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This report aimed to characterize clinical and imaging characteristics and outcomes of the patients with lower cervical spine injury combined with spinal cord paralysis who underwent posterior cervical spine surgery.Between January 2019 and December 2020, a retrospective evaluation of prospectively collected data at one institution was conducted. We included all patients who were diagnosed with subaxial cervical spine injuries (C3-7), had spinal cord paralysis, and underwent posterior cervical spine surgery. Clinical profile, preoperative characteristics, intraoperative data, and postoperative outcomes were retrieved from prospective patients' medical records and computerized database.Among 70 selected patients, most were male (66, 94.29%) and the average age was 48.41 ± 14.33 years. Most of them worked in agriculture (90.4%). Clinical symptoms included neck pain (58, 82.86%), cervical radiculopathy (50, 71.43%), loss of sensation (44, 62.86%), and decreased sensation (21, 30.00%). The most frequent cervical spinal injuries involved C5 (28.57%), followed by C7 (14.29%). Circular muscle dysfunction was present in 65 (92.86%) patients. Early complications included respiratory failure (12.85%), pneumonia (11.42%), bedsores (8.57%), and urinary tract infection (7.14%). Common late complications included movement disorder (48.21%), muscle weakness and stiffness (37.50%), sensory disturbances (32.14%), urinary tract infection (17.86%), bedsores (16.07%), and pneumonia (5.36%). Patients after surgery and at follow-up had a significant improvement compared to preoperative assessment according to the AIS classification, and recovery of smooth muscle. Three patients died within 1 month following surgery, 3 within 1-3 month(s), 2 within 3-6 months, and 1 case beyond 6 months.In hospital-based clinical condition with limited practice approach, our study indicated specific clinical and imaging characteristics of Vietnamese patients with lower cervical spine injury combined with spinal cord paralysis. With high postoperative mortality rate, commonly late complications after posterior cervical spine surgical approach were pain and difficulty in neck movement, muscle weakness and stiffness, and nerve root pain.

In order to study altered molecular mechanisms representative of the damage induced by the disease in patients, two HEK293 cell models were developed. The first model was obtained with CRISPR/CAS9-based MUT gene knock out (MUT-KO). The second cell model derived from a MUT-KO cell line engineered to rescue the stable expression of MUT protein (MUT-RES). To track the quantitative changes in the global proteome of MUT-KO and MUT-RES cells, a Data Independent Acquisition mass spectrometry-based proteomic experiment was performed.Results and Discussion: Isolated methylmalonic acidemia (MMA) is a rare inherited metabolic disease of propionyl-CoA and branched-chain amino acids catabolism that affects 1 in 100,000 newborn babies. It is caused by a total or partial deficiency of methylmalonyl-CoA mutase enzymatic activity (MUT0 and MUT- subtypes, respectively). Mutations in methylmalonyl-CoA mutase (MUT) gene impair the mitochondrial conversion of methylmalonyl-CoA to succinyl-CoA, metabolized within the Krebs cycle.

PKR-like kinase (PERK) plays a significant role in inducing angiogenesis in various cancer types including glioblastoma. By proteomics analysis of the conditioned medium from a glioblastoma cell line treated with a PERK inhibitor, we showed that peptidylglycine α-amidating monooxygenase (PAM) expression is regulated by PERK under hypoxic conditions. Moreover, PERK activation via CCT020312 (a PERK selective activator) increased the cleavage and thus the generation of PAM cleaved cytosolic domain (PAM sfCD) that acts as a signaling molecule from the cytoplasm to the nuclei. PERK was also found to interact with PAM, suggesting a possible involvement in the generation of PAM sfCD. Knockdown of PERK or PAM reduced the formation of tubes by HUVECs in vitro. Furthermore, in vivo data highlighted the importance of PAM in the growth of glioblastoma with reduction of PAM expression in engrafted tumor significantly increasing the survival in mice. In summary, our data revealed PAM as a potential target for antiangiogenic therapy in glioblastoma.

Background Accurate assessment of aortic annulus and left ventricular outflow tract (LVOT) anatomy is mandatory for appropriate device selection in order to achieve optimal deployment of transcatheter heart valves (THV). Aim To evaluate the impact of LVOT shape as determined by the sphericity index (ratio of long and short LVOT diameter) on THV hemodynamics. Methods 1000 consecutive patients diagnosed with severe symptomatic aortic stenosis and undergoing TAVI between May 2008 and July2017 were analyzed. Assessment of aortic root dimensions including the LVOT was performed by contrast-enhanced multidetector computed tomography (MDCT) in all patients. The primary endpoint was 30-day device success as defined by the VARC-2 criteria. Secondary endpoints included all-cause mortality, cardiovascular mortality, permanent pacemaker implantation (PPI), and a 30-day combined early safety endpoint (all-cause mortality, all strokes, life threatening bleeding, acute kidney injury stage 2 or 3, CAD obstruction requiring intervention, major vascular complication, valve related dysfunction requiring repeat intervention). Results Patients were divided into 3 groups according to LVOT sphericity index (SI) quartiles. The three groups (low-SI: 0.4–0.63, n=250; mid-SI: 0.64–0.75, n=500; high-SI: 0.76–1.0, n=250) were well balanced in terms of baseline characteristics, except for gender distribution with more female patients in the low-SI group (36.8% vs. 49.0% vs. 60.0%; p=0.ehz748.05941). Assessment of calcification volume and Agatston score demonstrated significantly higher aortic valve and LVOT calcification in the high-SI group. The primary endpoint of device success after 30-days did not differ between the 3 groups (92.4% vs 91.9% vs. 87.9%; p=NS). However, moderate or severe paravalvular regurgitation (PAR) occurred significantly more often in the high-SI as compared to the other groups (4.1% vs. 5.2% vs. 10.6%; p=0.004 for low-SI vs. high-SI). In contrast, PPI rates, the early safety endpoint at 30 days, and all-cause mortality at 1 year did not differ between the groups. In the high-SI group implantation of a BE valve was associated with a significantly higher rate of device success as compared to SE valves (93.8% vs. 82.2%, p=0.007). This difference was driven by a higher rate of moderate or severe PAR (6.9% vs. 15.3%, p=0.007) in patients treated with SE valves. Moreover, patients in the high-SI group receiving a SE valve required more often a PPI than those treated with a BE valve (26.2% vs 13.3%, p=0.012). There was no difference between the THV types in the other SI groups in terms of primary and secondary endpoints. Conclusion A more circular LVOT is associated with higher aortic valve and LVOT calcification. Implantation of a SE THV results in higher rates of moderate or severe PAR and persistent conduction disorder requiring PPI in such patients.

Background Accurate assessment of aortic stenosis (AS) severity is critical for the correct management of patients. This has become particularly important because the introduction of transcatheter aortic valve implantation (TAVI) has markedly increased the number of patients eligible for aortic valve replacement Aims To assess whether reclassification of aortic stenosis (AS) grading by integration of fusion imaging using data from transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) under consideration of the energy loss index (ELI) predicts outcome in patients undergoing transcatheter aortic valve implantation (TAVI). Methods 197 consecutive patients with symptomatic severe AS undergoing TAVI at our University Heart Center were included in this study. AS severity was determined according to current guidelines. Results Left ventricular outflow tract (LVOT) area derived from TTE was smaller than the planimetric area in MDCT due the ovoid shape of the LVOT (3.4±0.12 cm2 vs. 4.5±0.23 cm2; p0.6 cm2/m2. ELI was calculated for conventional AVAi and fusion AVAi each with ST-junction area determined by both TTE and MDCT. Calculating ELI with fusion AVAi resulted in significantly larger effective orifice area, with values >0.6 cm2/m2 in 83 patients (ST-junction area from echo) and 85 patients (ST-junction area from MDCT). Similarly, calculating ELI with conventional AVAi resulted in significantly larger effective orifice area as compared to AVAi alone. Reclassified patients had lower mean transvalvular pressure gradients, lower myocardial mass, less symptoms according to NYHA classification, and lower proBNP levels at baseline. While both groups exhibited improvement of functional status at 1 year of follow-up, the survival rate at 3 years after TAVI was higher in patients reclassified to moderate AS (81% versus 66%; p=0.02). Conclusion Integration of TTE and MDCT derived values for calculation of ELI reclassifies the severity of AS in 43% of patients initially diagnosed with severe AS.Although reclassified patients display less advanced valve disease at baseline, TAVI results in functional improvement in all patients. Furthermore, patients reclassified to moderate AS exhibit higher survival rates at 3 years after aortic valve replacement.

Many cellular events are driven by changes in protein expression, measurable by mass spectrometry or antibody-based assays. However, using conventional technology, the analysis of transcription factor or membrane receptor expression is often limited by an insufficient sensitivity and specificity. To overcome this limitation, we have developed a high-resolution targeted proteomics strategy, which allows quantification down to the lower attomol range in a straightforward way without any prior enrichment or fractionation approaches. The method applies isotope-labeled peptide standards for quantification of the protein of interest. As proof of principle, we applied the improved workflow to proteins of the unfolded protein response (UPR), a signaling pathway of great clinical importance, and could for the first time detect and quantify all major UPR receptors, transducers and effectors that are not readily detectable via antibody-based-, SRM- or conventional PRM assays. As transcription and translation is central to the regulation of UPR, quantification and determination of protein copy numbers in the cell is important for our understanding of the signaling process as well as how pharmacologic modulation of these pathways impacts on the signaling. These questions can be answered using our newly established workflow as exemplified in an experiment using UPR perturbation in a glioblastoma cell lines.

Polyaniline (PANI) dispersions consisting of 270 to 380 nm sized particles were prepared by oxidation with ammonium peroxydisulfate (APS) in n‐decylphosphonic acid (DPA) micellar solutions. The green dispersions do not undergo macroscopic precipitation for more than a year. The synthesized DPA doped PANI exhibited enhanced electrical conductivity (3.6 S cm⁻¹) compared with DPA‐PANI (2.3 x 10⁻⁴S cm⁻¹) prepared by postsynthesis treatment of the PANI‐base with DPA. It was shown that through protonation with decylphosphonic acid, polyaniline showed a significantly enhanced solubility in common organic solvents like chloroform, xylene, etc. The synthesized PANI was characterized by intrinsic viscosity, solubility, FT‐IR, conductivity, SEM, and TGA measurements. The wide‐angle X‐ray diffraction study revealed the appearance of a peak located at low angles (d = 29.4–35.3 A) suggesting the formation of layered structure of PANI backbone separated by long alkyl side chains of DPA. The anticorrosive performance of the bilayer coatings composed of a bottom layer of DPA doped polyaniline covered with a polyvinyl butyral topcoat, have been demonstrated for steel exposed to neutral saline solutions. It was found that the inhibitive properties of DPA dopant provides further protection to the base metal through smart release when damage is produced on the surface of the coating. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1606–1616

Sphingomyelin (SM)/cholesterol liposomes are currently investigated as drug carriers in cancer therapy. However, no data is available on the influence of SM itself on P-glycoprotein (P-gp) mediated multidrug resistance. P-gp is at least partly located in sphingolipid-enriched lipid raft domains of the plasma membrane, and its activity depends on the lipid profile of the membrane, which could be altered by therapeutical SM liposomes. Therefore, the aim of this study was to analyze the effect of liposomal SM on P-gp activity, P-gp distribution in microdomains, SM content of the membrane domains, and sensitivity of human lymphoblastic CEM cells toward cytotoxic drugs in vitro. Assays were conducted in CEM and multidrug resistant CEM/ADR5000 cells. SM-only liposomes were prepared by a newly developed ethanol injection protocol and thoroughly characterized. Inclusion of SM into the membrane was analyzed by fluorescence microscopy and flow cytometry. Influence of SM liposomes on P-gp activity was assessed by rhodamine efflux and calcein assay, and sensitivity toward cytotoxic drugs was analyzed by flow cytometric 7-AAD staining. Influence on P-gp distribution was analyzed by Western blot after density gradient centrifugation. SM 16:0, 18:0, and 24:1 were quantified by liquid chromatography coupled to tandem mass spectrometry. P-gp was mainly located in nonraft fractions, which did not change upon liposome treatment. Liposomes increased SM 16:0 and SM 24:1 content in nonraft domains, but not in raft domains of multidrug resistant cells. SM-only liposomes did not influence P-gp activity and chemosensitivity. In conclusion, SM-only liposomes in therapeutic amounts did not influence P-gp mediated multidrug resistance in CEM cells.

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune-mediated destruction of insulin-secreting pancreatic β cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at β-cell restoration is still hampered by the absence of means to measure β-cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public-private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in β-cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.

Validated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high-resolution computed tomography (HRCT) of the chest for the detection of SSc-related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT.Prospectively enrolled patients with SSc were assessed according to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research standards. The assessment included PFTs and HRCT. The HRCT images were evaluated in a blinded manner by 2 experienced radiologists. The performance parameters of PFTs for the diagnosis of SSc-related ILD were calculated. Predictors of significant ILD as determined by HRCT in patients with normal forced vital capacity (FVC) values were identified through logistic regression.Among the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while only 27 (26.0%) had an FVC80% of predicted, and 54 (53.0%) had a decrease in the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD on HRCT had a normal FVC value, translating into a high false-negative rate. Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult lung fibrosis; in 2 of these patients, the results of all of the PFTs were within normal limits. Patients with normal FVC values despite evidence of fibrosis on HRCT more frequently had anti-Scl-70 antibodies and diffuse SSc and less frequently had anticentromere antibodies (ACAs) compared with patients with both normal FVC values and normal HRCT results.The derived evidence-based data reveal a high risk of missing significant SSc-related ILD when relying solely on PFTs. More comprehensive screening algorithms for early detection are warranted. In particular, additional imaging investigations for the early detection of SSc-related ILD should be considered in ACA-negative patients with normal FVC values.

The portable multi-channel laser nephelometer was developed and applied for quantitative and qualitative researches of blood cells. Obtained findings were analyzed in comparison with results of laser diffractometry and microscopy.

Supported gold catalysts on γ-Al2O3 have been investigated in the catalytic reduction of NO x in simulated Diesel exhaust gas conditions. Different parameters have been examined essentially the mode of gold incorporation via classical deposition–precipitation and anionic exchange methods and the nature of the pre-activation thermal treatment. The resistance to thermal ageing under reactive conditions at 500 °C was found completely different with a significant rate enhancement on anionic-exchange samples. Further comparisons also show that the nature of the pre-activation thermal treatment influences the extent of surface reconstructions during thermal ageing with a detrimental effect of reductive pre-treatment on the catalytic performances.

This paper is devoted to a numerical investigation of the free convection flow about a horizontal cylinder maintained at 0 °C in a water ambient close to the point of maximum density. Complete numerical solutions covering both the transient as well as steady state have been obtained. Principal results indicate that the proximity of the ambient temperature to the point of maximum density plays an important role in the type of convection pattern that may be obtained. When the ambient temperature is within 4.7 °C

The activity of Vanadium pentoxide supported on silicagel for the photocatalytic oxidation of cyclohexane has been studied. It was found that this catalyst presents a stable activity after an or decrease depending on the surface concentration of VOshrd initial unsteady state period during which the activity might increase or decrease depending on the surface concentration of V2O5. An interpretation is proposed for the two phenomena affecting the activity during the unsteady state period. L'activite photocatalytique du pentoxyde de Vanadium depose sur silicagel, vis a vis de la reaction d'oxydation du cyclohexane, a ete etudiee. On a observe que le catalyseur presentait une activite stable apres une periode initiate a activite croissante ou decroissante selon la concentration superficielle de V2O5. On propose une interpretation pour les phenomenes affectant l'activite dans la periode transitoire.

In our preceding paper [Ratnam, M., Sargent, P. B., Sarin, V., Fox, J. L., Le Nguyen, D., Rivier, J., Criado, M., & Lindstrom, J. (1986) Biochemistry (preceding paper in this issue)], we presented results from peptide mapping studies of purified subunits of the Torpedo acetylcholine receptor which suggested that the sequence beta 429-441 is on the cytoplasmic surface of the receptor. Since this finding contradicts earlier theoretical models of the transmembrane structure of the receptor, which placed this sequence of the beta subunit on the extracellular surface, we investigated the location of the corresponding sequence (389-408) and adjacent sequences of the alpha subunit by a more direct approach. We synthesized peptides including the sequences alpha 330-346, alpha 349-364, alpha 360-378, alpha 379-385, and alpha 389-408 and shorter parts of these peptides. These peptides corresponded to a highly immunogenic region, and by using 125I-labeled peptides as antigens, we were able to detect in our library of monoclonal antibodies to alpha subunits between two and six which bound specifically to each of these peptides, except alpha 389-408. We obtained antibodies specific for alpha 389-408 both from antisera against the denatured alpha subunit and from antisera made against the peptide. These antibodies were specific to alpha 389-396. In binding assays, antibodies specific for all of these five peptides bound to receptor-rich membrane vesicles only after permeabilization of the vesicles to permit access of the antibodies to the cytoplasmic surface of the receptors, suggesting that the receptor sequences which bound these antibodies were located on the intracellular side of the membrane. Electron microscopy using colloidal gold to visualize the bound antibodies was used to conclusively demonstrate that all of these sequences are exposed on the cytoplasmic surface of the receptor. These results, along with our previous demonstration that the C-terminal 10 amino acids of each subunit are exposed on the cytoplasmic surface, show that the hydrophobic domain M4 (alpha 409-426), previously predicted from hydropathy profiles to be transmembranous, does not, in fact, cross the membrane. Further, these results show that the putative amphipathic transmembrane domain M5 (alpha 364-399) also does not cross the membrane. Our results thus indicate that the transmembrane topology of a membrane protein cannot be deduced strictly from the hydropathy profile of its primary amino acid sequence. We present a model for the transmembrane orientation of receptor subunit polypeptide chains which is consistent with current data.

In this retrospective study, the findings on abdominal sonograms in six patients newly diagnosed as having chronic disseminated histoplasmosis are reported. Five of six patients showed bilateral adrenal gland enlargement that was similar in degree from side to side. The most characteristic feature was the maintenance of a triangular shape in five glands and a cylindrical shape in two glands. Four glands had a nonspecific round or oval shape. All sonographic findings correlated well with the computed tomographic (CT) findings on each patient except that CT detected the one enlarged right adrenal gland not demonstrated sonographically. Abdominal sonography may provide the initial important clue to the diagnosis of chronic disseminated histoplasmosis.

Polyclonal and monoclonal antibodies were raised against pure human renin, but nothing was known about the regions against which they were directed. Using a three-dimensional model of mouse submandibular renin, we selected seven peptide sequences as belonging to potential epitopes. The main criteria for their choice were the location of the peptide sequences near the catalytic region and on the surface of the renin molecule and their hydrophilicity. After transposition of the regions to the 340-amino acid sequence of human renin, the seven peptides (corresponding to amino acids 50-60, 63-71, 81-90, 118-126, 162-169, 247-255, and 287-295) were synthesized, coupled to bovine serum albumin, and injected into rabbits. Five of these peptides elicited antibodies, and 50-68% binding of the corresponding iodinated peptide was obtained with a 1:25 dilution of antiserum. The antisera titers ranged from 1:5,000 to 1:100,000 when tested by enzyme-linked immunosorbent assay. The same antisera bound 15-65% of labeled pure human renin at a final dilution of 1:2.5, the highest percentage being obtained with peptide 81-90 antiserum. At a 1:5 dilution, the five antisera inhibited renin activity by 23-68% in human plasma with a high renin activity (40 ng of angiotensin I/h/ml). At a final dilution of 1:50, peptide 81-90 antiserum was still capable of producing 25% inhibition. Purified IgG (0.6 mg) from this antiserum inhibited pure human renin activity by up to about 40%, as measured by its reaction with pure synthetic human tetradecapeptide substrate. Antigenic peptides that mimic a part of the human renin sequence, especially peptide 81-90 representing the "flap" covering the cleft between the two renin lobes, constitute promising tools for the development of a synthetic antirenin vaccine.

In the experiments lincomycin hydrochloride LMC "F" with activity 820 UI/mg was used. It was established that in pigs, 5% water solution of LMC "F", applied intramuscularly in doses of 5 and 10 mg/kg m. and internally in doses 50 and 100 mg/kg m., penetrates comparatively quickly in the blood serum, and yet in the first hour established maximal concentrations. Intramuscular injection of LMC "F" of pigs, in doses of 5 and 10 mg/kg m., creates bacteriostatic concentrations in the blood serum for 12 hours, regardless of the quantity of the dose, and applied internally has a longer duration of the retention. The biological half-life of LMC "F" after muscular application in pigs is accordingly 1.7 and 3.5 hours, and after internal application 2.3 and 2.8 hours. Applied a single time intramuscularly in pigs in doses of 5 and 10 mg/kg m., LMC "F" is resorbed from the place of application and after 3 hours is established in most high quantities in the kidney in the lungs, the liver, the bile and in the urine. Mainly it is extracted with the urine in high concentrations--about 190 mg/cm3 (on the 3-rd hour), after intramuscular injection in dose of 10 mg/kg m. The longest time the antibiotic remains in the lungs, the urine and in the bile (up to 96 hours).