Optimisation of movement detection and artifact removal during laser speckle contrast imaging

Introduction Laser speckle contrast imaging (LSCI) allows an easy non-contact monitoring of the cutaneous blood flow (CBF), but is highly sensitive to movement artifacts (ARTm). Subtraction of a signal recorded on an adhesive opaque surface (AOS) close to the area of interest was reported as a mean of reducing noise from the raw skin LSCI (LSCIsk) signal, provided an individual calibration was performed. Assuming that AOS = a · CBF + b · ARTm, an ideal patch should completely block the light reflection due to CBF and thus be insensitive to skin blood flow changes (“a” ~ 0), while keeping a reflection signal amplitude similar to the one from the skin in case of artifact (“b” ~ 1). This ideal AOS has not been determined and may discriminate flow from movements during LSCI recordings. Materials and methods We tested different AOSs to determine their “a” and “b” parameters in 35 and 34 healthy volunteers, respectively. The AOS surface providing results as close as possible to an ideal AOS, was used for a point-by-point de-noising of post occlusive reactive hyperemia (PORH) on two different days in 15 new subjects. Correlation of raw, smoothed (average smoothing over 1 s intervals) and denoised signals was tested through a cross-correlation analysis of the two POHR tests. Results The optimal “a” and “b” values were obtained with a homemade bilayer adhesive patch (a = 0.06 ± 0.05 and b = 1.03 ± 0.17) whereas other tested AOS had “a” values ranging from 0.05 to 0.23 and “b” values ranging from 2.69 to 3.82. Using the bilayer adhesive patch the cross-correlation between the two tests of POHR increased from 0.330 ± 0.128 for raw, to 0.461 ± 0.168 for smoothed and 0.649 ± 0.128 for denoised signals respectively (p < 0.05 from raw coefficients). Conclusion The home-made bilayer adhesive seems the optimal AOS for the removal of ARTm from the LSCIsk signal while respecting CBF signal. This specific AOS allows for an efficient de-noising of LSCI measurements without the need for individual calibration

Vasodilator response to galvanic current stimulation of the skin accurately detects acetylsalicylic acid intake: A study in 400 vascular patients

Background and aims The first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients. Methods CIV was tested in 400 patients (277 males and 123 females, aged 65.4 ± 13.4 years). We focused on clinical characteristics, treatments, and comorbid conditions as covariates of CIV amplitude. We studied the CIV amplitude to covariate relationships with multivariate linear regression and receiver operating characteristics (ROC). Results The multivariate linear model determined that ASA intake within the last 48 h and the interaction between ASA intake and body mass index (BMI) were the sole covariates associated with CIV amplitude. For the whole population, the area under the ROC curve (AUC) for CIV to predict ASA intake was 0.853 [95% confidence interval (CI): 0.814–0.892]. Considering separately the areas observed for non-obese (BMI ≤30, n = 303) and obese (BMI>30, n = 93) patients, the AUC [95% CI] was 0.873 [0.832–0.915] and 0.776 [0.675–0.878], respectively (p = 0.083). Conclusions ASA is the only drug that affects the amplitude of CIV response observed after galvanic current application to the skin of vascular patients. CIV depends on BMI but not age or gender. As such, CIV appears to be a potential objective marker of ASA intake and could facilitate future non-invasive assessments of adherence to ASA treatment

Transcutaneous Exercise Oximetry for Patients With Claudication - A Retrospective Review of Approximately 5,000 Consecutive Tests Over 15 Years

BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is used to argue for the vascular origin of lower limb pain, especially at the proximal level, where the diagnosis of peripheral artery disease can be difficult. This study analyzed the principal indications, mean results, and limitations of Ex-tcPO2, as well as the relationship between the annual number of Ex-tcPO2 tests and internal iliac artery (IIA) revascularizations.Methods and Results:Data from our first 15 years\u27 experience (3,631 patients, 5,080 tests) with Ex-tcPO2 were analyzed retrospectively using the minimal value of the decrease from rest of oxygen pressure (DROP). We had 99.7% of expected DROPresults. The proportion of tests showing isolated proximal unilateral or bilateral ischemia ranged from ~5% to ~20%. A gradual increase with time was observed in both the annual number of Ex-tcPO2 tests (from 0 to ~500 per year) and the annual number of IIA revascularizations performed (from 0 up to 18 per year). At least 85% of patients (77/91) showed function improvement after IIA revascularization. CONCLUSIONS: Ex-tcPO2 (using DROP) provides an objective argument for exercise-induced ischemia, bilaterally at the distal and/or proximal level. Using Ex-tcPO2 has improved our diagnostic performance and markedly changed our therapeutic decisions, specifically for proximal claudication. The increased number of Ex-tcPO2 tests is associated with an increased number of IIA revascularizations, although a causal relationship was not proven

Ankle brachial index is equally predictive of exercise-induced limb ischemia in diabetic and non-diabetic patients with walking limitation

BACKGROUND: In diabetic patients, arterial stiffness may impair compressibility of vessels and result in higher ankle to brachial index (ABI) than in non-diabetic subjects. METHODS: We studied 1972 non-diabetic and 601 diabetic patients, with suspected peripheral artery disease, Exercise transcutaneous oxygen pressure (Ex-tcpO2), expressed in DROP index (limb tcpO2 change minus chest tcpO2 change), is insensitive to arterial stiffness and can estimate exercise-induced regional blood flow impairment (RBFI). A minimal DROP <-15 mm Hg indicates the presence of RBFI (positive test). ABI was simplified to a category variable (ABIc) by rounding ABI to the closest first decimal. RESULTS: In the ABIc range 0.4 to 1.1 linear regression for mean DROP values were: y = 34 x - 53; (R = 0.211) and y = 33 x - 52; (R = 0.186) in diabetic and Non-diabetic patients, respectively. Both Db and non-D patients showed a high proportion of positive Ex-tcpO2 tests for ABIc in the normal range (ABIc: 1.0 and over) from 27.1 to up to 58%. More than half of patients with borderline ABI (ABIc = 0.9) had RBFI during exercise. it was 65.6% in diabetic and 58.5% non-diabetic patients. CONCLUSIONS: Resting ABI was not a better predictor of exercise-induced RBFI in non-Db than in Diabetic patients. Our results highlights the interest of still measuring resting-ABI in diabetic patients to argue for the vascular origin of exertional limb pain, but also of performing exercise tests in patients with walking impairment

5-Oxoprolinuria in hyperammonemic encephalopathy: Coincidence or worsening factor?

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NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment

Transcriptional heterogeneity within embryonic stem cell (ESC) populations has been suggested as a mechanism by which a seemingly homogeneous cell population can initiate differentiation into an array of different cell types. Chromatin remodeling proteins have been shown to control transcriptional variability in yeast and to be important for mammalian ESC lineage commitment. Here we show that the Nucleosome Remodeling and Deacetylation (NuRD) complex, which is required for ESC lineage commitment, modulates both transcriptional heterogeneity and the dynamic range of a set of pluripotency genes in ESCs. In self-renewing conditions, the influence of NuRD at these genes is balanced by the opposing action of self-renewal factors. Upon loss of self-renewal factors, the action of NuRD is sufficient to silence transcription of these pluripotency genes, allowing cells to exit self-renewal. We propose that modulation of transcription levels by NuRD is key to maintaining the differentiation responsiveness of pluripotent cells

Mitochondrial complex I defect resulting from exercise-induced lower limb ischemia in patients with peripheral arterial disease

This study aims to compare the structural and mitochondrial alterations between muscle segments affected by exercise-induced ischemia and segments of the same muscle without ischemia, in the same subject. In a prospective analysis, 34 patients presenting either peripheral arterial disease or chronic coronary syndrome without any evidence of peripheral arterial disease were eligible for inclusion based on findings indicating a need for either a femoro-popliteal bypass or a saphenous harvesting for coronary bypass. Before surgery, we assessed the level of exercise-induced ischemia in proximal and distal sections of the thigh by the measurement of transcutaneous oxygen pressure during an exercise treadmill test. Distal and proximal biopsies of the sartorius muscle were procured during vascular surgical procedures to assess mitochondrial function and morphometric parameters of the sartorius myofibers. Comparisons were made between the distal and proximal biopsies, with respect to these parameters. Thirteen of the study patients that initially presented with peripheral arterial disease had evidence of an isolated distal thigh exercise-induced ischemia, associated with a 35% decrease in the mitochondrial complex I enzymatic activity in the distal muscle biopsy. This defect was also associated with a decreased expression of the manganese superoxide dismutase enzyme and with alterations of the shapes of the myofibers. No functional or structural alterations were observed in the patients with coronary syndrome. We validated a specific model ischemia in peripheral arterial disease characterized by muscular alterations. This "Distal-Proximal-Sartorius Model" would be promising to explore the physiopathological consequences specific to chronic ischemia. NEW & NOTEWORTHY We compared proximal versus distal biopsies of the sartorius muscle in patients with superficial femoral artery stenosis or occlusion and proof of, distal only, regional blood flow impairment with exercise oximetry. We identified a decrease in the mitochondrial complex I enzymatic activity and antioxidant system impairment at the distal level only. We validate a model to explore the physiopathological consequences of chronic muscle ischemia

Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency

Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cell enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with gastroenteritis requiring hospitalization; fortuitously, urine organic acid chromatography revealed a large peak of 5-oxoproline. Before the association between HA and 5-oxoprolinuria was noted, glutathione synthetase deficiency was suspected and confirmed by a low glutathione synthetase concentration and a collapse of glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of 5-oxoprolinuria and the clinical history discovered administration of acetaminophen in the 48 hours before hospitalization. Thus, in this patient, acetaminophen exposure allowed the diagnosis of a mild form of glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with bicarbonate, vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes. Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA

New guidelines for the prevention of imported malaria in France

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