Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab.

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

Auxiliary muscles and slow component during rowing.

The aim of this study was to investigate the contribution of the auxiliary muscles, utilized to sustain the subject's position on the ergometer, to the oxygen uptake slow component phenomenon. Three tests were performed at the same severe relative intensity on a rowing ergometer: a standard rowing exercise test, a rowing exercise performed with the arms and one performed with the legs only. During the three exercise modalities, oxygen uptake, local oxyhemoglobin saturation and surface electromyography signals of the trapezius and vastus lateralis muscles were measured. The slow component amplitude, in absolute values, resulted statistically lower for rowing (343.9 ml . min (-1)) than for arms (795.6 ml . min (-1)) and legs (695.8 ml . min (-1)) exercise modes. The same result was found when the slow component amplitude was calculated as percentage of V O (2peak) (7.1 % for rowing; 17.2 % for arms; 17.3 % for legs). The lower slow component amplitude measured for the rowing exercise mode with respect to both arms and legs modes, demonstrates that the auxiliary muscles involved in the exercise contribute to the increasing energetic cost due to the slow component.

Acute moderate hypoxia affects the oxygen desaturation and the performance but not the oxygen uptake response.

The purpose of this study was to examine the influence of hypoxia on the O2 uptake response, on the arterial and muscular desaturation and on the test duration and test duration at VO2max during exhaustive exercise performed in normoxia and hypoxia at the same relative workload. Nine well-trained males cyclists performed an incremental test and an exhaustive constant power test at 90 % of maximal aerobic power on a cycling ergometer, both in normoxia and hypoxia (inspired O2 fraction = 16 %). Hypoxic normobar conditions were obtained using an Alti Trainer200 and muscular desaturation was monitored by near-infrared spectroscopy instrument (Niro-300). The mean response time (66 +/- 4 s vs. 44 +/- 7 s) was significantly lower in hypoxia caused by the shorter time constant of the VO2 slow component. This result was due to the lower absolute work rate in hypoxia which decreased the amplitude of the VO2 slow component. The arterial (94.6 +/- 0.3 % vs. 84.2 +/- 0.7 %) and muscular desaturation (in the vastus lateralis and the lateral gastrocnemius) were reduced by hypoxia. The test duration (440 +/- 31 s vs. 362 +/- 36 s) and the test duration at VO2max (286 +/- 53 s vs. 89 +/- 33 s) were significantly shorter in hypoxia. Only in normoxia, the test duration was correlated with arterial and muscular saturation (r = 0.823 and r = 0.828; p < 0.05). At the same relative workload, hypoxia modified performance, arterial and muscular oxygen desaturation but not the oxygen uptake response. In normoxia, correlation showed that desaturation seems to be a limiting factor of performance.

The use of near infrared spectroscopy in sports medicine.

In the last 15 years the study of the human muscle energetics in sports medicine underwent a radical change thanks to the progressive introduction of non-invasive techniques, including near infrared (NIR) spectroscopy (NIRS). NIR light (700-1000 nm) penetrates skin, subcutaneous fat and underlying muscle, and is either absorbed (by oxy- and deoxy-haemoglobin) or scattered within the tissue. NIRS is a non-invasive and relatively low cost optical technique that is becoming a widely used instrument for measuring muscle O(2) saturation and changes in haemoglobin volume. Muscle O(2) saturation represents a dynamic balance between O(2) supply and O(2) consumption in the small vessels such as the capillary, arteriolar and venular bed. NIRS offers the advantage of being less restrictive than (31)P-magnetic resonance spectroscopy with regard to muscle performance and more comfortable and suitable for the monitoring, with high temporal resolution (up to 10 Hz), of multiple muscle groups. The aim of this review is to summarise the NIRS instrumentation and the measurable parameters, the role of NIRS in muscle exercise physiology, and the applications in sports medicine. The advantages and the problems of NIRS measurements, in resting and exercising skeletal muscles, are reported. The results of several studies suggest that NIRS is a powerful tool for being applied successfully in sports medicine. NIRS can objectively evaluate muscle oxidative metabolism in athletes and its modifications following potential therapeutic strategies and specific training programs.

VO2 slow component correlates with vastus lateralis de-oxygenation and blood lactate accumulation during running.

BACKGROUND: In the present study, vastus lateralis de-oxygenation was monitored contemporarily with VO2 changes along a severe constant intensity running exercise, after the 3rd min up to volitional exhaustion. Blood lactate accumulation was also measured before, during and after running. METHODS: Eleven male amateur soccer players volunteered for the study. Subjects mean age, height, and body weight were 22.9+/-2 yrs, 177.5+/-6.2 cm, 71.7+/-4 kg, respectively. Measurements were carried out during running on a treadmill. Ventilatory and gas exchange parameters were measured at the mouth on a breath-by-breath basis. For blood lactate concentration accumulation measurement, capillary blood samples were taken from the fingertip. The oxygenation of the vastus lateralis muscle were measured by a continuous wave NIRS portable instrument. By means of two pretests the onset of [La]b accumulation and its associated velocity (vOBLA), and the peak of oxygen uptake and its associated velocity (vVO2,peak) were assessed. The test consisted of running on the treadmill up to volitional exhaustion at a constant velocity corresponding to vOBLA plus 50% of the difference between vVO2,peak and vOBLA (v50%Delta). RESULTS: The principal finding of this study was that vastus lateralis de-oxygenation changes measured during running correlate with a) oxygen uptake changes between the 3rd min of exercise and the time corresponding to the subject's volitional exhaustion; b) blood lactate concentration increments measured at the 3rd and the 6th min of exercise and at the time corresponding to the subject's volitional exhaustion. CONCLUSIONS: In conclusion, the results of the present study support our hypothesis that the vastus lateralis de-oxygenation contributes consistently to the VO2 slow component development in running.

Comparison of two spatially resolved near-infrared photometers in the detection of tissue oxygen saturation: poor reliability at very low oxygen saturation.

Two spatially resolved oximeters, NIRO-300 and OM-200, were compared with regard to the measurement of oxygen saturation values in two forearm muscle groups at rest and during arterial occlusion in nine healthy volunteers. There was a significant correlation between the muscle oxygen saturation values obtained at rest using the two oximeters (n=33, r(2)=0.43, P<0.0001), whereas these values were significantly different during arterial occlusion. Thus, although there was good agreement between muscle oxygen saturation values measured using the two oximeters, the operating range of the tissue oximeters should be recognized and indicated.

Nonuniform quadriceps O2 consumption revealed by near infrared multipoint measurements.

Single location muscle monitoring does not reflect the heterogeneous activation of the muscle group(s) during a given exercise. Vastus lateralis and rectus femoris O2 consumption (VO2) was investigated, noninvasively, at rest and during maximal voluntary contractions (MVC) using a 12-channel near-infrared continuous wave spectroscopy (NIR(CWS)) system (0.1 s acquisition time). VO2 either at rest or during MVC was found to be nonuniform in the 11 out of 12 measurement sites over a surface of 8 x 8 cm2. As expected, VO2 during exercise was significantly higher than VO2 at rest (P < 0.01). However, at each muscle measurement site no difference was found between the mean values (n = 12) of VO2 measured during a 5-s intermittent MVC and the VO2 values measured during 30-s continuous MVC (P = 0.25). These results strengthen the role of NIR(CWS) as a powerful tool for investigating the spatial and temporal features of muscle oxygenation changes as well as muscle VO2.

Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans.

The effects of dynamic plantar flexion exercise [40, 60, and 80 contractions.min-1 (cpm)] on calf and shin muscle oxygenation patterns and common femoral artery blood flow (Qfa) were examined in six female subjects [mean age 21 (SD 1) years] who exercised for 1 min at 33% of their maximal voluntary contraction at ankle angles between 90 degrees and 100 degrees. Spatially resolved near-infrared spectroscopy was used to measure medial gastrocnemius, lateral soleus (synergist) and anterior tibialis (antagonist) muscle oxygen saturation (SO2, %). Qfa was measured by ultrasound Doppler. The SO2 changed significantly only in the medial gastrocnemius and its decrease (up to about 30%) was independent of the contraction frequencies examined. The increase in Qfa, at the end of exercise, was highest at 80 cpm. When the exercise at 60 cpm was prolonged until exhaustion [mean 2.7 (SD 1.1) min], medial gastrocnemius SO2 decreased, reaching its minimal value [mean 30 (SD 10)%] within the 1st min, and had partially recovered before the end of the exercise with concomitant increases in total haemoglobin content and Qfa. These results suggest that the medial gastrocnemius is the muscle mostly involved in dynamic plantar flexion exercise and its oxygen demand with increases in contraction frequency and duration is associated with an up-stream increase in Qfa.

Simultaneous near-infrared spectroscopy monitoring of left and right occipital areas reveals contra-lateral hemodynamic changes upon hemi-field paradigm.

In this study we have shown that in humans it is possible to monitor non-invasively and simultaneously both hemispheres revealing cortical oxygenation changes in the occipital area in response to a contra-lateral hemi-field paradigm. A novel multi-channel near infrared spectroscopy approach with a high temporal resolution was used. The results confirm previous findings obtained by functional magnetic resonance imaging and positron emission tomography with the advantage to measure directly not only concentration changes in deoxyhemoglobin as measured by functional magnetic resonance imaging (MRI), but also in oxyhemoglobin with low cost instrumentation potentially useful to investigate the pathophysiology of vision.

Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near infrared spectroscopy approaches.

Spatially resolved spectroscopy (SRS) is a new near infrared spectroscopy (NIRS) method that, using the multi-distance approach, measures local cerebral cortex hemoglobin oxygen saturation [J. Matcher, P. Kirkpatrick, K. Nahid, M. Cope, and D. T. Delpy, Proc. SPIE 2389, 486-495 (1995)]. Using a conventional continuous wave NIRS photometer, cerebral venous oxygen saturation (SvO2) can be calculated from oxyhemoglobin and total hemoglobin rise induced by partial occlusion of jugular vein [C. E. Elwell, S. J. Matcher, L. Tyszczuk, J. H. Meek, and D. T. Delpy, Adv. Exp. Med. Biol. 411, 453-460 (1997)]. The aim of this study was to compare direct measurements of forehead tissue oxygenation index (TOI) with the calculated SvO2 during venous occlusion in 16 adult volunteers using a clinical two-channel SRS oximeter (NIRO-300). Measured TOI and calculated SvO2 values of either right or left forehead did not significantly differ. A good agreement between the two NIRS methods was also demonstrated. On 16 other subjects, no significant differences were found between the right and left forehead TOI values measured simultaneously, and between the TOI values measured by channel 1 or 2 on the same side. The results confirm that cerebral cortex hemoglobin oxygen saturation, measured directly by the SRS method, reflects predominantly the saturation of the intracranial venous compartment of circulation.

Human calf microvascular compliance measured by near-infrared spectroscopy.

The purpose of this study is to develop a new method for the measurement in humans of the compliance of the microvascular superficial venous system of the lower limb by near-infrared spectroscopy (NIRS). This method is complementary to strain-gauge plethysmography, which does not allow compliance between deep and superficial venous or between venous and arterial compartments to be distinguished. In practice, hydrostatic pressure (P) changes were induced in a calf region of interest by head-up tilt of the subject from alpha = -10 to 75 degrees. For P < or = 24 mmHg, the measured compliance [0.086 +/- 0.005 (SD) ml. l(-1). mmHg(-1)] based on NIRS data of total, deoxygenated, and oxygenated hemoglobin, reflects essentially that of the superficial venous system. For P > or = 24 mmHg, no distinction can be made between arterial and venous volumes changes. However, by following the changes in oxy- and deoxyhemoglobin in the P range -16 to 100 mmHg, it appears to be possible to assess the characteristics of the vasomotor response of the arteriolar system.

Human motor-cortex oxygenation changes induced by cyclic coupled movements of hand and foot.

Near-infrared spectroscopy (NIRS) was used to assess human motor-cortex oxygenation changes in response to cyclic coupled movements of hand and foot. Using a highly sensitive NIRS instrument, we showed that it was possible to detect reproducible oxygenation patterns using single cycles (20 s) of easy and difficult association tasks. No significant differences in the time corresponding to the maximal changes in concentration of oxy- and deoxyhemoglobin ([O(2)Hb] and [HHb], respectively) were found during easy and difficult association as well as cycles. Only [O(2)Hb] showed a significantly higher value at the end of the difficult association during the first cycle. No significant differences were found for [O(2)Hb] and [HHb] in the other cycles. We conclude that NIRS is a useful addition to functional magnetic resonance imaging in investigating the time course of cortical activation.

Blood lactate accumulation and muscle deoxygenation during incremental exercise.

Near-infrared spectroscopy (NIRS) could allow insights into controversial issues related to blood lactate concentration ([La](b)) increases at submaximal workloads (). We combined, on five well-trained subjects [mountain climbers; peak O(2) consumption (VO(2peak)), 51.0 +/- 4.2 (SD) ml. kg(-1). min(-1)] performing incremental exercise on a cycle ergometer (30 W added every 4 min up to voluntary exhaustion), measurements of pulmonary gas exchange and earlobe [La](b) with determinations of concentration changes of oxygenated Hb (Delta[O(2)Hb]) and deoxygenated Hb (Delta[HHb]) in the vastus lateralis muscle, by continuous-wave NIRS. A "point of inflection" of [La](b) vs. was arbitrarily identified at the lowest [La](b) value which was >0.5 mM lower than that obtained at the following. Total Hb volume (Delta[O(2)Hb + HHb]) in the muscle region of interest increased as a function of up to 60-65% of VO(2 peak), after which it remained unchanged. The oxygenation index (Delta[O(2)Hb - HHb]) showed an accelerated decrease from 60- 65% of VO(2 peak). In the presence of a constant total Hb volume, the observed Delta[O(2)Hb - HHb] decrease indicates muscle deoxygenation (i.e., mainly capillary-venular Hb desaturation). The onset of muscle deoxygenation was significantly correlated (r(2) = 0.95; P < 0.01) with the point of inflection of [La](b) vs., i.e., with the onset of blood lactate accumulation. Previous studies showed relatively constant femoral venous PO(2) levels at higher than approximately 60% of maximal O(2) consumption. Thus muscle deoxygenation observed in the present study from 60-65% of VO(2 peak) could be attributed to capillary-venular Hb desaturation in the presence of relatively constant capillary-venular PO(2) levels, as a consequence of a rightward shift of the O(2)Hb dissociation curve determined by the onset of lactic acidosis.

Oxidation and reduction of cytochrome oxidase in the neonatal brain observed by in vivo near-infrared spectroscopy.

Near-infrared spectroscopy was used to determine the relationship between the redox state of mitochondrial cytochrome oxidase CuA and haemoglobin oxygenation in the isoflurane-anaesthetized neonatal pig brain. Adding 7% CO2 to the inspired gases increased the total haemoglobin concentration by 8 microM and oxidized CuA by 0.2 microM. Decreasing the inspired oxygen fraction to zero for 90 s dropped the oxyhaemoglobin concentration by 27 microM and reduced CuA by 1.8 microM. However, no change in the CuA redox state was observed until oxyhaemoglobin had decreased by more than 10 microM. The response of the CuA redox state to these stimuli was very similar following 80% replacement of the haemoglobin by a perfluorocarbon blood substitute; this demonstrates that the results in the normal haematocrit were not a spectral artefact due to the high haemoglobin/cytochrome oxidase ratio. We conclude that the large reductions in the CuA redox state during anoxia are caused by a decrease in the rate of oxygen delivery to the cytochrome oxidase oxygen binding site; the small oxidations, however, are likely to reflect the effects of metabolic changes on the redox state of CuA, rather than increases in the rate of oxygen delivery.