/n)3 and a Purcell factor up to 80, as calculated by two different numerical methods. We finally discuss the efficiency of the single photon source for different collection set-up.

Blazing evanescent grating orders: a spectral approach to beating the Rayleigh limit.

We develop a way to enhance the amplitudes of the nonpropagating evanescent orders of resonant dielectric gratings. We use this blazing to design gratings with spectra tailored to generate steerable sub-Rayleigh field concentrations on a surface. We investigate the enhancement and customization of evanescent fields necessary to create a virtual and passive scanning probe with no moving parts. Spot size can be decreased 1 order of magnitude below the free-space Rayleigh limit.

Leg ability factors in tennis players.

We investigated the effects of leg stiffness on running speed, jump height and leg power in 13 male 2(nd)- and 3(rd)-series ranked tennis players (23 ± 3 years old, 73.2 ± 8.4 kg, 1.81 ± 0.06 m). Leg stiffness and jump height were assessed using jumping and hopping tests. Mean running speeds over 20 m and 40 m (speed20 and speed40, respectively) were determined from a sprint test. Theoretical maximal leg power (P(maxth)) was extrapolated from a force-velocity test performed on a cycle ergometer. Leg stiffness averaged 478.7 ± 181.7 N.m⁻¹.kg⁻¹ (34,808 ± 12,573 N.m⁻¹. It was significantly correlated to speed20 and counter movement jump height (r=0.60, P=0.028 and r=0.58, P=0.0407, respectively). There were also significant correlations between P (maxth) and counter-movement jump height (r=0.59, P=0.0335) and between P(maxth) and speed40 (r=0.58, P=0.0393). This study characterizes leg stiffness in tennis players and brings new information concerning the way it is related to several other muscular biomechanical parameters.

Throwing performance is associated with muscular power.

The aim of the present study was to test the hypothesis that performance in throwing events is associated with muscular characteristics of both upper and lower limbs. Thirty-eight male throwers volunteered to participate. Bench press and half squat tests were conducted on a guided barbell. The barbell displacement signal was recorded using a kinematic system. Maximal power, corresponding optimal velocity and force (P(max)S, V(opt)S, F(opt)S and P(max)BP, V(opt)BP, F(opt)BP for half squat and bench press, respectively) were extrapolated from the power-velocity relationship. Lower limb stiffness (K) was determined during maximal hopping. The results demonstrated that P(max)S and P(max)BP were correlated with each thrower's season's best performance (SBP, R=0.54, P<0.01 and R=0.71, P<0.001, respectively). P(max)S expressed relative to body mass was not correlated with SBP. K was significantly correlated with SBP (R=0.66, P<0.001). The relationship between P (max)BP expressed relative to body mass and SBP remained significant ( R=0.54, P<0.001). The results of the study suggest that high strength and stiffness values for lower limbs and strength and velocity characteristics for upper limbs may be associated with athletic throwing performance.