Association of dietary pattern and physical activity with lipid-related indices among Chinese population: a cross-sectional study.
To explore the relationship between dietary patterns, physical activity and lipid-related indices in Chinese Population. This study included 21,472 (72.3% men) participants aged 16 to 78 years. Data of anthropometric measurements, biochemical tests and questionnaires were collected through a physical examination. Diet patterns were identified through factor analysis and five patterns were retained ("meat," "high-energy," "high-protein," "healthy" and "traditional Chinese"). Physical activity was classified into low, moderate, or high. Abnormalities in lipid indices were assessed using the Adult Treatment Panel III criterion. Higher factor scores of "high-protein" pattern and "healthy" pattern were found to be related to favorable lipid indices. Quartiles 3 and 4 of "meat" pattern showed increased risks of having elevates total cholesterol and low-density lipoprotein cholesterol concentrations. Participants with higher levels of physical activity showed lowest risk of abnormal lipid profiles. All the associations were equally established among men, while most were no longer significant among women. Higher physical activity level and a dietary pattern consists of high-quality protein foods, vegetables and fruits were associated with favorable lipid profiles, and these lifestyle factors were related to the risk of dyslipidemia in a sex-specific way.


The Presence of Phage Orthologous Genes in Helicobacter pylori Correlates with the Presence of the Virulence Factors CagA and VacA.
The bacterium Helicobacter pylori is associated with ulcers and the development of gastric cancer. Several genes, including cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), are associated with increased gastric cancer risk. Some strains of H. pylori also contain sequences related to bacteriophage phiHP33; however, the significance of these phage-related sequences remains unknown. We assessed the extent to which phiHP33-related sequences are present in 335 H. pylori strains using homology searches then mapped shared genes between phiHP33 and H. pylori strains onto an existing phylogeny. One hundred and twenty-one H. pylori strains contain phage orthologous sequences, and the presence of the phage-related sequences correlates with the presence of CagA and VacA. Mapping of the phage orthologs onto a phylogeny of H. pylori is consistent with the hypothesis that these genes were acquired by horizontal gene transfer. phiHP33 phage orthologous sequences might be of significance in understanding virulence of different H. pylori strains.


Morphologic, biochemical and physiologic alterations in a case of idiopathic hypoalbuminemia (analbuminemia).
A patient with idiopathic hypoalbuminemia is described. A study of albumin kinetics demonstrated slowed albumin degradation suggesting low albumin synthesis. Morphologic observation of hepatocellular alterations suggested decreased protein synthesis. The intra- and extravascular space was low with an abnormally large postural shift of intravascular fluid into the extravascular compartment. Disturbances in the concentration of plasma lipids and of several plasma proteins were detected. The effect of albumin infusion on these physiologic and biochemical abnormalities suggests that most occurred as a secondary response to the hypoalbuminemic state. Evaluation of the patient's kindred revealed no members with hypoalbuminemia.


Batch profiling calibration for robust NMR metabonomic data analysis.
Metabonomic studies involve the analysis of large numbers of samples to identify significant changes in the metabolic fingerprints of biological systems, possibly with sufficient statistical power for analysis. While procedures related to sample preparation and spectral data acquisition generally include the use of independent sample batches, these might be sources of systematic variation whose effects should be removed to focus on phenotyping the relevant biological variability. In this work, we describe a grouped-batch profile (GBP) calibration strategy to adjust nuclear magnetic resonance (NMR) metabolomic data-sets for batch effects either introduced during NMR experiments or samples work-up. We show how this method can be applied to data calibration in the context of a large-scale NMR epidemiological study where quality control samples are available. We also illustrate the efficiency of a batch profile correction for NMR metabonomic investigation of cell extracts, where GBP can significantly improve the predictive power of multivariate statistical models for discriminant analysis of the cell infection status. The method is applicable to a broad range of NMR metabolomic/metabonomic cohort studies.


Apparent noncompetitive inhibition of choline transport in erythrocytes by inhibitors bound at the substrate site.
According to the conventional carrier model, an inhibitor bound at the substrate transfer site inhibits competitively when on the same side of the membrane as the substrate, but noncompetitively when on the opposite side. This prediction was tested with the nonpenetrating choline analog dimethyl-n-pentyl (2-hydroxyethyl) ammonium ion. In zero trans entry and infinite trans entry experiments, where the labeled substrate and the inhibitor occupy the same compartment, the inhibition was competitive, but in zero trans exit it was noncompetitive, in accord with the model. Similar behavior was seen with dimethyl-n-decyl (2-hydroxyethyl) ammonium ion. With this property of the choline transport system established, it becomes possible to estimate the relative affinity inside and outside of inhibitors present on both sides of the membrane. The tertiary amine, dibutylaminoethanol, which enters the cell by simple diffusion, is such an inhibitor. Here the inhibition kinetics were the reverse of those for nonpenetrating inhibitors; zero trans and infinite trans exit was inhibited competitively, and zero trans entry noncompetitively. It follows that dibutylaminoethanol binds predominantly to the inner carrier form.


Establishment and characterization of NCC-GCTB1-C1: a novel patient-derived cancer cell line of giant cell tumor of bone.
Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor, accounting for approximately 5% of all primary bone tumors. GCTB is characterized by unique giant cells. It is also characterized by recurrent mutations in the histone tail of the histone variant H3.3, H3F3A, on chromosome 1, therapeutic implications of which have not been established yet. There are few effective standardized treatments for GCTB, and a novel therapy has long been required. Patient-derived cancer cells have facilitated the understanding of mechanisms underlying the etiology and progression of multiple cancers. Thus far, only 10 GCTB cell lines have been reported, and none of them are publicly available. The aim of this study was to develop an accessible patient-derived cell line of GCTB, which could be used as a screening tool for drug development. Here, we describe the establishment of a cell line, designated NCC-GCTB1-C1, from the primary tumor tissue of a male patient with GCTB on the right distal radius. NCC-GCTB1-C1 cells were maintained as a monolayer culture for over 23 passages for 7 months. These cells exhibited continuous growth, as well as spheroid formation and invasive ability. Using an oncology agent screen, we tested the effect of anticancer drugs on the proliferation of NCC-GCTB1-C1 cells. The cells displayed a remarkable response to romidepsin and vincristine. Thus, we established a novel GCTB cell line, NCC-GCTB1-C1, which could be a useful tool for studying GCTB tumorigenesis and the efficacy of anticancer drugs.


Molecular mechanisms of hepatoprotective effect of tectorigenin against ANIT-induced cholestatic liver injury: Role of FXR and Nrf2 pathways.
Cholestatic liver injury is caused by toxic action or allergic reaction, resulting in abnormality of bile formation and excretion. Few effective therapies have become available for the treatment of cholestasis. Herein, we found that tectorigenin (TG), a natural isoflavone, showed definite protective effects on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury, significantly reversing the abnormality of plasma alanine/aspartate aminotransferase, total/direct bilirubin and alkaline phosphatase, as well as hepatic reactive oxygen species, catalase and superoxide dismutase. Importantly, the targeted metabolomic determination found that BA homeostasis could be well maintained in TG-treated cholestatic mice, especially the levels of glycocholic acid, tauromuricholic acid, taurocholic acid, taurolithocholic acid, tauroursodeoxycholic acid and taurodeoxycholic acid. Overall, primary/secondary and amidated/unamidated bile acid (BA) levels were significantly altered upon ANIT stimulation but could be restored by TG intervention to certain extents. In addition, TG boosted the expression of farnesoid x receptor (FXR), which in turn upregulated multidrug resistance protein 2 (MRP2) and bile salt export pump (BSEP) to accelerate the excretion of BA. Meanwhile, TG enhanced the expression of Nrf2 and its upstream genes PI3K/Akt and downstream target genes HO-1, NQO1, GCLC and GCLM to strengthen the antioxidant capacity. Taken together, TG plays a vital role in maintaining BA homeostasis and ameliorating cholestatic liver injury through regulating FXR-mediated BA efflux and Nrf2-mediated antioxidative pathways.


Advances in Pediatric Gastrostomy Placement.
Placement of gastrostomy tubes in infants and children has become increasingly commonplace. A historical emphasis on use of open gastrostomy has been replaced by less invasive methods of placement, including percutaneous endoscopic gastrostomy and laparoscopically assisted gastrostomy procedures. Various complications, ranging from minor to the more severe, have been reported with all methods of placement. Many pediatric patients who undergo gastrostomy tube placement will require long-term enteral therapy. Given the prolonged time pediatric patients may remain enterally dependent, further quality improvement and education initiatives are needed to improve long-term care and outcomes of these patients.


Comparative effects of ethanol, n-propranol and isopropanol on lipid disposal by rat liver.
Besides ethanol, other aliphatic alcohols such as n-propanol and isopropanol induce a triacylglycerol (TAG) accumulation in the liver. To determine whether a common mechanism is responsible for the effects of these three alcohols on hepatic lipid metabolism, each was administered by gastric tube to female Wistar rats at the dose of 50 mmol/kg body wt. Whichever alcohol was administered, the hepatic triacylglycerol accumulation was found to be related to the duration of elevated blood alcohol concentration. After administration of n-propanol or isopropanol, the liver [14C]palmitate uptake was increased whereas hepatic palmitate oxidation to 14CO2 was impaired and palmitate esterification into TAG enhanced; these perturbations were however more discrete than after ethanol administration. In contrast to ethanol and n-propanol which, at the dose presently used, increase precursor incorporation into blood TAG, isopropanol inhibits this incorporation. Interference with the process of very low density lipoprotein (VLDL) synthesis and/or secretion, which appears only at a late stage of isopropanol intoxication, is probably responsible for the intensity and duration of the fatty liver observed after administration of this alcohol.


Inhibition of nuclear factor-κB enhances the antitumor effect of tumor necrosis factor-α gene therapy for hepatocellular carcinoma in mice.
Hepatocellular carcinoma (HCC) is often resistant to chemotherapy. Gene therapy using an adenoviral vector-expressing tumor necrosis factor (TNF)-α is a new therapeutic approach for chemoresistant malignancies. The efficacy of TNF-α, however, is limited, because it leads to the activation of nuclear factor (NF)-κB. We hypothesized that the NF-κB inhibitor nafamostat mesilate would enhance the antitumor effect of adenovirus vector-mediated TNF-α gene therapy for HCC. In vitro, we assessed the inhibitory effect of nafamostat mesilate on TNF-α-induced NF-κB activation and enhanced apoptosis in human HCC cell lines (Huh-7 and Hep3B). In vivo, we established a xenograft HCC model in mice by subcutaneous injection of Huh-7 and Hep3B cells. The animals received intraperitoneal (IP) injections of nafamostat mesilate 3 times a week (nafamostat mesilate group), intratumoral (IT) injections of the human TNF-α-expressing adenoviral vector (AxCAhTNF-α) once a week (TNF-α group), IT injections of AxCAhTNF-α once a week, or IP injections of nafamostat mesilate 3 times a week (combination group). In the combination group, TNF-α-induced NF-κB activation was inhibited and TNF-α-induced apoptosis was enhanced in comparison with the other groups both in vitro and in vivo. In the combination group, tumor growth was significantly slower and the apoptotic cell numbers were significantly greater than those of the TNF-α group. Inhibition of NF-κB by nafamostat mesilate enhances the antitumor effect of adenoviral vector-mediated TNF-α gene therapy for HCC in mice.


Efficacy of albendazole against Anisakis simplex larvae in vitro.
The growing popularity in western countries of eating uncooked seafood has resulted in an increased incidence of anisakidosis. To study the in vitro activity of different concentrations of albendazole against Anisakis simplex larvae under different media pH. A. simplex larvae were obtained from fresh hakes acquired from the fish market of Madrid. They were divided into groups and placed in culture dishes (15 larvae each) containing RPMI-1640, in the presence or absence of different concentrations of albendazole (300, 400 and 500 microg/mL). Albendazole dose-dependently reduced the survival of the larvae, its maximum activity being at 500 microg/mL when it killed almost all larvae at 48 h. Acidic medium pH significantly reduced the efficacy of albendazole. Albendazole is effective in killing A. simplex larvae at different pH in vitro, suggesting that this molecule could be useful in treating clinical manifestations of human anisakidosis.


Low-density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells.
Smooth muscle cells cultured from the intima of unaffected human aorta accumulate lipids during incubation with the blood serum of patients with coronary heart disease (CHD). Blood sera of most healthy subjects fail to induce the deposition of lipids in cultured cells. Very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins of two subclasses (HDL2 and HDL3) were isolated from the blood of healthy subjects and CHD patients. LDL from the blood of healthy individuals did not raise intracellular lipid levels within 24 hr of cultivation (the maximal concentration used, 1000 micrograms/ml). During the same incubation period, LDL obtained from the blood of CHD patients (200 to 1000 micrograms/ml) caused a 2- to 5-fold rise in cholesteryl esters as well as a 1.5- to 3-fold rise in free cholesterol and triglycerides, whereas intracellular phospholipid levels remained unchanged. There was a direct correlation (r = 0.95) between cholesterol accumulation in the cells incubated with whole sera of CHD patients and cholesterol level in the cells incubated with LDL isolated from these sera. In one of the three cases, the ability to raise the intracellular level of cholesteryl esters was demonstrated by VLDL (500 micrograms/ml) derived from CHD patients' blood. HDL2 and HDL3 did not affect lipid levels in smooth muscle cells cultured from unaffected intima. HDL3 from the blood of CHD patients and healthy subjects (50 to 250 micrograms/ml) reduced cholesteryl ester levels in cells cultured from atherosclerotic plaques 1.5- to 2-fold. HDL2 also decreased the content of cholesteryl esters in plaque cells, though less effectively than HDL3. The data obtained suggest that circulating LDL and, possibly, VLDL in the blood of CHD patients are capable of inducing the accumulation of fat in vascular wall cells.


Pirmenol for control of ventricular arrhythmias: oral dose-ranging and short-term maintenance study.
The antiarrhythmic efficacy and safety of oral pirmenol hydrochloride were assessed during a controlled, dose-ranging and short-term maintenance study in 12 patients with frequent (greater than 480/8 hours) premature ventricular complexes (PVCs). Eleven patients (92%) responded favorably (greater than 70% PVC suppression) to a trial of different doses. Mean interval (8-hour) suppression of PVC frequency was 95% in these 11 and 86% in the entire group. Twenty-four-hour suppression was similar in responders (88%). Repetitive PVCs were essentially eliminated. The mean effective dose was 316 mg/day (105 mg/8 hours). The average predose (trough) plasma concentration at the end of dose ranging was 1.4 micrograms/ml and the drug elimination half-life 7.3 hours (n = 12). Of 11 responding patients, 10 completed a 2-week outpatient trial. Pirmenol continued to be effective and tolerated in 8 patients, maintaining an overall average outpatient PVC suppression of 80%. The electrocardiographic intervals were mildly prolonged after multiple dosing (PR + 7%, QRS + 12%, QTc + 8%; all p less than 0.01). Blood pressure and heart rate did not change during treatment. The echocardiographic ejection fraction was maintained. Thus, oral pirmenol appears to be effective, conveniently administered and well tolerated as an antiarrhythmic agent for control of ventricular extrasystoles.


Neighbourhood Income and Risk of Having an Infant With Concomitant Preterm Birth and Severe Small for Gestational Age Birth Weight.
Socioeconomic position gradients have been individually demonstrated for preterm birth (PTB) at <37 weeks gestation and severe small for gestational age birth weight at <5th percentile (SGA). It is not known how neighbourhood income is related to the combination of PTB and severe SGA, a state reflective of greater placental dysfunction and higher risk of neonatal morbidity and mortality than PTB or severe SGA alone. This population-based study comprised all 1 367 656 singleton live births in Ontario from 2002 to 2011. Multinomial logistic regression was used to estimate the odds of PTB with severe SGA, PTB without severe SGA, and severe SGA without PTB, compared with neither PTB nor severe SGA, in relation to neighbourhood income quintile (Q). The highest income quintile, Q5, served as the exposure referent. Adjusted odds ratios (aORs) were adjusted for maternal age at delivery, parity, marital status, and world region of birth (Canadian Task Force Classification II-2). Relative to women residing in Q5 (2.3 per 1000), the rate of PTB with severe SGA was highest among those in Q1 (3.6 per 1000), with an aOR of 1.34 (95% confidence interval [CI] 1.20-1.50). The corresponding aORs were 1.23 (95% CI 1.09-1.37) for Q2, 1.14 (95% CI 1.02-1.28) for Q3, and 1.06 (95% CI 0.95-1.20) for Q4. Less pronounced aORs were seen for each individual outcome of PTB and severe SGA. Women residing in the lowest-income areas are at highest risk of having a fetus born too small and too soon. Future research should focus on identifying those women most predisposed to combined PTB and severe SGA.


Identification of a suitable layer for injecting calcium hydroxylapatite fillers in the hands.
Hand rejuvenation has become increasingly popular in esthetic medicine. Hand rejuvenation with injectables remains challenging, and there are no established practice guidelines. The calcium hydroxylapatite (CaHA) filler injection is currently one of the most common procedures. This study aimed to identify the layer of the hand dorsum that is lifted by skin pinching and to identify the layer where an injectable filler would be placed based on the anatomical study and ultrasound findings. The anatomic layers of the cadaveric hands were examined using the skin pinching method. Anatomic dissections and histological examinations were performed on four fixed and five fresh cadaveric hands to reveal the anatomical layers in which the CaHA filler was administered. Furthermore, 20 patients were treated with the CaHA filler, and the Doppler ultrasound was used to reveal the proper anatomical layers for filler placement. The study of the cadaveric hands showed that skin pinching can ensure safe entry points and can guide the cannula into safe planes without compromising the large superficial veins. A filler injection with skin pinching in cadaveric hands demonstrated that the filler was introduced primarily in the dorsal intermediate lamina where the veins are present. This was further confirmed by ultrasound findings. The dorsal intermediate lamina, which has the veins is a relatively loose structure, and the cannula was moved along this space. When the layer is stretched by skin pinching, the veins run underneath. The dorsal intermediate lamina is the appropriate layer to inject the filler.


Bacterial NLR-related proteins protect against phage.
Bacteria use a wide range of immune pathways to counter phage infection. A subset of these genes shares homology with components of eukaryotic immune systems, suggesting that eukaryotes horizontally acquired certain innate immune genes from bacteria. Here, we show that proteins containing a NACHT module, the central feature of the animal nucleotide-binding domain and leucine-rich repeat containing gene family (NLRs), are found in bacteria and defend against phages. NACHT proteins are widespread in bacteria, provide immunity against both DNA and RNA phages, and display the characteristic C-terminal sensor, central NACHT, and N-terminal effector modules. Some bacterial NACHT proteins have domain architectures similar to the human NLRs that are critical components of inflammasomes. Human disease-associated NLR mutations that cause stimulus-independent activation of the inflammasome also activate bacterial NACHT proteins, supporting a shared signaling mechanism. This work establishes that NACHT module-containing proteins are ancient mediators of innate immunity across the tree of life.


Histological and microscopy FT-IR imaging study on the proliferative activity and angiogenesis in head and neck tumours.
Micro Fourier transform infrared spectroscopy enables one to study small samples because of the high quality spectra that can be obtained. Biochemical and morphological changes between control and pathological tissues of head and neck tumours have been monitored drawing three-dimensional chemical maps of the main vibrational modes in the regions of interest. Comparison between spectral and histological data shows a satisfactory degree of accordance. Among all, proliferating and regressive states of the tumours can be identified.


A histologic study of regional choroidal dystrophy.
Light and electron microscopy studies of eyes removed from an 84-year-old man after death indicated a normal optic nerve despite severe peripapillary choroidal atrophy. In the area of atrophy, the choriocapillaris, retinal pigment epithelium, and photoreceptors were absent and there was a marked decrease in choroidal arteries and veins. Bruch's membrane was intact except for several breaks in the peripapillary region. Müller cells, in the region of atrophy, produced an aberrant, thick basement membrane either in the outer layers of the neurosensory retina or directly applied to Bruch's membrane. On the basis of this study, we postulate that the primary abnormality in this disease is of the choroidal vasculature.


[Evolution and treatment of storm cytoquine syndrome associated to SARS-CoV-2 infection among octogenarians].
Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.


Jugular phlebectasia.
The most common cause of a mass in the neck that appears only during straining is a laryngocele. However, the rare jugular phlebectasia may present in a similar manner. Dilatation of the internal jugular vein with a Valsalva maneuver suggests a mechanical obstruction in the neck or mediastinum, but the exact cause is still unknown. Nevertheless, dilated internal jugular veins have been excised, as in the case reported here, and found to have thinning of the wall but no associated abnormality.


Monomelic muscle atrophy.
Two patients with slowly progressive muscle atrophy limited to only one leg are reported. They had pes equinovarus deformity and muscle weakness in the affected leg but no symptom in the other limbs. Muscle biopsies from the affected leg showed dystrophic changes consisting of variation in muscle fiber size, endomysial fibrosis, and necrotic and regenerating fibers. Dystrophin was normally expressed at the surface membrane of the muscle fibers. These two patients possibly had a variant of distal muscular dystrophy, though a neural influence could not be completely excluded.


Saphenous neuralgia: a complication of arterial surgery.
The saphenous nerve may be damaged during arterial surgery in the thigh as it emerges through the aponeurotic covering of the adductor canal. A clean cut of the nerve gives rise to anaesthesia, but an incomplete cut or tearing of the nerve, followed by its involvement in scar tissue, leads to saphenous neuralgia--a painful sensation in the area supplied by the nerve. Two hundred and fifty-seven arterial operations involving the course of the saphenous nerve in the thigh have been reviewed. Twenty-six of these operations were complicated by early failure of the arterial procedure necessitating amputation and have not been considered in assessing the incidence of damage to the nerve. One in five superficial femoral thromboendarterectomies and one in nine femoropopliteal bypass grafts were complicated by saphenous neuralgia. Profundaplasty was not followed by this complication. Appreciation of this troublesome symptom should lead to greater care of the nerve during surgery.


Antenatal corticosteroid administration is associated with decreased growth of the fetal thymus: a prospective cohort study.
To examine the effect of antenatal corticosteroid administration (ACS) on fetal thymus growth in women who received ACS compared with gestational-age-matched controls. Fetal thymus size and growth were measured in women at risk for preterm delivery who received ACS and compared with a matched cohort of women who were at low risk for preterm delivery and did not receive ACS. Fetal thymus perimeter and diameter were measured by 2-D ultrasound at baseline and every 2 weeks until delivery. After adjusting for confounders, ACS exposure was associated with a significant reduction in thymus perimeter size (-0.70; 95% CI: -1.33, -0.07; P = 0.03). For every additional week of exposure, thymus growth trajectory was significantly decreased in ACS-exposed fetuses (P = 0.04). The association between ACS and reduced fetal thymus growth should be further examined to establish the impact of ACS on childhood thymus development and immune programming.


P-glycoprotein-170 inhibition significantly reduces cortisol and ciclosporin efflux from human intestinal epithelial cells and T lymphocytes.
To assess the role of P-glycoprotein-170 (P-gp) in transporting cortisol and ciclosporin from human intestinal epithelium and T lymphocytes. The effect of P-gp inhibitors (verapamil, 0-100 microM; PSC 833, 0-20 microM) on the intracellular accumulation of 3H-cortisol and 3H-ciclosporin was studied in confluent layers of human Caco-2 cells (n=6), a P-gp-dependent absorptive intestinal epithelial cell phenotype, and moderately resistant MDRhigh CEM/VBL 100 T cells (n=6). The transport of 3H-vinblastine, a strong multidrug resistance (MDR) substrate, and 3H-progesterone, a poor MDR substrate, was also studied. Caco-2 cells had a 2.4-, 6.6-, 6.7- and 1.03-fold higher net basal to apical transport (efflux) of 3H-cortisol, 3H-ciclosporin, 3H-vinblastine and 3H-progesterone, respectively. PSC 833 (20 microM) reduced cortisol efflux by 69% (0.23 +/- 0.04 to 0.07 +/- 0.01 pmol/cm2/h, P < 0.05) and ciclosporin efflux by 76% (11.1 +/- 1.4 to 2.7 +/- 0.6 pmol/cm2/h, P < 0.001). MDRlow CEM T cells had a 1.4-, 1.9-, 3.2- and 1.02-fold higher intracellular accumulation of cortisol, ciclosporin, vinblastine and progesterone than MDRhigh CEM/VBL 100 T cells. Increasing concentrations of PSC 833 (> 0.1 microM) and verapamil (> 1 microM) restored the intracellular level of 3H-cortisol and 3H-ciclosporin in MDRhigh CEM/VBL 100 T cells to that of MDRlow CEM cells with little change in accumulation in the MDRlow parental cell line. P-gp inhibitors significantly increase intracellular cortisol and ciclosporin levels in human intestinal epithelium and T lymphocytes in a dose-dependent manner, demonstrating a potential mechanism for overcoming poor response to immunosuppressant therapy in refractory inflammatory bowel disease.


Correlation between clarithromycin resistance, virulence factors and clinical characteristics of the disease in Helicobacter pylori infected patients in Shahrekord, Southwest Iran.
The purpose of this study was to determine the mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from biopsy samples that were collected from the endoscopic ward of Shahrekord Hajar teaching Hospital and also to study the frequency of virulence factor and their correlation and pathological findings with clarithromycin resistance during the years 2019-2020. In this cross-sectional descriptive study, 152 patients with Helicobacter pylori infection were considered, and then, two common A2142G and A2143G mutations in the 23SrRNA gene associated with resistance were analyzed by Real-time PCR (Taq man). The presence of vacA, iceA1, iceA2, cagA, babA2, and oipA virulence genes was investigated by PCR and electrophoresis in 8% polyacrylamide gel. Then, data were analyzed using the relevant statistical tests. In this study, the frequency of Helicobacter pylori was 76% and the frequency of mutant isolates was 57.2%. The frequencies of A2142G and A2143G point mutations were 42.1% and 28.3%. There was a significant correlation among oipA, vacA, and iceA1 virulence factors, type of disease, chronic inflammatory score, and glandular atrophy with the antibiotic resistance to clarithromycin. There was no significant correlation between the age and sex of the patients with antibiotic resistance. According to the results of this study, it seems that the use of clarithromycin to combat this bacterium should be limited.


DNA Markers, Pathogenicity Test, and Multilocus Sequence Analysis to Differentiate and Characterize Cereal-Specific Xanthomonas translucens Strains.
Xanthomonas translucens contains a group of bacterial pathogens that are closely related and have been divided into several pathovars based on their host range. X. translucens pv. undulosa (Xtu) and X. translucens pv. translucens (Xtt) are two important pathovars that cause bacterial leaf streak disease on wheat and barley, respectively. In this study, DNA markers were developed to differentiate Xtu and Xtt and were then used to characterize a collection of X. translucens strains with diverse origins, followed by confirmation and characterization with pathogenicity tests and multilocus sequence analysis/typing (MLSA/MLST). We first developed cleaved amplified polymorphic sequence markers based on the single-nucleotide polymorphisms within a cereal pathovar-specific DNA sequence. In addition, two Xtt-specific markers, designated Xtt-XopM and Xtt-SP1, were developed from comparative genomics among the sequenced Xtt/Xtu genomes. Using the developed markers, a collection of X. translucens strains were successfully identified as Xtu or Xtt. Pathogenicity tests on wheat and barley plants and MLSA of four housekeeping genes validated the pathovar assignation of those strains. Furthermore, MLSA revealed distinct subclades within both Xtu and Xtt groups. Seven and three sequence types were identified from MLST for Xtu and Xtt strains, respectively. The establishment of efficient Xtt/Xtu differentiation methods and characterization of those strains will be useful in studying disease epidemiology and host-pathogen interactions and breeding programs when screening for sources of resistance for these two important bacterial pathogens.


Association Between Serum Albumin and Hospital-Acquired Infections After Aneurysmal Subarachnoid Hemorrhage.
Low serum albumin levels have been identified as a predictor of infectious complications in critically ill patients. However, the association in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We aimed to evaluate the prognostic value of hypoalbuminemia using blood samples at admission in patients with aSAH. In a multicenter observational study of patients with aSAH, serum albumin counts were collected on admission. Hypoalbuminemia was defined as a total albumin level < 35 g/L. Multivariable logistic regression analyses and propensity score matching were performed to obtain the adjusted odds ratios (ORs) with 95% confidence intervals (CI) for the primary outcome of hospital-acquired infections. A total of 5448 patients were included in the observational cohort study. The odds of hospital-acquired infections were significantly higher in patients with albumin levels 30-34.9 g/L (OR 1.62, 95% CI 1.38-1.90), 25-29.9 g/L (OR 1.97, 95% CI 1.54-2.51), and < 24.9 g/L (OR 2.43, 95% CI 1.53-3.86) compared with patients with albumin level ≥ 35 g/L. The odds of hospital-acquired infections with a change in albumin levels from admission to 48-72 h later of lower than - 10 g/L and - 10 to - 5 g/L were 1.67 (95% CI 1.41-1.86) and 1.24 (95% CI 1.05-1.46), respectively, compared with a change in albumin levels of - 5 to 5 g/L. In this large study of matched patients with aSAH, hypoalbuminemia at admission was associated with hospital-acquired infections. A decrease in serum albumin levels within 72 h of admission was associated with higher hospital-acquired infections.


The relation between umbilical cord tissue prostaglandin E2 levels, mode of onset of labour, fetal distress and method of delivery.
The tissue concentrations of prostaglandin E2 (PGE2) were measured by radioimmunoassay in components of the umbilical cord. The levels were significantly higher in the walls of arteries than in non-vascular tissue from the umbilical cord. The highest values were found after emergency Caesarean sections and the lowest after induced ending in normal delivery. The use of forceps and the presence of fetal distress were both associated with significantly raised tissue concentrations of PGE2.


Fetal cricotracheal manipulation: effects on airway healing, cricoid growth and lung development.
The last decade has seen significant advance in the surgical management of pediatric subglottic stenosis, which remains one of the most fascinating problems of the laryngotracheal complex (LTC). Refined techniques for operating on these fragile structures should reduce cricotracheal scarring to a minimum, thus avoiding a lot of severe postoperative complications in a tricky moment of laryngeal's growing up. Experimental works indicates that the LTC growth is variously affected by longitudinal anterior, posterior or lateral incisions and actually the indications for laringotracheoplasty or cricotracheal resection in children with subglottic stenosis are still unclear. Reports on fetal manipulation of cricotracheal tissues are lacking as well as early effects on airway healing, LTC growth and lung development. The aim of this study was to evaluate if the airway mucosal healing is regenerative and scarless after cricotracheal manipulation in fetuses of New Zealand White Rabbits (NZWRFs). The consequences of fetal incisions on the cricoid growth and lung development are also examined, in a group of 12 NZWRFs, manipulated at 25+/-1 days of gestational age. The does underwent halothane anesthesia and all received a bilateral longitudinal cricoidotracheotomy. Twenty sham-operated fetuses were submitted to a limited cervicotomy (control's group). At the time of retrieval (31+/-0.5 days), en bloc laryngotracheobronchial tree and lungs were collected and processed for histological and morphometric analysis. Parameters recorded included: 1) histological full-thickness examinations focusing on inflammation, foreign body reaction, fibrosis, neochondrogenesis; 2) morphometric analysis, including the fetal Subglottic Diameter (FSD), the fetal Subglottic Area (FSA), the Radial Alveolar Count (rAC) and Computer Assisted Morphometric Colorimetry (CAmc); 3)analysis of lung hypoplasia (LH) by means of lung weight/body weight (LW/BW) ratio, protein and DNA indexes; 4) finally, different fractions of lung tissue phospholipids for lung maturity assessment were studied. Student's t test, when indicated, was performed for statistical analysis (p <0.05 = significant). There was no maternal mortality in this study. Ten fetuses were available for a final evaluation (16.6% mortality). In one case only, an incomplete closure of the fetal cricoidotomy was seen and could be probably due to a technical mistake. Mean fetal subglottic diameter and area were respectively 0.13+/-0.05 mm and 3.15+/-0.45 mm2 in both groups. As well as in fetal dermal repair, regeneration of the airway cartilage and mucosa were complete and scarless. LW/BW ratio, DNA content and analysis of different fractions of phospholipids were similar in experimental vs. the control group. These findings suggest that the healing processes were fibrosis-free and without evidence of scars. A complete closure of the incisions was achieved without stenosis of the fetal subglottic region. In addition, it seems that the fetal cricoidotracheotomy doesn't interfere with the laryngeal function which coordinate the amount of liquid leaving the lungs via the trachea. In addition, only a small leakage of amniotic fluid is shown and this could be responsible for normal and mature lungs.


Molecular cloning of the BCL-6 gene, a transcriptional repressor for B-cell differentiation, in torafugu (Takifugu rubripes).
B-cell lymphoma-6 (BCL-6) is a transcriptional repressor that prevents the terminal differentiation of mature B-cells to plasma cells, and is essential for germinal center formation in the primary lymphoid organs of mammals. In this study, we identified the BCL-6 gene in torafugu (Takifugu rubripes) using the torafugu genome database, and analyzed the expression of BCL-6 mRNA in various tissues of torafugu, using RT-PCR. The BCL-6 gene consisted of eight exons and seven introns spanning a genome of ca. 3.3 kb. BCL-6 mRNA contained a 2112 bp open reading frame encoding 703 amino acids, with a predicted protein size of 78.8 kDa. The predicted torafugu BCL-6 primary structure contains two conserved specific motifs, the BTB/POZ domain at the N-terminus and the sixC2H2-type zinc finger motifs at the C-terminal region. The homology of torafugu BCL-6 to those of zebrafish (Danio rerio), Xenopus laevis, mouse (Mus musculus) and human (Homo sapiens) is 76, 59, 60 and 60%, respectively. RT-PCR analysis revealed that BCL-6 mRNA is highly expressed in pronephros, thymus, intestine, ovary, brain, nasal cavity and muscle. These results imply that torafugu BCL-6 is involved in regulation of B-cell differentiation in torafugu.


Depression of diaphragmatic and external intercostal muscle activities elicited by stimulation of midpontine dorsal tegmentum in decerebrate cats.
This paper describes the inhibitory influences on external intercostal muscle activity and diaphragmatic activity, evoked by stimulation of the dorsal tegmental field (DTF) of the pons in decerebrate cats. Stimulation of the DTF along the midline decreased both the diaphragmatic and the external intercostal activities. However, the inhibitory influences on the above two kinds of respiratory muscle activities were different in nature. Diaphragmatic activity, once suppressed by stimulation, recovered in spite of the continuation of stimulation. In contrast, DTF stimulation depressed tonic discharges of external intercostal muscle, and the depressed or abolished tonic discharges did not resume even after termination of stimulation. Rhythmic external intercostal muscle activity, synchronized with diaphragmatic activity, was also suppressed by DTF stimulation and the suppressed rhythmic activity seemed difficult to recover during stimulation, compared with the recovery process of the diaphragmatic activity.


Structural and functional insights into the major mutations of SARS-CoV-2 Spike RBD and its interaction with human ACE2 receptor.
Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world jeopardizing the global economy and health. The rapid proliferation and infectivity of the virus can be attributed to many accumulating mutations in the spike protein leading to continuous generation of variants. The spike protein is a glycoprotein that recognizes and binds to cell surface receptor known as angiotensin-converting enzyme 2 (ACE2) leading to the fusion of the viral and host cell membranes and entry into the host cells. These circulating variants in the population have greatly impacted the virulence, transmissibility, and immunological evasion of the host. The present study is aimed at understanding the impact of the major mutations (L452R, T478K and N501Y) in the receptor-binding domain (RBD) of spike protein and their consequences on the binding affinity to human ACE2 through protein-protein docking and molecular dynamics simulation approaches. Protein-protein docking and Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) binding free energy analysis reveal that the spike mutants-L452R, T478K and N501Y have a higher binding affinity to human ACE2 as compared to the native spike protein. The increase in the number of interface residues, interface area and intermolecular forces such as hydrogen bonds, salt bridges and non-bonded contacts corroborated with the increase in the binding affinity of the spike mutants to ACE2. Further, 75 ns all-atom molecular dynamics simulation investigations show variations in the geometric properties such as root mean square deviation (RMSD), radius of gyration (Rg), total solvent accessible surface area (SASA) and number of hydrogen bonds (NHBs) in the mutant spike:ACE2 complexes with respect to the native spike:ACE2 complex. Therefore, the findings of this study unravel plausible molecular mechanisms of increase in binding affinity of spike mutants (L452R, T478K and N501Y) to human ACE2 leading to higher virulence and infectivity of emerging SARS-CoV-2 variants. The study will further aid in designing novel therapeutics targeting the interface residues between spike protein and ACE2 receptor.


Organization of the dorsal lateral geniculate nucleus in a cat with congenital microphthalmia.
The effects of congenital monocular microphthalmia on the development of the lateral geniculate nucleus were examined in a 10-week-old cat. The left eye and optic nerve in this animal appear normal. The right eye is about 30% smaller in volume than the left and the optic nerve from this eye has a cross-sectional area that is only 15% that of the left. In addition, this nerve contains few, if any, large myelinated axons. Both lateral geniculate nuclei are abnormal and the abnormality differs rostrally and caudally. The caudal portion most closely resembles the normal nucleus. Retinal input from both eyes is segregated into cellular laminae that are separated from each other by cell sparse interlaminar zones. However, the input from the microphthalmic eye seems to be sparse and patchy and it does not support normal cell growth. All neurons, including glutamic acid decarboxylase-positive (GAD+) neurons, in laminae innervated by the small eye are reduced in size in a pattern similar to that seen following the removal of retinal input. In comparison, the rostral portion of the nucleus receives very little input from the microphthalmic eye. Instead the normal eye densely innervates nearly the entire nucleus. In this region, interlaminar zones fail to form but the input from the normal eye is able to support cell growth including the growth of GAD+ neurons.


Assessment of Dimensional Changes in Submandibular Glands in Head-Neck Radiotherapy Patients by Ultrasonography.
The present study investigated the dimensional changes in the submandibular glands following radiotherapy using ultrasonography. Twenty-three patients planned to receive head-neck radiotherapy were included in this study. The anteroposterior, superoinferior, mediolateral length, and volumes of 46 submandibular glands were measured by ultrasonography at 3 different time periods (before radiotherapy and in the second and sixth months after the radiotherapy onset) and evaluated in terms of dimensional changes and the effect of the radiation dose on these changes. The data were statistically analyzed using repeated measures analysis of variance (ANOVA) and 2-factor repeated measures ANOVA. Before radiotherapy and in the second and sixth months after the radiotherapy onset, mean anteroposterior length of the submandibular glands was 32.39 ± 4.55, 30.38 ± 4.80, and 31.50 ± 3.68 mm, respectively; mean superoinferior length was 9.96 ± 1.54, 8.76 ± 1.26, and 9.08 ± 1.01 mm, respectively; mean mediolateral length was 24.66 ± 3.77, 22.03 ± 3.73, and 21.76 ± 4.01 mm, respectively; and mean volume was 4.21 ± 1.01, 3.08 ± 0.77, and 3.32 ± 0.63 cm3 , respectively. Moreover, there were significant differences in the anteroposterior (P < .01), superoinferior (P < .001), and mediolateral lengths (P < .001), as well as the volumes (P < .001) of the submandibular glands measured at the 3 different time periods. In the second and sixth months after the radiotherapy onset, the sizes of the submandibular glands were markedly reduced, but it partially recovered to normal as more time elapsed after radiotherapy.


Brownian dynamics simulations of interactions between aldolase and G- or F-actin.
Compartmentation of proteins in cells is important to proper cell function. Interactions of F-actin and glycolytic enzymes is one mechanism by which glycolytic enzymes can compartment. Brownian dynamics (BD) simulations of the binding of the muscle form of the glycolytic enzyme fructose-1,6-bisphosphate aldolase (aldolase) to F- or G-actin provide first-encounter snapshots of these interactions. Using x-ray structures of aldolase, G-actin, and three-dimensional models of F-actin, the electrostatic potential about each protein was predicted by solving the linearized Poisson-Boltzmann equation for use in BD simulations. The BD simulations provided solution complexes of aldolase with F- or G-actin. All complexes demonstrate the close contacts between oppositely charged regions of the protein surfaces. Positively charged surface regions of aldolase (residues Lys 13, 27, 288, 293, and 341 and Arg 257) are attracted to the negatively charged amino terminus (Asp 1 and Glu 2 and 4) and other patches (Asp 24, 25, and 363 and Glu 361, 364, 99, and 100) of actin subunits. According to BD results, the most important factor for aldolase binding to actin is the quaternary structure of aldolase and actin. Two pairs of adjacent aldolase subunits greatly add to the positive electrostatic potential of each other creating a region of attraction for the negatively charged subdomain 1 of the actin subunit that is exposed to solvent in the quaternary F-actin structure.


Endotoxemia in the neonatal lamb.
Although gram-negative sepsis is a major cause of neonatal morbidity and mortality, our understanding of endotoxemia in the neonate has been hampered by the lack of experimental models. Previous studies have suggested neonatal hyporesponsiveness to endotoxin. We studied unanesthetized neonatal lambs which had been exposed to the environment prior to study. These animals demonstrated the classic early phase changes of endotoxemia including pulmonary hypertension which was dependent upon prostanoid production. This model allows further studies of endotoxemia in the neonate.


Matrix effects in the gas chromatographic-mass spectrometric determination of brominated analogues of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone.
Brominated analogues (BMXs) of the strong drinking water mutagen MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) were found to be subject to strong matrix induced chromatographic response enhancement effects. We evaluated different ways to reduce errors in quantification including comparison of gas chromatographic inlet systems, improved clean up of sample extracts, and preparation of calibration standards in the sample matrix. The best quantitative accuracy and long term performance were achieved when the calibration standards were prepared in sample matrix, samples were cleaned up with C18-resin in conjunction with solid phase extraction (SPE) with Oasis HLB cartridges, and gas chromatography with PTV splitless injection was used. This method enables the determination of MX and BMXs from 500 ml water sample with quantitation limits of 1 ng/l or less.


Wilson's disease. Update of a systemic disorder with protean manifestations.
In Wilson's disease, a genetic defect in a copper transporter causes defective incorporation of copper into apo-ceruloplasmin and the failure to excrete copper into bile. Copper accumulated in hepatocytes generates damage via reactive oxygen species. Release of copper from necrotic hepatocytes leads to damage of other tissues, including the brain, urinary tract, red blood cells, heart, endocrine glands, skin, pancreas, bones, and joints. Treatment is designed to chelate the excess copper for urinary excretion, prevent copper absorption, and render tissue copper nontoxic. Liver transplantation, with replacement of the defective hepatic gene, may be necessary in some cases.


Once bitten, twice incised: recurrent gallstone ileus.
Uncommon causes of small bowel obstruction can provide interesting surgical decision-making challenges. This report describes a patient with recurrent gallstone ileus. According to most current reviews, erring on the side of enterolithotomy alone as the treatment of choice for gallstone ileus appears to be the most appropriate decision. Although a rare scenario, the situation of recurrent gallstone ileus presents an interesting learning opportunity. It is important to keep in mind the need for complete examination of the abdomen. Furthermore, evacuation of any remaining stones from the gallbladder is imperative if possible. Erring on the side of enterolithotomy alone as the treatment of choice for gallstone ileus has been shown to be a safe and effective treatment decision over a single-stage removal of the stone with closure of the cholecystoduodenostomy.


Intraperitoneal meropenem for peritoneal dialysis peritonitis with Serratia marcescens immediately on commencing dialysis.
A 67-year-old man developed Serratia marcescens peritonitis within a week of commencing peritoneal dialysis. Dialysate cultures isolated multidrug-resistant S. marcescens, which was treated with intraperitoneal meropenem. This unusual case highlights the problem of multidrug-resistant peritoneal dialysis infections and the potential viability of intraperitoneal meropenem as ambulatory peritonitis therapy.


Treatment of experimental brain tumors with trombospondin-1 derived peptides: an in vivo imaging study.
Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides derived from the type 1 repeats of thrombospondin (TSP1) were studied in rodent C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular parameters, we employed in vivo magnetic resonance (MR) imaging and corroborated results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac, n=13) or a control peptide (D-reverse amKRAKQAGGASHASPASSac, n=12) at 10 mg/kg, administered either intravenously or through subcutaneous miniosmotic pumps starting 10 days after tumor implantation. Eleven days later, the effect of peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7+/-44.2 mm3, n=7) and C6 tumors (41.3+/-34.2 mm3, n=6) were significantly smaller than tumors treated with control peptide (9L: 215.7+/-67.8 mm3, n=6; C6: 184.2+/-105.2 mm3, n=6). In contrast, the in vivo vascular volume fraction, the mean vascular area (determined by microscopy), and the microvascular density of tumors were not significantly different in any of the experimental groups. In cell culture, TSP1, and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6 with an IC of 45 nM for TSP1. These results indicate that TSP1-derived peptides retard brain tumor growth presumably as a result of slower de novo blood vessel formation and synergistic direct antiproliferative effects on tumor cells. We also show that in vivo MR imaging can be used to assess treatment efficacy of novel antiangiogenic drugs non-invasively, which has obvious implications for clinical trials.


Polymorphism of human salivary amylase: a preliminary communication.
Variation of human salivary amylase isoenzymes was investigated by isoelectric focusing on thin-layer polyacrylamide gel. Preliminary studies indicate a genetic polymorphism.


Water distillation modeling by disjoint CNT-based channels under the influence of external electric fields.
Using molecular dynamics method, the ion rejection and water flow inside flexible disjoint carbon-based channels were examined in the presence of electric fields. The effects of the carbon nanotube diameters and field magnitude on the nano-channel efficiency were investigated. It was observed that water flow through the filter was modified by increasing the radius of nanotubes, while the salt rejection was reduced. The particles' behaviors inside the channel were described in view of Van der Waals interactions between the water molecules, ions, and carbon atoms. Furthermore, the results indicated that the ion rejection and water flow were increased under the application of proper magnitude of electric fields. Graphical abstract Using MD simulation method, a disjoint CNT-based filter was designed to produce freshwater from a NaCl solution by the aid of external electric field. It was observed that the filter operation was significantly affected by channel structural parameters and amount of applied electric fields.


Time Required for Planned and Unplanned Episodes of Care in Aseptic Hip and Knee Revision Arthroplasty.
Studies indicate aseptic revision total hip arthroplasty (rTHA) and revision total knee arthroplasty (rTKA) requires much more effort but is reimbursed less than primary procedures per minute work time. This study quantified planned and unplanned work performed by the surgeon and/or their team during the entire episode of care "reimbursement window" and compared it to allowed reimbursement times by Centers for Medicare and Medicaid Services (CMS). Between October, 2010, and December, 2020, all unilateral aseptic rTHA and rTKA procedures performed by a single surgeon at a single institution were retrospectively reviewed. Time dedicated to planned work was calculated from surgery scheduling to 90 days postoperative. Impromptu patient inquiries and treatments after discharge but within the episode of care, involving the surgeon/surgeon team constituted unplanned work. Planned and unplanned work minutes were summed and divided by the number of patients reviewed to obtain average minutes of work per patient. Work time was compared to CMS allowable times for rTHA (617 minutes) and rTKA (520 minutes). There were 292 Aseptic rTKA and 63 aseptic rTHA procedures included. Based upon CMS allowable times per patient there were a mean of 4.4 hours (267 minutes) of uncompensated care time per rTKA patient and a mean of 2.4 hours (141 minutes) of uncompensated care time per rTHA patient. Aseptic revisions are substantially more complex than primaries, requiring work effort that is not commensurate with current reimbursements. Financially disincentivizing surgeons to care for patients requiring revision surgery could reduce patient access to care when high quality care is needed the most.


Molecular characterization and association analysis of porcine interferon regulatory factor 1 gene.
Interferon regulatory factor 1 (IRF1) is a member of IRF-family that was discovered to activate promoters in type I interferon (IFN) genes. It is shown to play functionally diverse role in the regulation of the immune system. In this report, the porcine IRF1 cDNA were cloned and a 7500 bp genomic DNA structure was identified. The putative IRF1 protein included 322 amino acids. Alignment and phylogenetic analysis of the predicted porcine IRF1 amino acids sequence with its homologies of other species show high identity (over 88%). Tissues expression of IRF1 mRNA was observed by RT-PCR, the results revealed IRF1 gene expressed widely in all analyzed tissues. Using the radiation hybrid panel, the porcine IRF1 gene was mapped to porcine chromosome 2 and closely linked to the locus IL4 (LOD = 7.09, 57cR). A SNP in exon2 of porcine IRF1 gene was demonstrated by sequencing and PCR-RFLP analysis. The further association analysis indicated that the SNP was significant associate with level of IFN-γ (day 20) in serum (P = 0.0001) and the ratio of IFN-γ to IL10 (day 20; day 35) in serum (P = 0.0165; P = 0.0095). The results suggested that the porcine IRF1 gene is strong candidate gene for these immune traits in pig.


Pancreatic granular cell tumor combined with carcinoma in situ.
A 58-year-old man was treated for a granular cell tumor (GCT) of the pancreas; a very rarely occurring tumor. The patient, who had been followed for 6 years due to alcoholic hepatitis, chronic pancreatitis and elevated carcinoembryonic antigen (CEA) levels from smoking, was admitted to our hospital for evaluation of back pain, diarrhea and constipation. The patient was diagnosed as having pancreatic head cancer using clinical imaging studies, and a pylorus-preserving pancreatico-duodenectomy was done. In the resected specimen, a white tumor measuring 13 mm in diameter was observed at the pancreatic head, and there was marked fibrous change surrounding the tumor. The microscopic appearance of the pancreas showed atrophy of acinar cells, fibrosis, and dilatation of the main pancreatic duct (MPD). Within the tumor were oval cells with low-grade atypia and an increased number of diffuse eosinophilic granules. Neither mitosis nor invasive findings were observed. Periodic acid-Schiff staining and immunohistochemical staining for the S-100 protein were positive, thus the tumor was diagnosed as a benign GCT. In addition, carcinoma in situ was found at the dilated MPD. Therefore, this patient was diagnosed as having GCT with carcinoma in situ of the pancreas. To the best of our knowledge, this is only the fourth case of GCT of the pancreas to be reported.


Dehydration and Rehydration Mechanisms of Pharmaceutical Crystals: Classification Of Hydrates by Activation Energy.
Dehydration strongly influences the stability of hydrate drug substances. Consequently, the ability to predict dehydration of crystalline hydrate using the intermolecular interactions of water molecules contained in the crystals is essential for drug development. The conventional method employed to predict the propensity for dehydration uses the dehydration temperature, which is related to how tightly water molecules are bound in the crystal lattice. However, it is difficult to predict the dehydration propensity of a particular hydrate using only the dehydration temperature because other kinetic factors affect dehydration behavior, such as intermolecular interactions, and drug-substance-to-water molar ratio in a hydrate. In this study, we explored the use of the dehydration activation energy Ea and rehydration behavior to classify 11 pharmaceutical hydrates into three classes according to their kinetic behavior related to the thermodynamic factors of hydrates. There is good agreement between these classes and hydrate crystal structures determined from single-crystal X-ray diffraction, and thus, the classification reflects their crystal structural features. We compared Ea to the dehydration temperatures for each class and found that Ea plays a crucial role and is better than the temperature for quantitative differentiation of the dehydration propensities in these hydrates.


Examining tensions in the past and present uses of concepts.
Examining tensions between the past and present uses of scientific concepts can help clarify their contributions as tools in experimental practices. This point can be illustrated by considering the concepts of mental imagery and hallucinations: despite debates over their respective referential reliabilities remaining unresolved within their interdependent histories, both are used as independently stable concepts in neuroimaging experiments. Building on an account of how these concepts function as tools structured for pursuit of diverging goals in experiments, this paper explores this tension by re-examining the continued reliance of each concept on inverse characterisations inherited from the nominally-discarded 'mediator-view' of sensory-like mental phenomena (SLMP). In doing so, I seek to demonstrate how examining unresolved tensions can help highlight that entrenched associations can remain both integral to, and obscured by, the uses of concepts as goal-directed tools within experimental practices.


Fifteen years follow-up of photorefractive keratectomy up to 10 D of myopia: outcomes and analysis of the refractive regression.
To evaluate outcomes of photorefractive keratectomy up to -10.00 D of myopia and -4.50 of astigmatism and to develop a predictive model for the refractive changes in the long term. Vissum Corporation and Miguel Hernandez University (Alicante, Spain). Retrospective-prospective observational series of cases. This study included 33 eyes of 33 patients aged 46.79±7.04 years (range 40-57) operated with the VISX 20/20 excimer laser with optical zones of 6 mm. No mitomycin C was used in any of these cases. The minimum follow-up was 15 years. The main outcome measures were: uncorrected and corrected distance visual acuity, manifest refraction and corneal topography. Linear regression models were developed from the observed refractive changes over time. Safety and efficacy indexes at 15 years were 1.18 and 0.83, respectively. No statistically significant differences were detected for any keratometric variable during the follow-up (p≥0.103). 15 years after the surgery 54.55% of the eyes were within ±1.00 D of spherical equivalent and 84.85% within ±2.00 D. The uncorrected distance visual acuity at 15 years was 20/25 or better in 60.6% of the eyes and 20/40 or better in 72.73% of the eyes. The correlation between the attempted and the achieved refractions was r=0.948 (p<0.001) at 1 year, and r=0.821 (p<0.001) at 15 years. No corneal ectasia was detected in any case during the follow-up. Photorefractive keratectomy is a safe refractive procedure in the long term within the range of myopia currently considered suitable for its use, although its efficacy decreases with time, especially, in high myopia. The model developed predicts a myopic regression of 2.00 D at 15 years for an ablation depth of 130 µm.


The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.
Inborn errors of metabolism (IEMs) often result from single-gene mutations and collectively cause liver dysfunction in neonates leading to chronic liver and systemic disease. Current treatments for many IEMs are limited to maintenance therapies that may still require orthotropic liver transplantation. Gene therapies offer a potentially superior approach by correcting or replacing defective genes with functional isoforms; however, they face unique challenges from complexities presented by individual diseases and their diverse etiology, presentation, and pathophysiology. Furthermore, immune responses, off-target gene disruption, and tumorigenesis are major concerns that need to be addressed before clinical application of gene therapy. The current treatments for IEMs are reviewed as well as the advances in, and barriers to, gene therapy for IEMs. Attention is then given to ex vivo and in vivo gene therapy approaches for hereditary tyrosinemia type 1 (HT1). Of all IEMs, HT1 is particularly amenable to gene therapy because of a selective growth advantage conferred to corrected cells, thereby lowering the initial transduction threshold for phenotypic relevance. It is proposed that not only is HT1 a safe indication for gene therapy, its unique characteristics position it to be an ideal IEM to develop for clinical investigation.


Diurnal changes in chlorophylla fluorescence and carotenoid composition inOpuntia ficus-indica, a CAM plant, and in three C3 species in Portugal during summer.
Diurnal changes in chlorophylla fluorescence were determined in four species, differing in life form, in Portugal during the summer of 1989. These includedOpuntia ficus-indica, a CAM plant, andHelianthus annuus, Ficus carica andArbutus unedo, three C3 species. Steady state fluorescence yield,F S, and maximum fluorescence yield,F M', were determined at different times of the day. Using the model of Genty et al. (1989), the photon use efficiency of photosystem II electron transport,φ e, was calculated from (F M'-F S)/F M'. Diurnal changes in relative rate of non-cyclic electron transport through photosystem II,J e, were derived by multiplyingφ e by the incident photon flux density (PFD). WhenJ e, determined for each species for various points in time throughout the day, was plotted against corresponding values of PFD, the light response curves obtained showed thatJ e was linearly dependent on PFD in low light and approached saturation in high light. The highest values ofJ e were observed inHelianthus annuus, followed byOpuntia ficus-indica, Ficus carica andArbutus unedo. The proportion of the xanthophyll zeaxanthin to total carotenoids, determined around noon, was inversely related to maximum rates ofJ e.


Bilateral hypothenar hammer syndrome: an unusual and preventable cause of digital ischemia.
Unilateral ischemia of hand digits is usually caused by thoracic outlet obstruction, arterial emboli from a cardiac source, or atherosclerosis. The case of a metal press worker with unilateral ischemia due to hypothenar hammer syndrome, a condition caused by the repetitive use of the hypothenar eminence as a hammer with resultant damage to the ulnar artery, is described. Most such patients present with unilateral ischemia in the ulnar artery distribution of the dominant hand. This patient had used both hands repeatedly to pound the edges of large steel plates and presented with nondominant-hand ischemia, but was found to have the syndrome bilaterally by angiography. The distinctive features of this syndrome, a preventable and treatable cause of digital ischemia, are emphasized.


Signal transduction pathways of group I metabotropic glutamate receptor-induced long-term depression at sensory spinal synapses.
Activation of spinal group I metabotropic glutamate receptors (mGluRs) may have antinociceptive or pro-nociceptive effects in different pain models. Pharmacological activation of group I mGluRs leads to long-term depression (LTD) of synaptic strength between Adelta-fibers and neurons in lamina II of spinal dorsal horn of the rat. Here, we studied the signal transduction pathways involved. Synaptic strength between Adelta-fibers and lamina II neurons was assessed by perforated whole-cell patch-clamp recordings in a spinal cord-dorsal root slice preparation of young rats. Bath application of the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine [(S)-3,5-DHPG] produced an LTD of Adelta-fiber-evoked responses. LTD induction by (S)-3,5-DHPG was prevented, when intracellular Ca(2+) stores were depleted by thapsigargin or cyclopiazonic acid (CPA). Preincubation with ryanodine to inhibit Ca(2+)-induced Ca(2+) release had no effect on LTD-induction by (S)-3,5-DHPG. In contrast, pretreatment with 2-aminoethoxydiphenyl borate (2-APB), an inhibitor of inositol-1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) stores prevented LTD induction. Preincubation with the specific protein kinase C (PKC) inhibitors bisindolylmaleimide I (BIM) or chelerythrine, respectively, had no effect. Inhibition of L-type VDCCs by verapamil or nifedipine prevented LTD-induction by (S)-3,5-DHPG. The presently identified signal transduction cascade may be relevant to the long-term depression of sensory information in the spinal cord, including nociception.


Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment.
We have demonstrated that seizures induced by kainic acid (KA) are, at least in part, mediated via oxidative stress in rats [Life. Sci. 61 (1997) PL373; Brain Res. 853 (2000) 215; Brain Res. 874 (2000) 15; Neurosci. Lett. 281 (2000) 65]. In order to extend our findings, we employed the rodent aging model in this study. After KA treatments (once a day for 5 days; 20,20,20,20 and 40 mg/kg, i.p.), several parameters reflecting neurotoxic behaviors, oxidative stress [malondialdehyde (MDA) and protein carbonyl] and aging (lipofuscin-like substances) were compared between senile-prone (P8) and resistant (R1) strains of 9-month-old male senescence-accelerated mice (SAM). KA-induced neurotoxic signs as shown by mortality and seizure activity were more accentuated in the SAM-P8 than in the SAM-R1. Levels of MDA and carbonyl are consistently higher in the hippocampus of SAM-P8 than that of SAM-R1. Significant increases in the values of MDA and carbonyl were observed 4 h or 2 days after the final KA administration. This finding was more pronounced in the SAM-P8 than in the SAM-R1. Although a significant loss of hippocampal neurons was observed 7 days post-KA, at this time the MDA and carbonyl content had returned to near control levels. In contrast, fluorescent lipofuscin-like substances and lipofuscin granules were significantly increased 7 days after KA treatments. Therefore, our data suggests that mice in the senescence model are more susceptible to KA-induced seizures/oxidative damage, and that oxidative damage could be one of the casual factors in the accumulation of lipofuscin.


Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions.
IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague-Dawley rats to evaluate their kidney conditions. The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.


Photopic vision in eels: evidences of color discrimination.
Several classes of second-order retinal neurons have been studied electrophysiologically in European eel (Anguilla anguilla) from two different localities, Lake Seliger in Russia and the coastal waters of the Adriatic Sea in Montenegro. The majority of L-horizontal cells (68 explored) had both rod and cone inputs, an uncommon phenomenon among teleosts. Pronounced color-opponent properties, often taken as pointing to the capacity of color vision, were identified in one amacrine cell, apparently of the "blue/yellow" (or "blue/green") type. Microspectrophotometric measurements revealed two different spectral classes of cones with absorption maxima at about 525 and 434 nm. The existence of green-sensitive and blue-sensitive cone units was thus revealed by both electrophysiological and microspectrophotometric techniques.


Long-Term Zonal Average Analysis of Corneal Tomography in Keratoconus Eyes.
The scope of this study was to investigate keratoconus progression using zonal average analysis of corneal tomography. The corneal tomographies of patients participating in initial baseline and all scheduled follow-up visits up to 4 years were analyzed. Data were exported in custom software, which delineated 4 zones of analysis and calculated the average values of the anterior and posterior curvature and the average thickness for each zone at each visit. In particular, a 3.1 mm 2 area containing the K max , termed "keratoconus cone zone," was defined for assessing disease progression during the follow-up. A total of 201 patients were enrolled in this prospective study. At 4 years, 31% of the eyes (n = 62) had an average increase of ≥1.0 D in the keratoconus cone zone in baseline visit, whereas only 11% of the eyes (n = 22) had ≥1.0 D K max increase in the same period. The zonal anterior average curvature (+1.1 D; P < 0.001) and thickness (-14 μm; P < 0.001) values of the keratoconus cone zone progressed significantly during the follow-up. A high correlation was found between the 4-year changes of K max and central corneal thickness values and the change of the average anterior curvature and thickness values in the keratoconus cone zone. The posterior cornea did not show significant average changes (<-0.2 D; P > 0.05) during the follow-up. Single-point tomography indexes for keratoconus progression did not capture the overall structure and shape changes of the cornea. It would be recommended to update criteria for keratoconus management including the zonal average analysis of curvature and thickness values for tracking disease progression over observation periods longer than 1 year.


Microwave-Assisted Syntheses in Recyclable Ionic Liquids: Photoresists Based on Renewable Resources.
The copoly(2-oxazoline) pNonOx80 -stat-pDc(=) Ox20 can be synthesized from the cationic ring-opening copolymerization of 2-nonyl-2-oxazoline NonOx and 2-dec-9'-enyl-2-oxazoline Dc(=) Ox in the ionic liquid n-hexyl methylimidazolium tetrafluoroborate under microwave irradiation in 250 g/batch quantities. The polymer precipitates upon cooling, enabling easy recovery of the polymer and the ionic liquid. Both monomers can be obtained from fatty acids from renewable resources. pNonOx80 -stat-pDc(=) Ox20 can be used as polymer in a photoresist (resolution of 1 μm) based on UV-induced thiol-ene reactions.


Silica-shell cross-linked micelles encapsulating fluorescent conjugated polymers for targeted cellular imaging.
A bioinspired silification approach was successfully used to encapsulate fluorescent conjugated polymers inside silica-shell cross-linked polymeric micelles (CP-SSCL) in the highly benign synthesis environment of room temperature and near-neutral aqueous environment. Four different conjugated polymers were employed to demonstrate the versatility of the bioinspired silification, resulting in the formation of CP-SSCL with different emission wavelengths across the visible spectrum. The CP-SSCL are characterized by a large absorption coefficient and high quantum yield, indicating that they exhibit the required high fluorescence brightness for cellular imaging application. In addition, the CP-SSCL also exhibit a high colloidal stability and low cytotoxicity. The in vitro studies of using MDA-MB-231 breast cancer cells show that the CP-SSCL are successfully uptaken by the cancer cells and located at the cytoplasm of the cells. Furthermore, by conjugating folic acid on their surfaces, the uptake of CP-SSCL by MDA-MB-231 cells was enhanced significantly, suggesting their great potential for targeted imaging and early detection of cancer cells.


TET2 chemically modifies tRNAs and regulates tRNA fragment levels.
The ten-eleven translocation 2 (TET2) protein, which oxidizes 5-methylcytosine in DNA, can also bind RNA; however, the targets and function of TET2-RNA interactions in vivo are not fully understood. Using stringent affinity tags introduced at the Tet2 locus, we purified and sequenced TET2-crosslinked RNAs from mouse embryonic stem cells (mESCs) and found a high enrichment for tRNAs. RNA immunoprecipitation with an antibody against 5-hydroxymethylcytosine (hm5C) recovered tRNAs that overlapped with those bound to TET2 in cells. Mass spectrometry (MS) analyses revealed that TET2 is necessary and sufficient for the deposition of the hm5C modification on tRNA. Tet2 knockout in mESCs affected the levels of several small noncoding RNAs originating from TET2-bound tRNAs that were enriched by hm5C immunoprecipitation. Thus, our results suggest a new function of TET2 in promoting the conversion of 5-methylcytosine to hm5C on tRNA and regulating the processing or stability of different classes of tRNA fragments.


Yield and Nutritional Characterization of Thirteen Quinoa (Chenopodium quinoa Willd.) Varieties Grown in North-West Europe-Part I.
The cultivation of quinoa has gained increasing interest in Europe. Different European varieties exist, but more research is required to understand the individual variety characteristics for end-use applications. The objective of this study is to evaluate the agronomic performance of 13 quinoa varieties under North-West European field conditions during three growing seasons (2017-2019). Furthermore, seeds were qualitatively characterized based on characteristics and composition. Yield differed among varieties and growing seasons (0.47-3.42 ton/ha), with lower yields obtained for late-maturing varieties. The saponin content varied from sweet to very bitter. The seeds contained high protein levels (12.1-18.8 g/100 g dry matter), whereas varieties had a similar essential amino acid profile. The main fatty acids were linoleic (53.0-59.8%), α-linolenic (4.7-8.2%), and oleic acid (15.5-22.7%), indicating a high degree of unsaturation. The clustering of varieties/years revealed subtle differences between growing seasons but also reflected the significant interaction effects of variety and year. Most varieties perform well under North-West European conditions, and their nutritional content is well within the values previously described for other cultivation areas. However, optimal yield and quality traits were not combined in one variety, illustrating the importance of breeding for adapted quinoa varieties.


Perfluoroalkyl Substances (PFAS) and Their Effects on the Placenta, Pregnancy, and Child Development: a Potential Mechanistic Role for Placental Peroxisome Proliferator-Activated Receptors (PPARs).
This review summarizes studies highlighting perfluoroalkyl substances (PFAS) and their effects on the placenta, pregnancy outcomes, and child health. It highlights human population-based associations as well as in vitro-based experimental data to inform an understanding of the molecular mechanisms underlying these health effects. Among the mechanisms by which PFAS may induce toxicity is via their interaction with the peroxisome proliferator-activated receptors (PPARs), nuclear receptors that regulate lipid metabolism and placental functions important to healthy pregnancies, as well as fetal and child development. In utero exposure to prevalent environmental contaminants such as PFAS is associated with negative health outcomes during pregnancy, birth outcomes, and later in life. Specifically, PFAS have been associated with increased incidence of gestational diabetes, childhood obesity, preeclampsia, and fetal growth restriction. In terms of placental molecular mechanisms underlying these associations, studies demonstrate that PFAS interfere with trophoblast lipid homeostasis, inflammation, and invasion. Moreover these effects could be mediated in part by the interaction between PFAS and PPARs, as well as other biological mechanisms. This review summarizes how PFAS, critical environmental contaminants, may contribute to diseases of pregnancy as well as early and later child health.


Diurnal mood variation symptoms in major depressive disorder associated with evening chronotype: Evidence from a neuroimaging study.
Major depressive disorder (MDD) is often accompanied with classic diurnal mood variation (DMV) symptoms. Patients with DMV symptoms feel a mood improvement and prefer activities at dusk or in the evening, which is consistent with the evening chronotype. Their neural alterations are unclear. In this study, we aimed to explore the neuropathological mechanisms underlying the circadian rhythm of mood and the association with chronotype in MDD. A total of 126 depressed patients, including 48 with DMV, 78 without, and 67 age/gender-matched healthy controls (HC) were recruited and underwent a resting-state functional magnetic resonance imaging. Spontaneous neural activity was investigated using amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) analyses were conducted. The Morningness-Eveningness Questionnaire (MEQ) was utilized to evaluate participant chronotypes and Pearson correlations were calculated between altered ALFF/FC values and MEQ scores in patients with MDD. Compared with NMV, DMV group exhibited lower MEQ scores, and increased ALFF values in the right orbital superior frontal gyrus (oSFG). We observed that increased FC between the left suprachiasmatic nucleus (SCN) and supramarginal gyrus (SMG). ALFF in the oSFG and FC of rSCN-SMG were negatively correlated with MEQ scores. Some people's chronotypes information is missing. Patients with DMV tended to be evening type and exhibited abnormal brain functions in frontal lobes. The synergistic changes between frontotemporal lobe, SCN-SMG maybe the characteristic of patients with DMV symptoms.


Effect of vitamin A pretreatment on Escherichia coli-induced lipid peroxidation and level of 3-nitrotyrosine in kidney of guinea pig.
In the present study, we report the effect of vitamin A (Vit A, retinol palpitate) on kidney lipid peroxidation and 3-nitrotyrosine (3-NT) levels induced after Escherichia coli administration to guinea pigs. Vit A was administrated intraperitoneally (i.p.) to guinea pigs at a dose 15,000 IU/kg per day for 7 days prior to E. coli injection. On day 8, the animals were injected i.p. with E. coli dosed at 12 x10(9) colony forming units per kilogram. Kidneys were collected 6 h after administration of E. coli. Malondialdehyde (MDA) as a lipid peroxidation product, and 3-NT levels were measured by reverse phase high-performance liquid chromatography. There was a significant increase in MDA and 3-NT levels in lipopolysaccaharide-induced group (p<0.001). 3-NT was not detectable in kidney of normal control animals. However, Vit A administration prior to E. coli injection prevented 3-NT formation but did not prevent the rice in MDA level of kidney (p<0.001). Vit A alone did not alter the MDA level in the kidney of the control group.


Mechanical behaviour of reconstructed defected skull with custom PEEK implant and Titanium fixture plates under dynamic loading conditions using FEM.
Skull reconstruction using cranial implants is often required for repairing skull defects caused due to trauma, diseases, or malignancy to protect intracranial structures. For relieving Intracranial Pressure (ICP) surgeons restore cranial defects either using natural bones or fabricated custom cranial implants. With the increase in Traumatic Brain Injuries (TBI) and challenges faced by TBI patients to regain normalcy, it is imperative to analyse the mechanical behaviour of skull-implant assemblies under some Head Injury Criteria (HIC). Medical grade materials including Titanium Alloys (Ti-6Al-4V) and Polyether-ether-ketone (PEEK) are used by fabricating Patient-Specific Implants (PSI) manufactured using 3D imaging, modelling and printing techniques. 3D technologies are preferred over conventional manufacturing methods, as they enable fabrication of custom shapes, sizes and properties for these PSI. For an effective attachment of PSI with a defective skull, a stable joint and plate arrangement as fixture plates is necessary at their interface. These fixtures can have variable numbers, design shapes, materials and location arrangements. This paper presents the Finite Element Method/Analysis (FEM/FEA) study of PSI attached to a defected skull for reconstruction, with linear shaped fixture configuration, when subjected to an external dynamic loading at 5 m/s, strain rate of 10s-1 to 243s-1 and ICP of 15mm Hg from three sides of the skull faces. Three different materials as Neoprene (soft), Concrete (medium rigid) and E-Glass (highly rigid) have been used, in the form of a rectangular thin cuboidal wall structure, at an angle of 45° with the skull face. Four linear shaped fixture plates which were simplest to design, were used to attach the PSI-skull assembly, to ensure that weight of the PSI-fixation assembly on the patient remains minimal, overall assembly has symmetrical fixations and efforts required by a surgeon for fitment of these plates remain minimal. Placement of these fixture plates has been optimized to encompass the complete PSI-skull interface section, due to which the stresses within all the assembly components (PSI, fixture plate and skull) reduced by nearly 2.5 times than the initial design and remained within yielding limits, thereby, averting any failure under heavy external dynamic loading.


Bacterial Microarrays for Examining Bacterial Glycosignatures and Recognition by Host Lectins.
The surface of bacteria displays diverse carbohydrate structures that may significantly differ among bacteria with the same cell wall architecture and even among strains of a given bacterial species. These structures are often recognized by lectins of the innate immune system for triggering defense responses, although some bacterial pathogens exploit recognition by host lectins for favoring infection. Bacterial microarrays are a useful tool for profiling accessible bacterial surface glycans and for exploring their recognition by innate immune lectins. The use of array-printed bacterial cells enables evaluation of the recognition of the glycan epitopes in their natural presentation, i.e., preserving their real density and accessibility. Glycosylation patterns of bacterial surfaces can be examined by testing the binding to the bacterial arrays of a panel of lectins with known carbohydrate-binding preferences, and the recognition of surface glycans by innate immune lectins can easily be assessed using similar binding assays.


Disturbed flow in a patient-specific arteriovenous fistula for hemodialysis: Multidirectional and reciprocating near-wall flow patterns.
Actual surgical creation of vascular access has unacceptable failure rates of which stenosis formation is a major cause. We have shown previously in idealized models of side-to-end arteriovenous fistula that disturbed flow, a near-wall hemodynamic condition characterized by low and oscillating fluid shear stress, develops in focal points that corresponds closely to the sites of future stenosis. Our present study was aimed at investigating whether disturbed flow occurs in patient-specific fistulae, too. We performed an image-based computational fluid dynamics study within a realistic model of wrist side-to-end anastomosis fistula at six weeks post-surgery, with subject-specific blood rheology and boundary conditions. We then categorized disturbed flow by means of established hemodynamic wall parameters. The numerical analysis revealed laminar flow within the arterial limbs and a complex flow field in the swing segment, featuring turbulent eddies leading to high frequency oscillation of the wall shear stress vectors. Multidirectional disturbed flow developed on the anastomosis floor and on the whole swing segment. Reciprocating disturbed flow zones were found on the distal artery near the floor and on the inner wall of the swing segment. We have found that both multidirectional and reciprocating disturbed flow develop on the inner side of the swing segment in a patient-specific side-to-end fistula used for vascular access after six weeks post-operatively. This has obvious implications for elucidating the hemodynamic forces involved in the initiation of venous wall thickening in vascular access.


A schwannoma of the greater petrosal nerve located within the petrous apex and treated with stereotactic radiotherapy.
A 26 year-old female experienced progressive left sided pulsatile tinnitus and conductive hearing loss for two years, which following an extensive clinical workup, was diagnosed as a left greater petrosal nerve schwannoma located within the petrous apex of the temporal bone. Between neurosurgical management and radiation therapy, multiple therapeutic options were presented to the patient, who ultimately chose stereotactic radiotherapy as an alternative to surgical resection due to the potential morbidity associated with surgery. The patient received three fractions of 600 cGy without subsequent worsening of her symptoms, new onset neurologic symptoms or radiation induced side effects reported at a 3, 6 and 12 month clinic visits. A follow-up MRI at 6 and 12 months post radiation administration demonstrated no further tumor growth.


Role of coating agent in iron oxide nanoparticle formation in an aqueous dispersion: Experiments and simulation.
Iron oxide (Fe3O4) nanoparticle was synthesized by coprecipitation and was modeled and solved using a hybrid (discrete-continuous) model, based on a kinetic Monte Carlo (kMC) simulation scheme. The latter was combined with the constant number MC method, to improve both speed and accuracy of the simulation. Complete particle size distribution (PSD) from simulation matches very well with PSD of both uncoated and coated (with either polyacrylic acid or dextran) Fe3O4 nanoparticles, obtained from our experiments. The model is general, as the time scales of various processes (nucleation, diffusion-growth and coagulation-growth) are incorporated in rate equations, while, input simulation parameters are experimentally measured quantities. With the help of the validated model, effect of coating agent on coagulation-growth was estimated by a single, fitted, coagulation-efficiency parameter. Our simulation shows that, logarithm of coagulation-efficiency scales linearly with logarithm of inverse of the molecular weight of the coating agent. With this scaling law, our model is able to a priori predict the experimental PSD of Fe3O4 nanoparticles, synthesized with an even higher molecular weight of dextran.


Effect of aspirin on platelet 5-hydroxytryptamine and beta-thromboglobulin plasma levels in patients with myeloproliferative diseases.
14 patients with myeloproliferative diseases (MD) showed low 5-hydroxytryptamine (5-HT) platelet content and high beta-thromboglobulin (beta-TG) plasma levels. This pattern could support the view that MD platelets undergo "in vivo" degranulation. A single dose of aspirin was unable to induce modifications of platelet 5-HT and plasma beta-TG, whereas 6 out of 14 patients treated over 7 days period with the drug showed a decrease but not normalization in their beta-TG levels. No modification of platelet 5-HT was obtained suggesting that the cause of dense bodies deficiency may lie in the production of abnormal platelets and not be related to "in vivo" degranulation.


Effect of Apremilast on LPS-induced immunomodulation and inflammation via activation of Nrf2/HO-1 pathways in rat lungs.
Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: "apremilast (AP)" is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1β, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1β, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.


The energy intake through regular nontherapeutic meals provision in long-term care: impact on nutritional status and related Geriatric Nutritional Risk Index.
To investigate how the energy intake of institutionalized long-term-care patients through the regular nontherapeutic meals provision is associated with the nutritional status and the Geriatric Nutritional Risk Index (GNRI). A 9 month longitudinal, observational study. Long-term-care Hospital. 66 long-term-care patients with multiple medical conditions and solely oral food-intake. 47 (71 %) patients, predominantly women (n = 39/47), with a mean age of 83.04 (±9.58) years completed study time and 19 (29 %) deceased. At week 1 and week 36 of observation time energy intake was measured by means of three-days-weighing-records. Body composition was assessed with bioelectrical impedance analysis. Serum albumin, body weight and body height were taken from the medical report. Albumin content, body weight and height were used to calculate the Geriatric Nutritional Risk Index: GNRI = [1.489 × albumin (g/L)] + [41.7 × (weight/ideal body weight)]. Energy intake was significantly below 24 kcal/kg body weight per day. The GNRI of the deceased patients was significantly (p = 0.002) lower than the GNRI of the completers. During observation time energy-intake p < 0.001, body fat (p = 0.001) and phase angle (PA) of bio impedance measurement (p = 0.018) and likewise the GNRI (p = 0.021) of the completers decreased significantly. At the beginning and at the end of observation time energy intake correlated significantly with PA (p = 0.028/p < 0.001) and GNRI (p = 0.436/p = 0.004). Also GNRI and PA correlated significantly at the beginning (p = 0.001) and at the end (p < 0.001) of observation time. The energy intake through non therapeutic meals provision was too low for sustaining the nutritional status and likewise the GNRI. The malnourishment and the nutrition related clinical risk of the geriatric patients aggrevated during observation time.