Optical diffraction tomography of 3D microstructures using a low coherence source.

Optical diffraction tomography (ODT) is a label-free technique for three dimensional imaging of micron-sized objects. Coherence and limited sampling of 3D Fourier space are often responsible for the appearance of artifacts. Here we present an ODT microscope that uses low temporal coherence light and spatial light modulators to retrieve reliable 3D maps of the refractive index. A common-path interferometer, based on a spatial light modulator, measures the complex fields transmitted by a sample. Measured fields, acquired while scanning the illumination direction using a digital micro-mirror device, are fed into a Rytov reconstruction algorithm to obtain refractive index maps whose accuracy is directly evaluated on microfabricated 3D test objects. Even for challenging shapes such as pyramids, bridges, and dumbbells, we obtain volumetric reconstructions that compare very well with electron microscopy images.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19).Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women.The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%).In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2 < 92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

ANTECEDENTES: Trabajos previos parecen coincidir en la mayor mortalidad de los pacientes con cáncer y COVID-19. La identificación de posibles factores pronósticos en el momento del ingreso podría ayudar a identificar a los pacientes con mal pronóstico. MÉTODOS: Nos propusimos explorar las características y la evolución de los pacientes con cáncer y COVID-19 ingresados en un registro internacional multicéntrico (HOPE COVID-19).Nuestro objetivo principal es definir aquellas características que nos permitan identificar a los pacientes con cáncer de peor pronóstico (mortalidad en los 30 días siguientes al diagnóstico de COVID-19). RESULTADOS: En este registro se ha recogido a 5.838 pacientes, de los cuales 770 tenían cáncer entre sus antecedentes. La mortalidad hospitalaria alcanzó a 258 pacientes (33,51%). La mediana fue de 75 años (65-82). En cuanto a la distribución por sexo, el 34,55% de los pacientes eran mujeres (266/770).La distribución por tipo de cáncer: genitourinario 238/745 (31,95%), digestivo 124/745 (16,54%) y hematológico 95/745 (12,75%).En el análisis de regresión multivariante, los factores que se asocian de forma independiente con la mortalidad al ingreso son: insuficiencia renal (OR 3,45; IC 97,5%: 1,85-6,58), cardiopatía (2,32; 1,47-3,66), hepatopatía (4,69; 1,94-11,62), dependencia parcial (2,41; 1,34-4,33), dependencia total (7,21; 2,60-21,82), fatiga (1,84, 1;16-2,93), artromialgias (0,45; 0,26-0,78), SatO2 < 92% (4,58; 2,97-7,17), LDH elevada (2,61; 1,51-4,69) y disminución anormal de la presión arterial (3,57; 1,81-7,15). Los parámetros analíticos también están significativamente alterados. CONCLUSIÓN: En los pacientes con cáncer del registro HOPE, la mortalidad a los 30 días por cualquier causa es elevada y se asocia a factores clínicos fácilmente identificables a su llegada al hospital. La identificación de estos pacientes puede ayudar a iniciar tratamientos más intensivos desde el principio y evaluar el pronóstico de estos pacientes.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19). Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women. The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%). In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2<92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

ATP release during cell swelling activates a Ca2+-dependent Cl- current by autocrine mechanism in mouse hippocampal microglia.

Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl- channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 +/GFP mice by whole-cell patch-clamp and imaging techniques. The exposure of cells to a mild hypotonic medium, caused an outward rectifying current, developing in 5-10 minutes and reverting upon stimulus washout. This current, required for microglia ability to extend processes towards a damage signal, was carried mainly by Cl- ions and dependent on intracellular Ca2+. Moreover, it involved swelling-induced ATP release. We identified a purine-dependent mechanism, likely constituting an amplification pathway of current activation: under hypotonic conditions, ATP release triggered the Ca2+-dependent activation of anionic channels by autocrine purine receptors stimulation. Our study on native microglia describes for the first time the functional properties of stretch/swelling-activated currents, representing a key element in microglia ability to monitor the brain parenchyma.

Cell mechanotactic and cytotoxic response to zinc oxide nanorods depends on substrate stiffness.

Bio-nanomaterials offer promise in the field of tissue engineering. Specifically, environmental cues such as the material chemistry, topography and rigidity of the surface to which cells adhere to, can alter and dictate cell shape, proliferation, migration, and gene expression. How deeply each factor (topographical, chemical and mechanical) drives cell response remains incompletely understood. To illustrate cell sensitivities to different factors, we herein present ZnO nanorods (ZnO-Nrds) coated on glass and polydimethylsiloxane (PDMS) substrates and analyzed cell viability and proliferation. The work presented here shows a clear response of various cell lines (mouse embryonic fibroblasts 3T3, human cervix carcinoma HeLa and human osteoblast-like cells MG63) to the rigidity of the underlying surface. The chemical counterpart, given by the presence of ZnO-Nrds, strongly reduced the cell viability of all cell lines. However, the substrate underlying the ZnO coating impacted cell spreading and viability. The substrates exhibited a better ability to neglect cell attachment and proliferation with the ZnO coating and pro-apoptoticity specifically with the PDMS as the underlying substrate which exhibited a "softer" environment with respect to a glass substrate. The results also revealed that the few cells that adhered to the ZnO-Nrds on PDMS and glass showed a rounded morphology. On the basis of these observations, we can correlate common features of phenomenological cell response to chemotactic and durotactic cues. The work presented herein reinforces the response of cells to changes in substrate rigidity. These observations provide a foundation for a potentially promising approach to decrease cell adhesion and thus as an optimal substrate for different applications such as prosthesis design, tissue engineering, anti-bio fouling materials and diagnostics.

Chemically resistant microfluidic valves from Viton® membranes bonded to COC and PMMA.

We present a reliable technique for irreversibly bonding chemically inert Viton® membranes to PMMA and COC substrates to produce microfluidic devices with integrated elastomeric structures. Viton® is widely used in commercially available valves and has several advantages when compared to other elastomeric membranes currently utilised in microfluidic valves (e.g. PDMS), such as high solvent resistance, low porosity and high temperature tolerance. The bond strength was sufficient to withstand a fluid pressure of 400 kPa (PMMA/Viton®) and 310 kPa (COC/Viton®) before leakage or burst failure, which is sufficient for most microfluidic applications. We demonstrate and characterise on-chip pneumatic Viton® microvalves on PMMA and COC substrates. We also provide a detailed method for bonding fluorinated Viton® elastomer, a highly chemically compatible material, to PMMA and COC polymers. This allows the production of microfluidic devices able to handle a wide range of chemically harsh fluids and broadens the scope of the microfluidic platform concept.

Examining lactate in severe TBI using proton magnetic resonance spectroscopy.

PRIMARY OBJECTIVE: Clinical management of acute traumatic brain injury (TBI) has emphasized identification of secondary mechanisms of pathophysiology. An important objective in this study is to use proton magnetic resonance spectroscopy (pMRS) to examine early metabolic disturbance due to TBI. RESEARCH DESIGN: The current design is a case study with repeated measures. METHOD AND PROCEDURE: Proton magnetic resonance imaging was used to examine neurometabolism in this case of very severe brain trauma at 9 and 23 days post-injury. MRI was performed on a clinical 1.5 Tesla scanner. MAIN OUTCOMES AND RESULTS: These data also reveal that pMRS methods can detect lactate elevations in an adult surviving severe head trauma and are sensitive to changes in basic neurometabolism during the first month of recovery. CONCLUSIONS: The current case study demonstrates the sensitivity of pMRS in detecting metabolic alterations during the acute recovery period. The case study reveals that lactate elevations may be apparent for weeks after severe neurotrauma. Further work in this area should endeavour to determine the ideal time periods for pMRS examination in severe TBI as well as the ideal locations of data acquisition (e.g. adjacent or distal to lesion sites).

Echocardiographic evaluation in type 1 diabetic patients on waiting list for isolated pancreas or kidney-pancreas transplantation.

Type 1 diabetic patients may display abnormalities of left ventricular geometry and systolic and diastolic function. Patients on the waiting list for solitary pancreas or kidney-pancreas transplantation were evaluated by Doppler echocardiography to assess left ventricular geometry and systolic and diastolic function, and correlate these parameters with clinical characteristics. We evaluated 78 patients including 45 men with an overall mean age of 39.5 +/- 7.2 years and a disease duration of 24 +/- 9.8 years. Among these 78 patients, 13 showed isolated retinopathy, 9 isolated arterial hypertension, 45 concomitant retinopathy and hypertension and overt nephropathy, while 11 were free of complications. The results of our study showed an increased left ventricular mass and abnormal diastolic function among patients with simultaneous target organ complications and with hypertension, as has been reported in many previous studies. In contrast study patients with no complications showed normal left ventricular structure and function. This finding conflicts with data from several reports in the medical literature in which diastolic impairment was present in type 1 diabetic patients at an early stage of disease and with no evident microvascular and macrovascular complications.

Effects of prenatal ethanol exposure on hippocampal theta activity in the rat.

This study examined the effects of prenatal ethanol exposure on hippocampal theta activity in adult rats. Subjects were randomly selected from four prenatal treatment conditions: untreated, 0, 3, or 5 g/kg/day ethanol. At approximately 90 days of age, all subjects were surgically implanted with a bipolar electrode in the CA1 region of the hippocampus. Four epochs of hippocampal theta rhythm activity were recorded while the subjects were moving and four more while still, and a normalized theta score was computed and compared among groups. The 5 g/kg male group demonstrated a significantly higher theta score than controls, indicating either an increase in type I (movement-associated) theta and/or a decrease in type II (information-processing) theta activity. These results are consistent with prior reports that prenatal ethanol exposure alters hippocampal function and support clinical indications that monitoring the EEG of children may prove to be useful in the diagnosis of fetal alcohol syndrome and/or the detection of alcohol-related birth defects.

Scopolamine does not differentially affect Morris maze performance in adult rats exposed prenatally to alcohol.

Rats exposed prenatally to alcohol have shown deficits in spatial learning in radial-arm and Morris mazes. Prenatal exposure to alcohol in rats has also been shown to alter central nervous system (CNS) cholinergic function. Since cholinergic dysfunction disrupts spatial learning in normal rats, the present experiment assessed the role of putative prenatal alcohol-induced cholinergic dysfunction in spatial learning in rats. Pregnant rats were fed alcohol via liquid diet from gestation day 6 to 20. Control dams were pair-fed liquid diet without alcohol or fed ad lib lab chow and water. Group housed adult male and female offspring (postnatal days 110 to 135) were given scopolamine-HCl (0, 0.5, or 1.0 mg/kg/day) and tested in a Morris maze, with four trials per day for four days. A 15-s probe trial preceded testing on days 2-4. On day 5, the rats were given four trials to learn a new platform location. Scopolamine produced dose-dependent increases in latency to find the platform for all groups. There were no significant differences among prenatal treatment groups in scopolamine-induced shifts in performance. The results did not support the hypothesis that prenatal alcohol-induced CNS cholinergic dysfunction is related to spatial learning performance in these rats.

Ectopic twin gestation discordant for anencephaly. A case report.

A 30-year-old white woman thought to have a 12-week intrauterine pregnancy developed a large cul-de-sac mass, which proved to be an ectopic, monoamnionic twin pregnancy (males) discordant for anencephaly. While twin pregnancies discordant for neural tube defects are well known, the extrauterine location made this case remarkable.