Respiratory challenges and ventilatory management in different types of acute brain-injured patients.

Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.

The mechanical power in neurocritical care patients: is it useful?

Patients with acute brain injury have been excluded in the majority of the randomized clinical trials which evaluated a lung protective strategy in patients with acute respiratory failure. It remains unclear if low tidal volume, higher PEEP levels and recruitment maneuvers by increasing both the intracranial and intrathoracic pressure and by leading to a permissible hypercapnia could furthermore deteriorate the acute brain injury and the final outcome. Mechanical power has been associated with the outcome in ARDS patients without brain injury. Jiang et al. demonstrated in neurocritical patients that non-survivors had a higher mechanical power compared to survivors. Mechanical power was associated with an increase in intensive care mortality risk and also to an enhanced risk of hospital mortality, prolonged intensive care length of stay and fewer ventilatory free days; in addition, the mechanical power could better predict mortality compared to the Glasgow Coma Scale.

Analysis of anaerobic digester mixing: comparison of long shafted paddle mixing vs gas mixing.

The anaerobic digestion (AD) process is influenced by a variety of operation parameters, such as sludge rheology, mixing, temperature, solid retention time (SRT), hydraulic retention time (HRT) and solids concentration. The optimum in the mixing lies somewhere between no-mixing and continuous mixing, as the lack or excessive mixing can lead to poor AD performance instead. A three-dimensional computational fluid dynamics steady/unsteady model, incorporating the rheological properties of the sludge, was developed and applied to quantify mixing in a full-scale anaerobic digester. Mechanical and gas mixing solutions were taken into account, keeping constant the daily energy consumption. Results, consisting of velocity magnitude and patterns, dead zone formation and turbulence levels were discussed. Compared to the mechanical mixing, gas mixing had lower percentage of dead zones (about 5% against 50%), larger maximum velocity (about 3 m/s against 1 m/s) as well as larger turbulent kinetic energy levels (0.24 m2/s2 against 0.001 m2/s2).

Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: interplay between nanostructure and composition.

Here we present a quantitative mechanism-based investigation aimed at comparing the cell uptake, intracellular trafficking, endosomal escape and final fate of lipoplexes and lipid-protamine/deoxyribonucleic acid (DNA) (LPD) nanoparticles (NPs) in living Chinese hamster ovary (CHO) cells. As a model, two lipid formulations were used for comparison. The first formulation is made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC), while the second mixture is made of the cationic 3ß-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE). Our findings indicate that lipoplexes are efficiently taken up through fluid-phase macropinocytosis, while a less efficient uptake of LPD NPs occurs through a combination of both macropinocytosis and clathrin-dependent pathways. Inside the cell, both lipoplexes and LPD NPs are actively transported towards the cell nucleus, as quantitatively addressed by spatio-temporal image correlation spectroscopy (STICS). For each lipid formulation, LPD NPs escape from endosomes more efficiently than lipoplexes. When cells were treated with DOTAP-DOPC-containing systems the majority of the DNA was trapped in the lysosome compartment, suggesting that extensive lysosomal degradation was the rate-limiting factors in DOTAP-DOPC-mediated transfection. On the other side, escape from endosomes is large for DC-Chol-DOPE-containing systems most likely due to DOPE and cholesterol-like molecules, which are able to destabilize the endosomal membrane. The lipid-dependent and structure-dependent enhancement of transfection activity suggests that DNA is delivered to the nucleus synergistically: the process requires both the membrane-fusogenic activity of the nanocarrier envelope and the employment of lipid species with intrinsic endosomal rupture ability.

Spontaneous assembly of carbon-based chains in polymer matrixes through surface charge templates.

Stable chains of carbon-based nanoparticles were formed directly in polymer matrixes through an electrode-free approach. Spontaneous surface charges were generated pyroelectrically onto functionalized ferroelectric crystals, enabling the formation of electric field gradients that triggered the dipole-dipole interactions responsible for the alignment of the particles, while embedded in the polymer solution. The phenomenon is similar to the dielectrophoretic alignment of carbon nanotubes reported in the literature. However, here the electric fields are generated spontaneously by a simple heat treatment that, simultaneously, aligns the particles and provides the energy necessary for curing the host polymer. The result is a polymer sheet reinforced with well-aligned chains of carbon-based particles, avoiding the invasive implementation of appropriate electrodes and circuits. Because polymers with anisotropic features are of great interest for enhancing the thermal and/or the electrical conductivity, the electrode-free nature of this technique would improve the scaling down and the versatility of those interconnections that find applications in many fields, such as electronics, sensors, and biomedicine. Theoretical simulations of the interactions between the particles and the charge templates were implemented and appear in good agreement with the experimental results. The chain formation was characterized by controlling different parameters, including surface charge configuration, particle concentration, and polymer viscosity, thus demonstrating the reliability of the technique. Moreover, micro-Raman spectroscopy and scanning electron microscopy were used for a thorough inspection of the assembled chains.

Graded-size microlens array by the pyro-electrohydrodynamic continuous printing method.

In the present work, the pyro-electrohydrodynamic technique was used for the realization of tunable-size microlens arrays. Poly(methyl methacrylate) dissolved in different solvent mixtures was used as the polymeric material for the realization of the microstructures. By controlling the experimental parameters and in particular, the volume of the drop reservoir, graded-size square arrays of tens of microlenses with focal length in the range 1.5-3 mm were produced. Moreover, the optical quality and geometrical features were investigated by profilometric and interferometric analysis.

The treatment of desmoid tumors: a stepwise clinical approach.

Aggressive fibromatosis (AF) is a monoclonal proliferative disease but does not metastasize and does not dedifferentiate to a high-grade malignancy in case of recurrence. Biopsy is usually necessary to confirm the diagnosis. A hallmark is its apparent unpredictable clinical course producing a large heterogeneity even with an indistinguishable morphology. Additional studies of the molecular determinants of desmoid behavior are needed to guide selection of the various therapeutic modalities. During the last 10 years, the treatment of AF has evolved and the role of routine, aggressive first-line treatment (radiotherapy and surgery) is now debated. If a wait-and-see policy is used at initial presentation, it is observed that >50% of patients will have relatively indolent disease. Aggressive treatments that take their indications from retrospective studies should be re-evaluated in the light of new data. The objective of this article is to propose an algorithm that commences with more conservative approaches before treatments that have associated long-term morbidity, the more aggressive therapies being reserved only for those who really need it.

Printing of polymer microlenses by a pyroelectrohydrodynamic dispensing approach.

The investigation of a method for fabricating microlenses by a nozzle-free inkjet printing approach is reported. The new method, based on a pyroelectrohydrodynamic mechanism, is also able to dispense viscous liquids and to draw liquid phase drops directly from the reservoir. Specifically, by dispensing optical grade polymer dissolved in different solvent mixtures, microlenses were printed with a pattern defined directly through this deposition method. The reliability of the microlenses and the tunability of their focal properties were demonstrated through profilometric and inteferometric analyses.

[Laparoscopic treatment of UPJ obstruction in ectopic pelvic kidneys in children]. / Trattamento laparoscopico dell'Ostruzione del Giunto Pielo-Ureterale nei reni ectopici in età pediatrica.

AIMS: To assess the feasibility and safety of a laparoscopic approach to UPJ obstruction (UPJO) in ectopic pelvic kidneys. MATERIAL AND METHODS: In a retrospective analysis we selected 14 children, aged 6 months to 17 years, 12 males, 2 females, who had been treated in our Department between January 2004 and June 2011. 9 patients presented ureteropelvic junction obstruction (in 3 cases pelvic stones coexisted) with normal/moderately reduced (> or = 25%) relative function at radionuclide scan (MAG3), 3 nonfunctioning kidneys associated or not to hypertension, 2 congenital hypo-dysplastic kidneys. The evaluation of each patient involved the medical history, ultrasound examination, VCUG, MAG3 diuresis renogram and MRI in some cases. Of the patients presenting UPJO, 5 underwent dismembered pyeloplasty with pyelolithotomy, if required, and 4 pelvic derotation with straightening of the uretero-pelvic junction. A previous cystoscopic placement of a Double J stent was utilized. This facilitated the identification and dissection around the pelvis. With the patient in Trendelenburg position we utilized an umbilical trocar and two trocar in the right and left iliac fossae; an additional trocar, when required, was inserted more cephalad on the midclavear line contralaterally to the lesion. The derotation of ureteropelvic junction was obtained by freeing the kidney's lower pole and by placing intraperitoneally the junction protected with a Double J stent. This was obtained by suturing the peritoneum behind the ureteropelvic junction resulting in a forward rotation of the major axis of the kidney and a straightening of the junction. The 5 patients presenting nonfunctioning ectopic kidneys underwent laparoscopic nephrectomy. While the removal of congenital hypoplasic kidneys resulted easy, the removal of nonfunctioning kidneys was more difficult due to their complex vascular situation and for the embryonic disposition. RESULTS: The operating time varied between 40 to 200 minutes. No patient required conversion to open surgery. The hypertension resolved after nephrectomy in all cases. 2 cases of dismembered pyeloplasty required a placement of Double J stent due the recurrence of symptoms and ! patient is waiting for redo operation. The pelvic derotation showed an improvement of diuretic MAG3 renogram and the function remained stable and patiens are symptoms-free. CONCLUSION: The UPJO in ectopic pelvic kidneys presents a large spectrum of presentation. The laparoscopic approach provides good surgical exposure, and operative times are acceptable compared to those of laparoscopic procedure in anatomically normal kidneys. It has also proved a very useful tool in the non-functioning kidney nephrectomy thank to the help of magnification in the identification of numerous aberrant vessels that are quite often found in the pelvic kidneys. The derotation of the pelvis seems a useful procedure in moderate obstruction even if a longer followup is needed.

A validation study of a continuous automatic measurement of the mechanical power in ARDS patients.

The mechanical power (MP) is the energy delivered into the respiratory system over time. It can be computed as a direct measurement of the inspiratory area of the airway pressure and volume loop during the respiratory cycle or calculated by "power equations". The absence of a bedside computation limited its widespread use. Recently, it has been developed an automatic monitoring system inside of a mechanical ventilator. PURPOSE: Our aim was to investigate the repeatability and the accuracy of the measured MP at different PEEP values and tidal volume compared with the calculated MP. MATERIAL AND METHODS: MP was measured and calculated in sedated and paralyzed ARDS patients at low and high tidal volume, at 5-10-15 cmH2O of PEEP both in volume and pressure-controlled ventilation. The same measurements were performed twice. RESULTS: Fifty ARDS patients were enrolled. MP was measured and calculated for a total of 300 measurements. The bias and limits of agreement were 0.38 from -1.31 to 2.0 J/min. The measured and calculated MP were similar in each ventilatory condition. CONCLUSIONS: The mechanical power measured by a new automatic real time system implemented in a mechanical ventilator was repeatable and accurate compared with the computed one.

Respiratory and peripheral muscular ultrasound characteristics in ICU COVID 19 ARDS patients.

PURPOSE: Severe cases of coronavirus disease 2019 develop ARDS requiring admission to the ICU. This study aimed to investigate the ultrasound characteristics of respiratory and peripheral muscles of patients affected by COVID19 who require mechanical ventilation. MATERIALS AND METHODS: This is a prospective observational study. We performed muscle ultrasound at the admission of ICU in 32 intubated patients with ARDS COVID19. The ultrasound was comprehensive of thickness and echogenicity of both parasternal intercostal and diaphragm muscles, and cross-sectional area and echogenicity of the rectus femoris. RESULTS: Patients who survived showed a significantly lower echogenicity score as compared with those who did not survive for both parasternal intercostal muscles. Similarly, the diaphragmatic echogenicity was significantly different between alive or dead patients. There was a significant correlation between right parasternal intercostal or diaphragm echogenicity and the cumulative fluid balance and urine protein output. Similar results were detected for rectus femoris echogenicity. CONCLUSIONS: The early changes detected by echogenicity ultrasound suggest a potential benefit of proactive early therapies designed to preserve respiratory and peripheral muscle architecture to reduce days on MV, although what constitutes a clinically significant change in muscle echogenicity remains unknown.

Applying deep neural networks and inertial measurement unit in recognizing irregular walking differences in the real world.

Falling injuries pose serious health risks to people of all ages, and knowing the extent of exposure to irregular surfaces will increase the ability to measure fall risk. Current gait analysis methods require overly complicated instrumentation and have not been tested for external factors such as walking surfaces that are encountered in the real-world, thus the results are difficult to extrapolate to real-world situations. Artificial intelligence approaches (in particular deep learning networks of varied architectures) to analyze data collected from wearable sensors were used to identify irregular surface exposure in a real-world setting. Thirty young adults wore six Inertial Measurement Unit (IMU) sensors placed on their body (right wrist, trunks at the L5/S1 level, left and right thigh, left and right shank) while walking over eight different surfaces commonly encountered in the living community as well as occupational settings. Three variations of deep learning models were trained to solve this walking surface recognition problem: 1) convolution neural network (CNN); 2) long short term memory (LSTM) network and 3) LSTM structure with an extra global pooling layer (Global-LSTM) which learns the coordination between different data streams (e.g. different channels of the same sensor as well as different sensors). Results indicated that all three deep learning models can recognize walking surfaces with above 0.90 accuracy, with the Global-LSTM yielding the best performance at 0.92 accuracy. In terms of individual sensors, the right thigh based Global-LSTM model reported the highest accuracy (0.90 accuracy). Results from this study provide further evidence that deep learning and wearable sensors can be utilized to recognize irregular walking surfaces induced motion alteration and applied to prevent falling injuries.

Lung recruitment: What has computed tomography taught us in the last decade?

Although chest X-ray remains a fundamental lung imaging technique, through the years, CT scan has significantly improved our knowledge of the pathophysiological process and currently is the reference lung imaging tool for both a visual and quantitative computer-based analysis. The application of lung CT in the early phase of ARDS has led to changes in the clinical management in up of thirty percent of the patients. Although CT requires the transportation of the patient to the radiological department and exposes the patient to high dose of radiation, given the several information that CT can offer, it should be applied at least one time, in the early phase in all ARDS patients. CT plays an irreplaceable role to describe and assess the lung recruitability and to help a more physiological setting of mechanical ventilation.

Easy Printing of High Viscous Microdots by Spontaneous Breakup of Thin Fibers.

Electrohydrodynamic jetting is emerging as a successful technique for printing inks with resolutions well beyond those offered by conventional inkjet printers. However, the variety of printable inks is still limited to those with relatively low viscosities (typically <20 mPa s) due to nozzle clogging problems. Here, we show the possibility of printing ordered microdots of high viscous inks such as poly(lactic-co-glycolic acid) (PLGA) by exploiting the spontaneous breakup of a thin fiber generated through nozzle-free pyro-electrospinning. The PLGA fiber is deposited onto a partially wetting surface, and the breakup is achieved simply by applying an appropriate thermal stimulation, which is able to induce polymer melting and hence a mechanism of surface area minimization due to the Plateau-Rayleigh instability. The results show that this technique is a good candidate for extending the printability at the microscale to high viscous inks, thus extending their applicability to additional applications, such as cell behavior under controlled morphological constraints.

Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line.

Vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain-containing receptor (KDR) is expressed in primitive hematopoietic cells, in megakaryocytes and platelets. In primitive hematopoiesis KDR mediates cell survival via autocrine VEGF, while its effect on cell growth and differentiation has not been elucidated. We induced enforced KDR expression in the granulocyte macrophage-colony-stimulating factor (GM-CSF)-dependent TF1 progenitor cell line (TF1-KDR), treated the cells with VEGF and analyzed their response. In GM-CSF-deprived cells, VEGF induces cell proliferation and protection against apoptosis, followed by enhanced expression of megakaryocytic (MK) markers. Combined with GM-CSF, VEGF induces a mild proliferative stimulus, followed by cell adherence, accumulation in G0/G1, massive MK differentiation and Fas-mediated apoptosis. Accordingly, we observed that MK-differentiating cells, derived from hematopoietic progenitors, produce VEGF, express KDR, inhibition of which reduces MK differentiation, indicating a key role of KDR in megakaryopoiesis. In conclusion, TF1-KDR cells provide a reliable model to investigate the biochemical and molecular mechanisms underlying hematopoietic progenitor proliferation, survival and MK differentiation.

The cleavage mode of apoptotic nuclear vesiculation is related to plasma membrane blebbing and depends on actin reorganization.

In U937 monocytic cells induced to apoptosis, plasma membrane blebbing of different intensities appears, before the development of nuclear alterations; this latter phenomenon can occur through two major pathways, namely the cleavage and the budding mode (Dini et al., 1996). Strongly blebbing cells develop deep nuclear constrictions leading to nuclear fragmentation according to the cleavage mode, while cells with milder forms of blebbing, or no blebbing at all, undergo nuclear fragmentation along the budding mode. Compounds interfering with different cytoskeletal components affect blebbing, which is completely inhibited by the actin polymerization inhibitors, cytochalasins, while disturbance of tubulin network with taxol limits blebbing to milder forms. At the same time, the cytoskeletal poisons affect the type of nuclear fragmentation, abolishing the cleavage mode, shifting all events into the budding pathway. Adherent cells, which possess a more structured cytoskeleton, do not develop strong blebs and undergo nuclear fragmentation via budding. These observations suggest that the deep cytoskeletal movements that cause the strongest forms of plasma membrane blebbing strangle the nucleus, leading to the constrictions that later evolve into nuclear fragmentation by cleavage. The trigger for the cytoskeletal movements, known to be redox-sensitive, is probably the apoptotic GSH extrusion.

Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis.

Bax is a cytosolic protein, which in response to stressing apoptotic stimuli, is activated and translocates to mitochondria, thus initiating the intrinsic apoptotic pathway. In spite of many studies and the importance of the issue, the molecular mechanisms that trigger Bax translocation are still obscure. We show by computer simulation that the two cysteine residues of Bax may form disulfide bridges, producing conformational changes that favor Bax translocation. Oxidative, nonapoptogenic treatments produce an up-shift of Bax migration compatible with homodimerization, which is reverted by reducing agents; this is accompanied by translocation to mitochondria. Dimers also appear in pure cytosolic fractions of cell lysates treated with H2O2, showing that Bax dimerization may take place in the cytosol. Bax dimer-enriched lysates support Bax translocation to isolated mitochondria much more efficiently than untreated lysates, indicating that dimerization may promote Bax translocation. The absence of apoptosis in our system allows the demonstration that Bax moves because of oxidations, even in the absence of apoptosis. This provides the first evidence that Bax dimerization and translocation respond to oxidative stimuli, suggesting a novel role for Bax as a sensor of redox imbalance.

Forward electrohydrodynamic inkjet printing of optical microlenses on microfluidic devices.

We report a novel method for direct printing of viscous polymers based on a pyro-electrohydrodynamic repulsion system capable of overcoming limitations on the material type, geometry and thickness of the receiving substrate. In fact, the results demonstrate that high viscosity polymers can be easily manipulated for optical functionalizing of lab-on-a-chip devices through demonstration of direct printing of polymer microlenses onto microfluidic chips and optical fibre terminations. The present system has great potential for applications from biomolecules to nano-electronics. Moreover, in order to prove the effectiveness of the system, the optical performance of such microlenses has been characterized by testing their imaging capabilities when the fibroblast cells were allowed to flow inside the microfluidic channel, showing one of their possible applications on-board a LoC platform.

Response of Escherichia coli O157:H7, Listeria monocytogenes, Salmonella typhimurium, and Staphylococcus aureus to the thermal stress occurring in model manufactures of Grana Padano cheese.

The purpose of this research was to investigate the effect of temperature in the technology of production of Grana cheese against Escherichia coli O157:H7, Listeria monocytogenes, Salmonella Typhimurium, and Staphylococcus aureus. According to the technology of production, the cheese curds are cooked at 55 degrees C and then cooled at room temperature (25 degrees C). A curd-cooling model was developed to estimate the temperature variation across the curd during cooling, and the thermal stress was applied to the pathogens according to the model in model-scale productions of Grana cheese artificially contaminated with approximately 10(4) cfu/mL of the selected pathogens. According to the numerical results, the initial temperature inside the cheese is kept at almost the initial value (above 50 degrees C) for at least 4 h during cooling, whereas the crust of the curd cools rapidly to 30 degrees C in the first hour. The best case was that of the core of the cheese where the high temperature was able to efficiently eliminate the contaminating pathogens. Moreover, the worst case was where the external ring of the curd in which a more rapid cooling allowed bacterial survival. Therefore, the thermal stress in the technology of production of Grana cheese can be only partially effective in the control of the selected pathogens. However, the whole technology of production includes other hurdles that can affect the survival of the pathogens and that need to be taken into account as a whole to evaluate the safety of Grana Padano cheese.