Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

Intracranial arterial dolichoectasia in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder with a variety of cardiovascular manifestations. This study presents a group of patients with ADPKD who had intracranial arterial dolichoectasia. One hundred seventy-eight ADPKD patients were screened with magnetic resonance angiography, 40 ADPKD patients had conventional angiography, and 98 ADPKD patients underwent a brain autopsy. For comparison, 360 patients without ADPKD who had magnetic resonance angiography and conventional angiography or brain autopsy were also studied. The prevalence of asymptomatic intracranial arterial dolichoectasia was 2.2% (4 of 178), 2.5% (1 of 40), and 2.0% (2 of 98) in the three ADPKD groups, respectively. None of the patients without ADPKD had intracranial arterial dolichoectasia. In addition to the seven patients with asymptomatic disease, two ADPKD patients with vertebrobasilar dolichoectasia had posterior circulation ischemic symptoms. The mean age of the nine patients (five men and four women) was 56.6 yr (range, 41 to 67 yr). The posterior circulation was involved in five patients, the anterior circulation was involved in two patients, and both were involved in two patients. Arterial dissection was believed to have caused middle cerebral artery dolichoectasia in one patient, and intracranial arterial dissections were strongly suspected in two other patients. Six of the nine patients with intracranial arterial dolichoectasia had additional vascular manifestations of ADPKD. Some patients with ADPKD are at an increased risk of developing intracranial arterial dolichoectasia and dissections. Recognizing this association is important because (1) it may be a cause of stroke; (2) it may mimic a saccular aneurysm on radiographic studies; and (3) it suggests that the arteriopathy of ADPKD may be more generalized than previously believed.     

Runoff and infiltration characteristics of pavement structures--review of an extensive monitoring program.

The stormwater runoff and infiltration performance of permeable pavements has been systematically evaluated within an intensive monitoring program. The primary objective of the investigation was to generate a broad database, which enables the development of an advanced simulation module for urban drainage modelling. Over 160 field and lab scale experiments have been completed and analyzed for surface runoff and infiltration characteristics. The test series include several pavement types under various boundary conditions such as diverse precipitation impacts, varying surface slope and layer construction as well as different stages of surface clogging and several base and subgrade layer characteristics. The results represent a reliable and comprehensive database that allows profound conclusions and substantial recommendations.     

Membrane topology and glycosylation of the human multidrug resistance-associated protein

The membrane topology of the human multidrug resistance-associated protein (MRP) was examined by flow cytometry phenotyping, immunoblotting, and limited proteolysis in drug-resistant human and baculovirus-infected insect cells, expressing either the glycosylated or the underglycosylated forms of this protein. Inhibition of N-linked glycosylation in human cells by tunicamycin did not inhibit the transport function or the antibody recognition of MRP, although its apparent molecular mass was reduced from 180 kDa to 150 kDa. Extracellular addition of trypsin or chymotrypsin had no effect either on the function or on the molecular mass of MRP, while in isolated membranes limited proteolysis produced three large membrane-bound fragments. These experiments and the alignment of the MRP sequence with the human cystic fibrosis transmembrane conductance regulator (CFTR) suggest that human MRP, similarly to CFTR, contains a tandem repeat of six transmembrane helices, each followed by a nucleotide binding domain, and that the C-terminal membrane-bound region is glycosylated. However, the N-terminal region of MRP contains an additional membrane-bound, glycosylated area with four or five transmembrane helices, which seems to be a characteristic feature of MRP-like ATP-binding cassette transporters.     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Liquid-liquid separations in a conventional hydrocyclone

The performance of a conventional hydrocyclone for separation of immiscible liquids was investigated experimentally. The results are particularly useful for evaluation of multi-cyclone process design of same system. The effect of materials of constructions of the hydrocyclone on the separation efficiency was also tested. Significant differences in performance were noted depending on the preferential wettability characteristics of the solid surfaces for the liquids being separated.     

Design and Fabrication of Transparent and Gas‐Tight Optical Windows in Low‐Temperature Co‐Fired Ceramics

Low‐temperature co‐fired ceramics (LTCC) enable the fabrication of microfluidic elements such as channels and embedded cavities in electrical devices. Hence, LTCC facilitate the realization of complex and integrated microfluidic devices. Examples can be applied in many areas like reaction chambers for synthesis of chemical compounds. However, for many applications it is necessary to have an optically transparent interface to the surroundings. The integration of optical windows in LTCC opens up a wide field of new and innovative applications such as the observation of chemiluminescent reactions. These chemical reactions emit electromagnetic radiation and thus offer a method for noninvasive detection. Thin glasses (≤500 μm) were bonded by thermocompression onto a LTCC substrate. As the bonding agent, a glass frit paste was used. Borosilicate glasses, fused silica as well as silicon were successfully bonded onto LTCC. To join materials with a large coefficient of thermal expansion mismatch (i.e., fused silica and LTCC), it is necessary to limit the heat input to the bond interface. Therefore, a heating structure was integrated into the LTCC substrate beneath the bond interface. This bonding process provides a gas‐tight optical port with a high bond strength.     

Multiyear Performance of a Pervious Concrete Infiltration Basin BMP

The use of infiltration storm-water best management practices (BMPs) has become a more commonly used approach as a means of reducing postdevelopment runoff volumes in many areas throughout the United States. Although studies regarding the performance of infiltration BMPs are emerging, much remains to be learned about their design, construction, and operation. The increase in knowledge will improve the performance and longevity of these BMPs. The performance of one such infiltration basin over a 2-year cycle is presented in this paper. The study site is a pervious concrete infiltration basin BMP built in 2002 in a courtyard common area at Villanova University. The system consists of three linked infiltration beds lined with geotextile filter fabric, filled with coarse aggregate, and overlaid with pervious concrete. The natural soil beneath the infiltration BMP is a silty sand. The BMP is extensively instrumented to facilitate water quantity and quality research. Both water-quantity and -quality results are presented. The water-quantity analysis showed that the performance of the basin was directly related to its infiltration characteristics. The infiltration rate of the silty sand is cyclic, with higher rates during warmer periods and lower rates during colder periods. The water quality analysis investigated the pollutant reduction for chloride, copper, nitrogen, and phosphorus from the inlet to the surface-water outlet of the structure, as well as differences in pollutant concentration levels between the basin, surrounding ground, and varying soil layer elevations beneath the basin. In general, the pollutant reduction to the surface waters was greater than 90% from inlet to outlet, primarily influenced by the infiltration of the storm water into the natural soils below the BMP. The pollutant concentration of the infiltrating runoff was found to be higher than expected in the area adjacent to the bed when compared to concentration levels found at a similar depth beneath the infiltration bed. Comparison of pollutant concentration levels, as the water moved from within the storage bed to the soil beneath the bed, were shown to vary, with statistical differences found for mean concentration levels of both pH and copper levels; and no statistical differences were found for conductivity, total phosphorous, and chloride at each elevation.