Impaired memory and reduced sensitivity to the circadian period lengthening effects of methamphetamine in mice selected for high methamphetamine consumption.
Drug abuse runs in families suggesting the involvement of genetic risk factors. Differences in addiction-related neurobiological systems, including learning and memory and circadian rhythms, may exist prior to developing addiction. We characterized the cognitive phenotypes and the free-running circadian period of mouse lines selectively bred for high methamphetamine (MA) drinking (MA high drinking or MAHDR) and low MA drinking (MA low drinking or MALDR). MA-naïve MALDR mice showed spatial memory retention while MAHDR mice did not. MA-naïve MAHDR mice had elevated hippocampal levels of the AMPA receptor subunits GluA2 (old terminology: GluR2), but not GluA1 (old terminology: GluR1). There were no line differences in the free running period (τ) when only water was available. During a 25 mg/L MA solution access period (vs water), there was an increase in τ in MALDR but not MAHDR mice, although MAHDR mice consumed significantly more MA. During a 50 mg/L MA solution access period (vs water), both lines showed an increased τ. There was a positive correlation between MA consumption and τ from baseline in MALDR, but not MAHDR, mice. Thus, a heritable proclivity for elevated MA self-administration may be associated with impairments in hippocampus-dependent memory and reduced sensitivity to effects of MA on lengthening of the circadian period.


Influence of palladium content dispersed in the TiO2 photocatalyst for degradation of volatile organic compounds in gas emission.
Heterogeneous photocatalysis is highlighted to treat volatile organic compound (VOC) emission. Then, this work analysed the influence of palladium (Pd) content loaded in TiO2 on n-octane and iso-octane photodegradation. For this, TiO2 was loaded with Pd in different contents: 0.4%, 0.7%, and 1.0%. The samples were characterized, and the photodegradation experiments were conducted by Pd/TiO2/UV process. The characterization analyses showed that the metal presence did not change the catalyst structure or its surface area; however, it reduced the bandgap energy. The photocatalytic results proved that palladium improved n-octane degradation from 62% (pure TiO2) to 92.6% (0.4%Pd/TiO2) and, iso-octane degradation enhanced from 59% (pure TiO2) to 90.6% (0.7%Pd/TiO2); all results were obtained in the space time of 39 s. Therefore, 0.4%Pd/TiO2 and 0.7%Pd/TiO2 showed better oxidation results to degradation n-octane and iso-octane, respectively. The kinetic model of pseudo-first order showed a good fit for the data of both VOCs. Heterogeneous photocatalysis with Pd/TiO2 showed to be an adequate technique to reduce VOCs emission.


Modified high varicocelectomy: outpatient microsurgical procedure.
Fifty patients underwent modified high varicocelectomy as outpatients. Twelve of the 22 unilateral varicocelectomies were performed under local anesthesia. All patients tolerated the procedures well, and none required admission to the hospital. The modified high approach, which exposes the area above the internal inguinal ring and of the posterior spermatic cord, is straightforward and insures that both internal spermatic and cremasteric veins can be ligated. Use of the operating microscope prevents the inadvertent ligation of the testicular artery and lymphatics.


Pivotal resection of heel spurs in sports medicine: a case study and presentation.
Using the cresentic pivotal saw for resecting a heel spur in a new method whereby a plantar heel spur can be removed in toto with no irregular osseous margins remaining. Consequently, less trauma to the calcaneus occurs and the process of postoperative recovery is enhanced. This technique is new to the literature. Presently, we are developing a more sophisticated blade.


Non-protein-mediated transfer of phosphatidic acid between microsomal and mitochondrial membranes.
The transfer of phosphatidic acid between rat liver microsomes loaded with [32P]-phosphatidic acid and rat liver mitochondria was studied in the absence of added lipid transfer proteins. It was found that during 1 h at 37 degrees C in the medium containing 100 mM KCl, 20-30% of phosphatidic acid but only 2.5% of phosphatidylcholine were transferred. This spontaneous transfer of phosphatidic acid remained the same after pretreatment of microsomes and mitochondria with 125 mM KCl or microsomes alone with 1 mM Tris, pH 8.6, procedures reported to remove adsorbed lipid transfer proteins. This transfer was insensitive to thiol-blocking reagents. The initial rate of this non-protein-mediated transfer of phosphatidic acid was virtually independent of the concentration of the acceptor membranes (mitochondria), thus indicating that it occurs by diffusion of the phospholipid through the aqueous phase rather than by membrane collision. About 80% of phosphatidic acid synthesized in the outer mitochondrial membrane was recovered in the inner membrane after a 1-h incubation, pointing to a high rate of the intermembrane transfer of this phospholipid within intact mitochondrion.


An experimental approach to determining fatigue crack size in polyethylene tibial inserts.
A major limiting factor to the longevity of prosthetic knee joints is fatigue crack damage of the polyethylene tibial insert. Existing methods to quantify fatigue crack damage have several shortcomings, including limited resolution, destructive testing approach, and high cost. We propose an alternative fatigue crack damage visualization and measurement method that addresses the shortcomings of existing methods. This new method is based on trans-illumination and differs from previously described methods in its ability to non-destructively measure subsurface fatigue crack damage while using a simple and cost-effective bench-top set-up. We have evaluated this method to measure fatigue crack damage in two tibial inserts. This new method improves on existing image-based techniques due to its usability for subsurface damage measurement and its decreased reliance on subjective damage identification and measurement.


Experience with three-port laparoscopic cholecystectomy.
After considerable experience with laparoscopic cholecystectomy (LC) using four ports, we began using three-port LC in October 1993 and have performed 130 LCs with this procedure up to May 1996. The procedure was successful in 119 patients. In 6 patients fourth port was used, and in another 5, the procedure was converted to open laparo-tomy. Cooperative manipulation of the surgical instruments between the operator and assistant is very important for this procedure, for exposing Calot's triangle and dissecting the gallbladder from the gallbladder bed. The use of an ultrasonic aspiration system (Sumisonic ME 2400; Sumitomo Bakelite, Tokyo, Japan) made it easier to identify the cystic duct and artery, especially in patients with chronic inflammation or dense adhesions. We encountered no problems with cannulation into the cystic duct for intraoperative cholangiography, and there were no intra- and postoperative complications in this series. We achieved good results, similar to those achieved with the four-port technique. This technique is technically feasible and safe, and it has esthetic and cost advantages compared with the four-port technique. However, the operator who performs three-port LC should not hesitate to add another port, or to convert to open laparotomy, whenever any difficulties occur during this procedure, to prevent critical complications.


Central and coronary circulation of the normal man during orthostatic and lower body negative pressure tests.
The effects of the tilt test (at 60-70 degrees for 20 min) and LBNP test (at -30 and -60 mm Hg for 20 min each) on the basic parameters of central circulation (15 test subjects) and coronary circulation (11 test subjects) were investigated. The study was performed using thermistor-equipped catheters implanted into the pulmonary artery and coronary sinus and Teflon catheters implanted into the brachial artery. In the study, the basic parameters of central circulation (pressure in the right atrium and pulmonary artery, transmural pressure in these compartments, cardiac index, stroke index, etc.) and coronary circulation (blood flow in the coronary sinus, left ventricle oxygen consumption, coronary resistance, etc.) were measured. Correlation between circulation variations and metabolic requirements was assessed (with respect to changes in acid-base equilibrium of blood). The effect of the tilt test and LBNP test on the basic parameters of central and coronary circulation, blood acid-base equilibrium and oxygenation was compared.


Bioaccumulation and biomagnification of emerging poly- and perfluoroalkyl substances in marine organisms.
Accumulating evidence has demonstrated the wide environmental presence of 6:2 chlorinated polyfluoroalkyl ether sulfonates (6:2 Cl-PFAES) and p-perfluorous nonenoxybenzene sulfonate (PFNOBS). However, data on the bioaccumulation and trophic magnification of these emerging poly- and perfluoroalkyl substances (PFASs) in subtropical marine environment is still limited. In this study, seawater (n = 17), sediment (n = 14), and marine organism (27 species; n = 177) samples were collected from East China Sea, and analyzed them for legacy and emerging PFASs. Besides perfluoroalkyl carboxylates and perfluorooctane sulfonate (PFOS), 6:2 Cl-PFAES was always among the predominant PFASs detected in seawater, sediment, and marine organism. For emerging PFASs, 6:2 Cl-PFAES (mean ± SD, 3.1 ± 0.17), 8:2 Cl-PFAES (3.3 ± 0.35), and PFNOBS (3.3 ± 0.19) had lower bioaccumulation factors (BAF) than PFOS (3.4 ± 0.22) in marine fish. In crab, PFNOBS (3.7 ± 0.33) had a lower biota-sediment accumulation factor (BSAF) than PFOS (3.9 ± 0.45). In snail, among all detected PFASs, PFNOBS (4.0 ± 0.42) had the highest mean log BSAF value. 8:2 Cl-PFAES consistently had a higher log BSAF value than 6:2 Cl-PFAES in snail and crab. Notably, these differences in BAF and BSAF are not significant. Among PFASs, 6:2 Cl-PFAES (2.3; 95 % confidence interval, CI: 1.9-2.6) displayed the highest trophic magnification factor (TMF). PFNOBS had the lowest TMF value (1.8, 95 % CI: 1.4-2.1), but which still indicates its weak biomagnification through the current marine food web. This is the first study reporting the bioaccumulation and biomagnification of PFNOBS in marine organisms, which deepens the understanding of its environmental behavior in the marine ecosystem.


EUF1 - a newly identified gene involved in erythritol utilization in Yarrowia lipolytica.
The gene YALI0F01562g was identified as an important factor involved in erythritol catabolism of the unconventional yeast Yarrowia lipolytica. Its putative role was identified for the first time by comparative analysis of four Y. lipolytica strains: A-101.1.31, Wratislavia K1, MK1 and AMM. The presence of a mutation that seriously damaged the gene corresponded to inability of the strain Wratislavia K1 to utilize erythritol. RT-PCR analysis of the strain MK1 demonstrated a significant increase in YALI0F01562g expression during growth on erythritol. Further studies involving deletion and overexpression of the selected gene showed that it is indeed essential for efficient erythritol assimilation. The deletion strain Y. lipolytica AMM∆euf1 was almost unable to grow on erythritol as the sole carbon source. When the strain was applied in the process of erythritol production from glycerol, the amount of erythritol remained constant after reaching the maximal concentration. Analysis of the YALI0F01562g gene sequence revealed the presence of domains characteristic for transcription factors. Therefore we suggest naming the studied gene Erythritol Utilization Factor - EUF1.


Specific phosphorylation of microtubule-associated protein 2c by extracellular signal-regulated kinase reduces interactions at its Pro-rich regions.
Microtubule-associated protein 2 (MAP2) is an important neuronal target of extracellular signal-regulated kinase 2 (ERK2) involved in Raf signaling pathways, but mechanistic details of MAP2 phosphorylation are unclear. Here, we used NMR spectroscopy to quantitatively describe the kinetics of phosphorylation of individual serines and threonines in the embryonic MAP2 variant MAP2c. We carried out real-time monitoring of phosphorylation to discover major phosphorylation sites that were not identified in previous studies relying on specific antibodies. Our comparison with the phosphorylation of MAP2c by a model cyclin-dependent kinase CDK2 and with phosphorylation of the MAP2c homolog Tau revealed differences in phosphorylation profiles that explain specificity of regulation of biological functions of MAP2c and Tau. To probe the molecular basis of the regulatory effect of ERK2, we investigated the interactions of phosphorylated and unphosphorylated MAP2c by NMR with single-residue resolution. As ERK2 phosphorylates mostly outside the regions binding microtubules, we studied the binding of proteins other than tubulin, namely regulatory subunit RIIα of cAMP-dependent PKA, adapter protein Grb2, Src homology domain 3 of tyrosine kinases Fyn and Abl, and ERK2 itself. We found ERK2 phosphorylation interfered mostly with binding to proline-rich regions of MAP2c. Furthermore, our NMR experiments in SH-SY5Y neuroblastoma cell lysates showed that the kinetics of dephosphorylation are compatible with in-cell NMR studies and that residues targeted by ERK2 and PKA are efficiently phosphorylated in the cell lysates. Taken together, our results provide a deeper characterization of MAP2c phosphorylation and its effects on interactions with other proteins.


P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas.
Molecular characterization of gliomas has uncovered genomic signatures with significant impact on tumor diagnosis and prognostication. CDKN2A is a tumor suppressor gene involved in cell cycle control. Homozygous deletion of the CDKN2A/B locus has been implicated in both gliomagenesis and tumor progression through dysregulated cell proliferation. In histologically lower grade gliomas, CDKN2A homozygous deletion is associated with more aggressive clinical course and is a molecular marker of grade 4 status in the 2021 WHO diagnostic system. Despite its prognostic utility, molecular analysis for CDKN2A deletion remains time consuming, expensive, and is not widely available. This study assessed whether semi-quantitative immunohistochemistry for expression of p16, the protein product of CDKN2A, can serve as a sensitive and a specific marker for CDKN2A homozygous deletion in gliomas. P16 expression was quantified by immunohistochemistry in 100 gliomas, representing both IDH-wildtype and IDH-mutant tumors of all grades, using two independent pathologists' scores and QuPath digital pathology analysis. Molecular CDKN2A status was determined using next-generation DNA sequencing, with homozygous CDKN2A deletion detected in 48% of the tumor cohort. Classifying CDKN2A status based on p16 tumor cell expression (0-100%) demonstrated robust performance over a wide range of thresholds, with receiver operating characteristic curve area of 0.993 and 0.997 (blinded and unblinded pathologist p16 scores, respectively) and 0.969 (QuPath p16 score). Importantly, in tumors with pathologist-scored p16 equal to or less than 5%, the specificity for predicting CDKN2A homozygous deletion was 100%; and in tumors with p16 greater than 20%, specificity for excluding CDKN2A homozygous deletion was also 100%. Conversely, tumors with p16 scores of 6-20% represented gray zone with imperfect correlation to CDKN2A status. The findings indicate that p16 immunohistochemistry is a reliable surrogate marker of CDKN2A homozygous deletion in gliomas, with recommended p16 cutoff scores of ≤ 5% for confirming and > 20% for excluding biallelic CDKN2A loss.


Distinction between coeliac disease and refractory sprue: a simple immunohistochemical method.
We recently showed that refractory sprue is distinct from coeliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCRgamma gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 - intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish coeliac disease from refractory sprue. Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 - IEL and TCRgamma gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCRgamma gene rearrangements. Both patients had coeliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active coeliac disease from refractory sprue and should prove useful in clinical practice.


Effects of microplastics and carbon nanotubes on soil geochemical properties and bacterial communities.
A 100-day soil incubation experiment was conducted to explore the effects of conventional (high-density polyethylene, HDPE) and biodegradable (polylactic acid, PLA) microplastics (MPs) and multiwall carbon nanotubes (MWCNTs) on soil geochemical properties and bacterial communities. Generally, soil pH was increased by 10% HDPE and 10% PLA, but decreased by increasing MWCNTs. Soil dissolved organic carbon content was only increased by 10% PLA. NO3--N content was significantly decreased by MPs, with a decrement of 99% by 10% PLA. Similarly, available P content was reduced by 10% MPs. The activities of urease and alkaline phosphatase were stimulated by 10% PLA, but generally inhibited by HDPE. Conversely, FDAse activity was stimulated by HDPE, but inhibited by 10% PLA, whereas invertase activity decreased with increasing MWCNTs. Overall, both MPs and MWCNTs changed soil bacterial diversity. Co-exposure to 10% MPs and MWCNTs of 1 and 10 mg/kg caused the lowest species richness and Shannon indexes. MPs especially at the 10% dose changed bacterial community composition and the associated metabolic pathways, causing the enrichment of specific taxa and functional genes. Our findings show that conventional and biodegradable MPs differently change soil geochemical properties and microbial community structure and functions, which can be further modified by co-existing MWCNTs.


Polyenylphosphatidylcholine pretreatment ameliorates ischemic acute renal injury in rats.
Polyenylphosphatidycholine has been demonstrated to have antioxidant, cytoprotective and anti-inflammatory effects. Whether polyenylphosphatidycholine pretreatment affects ischemia/reperfusion-induced renal damage in vivo is not known and was investigated here in rats. Forty female Sprague-Dawley rats were divided into three groups. Group 1 (n = 10) was given saline (control, sham operated). Group 2 (n = 15) were given saline, and Group 3 (n = 15) were given polyenylphosphatidycholine (100 mg/day for 10 days prior to experiment). Groups 2 and 3 were subjected to bilateral renal ischemia (60 min) followed by reperfusion (6 h). After the reperfusion period, the rats were sacrificed and kidney tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde and myeloperoxidase levels, plasma aspartate aminotransferase, blood urea nitrogen and creatinine concentrations, and nuclear factor kappa beta expression were determined. Serum levels of aspartate aminotransferase, blood urea nitrogen and creatinine were significantly decreased (P < 0.05) in the treatment group compared to those in the ischemic group. There were significant differences between treatment and ischemic groups regarding the tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde, and myeloperoxidase levels (P < 0.05). In addition, polyenylphosphatidycholine pretreatment reduced nuclear factor kappa beta expression in ischemic kidney tissue. Kidneys obtained from rats pretreated with polyenylphosphatidycholine demonstrated marked reduction of the histological features of renal injury compared to kidneys obtained from Group 2 rats, including a little vacuolization, pyknosis and necrosis. Polyenylphosphatidycholine pretreatment provided significant protection against ischemia/reperfusion injury to the kidney. This treatment could be therapeutic in kidney transplantation and other conditions associated with ischemia/reperfusion injury to the kidney.


Epigenetic regulation of nuclear steroid receptors.
Histone modifier proteins have come to the forefront in the study of gene regulation. It is now known that histone methyltransferases, acetytransferases, kinases, ubiquitinases, deacetylases and demethylases orchestrate expression of target genes by modifying both histone and non-histone proteins. The nuclear receptor (NR) superfamily govern such diverse biological processes as development, physiology and disease, including human cancer. The involvement of NR in complexes with coactivators and corepressors is necessary for regulation of target genes. This review focuses on the newly recognized interactions between the NR and histone modifying enzymes. In addition to regulating histones, the histone modifying proteins directly modify and thereby regulate NR activity. In the same manner that signaling platforms exist within the histone tails that are post-translationally processed by histone modifying proteins, cascades of post-translational modification have been identified within the NR that coordinate their activity. This review focuses on the regulation of the NR estrogen receptor (ERalpha), androgen receptor (AR) and peroxisome proliferator activated receptor-gamma (PPARgamma), given their role in tumor onset and progression.


Changes in freeze-fractured mitochondrial membranes correlated to their energetic state. Dynamic interactions of the boundary membranes.
Structural changes of mitochondria in correlation to their energetic state have been observed as matrix expansion and condensation. In this communication we describe a morphological correlation in freeze-fractured mitochondrial membranes which is also dependent on the metabolic state of the organelle: the frequency by which the fracture plane following the inner or outer boundary membrane deviates by jumping from one membrane to the other is higher in phosphorylating mitochondria when compared to freshly isolated or energized mitochondria. These deflections of the fracture plane occur mostly in minimal, short steps showing close apposition of the two boundary membranes. We therefore conclude that the observed change in morphological appearance is produced by a change in interactions between the inner and outer membranes correlated to the different functional states of the inner membrane.


Evaluation of bactericidal activity of cefotaxime and other beta-lactams by a novel method.
In previous studies on Streptococcus faecium we proposed that the minimum beta-lactam concentration killing 99.9% of a bacterial population within 3 hours be defined as the minimum directly bactericidal concentration (MDBC) of that drug. In the present study we first evaluated the kinetics of cellular killing by various beta-lactams as related to penicillin-binding-protein (PBP) binding in Escherichia coli DC2, a hyperpermeable mutant. We concluded that in E. coli the MDBC for beta-lactams coincides with the minimum concentration capable of saturating PBPs 1b, 2 and 3. Of the antibacterial drugs we studied, cefsulodin, mecillinam and aztreonam had a much greater affinity for one essential PBP (PBP 1b, 2 and 3, respectively) than for all others, whereas cefotaxime had close affinities for all the above PBPs. MDBC values of greater than 500, 500, greater than 50, 10 and 1.5 mg/L were obtained for cefsulodin, mecillinam, aztreonam, ampicillin and cefotaxime, respectively. On the basis of the pharmacokinetic properties of these drugs, our results indicate that mecillinam, ampicillin and cefsulodin may be bactericidal in urine but not at other body sites; aztreonam is probably bactericidal in urine and blood, but not elsewhere; and cefotaxime is bactericidal in all the biological fluids we studied.


Phenylboronic acid modified lipid nanocarriers mediated co-delivery of immunocytokine TRAIL and gamma-secretase inhibitor to triple negative breast cancer cells and cancer stem cells.
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high rates of tumor relapse and metastasis. The existing drugs for treatment of TNBC are unable to target the cells of origin (breast cancer stem cells) of TNBC. TNF-α related apoptosis inducing ligand (TRAIL) has propensity to target TNBC cells including cancer stem cells. However, resistance to TRAIL due to activation of anti-apoptotic mechanisms is a limitation for TRAIL based anticancer therapy for TNBC. In the present study we propose an hypothesis for effective targeting of triple negative breast cancer by overcoming TRAIL resistance.


Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance.
The prevalence of type 2 diabetes mellitus is growing worldwide. By the year 2020, 250 million people will be afflicted. Most forms of type 2 diabetes are polygenic with complex inheritance patterns, and penetrance is strongly influenced by environmental factors. The specific genes involved are not yet known, but impaired glucose uptake in skeletal muscle is an early, genetically determined defect that is present in non-diabetic relatives of diabetic subjects. The rate-limiting step in muscle glucose use is the transmembrane transport of glucose mediated by glucose transporter (GLUT) 4 (ref. 4), which is expressed mainly in skeletal muscle, heart and adipose tissue. GLUT4 mediates glucose transport stimulated by insulin and contraction/exercise. The importance of GLUT4 and glucose uptake in muscle, however, was challenged by two recent observations. Whereas heterozygous GLUT4 knockout mice show moderate glucose intolerance, homozygous whole-body GLUT4 knockout (GLUT4-null) mice have only mild perturbations in glucose homeostasis and have growth retardation, depletion of fat stores, cardiac hypertrophy and failure, and a shortened life span. Moreover, muscle-specific inactivation of the insulin receptor results in minimal, if any, change in glucose tolerance. To determine the importance of glucose uptake into muscle for glucose homeostasis, we disrupted GLUT4 selectively in mouse muscles. A profound reduction in basal glucose transport and near-absence of stimulation by insulin or contraction resulted. These mice showed severe insulin resistance and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport in muscle is essential to the maintenance of normal glucose homeostasis.


Distribution pattern of CART-containing neurons and cells in the human pancreas.
Cocaine- and amphetamine-regulated transcript (CART) has been shown to play a critical role in appetite suppression, cell survival, thermoregulation, glucose sensing, stimulation of hormone secretion, as well as for the regulatory function of the islets of Langerhans. Although the principal site of CART synthesis has already been reported, our knowledge of the subject is mainly based on and limited to research conducted on animals owing to difficulties in obtaining human samples. Therefore, the primary goal of the reported study was an attempt to identify and localize CART in healthy human pancreas. Nineteen deceased subjects (donors of organs) with normal pancreas and alimentary tract were used in the study. After determination of brain death and confirmation of death by the relevant doctors committee, pancreas samples, about 1cm long, were collected from each corpse (the same part of the pancreas) after the organs were harvested for transplantation. Paraffin sections were made and stained with hematoxylin and eosin and then subjected to CART immunohistochemistry. In the normal pancreas of human adults, CART is mainly present in both nerve fibers and in nerve cell bodies in pancreatic ganglia. In addition to pancreatic neurons, immunoreactivity to CART was also seen in islet endocrine cells. This is the first report on the presence of CART-IR structures in the normal human pancreas. CART should be now added to the numerous regulatory peptides that are involved in the complex regulation of pancreatic endocrine and exocrine processes.


Comparison of internal escape channels with die spacing and occlusal venting.
The effectiveness of the following procedures in improving the seating of full cast crowns were compared: internal escape channels, die spacing, occlusal venting, and a combination of die spacing with an escape channel. All techniques were shown to be similar in effectiveness. Die spacing produced the least consistent results. An internal escape channel, occlusal venting, die spacing, or a combination of an escape channel and die spacing did not influence the retention of full cast crowns.


Endoscopic drainage of obstructed biliary system in altered gastrointestinal anatomy: An experience from a tertiary center in India.
With the advances in imaging and endoscopic technology, scope of endoscopic interventions in biliary obstruction associated with altered gastrointestinal (GI) anatomy has increased. We analyzed our experience on single-balloon enteroscopy and endoscopic ultrasound (EUS)-guided ERCP (SBE-ERCP) and EUS-guided hepatogastrostomy (EUS-HG) in the presence of altered GI anatomy. Data of 15 patients (SBE-ERCP in 12, and EUS-HG in 3) over a period of 1 year (April 2016-March 2017) and followed up for 90 to 270 days were retrospectively analyzed. Inclusion criteria were (a) age 18-80 years, (b) fit for anesthesia, (c) intact primary confluence, (d) failed percutaneous transhepatic biliary drainage (PTBD) or difficult EUS-HG (due to poor visualization of intrahepatic ducts due to pneumobilia after PTBD; SBE-ERCP was undertaken in them), and (e) cholangitis without shock. Exclusion criteria were (a) involved or separated primary biliary confluence, (b) shock, (c) unfit for anesthesia, and (d) liver metastasis in the left lobe (EUS-HG). All were symptomatic with pain, jaundice, and cholangitis. The median serum bilirubin and serum alkaline phosphatase (SAP) were 2.8 mg/dL and 273 IU/mL, respectively. SBE-ERCP in 12 and EUS-HG in 3 cases were done successfully with observed success rate of 91.6% and 100% (3/3), respectively. Three patients had minor complications (post-procedure pain, fever, and pneumoperitoneum), which were managed conservatively. Endoscopic interventions in patients with altered GI anatomy are safe.


Nutrient Competition: A New Axis of Tumor Immunosuppression.
It is thought that cancer cells engage in Warburg metabolism to meet intrinsic biosynthetic requirements of cell growth and proliferation. Papers by Chang et al. and Ho et al. show that Warburg metabolism enables tumor cells to restrict glucose availability to T cells, suppressing anti-tumor immunity.


The effect of duration of therapy for treatment of Staphylococcus aureus blood stream infection: an application of cloning to deal with immortal-time bias in an analysis of data from a cohort study (BSI-FOO).
To estimate the effect of treatment duration on in-hospital mortality in patients with Staphylococcus aureus blood stream infection and demonstrate the biases that can arise when immortal-time bias is ignored. We compared three treatment strategies: short therapy (<10 days), intermediate (10-18 days) and long (>18 days). Twenty-eight-day all-cause in-hospital mortality. Using data from the BSI-FOO study, we implemented an approach proposed by Hernán to overcome confounding and immortal-time biases. The first stage is to clone all participants, so that each participant is assigned to each treatment strategy. Second, observations are censored when their data becomes inconsistent with their assigned strategy. Finally, inverse-probability weights are applied to adjust for potential selection. We compared our results to a naïve approach where immortal-time bias is ignored. Of the 1903 participants in BSI-FOO, 587 were eligible and included in the analysis. After cloning, the weighted estimates of hazard ratio of mortality for short versus long therapy was 1.74 (95% CI 1.36, 2.24) and for intermediate versus long therapy was 1.09 (0.98, 1.22). In the naïve approach, the hazard ratios with reference to the long therapy group are 37.4 (95% CI 18.9 to 74.4) in the short therapy group and 4.1 (95% CI 1.9 to 8.9) in the intermediate therapy group. Our findings suggest that duration of therapy >18 days is beneficial with respect to 28-day in-hospital mortality, however, there remains uncertainty around the efficacy of reducing duration of treatment to 10-18 days.


Physicochemical studies of glucose, gellan gum, and hydroxypropyl cellulose--inhibition of cast iron corrosion.
Glucose, gellan gum, and hydroxypropyl cellulose were studied against the acid corrosion of cast iron by means of weight loss, potentiodynamic polarization, and AC impedance spectroscopy techniques. The inhibition efficiency was found to increase with increasing concentration of the inhibitors. The effect of immersion time and temperature were also studied. The addition of potassium iodide to the corrosion-inhibition system showed both antagonism and synergism toward inhibition efficiency. Polarization studies revealed the mixed-type inhibiting nature of the carbohydrates. The adsorption of inhibitors on the cast iron surface obeys Langmuir adsorption isotherm model, both in presence and absence of KI. Physical interaction between the inhibitor molecules and the iron surface was suggested by the thermochemical parameters, rather than chemical interaction.


Diagnostic monitoring of a changing environment: an alternative UK perspective.
Adaptive management of the marine environment requires an understanding of the complex interactions within it. Establishing levels of natural variability within and between marine ecosystems is a necessary prerequisite to this process and requires a monitoring programme which takes account of the issues of time, space and scale. In this paper, we argue that an ecosystem approach to managing the marine environment should take direct account of climate change indicators at a regional level if it is to cope with the unprecedented change expected as a result of human impacts on the earth climate system. We discuss the purpose of environmental monitoring and the importance of maintaining long-term time series. Recommendations are made on the use of these data in conjunction with modern extrapolation and integration tools (e.g. ecosystem models, remote sensing) to provide a diagnostic approach to the management of marine ecosystems, based on adaptive indicators and dynamic baselines.


The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase.
This study aimed to evaluate, through polysomnographic analysis, the prognostic value of sleep patterns, compared to other prognostic factors, in patients with disorders of consciousness (DOCs) in the sub-acute phase. Twenty-seven patients underwent 24-h polysomnography and clinical evaluation 3.5 ± 2 months after brain injury. Their clinical outcome was assessed 18.5 ± 9.9 months later. Polysomnographic recordings were evaluated using visual and quantitative indexes. A general linear model was applied to identify features able to predict clinical outcome. Clinical status at follow-up was analysed as a function of the baseline clinical status, the interval between brain injury and follow-up evaluation, patient age and gender, the aetiology of the injury, the lesion site, and visual and quantitative sleep indexes. A better clinical outcome was predicted by a visual index indicating the presence of sleep integrity (p=0.0006), a better baseline clinical status (p=0.014), and younger age (p=0.031). Addition of the quantitative sleep index strengthened the prediction. More structured sleep emerged as a valuable predictor of a positive clinical outcome in sub-acute DOC patients, even stronger than established predictors (e.g. age and baseline clinical condition). Both visual and quantitative sleep evaluation could be helpful in predicting clinical outcome in sub-acute DOCs.


Long-Term Outcomes of Adult Patients with Homocystinuria before and after Newborn Screening.
Homocystinuria (HCU) is a rare inherited metabolic disease. In Japan, newborn screening (NBS) for HCU (cystathionine β-synthase deficiency) was initiated in 1977. We compared the outcomes between patients detected by NBS (NBS group) and clinically detected patients (non-NBS group). We administered questionnaires about clinical symptoms and social conditions to 16 attending physicians of 19 adult HCU patients treated with methionine-free formula. Eighteen patients (nine patients each in the NBS and non-NBS groups) participated. The frequency of patients with ocular, vascular, central nervous system, and skeletal symptoms in the NBS group was lower than that in the non-NBS group. Intellectual disability was observed in one and eight patients in the NBS and non-NBS groups, respectively. Concerning their social conditions, all patients in the NBS group were employed or still attending school, while only two patients in the non-NBS group were employed. Three of the four patients who discontinued treatment presented some symptoms, even in the NBS group. The social and intellectual outcomes of adult Japanese patients with HCU detected by NBS were favorable. However, even in the patients in the NBS group, some symptoms might not be preventable without continuous treatment.


Morphological landscapes from high content imaging reveal cytokine priming strategies that enhance mesenchymal stromal cell immunosuppression.
Successful clinical translation of mesenchymal stromal cell (MSC) products has not been achieved in the United States and may be in large part due to MSC functional heterogeneity. Efforts have been made to identify "priming" conditions that produce MSCs with consistent immunomodulatory function; however, challenges remain with predicting and understanding how priming impacts MSC behavior. The purpose of this study was to develop a high throughput, image-based approach to assess MSC morphology in response to combinatorial priming treatments and establish morphological profiling as an effective approach to screen the effect of manufacturing changes (i.e., priming) on MSC immunomodulation. We characterized the morphological response of multiple MSC lines/passages to an array of Interferon-gamma (IFN-γ) and tumor necrosis factor-⍺ (TNF-⍺) priming conditions, as well as the effects of priming on MSC modulation of activated T cells and MSC secretome. Although considerable functional heterogeneity, in terms of T-cell suppression, was observed between different MSC lines and at different passages, this heterogeneity was significantly reduced with combined IFN-γ/TNF-⍺ priming. The magnitude of this change correlated strongly with multiple morphological features and was also reflected by MSC secretion of immunomodulatory factors, for example, PGE2, ICAM-1, and CXCL16. Overall, this study further demonstrates the ability of priming to enhance MSC function, as well as the ability of morphology to better understand MSC heterogeneity and predict changes in function due to manufacturing.


An assessment of the impact of Indian summer monsoon droughts on atmospheric aerosols and associated radiative forcing at a semi-arid station in peninsular India.
A continuing increase in droughts/floods in Asian monsoon regions and worsening air quality due to aerosols are the two biggest threats to the health and well being of over 60% of the world's population. This study focuses on in-situ observations of atmospheric aerosols and their impact on shortwave direct aerosol radiative forcing (SDARF) during the southwest monsoon season (June-September) from 2015 to 2020 over a semi-arid station in Southern India. The Standardized precipitation index (SPI) is used to identify the droughts and normal monsoon years. Based on the SPI index, 2015, 2016, and 2018 were considered the drought monsoon years, while 2017, 2019, and 2020 were chosen as the normal monsoon years. During the drought monsoon years (normal monsoon years), the monthly mean black carbon (BC) was 1.17 ± 0.25 (0.72 ± 0.18), 1.02 ± 0.31 (0.64 ± 0.17), 1.02 ± 0.38 (0.74 ± 0.28), and 1.28 ± 0.35 μg/m3 (0.88 ± 0.21 μg/m3), for June, July, August and September respectively. The lower BC concentration during the normal monsoon years is mainly due to the enhanced wet-removal rates by high rainfall over the measurement location. In July, there was a high ventilation coefficient (VC) and low concentration of BC, while in September, low VC, and a high concentration of BC was observed in both the drought and the normal monsoon years. In addition, a plane-parallel radiative transfer model was used to estimate shortwave direct aerosol radiative forcing for composite and without BC at various surfaces, including the surface (SUF), atmosphere (ATM), and top of the atmosphere (TOA). During the drought monsoon years (normal monsoon years), the estimated monthly mean ATM forcing was 17.6 ± 2.4 (13.9 ± 2.1), 17.5 ± 7.5 (12.7 ± 4.4), 17.2 ± 4.0 (13.5 ± 1.9), and 17.4 ± 2.8 Wm-2 (14.6 ± 0.7 Wm-2) for June, July, August, and September, respectively. During the drought monsoon years, the estimated BC forcing was substantially larger (8.8 ± 2.6 Wm-2) than that of normal monsoon years (6.0 ± 1.5 Wm-2). It indicates the important role of absorbing BC aerosols during the drought monsoon years in introducing additional heat to the lower atmosphere, particularly over peninsular India.


Value of a Growth Mindset: Improving Endoscopy Coaching and Mentoring.
The teaching of endoscopic procedures to trainees has radically changed from the previous "see one, do one, teach one" approach to the method termed "competency-based medical education" (CBME), which has transformed endoscopic training. Successful implementation of a CBME program requires learners to direct their own learning. Learners with a growth approach are more likely to thrive in such a system since they are learning-oriented and not performance-oriented. This method dictates that endoscopy mentors take a longer-term and broader view of the development of the trainee and are vital to cultivate a growth mindset in learners, while an endoscopy coach focuses on helping trainees apply principles of mastery learning and deliberate practice. The goal of the authors was to describe some principles of effective coaching and mentoring methods as applied to endoscopy training.


Boron-doped diamond electrode: Preparation, characterization and application for electrocatalytic degradation of m-dinitrobenzene.
Boron-doped diamond (BDD) electrode was successfully prepared via microwave plasma chemical vapor deposition method and it was used in electrocatalytic degradation of m-dinitrobenzene (m-DNB). The electrocatalytic degradation efficiency of m-DNB was evaluated under different experimental parameters including current density, temperature, pH, Na2SO4 concentration and initial m-DNB concentration. Under optimal parameters, degradation efficiency of m-DNB reached up to 82.7% after 150min. The degradation process of m-DNB was fitted well with pseudo first-order kinetics. Moreover, UV and HPLC analyses implied that m-DNB was totally destroyed and mineralized after 240min degradation, and the proposed mechanism during the electrocatalytic degradation process was analyzed. All these results demonstrated that BDD electrode possessed excellent electrocatalytic property and showed a great potential application in wastewater treatment.


Effects of anaesthesia and chronic catheterization on circulating levels of prostaglandins (PGE2 and PGF2alpha in dogs.
Chronic catheterization of aorta and inferior vena cava in dogs did not significantly affect circulating levels of prostaglandins (PGE2 and PGF2alpha). Pentobarbital (30 mg/kg i.v.) anaesthesia produced a significant decrease in PGF2alpha.


The nitric oxide donor sodium nitroprusside requires the 18 kDa Translocator Protein to induce cell death.
Various studies have shown that several lethal agents induce cell death via the mitochondrial 18 kDa Translocator Protein (TSPO). In this study we tested the possibility that nitric oxide (NO) is the signaling component inducing the TSPO to initiate cell death process. Cell viability assays included Trypan blue uptake, propidium iodide uptake, lactate dehydrogenase release, and DNA fragmentation. These assays showed that application of the specific TSPO ligand PK 11195 reduced these parameters for the lethal effects of the NO donor sodium nitroprusside (SNP) by 41, 27, 40, and 42 %, respectively. TSPO silencing by siRNA also reduced the measured lethal effects of SNP by 50 % for all of these four assays. With 2,3-bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxyanilide (XTT) changes in metabolic activity were detected. PK 11195 and TSPO knockdown fully prevented the reductions in XTT signal otherwise induced by SNP. Collapse of the mitochondrial membrane potential was studied with the aid of JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine chloride). PK 11195 and TSPO knockdown reduced, respectively by 36 and 100 %, the incidence of collapse of the mitochondrial membrane potential otherwise induced by SNP. 10-N-Nonyl-Acridine Orange (NAO) was used to detect mitochondrial reactive oxygen species generation due to SNP. PK 11195 and TSPO knockdown reduced this effect of SNP by 65 and 100 %, respectively. SNP did not affect TSPO protein expression and binding characteristics, and also did not cause TSPO S-nitrosylation. However, β-actin and various other proteins (not further defined) were S-nitrosylated. In conclusion, TSPO is required for the lethal and metabolic effects of the NO donor SNP, but TSPO itself is not S-nitrosylated.


Localization of NGF and TrkA at mitotic apparatus in human glioma cell line U251.
It has previously been implicated that nerve growth factor (NGF) with its high-affinity receptor tyrosine kinase A (TrkA) could play an important role in the growth modulation of human tumor cells, such as glioblastoma multiform cell lines and human breast cancer cell lines. However, the direct mitogenic effects of NGF and TrkA in these tumor cells still remain to be elucidated. Herein we show, by immunofluorescence staining, that NGF was colocalized with gamma-tubulin at the centrosomes or the spindle poles throughout the cell cycle and phosphorylated TrkA was colocalized with alpha-tubulin at mitotic spindle in the glioma cell line U251. The results suggest that NGF concentrated to centrosome can recruit its receptor TrkA there and cause phosphorylation of the latter. The phosphorylated TrkA with the tyrosine kinase activity may phosphorylate the tubulin and promote the mitotic spindle assembly. By these mechanisms, NGF can modulate the mitosis of human glioma cells.


Cannabidiol-induced crosstalk of apoptosis and macroautophagy in colorectal cancer cells involves p53 and Hsp70.
Although it has been established that cannabidiol (CBD), the major non-psychoactive constituent of cannabis, exerts antitumoral activities, the exact mechanism(s) via which tumor cells are killed by CBD are not well understood. This study provides new insights into the potential mechanisms of CBD-induced mutual antagonism of apoptosis and macroautophagy using wild type (HCT116 p53wt, LS174T p53wt), knockout (HCT116 p53-/-) and mutant (SW480 p53mut) human colorectal cancer cells (CRC). CBD causes a more pronounced loss in the viability of p53wt cells than p53-/- and p53mut cells, and a 5-week treatment with CBD reduced the volume of HCT116 p53wt xenografts in mice, but had no effect on the volume of HCT116 p53-/- tumors. Mechanistically, we demonstrate that CBD only significantly elevates ROS production in cells harboring wild-type p53 (HCT116, LS174T) and that this is associated with an accumulation of PARP1. CBD-induced elevated ROS levels trigger G0/G1 cell cycle arrest, a reduction in CDK2, a p53-dependent caspase-8/9/3 activation and macroautophagy in p53wt cells. The ROS-induced macroautophagy which promotes the activation of keap1/Nrf2 pathway might be positively regulated by p53wt, since inhibition of p53 by pifithrin-α further attenuates autophagy after CBD treatment. Interestingly, an inhibition of heat shock protein 70 (Hsp70) expression significantly enhances caspase-3 mediated programmed cell death in p53wt cells, whereas autophagy-which is associated with a nuclear translocation of Nrf2-was blocked. Taken together, our results demonstrate an intricate interplay between apoptosis and macroautophagy in CBD-treated colorectal cancer cells, which is regulated by the complex interactions of p53wt and Hsp70.


Hericium erinaceus ethanol extract and ergosterol exert anti-inflammatory activities by neutralizing lipopolysaccharide-induced pro-inflammatory cytokine production in human monocytes.
Edible mushrooms are known to exert anti-inflammatory effects. In this study, the effects of ethanol extracts from edible mushrooms, such as Hericium erinaceus, and other edible mushrooms on inflammatory responses were investigated. Experiments were conducted using the inflammatory responses of human monocytes induced by lipopolysaccharide (LPS), a bacterial component, that provokes inflammation. Notably, we demonstrated that LPS mixed with ethanol and hot water extracts derived from edible mushrooms attenuated the production of inflammatory cytokines, such as interleukin (IL)-1β, -6, and -8, induced by LPS in human monocytic cell cultures. Moreover, we found that the ethanol extract of H. erinaceus contained ergosterol, which attenuated IL-8 production in LPS-stimulated cells. Subsequent component analysis of the ethanol extract of H. erinaceus revealed that ergosterol binds to lipid A to attenuate LPS-induced inflammation. Together, our findings suggest that ergosterol in ethanol extracts from edible mushrooms can prevent the induction of inflammation by binding to LPS.


Ovariectomy induces abdominal fat accumulation by improving gonadotropin-releasing hormone secretion in mouse.
The ovariectomy would induce the occurrence of obesity, but its regulatory mechanism is not clear. This study aimed to elucidate the regulation on fat accumulation for ovariectomy in mouse. In the current study, the abdominal fat mass dramatically increased in OVX mice compared with sham mice at eighth week after ovariectomy, accompanied with the higher GnRH level in blood and abdominal fat tissue. Also, a decrease of the abdominal fat mass was occurred in OVX mice with a GnRH-antagonist injection. Furthermore, the results in vivo and in vitro confirmed that GnRH promoted the transition of G1/S phase by upregulating CCND1 and CCNE1 mRNA levels by the mediation of GnRHR via the PKA-CREB pathway. Meanwhile, the higher FSH secretion was induced by increase GnRH and accelerate fat deposition in abdominal fat tissue. Our findings are the first to elucidate the effect mechanism of ovariectomy on obesity in mouse. GnRH stimulates fat accumulation in adipocytes via PKA-CREB pathway by directly promoting cell proliferation for driving the cell cycle and simultaneously accelerating differentiation for improving the FSH secretion.


[Biological mechanisms of radiation effects].
Exposure to ionizing radiation for diagnostic purposes is inevitable in modern medicine. The therapeutic application of irradiation is highly effective against cancer; however, this implies exposure of normal tissue structures to significant doses of radiation. Diagnostic or therapeutic exposure to ionizing radiation can result in tissue changes and tumor induction in the long term. Knowledge of the biological mechanisms underlying these effects is essential for individualization of the application. This article examines the biological mechanisms at the tissue and molecular level, the clinical manifestation of radiation effects, dose-dependence of the risk and the temporal progression as well as influencing factors. The time course of the reaction of tissues to radiation exposure extends over wide ranges up to many decades. The effects of radiation on tissues are classified into early and late and their pathobiology is significantly different. Various factors (R) influencing the clinical manifestation of radiation effects have been identified related to the exposure pattern. The radiation tolerance of normal tissue structures regarding the induction of functional deficits shows great variation but always has a threshold value, which is usually not exceeded in diagnostic procedures. The risk of a radiation-induced fatal malignancy (total body exposure 5%/Gy) for a medical administration of radiation must be considered as very low in comparison to the natural risks. Informed consent of patients must reflect this in a balanced way.


Trophoblast fusion: fusogenic proteins, syncytins and ADAMs, and other prerequisites for syncytial fusion.
Trophoblast fusion in the placenta is an event of major importance for the preservation of a healthy pregnancy. This process takes place throughout pregnancy and is crucial for the maintenance of the syncytiotrophoblast layer, the direct border between maternal blood and fetal tissues. Different regulatory proteins have been reported that are involved in trophoblast fusion. Syncytin-1 is a candidate regulator of fusion together with its receptors ASCT2 (RDR) and ASCT1. Little is known about the receptor properties and the interactions between receptor and ligand. Syncytin-2 or HERV-FRD is another strong candidate also of retroviral origin; while its actual function still remains to be explored. ADAM12 has been proposed to be a candidate regulator of trophoblast fusion since it is known to be involved in myoblast fusion, a process with a variety of similarities to trophoblast fusion. Beside these regulatory proteins, there is the necessity of a flip of phosphatidylserine from the inner to the outer leaflet of the plasma membranes of the fusing cells. Moreover, appropriate events of the early and still reversible stages of the apoptosis cascade are indispensable for trophoblast fusion. In this review, we present some details on the above events and proteins with their most important properties that could explain their roles in trophoblast fusion.


iMAP™ imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4.
A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP™, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.


Modified procedure for the quantitative estimation of pore volumes in carious dental enamel by polarizing microscopy.
The polarizing microscope was used to make two estimates of pore-volume fraction in carious enamel. Estimates from form birefringence were always much lower than estimates from the intrinsic birefringence of the enamel solid and were too low for carious enamel. The discrepancy cannot be explained except in part as being due to re-precipitation of mineral during lesion formation. The discrepancy may arise largely from the unjustified assumption that the whole tissue acts as a Wiener composite body. Form birefringence is probably produced only by a fraction of the tissue. A model which reconciles the two pore-volume estimates and enables calculation of the composite body fraction and of the volume fractions of solid within this fraction and in the tissue as a whole is described. It appears that polarizing microscopy will require the conjoint application of other techniques for quantitative estimation of pore-volume fractions.


What proportion of healthcare worker masks carry virus? A systematic review.
Concerns have been raised by healthcare organisations in New Zealand that routine mask use by healthcare workers (HCW) may increase the risk of transmission of SARS-CoV-2 through increased face touching. Routine mask use by frontline HCW was not recommended when seeing 'low risk' patients. The aim of this review was to determine the carriage of respiratory viruses on facemasks used by HCW. A systematic review was conducted with structured searches of medical and allied health databases. Two authors independently screened articles for inclusion, with substantial agreement (k = 0.66, 95% CI 0.54-0.79). Studies that at least one author recommended for full text review were reviewed in full for inclusion. Two authors independently extracted data from included studies including the setting, method of analysis and results. There was exact agreement on the proportion of virus detected on masks. We retrieved 1233 titles, 47 underwent full text review and five studies reported in four articles were included. The studies were limited by small numbers and failure to test all eligible masks in some studies. The proportion in each study ranged from 0 (95% CI 0-10) to 25% (95% CI 8-54). No study reported clinical respiratory illness as a result of virus on the masks. Although limited, current evidence suggests that viral carriage on the outer surface of surgical masks worn by HCW treating patients with clinical respiratory illness is low and there was not strong evidence to support the assumption that mask use may increase the risk of viral transmission.


Aortic stenosis is an independent predictor for outcome in patients with in-hospital cardiac arrest.
Prognostic tools for decision-making whether to continue advanced life support or limit life sustaining interventions in In-Hospital Cardiac Arrest (IHCA), remain scarce and inconclusive. In this regard it seems intuitive that the presence of aortic stenosis (AS) impacts on both central and peripheral perfusion during resuscitative attempts and might worsen outcome. Therefore, we aimed to investigate the prognostic value of AS on outcome after IHCA. Out of 11,641 patients presenting with acute coronary syndrome, a total of 151 patients were identified that received a standardized echocardiographic diagnostic immediately prior to an IHCA. Binary logistic regression analysis was used to elucidate the prognostic impact of AS on outcome. Within the entire study population, a total of 51 individuals with AS (mild: n = 19 [12.5%]; moderate: n = 11 [7.2%]; severe: n = 21 [13.8%]) were identified. We observed that 81% of patients with severe AS did not survive until hospital discharge. Additionally, the presence of AS showed a strong and independent inverse association with return of spontaneous circulation (adjusted odds ratio [OR] of 0.10 [95%CI:0.03-0.36], p < 0.001), survival (adj. OR of 0.14 [95%CI: 0.04-0.48]; p = 0.002) and favourable neurological outcome (OR of 0.16 [95%CI: 0.06-0.49]; p = 0.001). The observed prognostic impact remained stable irrespective of AS severity. AS proved to be a strong and independent predictor for mortality and poor outcome after IHCA. Therefore, the presence of AS mirrors an easily available predictive tool for risk stratification and decision-making.


The safety of robot-assisted cystectomy in patients with previous history of pelvic irradiation.
To determine the safety of robot-assisted cystectomy (RAC) in patients with an irradiated pelvis, by comparing perioperative complication outcomes after RAC in patients with and without a history of pelvic irradiation. In all, 252 consecutive patients underwent RAC at a tertiary referral centre from 2002 to 2013. Of all patients, 46 (18%) had a history of pelvic irradiation. Complications occurring at ≤30 days and ≤90 days of RAC were graded using the modified Clavien-Dindo classification system and additionally categorised by organ system. Baseline variables and outcomes of irradiated and non-irradiated patients were compared using descriptive statistics. Multivariable logistic regression models were generated to test the effect of previous pelvic irradiation on complications. The indications for RAC in patients with a history of pelvic irradiation were: bladder cancer (30 patients, 65%), prostate cancer (two, 4%), fistulae (five, 11%), and intractable symptoms from radiation cystitis (nine, 20%). In all, 25 (54%) irradiated and 112 (54%) non-irradiated patients had complications at ≤90 days (P > 0.9), of which 11 (24%) and 43 (21%) respectively had major complications (P = 0.7). One (2%) patient with and two (1%) patients without a history of irradiation died from surgical complications (P = 0.5). Infectious, bleeding, and gastrointestinal complications were the most common events in both groups. In multivariable analyses, a history of pelvic irradiation was not associated with a higher risk of complications. RAC performed by an experienced surgeon is a reasonable option in selected patients with a history of pelvic irradiation, as complication rates do not significantly differ compared with non-irradiated patients.


Ultrasound diagnosis of a case of transient bilateral vocal cord paralysis secondary to local anesthetic infiltration.
One of the most important complications associated with thyroid and parathyroid surgery is vocal cord paralysis due to a recurrent laryngeal nerve injury. Recurrent laryngeal nerve injury paralysis induced by local anesthetics is a rare complication with very few published cases Various techniques are available for diagnosing vocal cord paralysis, including, flexible fiberoptic laryngoscopy, videostrobolaryngoscopy and indirect laryngoscopy. However, these techniques are expensive and are often associated with pain and discomfort among patients. Considering these disadvantages, transcutaneous laryngeal ultrasound is an alternative imaging tool for vocal cord examination in patients undergoing thyroid and parathyroid surgery. We describe a case which was sonographically diagnosed a transient bilateral vocal cord paralysis after the local infiltration of 10mL of 2% mepivacaine administered for the revision of the surgical wound due to a subcutaneous hematoma that occurred after a subtotal parathyroidectomy.


A congenital aneurysm of the non-coronary sinus of Valsalva extending into the wall of the left ventricle.
We describe a congenital aneurysm of the non-coronary sinus of Valsalva which extended into the posterior wall of the left ventricle.


Moderate compared to low dietary intake of trans-fatty acids impairs strength of old and aerobic capacity of young SAMP8 mice in both sexes.
The senescence accelerated SAMP8 mouse is a model for sarcopenia and provides an opportunity to study the effects of lifelong dietary composition on the loss of physical function with age. We studied the effects of trans-fatty acids (2 % of total energy, TFA diet) on the loss of strength and aerobic exercise capacity (VO₂peak) with age. SAMP8 mice were studied at two ages (young, 25 weeks; old, 60 weeks) and on two diets (control vs TFA). Body composition, grip strength, VO₂peak, blood metabolites, and biochemical parameters were assessed. Body weight, fat mass, and body fat percentage all increased with age (p < 0.05) but were not significantly impacted by diet. There was a significant age-related decline in total grip strength as well as that normalized to fat-free mass (FFM) (p < 0.05) with a further decrease at old age in these metrics of strength on the TFA diet vs control diet (p < 0.05). Total VO₂peak exhibited no change with age or diet, but when normalized to FFM, VO₂peak exhibited age and TFA-related declines (p < 0.05). Intramuscular triacylglycerol (p < 0.05) and collagen content (p < 0.05) significantly increased with age, while blood triacylglycerol was increased by the TFA diet (p < 0.05). These data further characterize the SAMP8 mouse as a model for sarcopenia and indicate that dietary fatty acid composition can impact the degree of this age-related loss of physical function.


Possible protein binding displacement interaction between glibenclamide and metolazone.
The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the free fraction of glibenclamide in patients receiving both drugs.


Passive Underwater Noise Attenuation Using Large Encapsulated Air Bubbles.
Measurements demonstrating low-frequency underwater sound attenuation using arrays of large, tethered, stationary encapsulated bubbles to surround a sound source were compared with various effective medium models for the acoustic dispersion relationship in bubbly liquids. Good agreement was observed between measurements for the large bubbles (on the order of 10 cm) at frequencies below 1 kHz and a model originally intended to describe the acoustic behavior of ultrasound contrast agents. The primary goal is to use the model for designing encapsulated-bubble-based underwater noise abatement systems and to reduce uncertainty in system performance.


The carvedilol hibernation reversible ischaemia trial; marker of success (CHRISTMAS). The CHRISTMAS Study Steering Committee and Investigators.
Carvedilol improves left ventricular (LV) function when heart failure is due to LV systolic dysfunction, but the magnitude of the response is heterogeneous among patients with coronary disease, possibly reflecting the presence or volume of hibernating myocardium. The primary objective of the study is to determine whether the presence of hibernating myocardium predicts the magnitude of improvement in LV ejection fraction in response to carvedilol among patients with heart failure and LV systolic dysfunction due to coronary disease. The study is a prospective, randomised, parallel-group, double-blind, multi-centre study comparing carvedilol and placebo over a period of approximately 6 months in the above patient population. The primary end-point is the comparison of the mean change, from baseline to the final visit, in radionuclide-determined LV ejection fraction among patients on placebo with those on carvedilol stratified according to the presence of hibernating myocardium. Hibernating status will be determined by a combination of echocardiographic and myocardial perfusion (technetium-99m sestamibi) imaging. 255 patients have undergone screening tests of which 207 have been randomised so far. The study intends to randomise 400 patients and the first report of results is expected in 2000. As far as we are aware this is the first randomised controlled trial to investigate the effects of treatment in patients stratified according to the presence of hibernating myocardium. The study will provide insights into the prevalence of myocardial hibernation, its natural history, and its influence on prognosis as well as the interaction between the presence of hibernating myocardium and the effects of treatment with carvedilol.


The perceptual use of semantic rules by normal-hearing and hard-of-hearing children.
This study investigated the effects of varying degrees of linguistic constraint upon the performance of hard-of-hearing subjects in a repetition task. Experimental stimuli consisted of three sets of sentence strings: grammatical, semantically anomalous, and ungrammatical, respectively. While the control group performed essentially equally across all three conditions, the hard-of-hearing group performed best to the grammatical stimuli and worst to the ungrammatical stimuli. It was hypothesized that the hard-of-hearing subjects employed a primitive sentence dictionary, while the normal-hearing subjects had developed a more sophisticated word dictionary.


Effect of clipping anterior communicating artery aneurysms via pterional approach contralateral to supply of dominant blood: report of 15 patients.
Anterior communicating artery aneurysm (ACoAA) is a common cerebrovascular disease. This research is to observe the curative effect and safety of clipping anterior communicating artery (ACoA) aneurysms by microsurgery through the pterional approach contralateral to supply of dominant blood. Before the surgery, three-dimensional-DSA (3D-DSA) was performed to study the regional anatomy of ACoA complexes in all 15 patients with ACoA aneurysms. According to 3D-DSA, the aneurysms and ACoA complexes could be satisfactorily exposed by the microsurgery through the pterional approach contralateral to the supply of dominant blood. And then the microsurgery through the pterional approach contralateral to the supply of dominant blood was performed in 15 patients with ACoA aneurysms. Clipping of ACoA aneurysms were successfully performed in all patients. The aneurysms and ACoA complexes were satisfactorily exposed via 3D-DSA. Among 15 patients with ACoA aneurysms, 14 cases were cured and 1 case need further care. The ideal side of pterional approach may be cheese via simulation of pterional approach with 3D-DSA. The ACoA complex and aneurysm can be clearly exposed, and the aneurysm may be smoothly clipped safely by the microsurgery through the ideal side pterional approach contralateral to supply of dominant blood in the patients with ACoA aneurysms.


Does the Hospital Predict Readmission? A Multi-level Survival Analysis Approach.
Time to psychiatric rehospitalization was predicted for a sample of 1473 Medicaid-insured youth in Illinois in 2005 and 2006. A multi-level model statistical strategy was employed to account for the fact that youth days to rehospitalization were nested within hospital and to test the hypothesis that hospitals would vary significantly in return rates, controlling for individual-level (e.g., symptom, demographic) variables. Hospitals did not vary significantly in days to rehospitalization. At the individual-level, level of externalizing behavior and residential treatment placement predicted a faster return to the hospital. These results support the perspective that hospital outcomes are best operationalized using variables tied more directly to the inpatient episode (e.g., LOS, reductions in acuity).


Late management of secondarily grafted clefts.
34 patients (40 sides) received alveolo-palatal bone grafts for closure of the residual cleft, thus guiding a lateral incisor or canine into the arch. Long-term follow-up shows that in 41% of the patients uninterrupted arches were achieved with a normal relationship by orthodontic treatment only. 38% needed segmental osteotomies to eliminate the edentulous space, and in only 20% were bridges made to restore the dental arch. 9 (25%) patients still required a Le Fort I advancement osteotomy, despite optimal orthodontic treatment. The use of segmental osteotomies for eliminating edentulous spaces in cleft palate patients is discussed, and their advantage in relation to nasal base support is emphasized. It should be the aim to achieve in every cleft palate patient a complete archform without the need for bridges or removable prostheses. A rational orthodontic-surgical approach to the cleft, lip and palate patient is suggested with respect to naso-maxillary growth and development.


Imaging the time course, morphology, neuronal tissue compression, and resolution of cerebral microhemorrhages in mice using intravital two-photon microscopy: insights into arteriolar, capillary, and venular origin.
Cerebral microhemorrhages (CMHs, microbleeds), a manifestation of age-related cerebral small vessel disease, contribute to the pathogenesis of cognitive decline and dementia in older adults. Histological studies have revealed that CMHs exhibit distinct morphologies, which may be attributed to differences in intravascular pressure and the size of the vessels of origin. Our study aimed to establish a direct relationship between the size/morphology of CMHs and the size/anatomy of the microvessel of origin. To achieve this goal, we adapted and optimized intravital two-photon microscopy-based imaging methods to monitor the development of CMHs in mice equipped with a chronic cranial window upon high-energy laser light-induced photodisruption of a targeted cortical arteriole, capillary, or venule. We assessed the time course of extravasation of fluorescently labeled blood and determined the morphology and size/volume of the induced CMHs. Our findings reveal striking similarities between the bleed morphologies observed in hypertension-induced CMHs in models of aging and those originating from different targeted vessels via multiphoton laser ablation. Arteriolar bleeds, which are larger (> 100 μm) and more widely dispersed, are distinguished from venular bleeds, which are smaller and exhibit a distinct diffuse morphology. Capillary bleeds are circular and smaller (< 10 μm) in size. Our study supports the concept that CMHs can occur at any location in the vascular tree, and that each type of vessel produces microbleeds with a distinct morphology. Development of CMHs resulted in immediate constriction of capillaries, likely due to pericyte activation and constriction of precapillary arterioles. Additionally, tissue displacement observed in association with arteriolar CMHs suggests that they can affect an area with a radius of ~ 50 μm to ~ 100 μm, creating an area at risk for ischemia. Longitudinal imaging of CMHs allowed us to visualize reactive astrocytosis and bleed resolution during a 30-day period. Our study provides new insights into the development and morphology of CMHs, highlighting the potential clinical implications of differentiating between the types of vessels involved in the pathogenesis of CMHs. This information may help in the development of targeted interventions aimed at reducing the risk of cerebral small vessel disease-related cognitive decline and dementia in older adults.


Linguistic Adaptation and Cognitive Function in Older Chinese and Korean Immigrants in the United States: A Cross-Sectional Study.
To examine the cross-sectional association of linguistic adaptation with cognitive function, as well as its interactions with sociodemographic and health profiles in older Chinese and Korean immigrants in the U.S. Using harmonized data (N = 5063) from the Population Study of Chinese Elderly (PINE) and the Study of Older Korean Americans (SOKA), we examined between- and within-group differences in the role of linguistic adaptation (English use in older Chinese Americans and English proficiency in older Korean Americans) in cognitive function. The positive association between linguistic adaptation and cognitive function was common in both groups. We also found that the relationship was pronounced among subgroups with the underlying linguistic and cognitive vulnerabilities (i.e., the very old, women, those with low education, and newly immigrated individuals). Findings show the importance of linguistic adaptation in older immigrants' cognitive health and suggest a need for targeted interventions for high-risk groups.


Iatrogenic vertebral artery injury during anterior cervical spine surgery.
Iatrogenic injury to the vertebral artery during an anterior cervical decompression is a rarely mentioned but potentially catastrophic complication. This study was designed to examine the incidence and management of iatrogenic vertebral artery injury (IVAI) in a large database. This was a retrospective study performed at a large teaching institution over a 7-year period (1994-2001). All anterior cervical spinal procedures performed for herniated or degenerative disc disease, or cervical spondylosis were identified, as were incidences of IVAI. Anterior cervical procedures performed for trauma, neoplasia, or infection were excluded from this study. Neurological and associated morbidity as well as mortality were recorded. Data were accessed through an institution-wide electronic medical record search through the operative reports of 10 spine surgeons. Hospital and clinical charts of IVAI cases were subsequently reviewed. Demographic data and intraoperative strategies for repair were recorded. A total of 1,976 patients underwent anterior cervical spinal procedures in the review period. Six cases of IVAI were identified. In three of the six patients, arterial bleeding was controlled with hemostatic agents. Of these three, two suffered complications. The initial management of controlling arterial bleeding is by hemostatic agents; however, one must also consider repair or ligation. The remaining three patients were treated with primary repair or ligation, and no complications were noted. IVAI is a rare complication (0.3%) of anterior cervical procedures. The arterial bleeding can usually be controlled with topical hemostatic agents, but mortality may occur in instances where it cannot be adequately addressed in a timely fashion.


Impact of Cardiovascular Interventions on the Quality of Life in the Elderly.
The elderly population is growing rapidly. Political and socio-economic changes led to the demographic transition in this population with the highest number of surgeries and as well as many comorbidities. To evaluate the impact of cardiovascular intervention on quality of life of elderly patients after three and six months. Analytical prospective cohort study with elderly between 60 and 80 years of age, of both sexes, with a diagnosis of coronary artery disease and underwent cardiovascular intervention during the period June 2010 to June 2011. Data were collected by individual interviews in the pre and postoperative periods (after three and six months) by telephone. We used the SF-36 to analyse quality of life in order to assess the physical and mental health of the study population. Of the 44 individuals evaluated, 59.1% were men, 75% in the range of 65 to 74 years, 38.6% were white and 38.6% were black, 31.8% were uneducated, 43.2% were married and 68.2% had less than a minimum wage. Prevailed patients: non-diabetics (68.2%), non-obese (81.8%), hypertensive (84.1%), non-alcoholic and non-smokers (68.2% and 61.4%, respectively). A significant increase in the average of the SF-36 scores between pre and post-surgical periods (three and six months) for the domains: functional capacity, pain, general health, vitality and emotional aspect. The elderly population undergoing intervention may have cardiovascular benefits and improvements of quality of life. Physical fitness improvement measures can be taken to resume that capability.


Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma.
Tumor-infiltrating lymphocytes play an essential role in improving clinical outcome of neuroblastoma (NB) patients, but their relationship with other tumor-infiltrating immune cells in the T cell-inflamed tumors remains poorly investigated. Here we show that dendritic cells (DCs) and natural killer (NK) cells are positively correlated with T-cell infiltration in human NB, both at transcriptional and protein levels, and associate with a favorable prognosis. Multiplex imaging displays DC/NK/T cell conjugates in the tumor microenvironment of low-risk NB. Remarkably, this connection is further strengthened by the identification of gene signatures related to DCs and NK cells able to predict survival of NB patients and strongly correlate with the expression of PD-1 and PD-L1. In summary, our findings unveil a key prognostic role of DCs and NK cells and indicate their related gene signatures as promising tools for the identification of clinical biomarkers to better define risk stratification and survival of NB patients.


Investigator-initiated clinical study of a functional peptide, SR-0379, for limb ulcers of patients with Werner syndrome as a pilot study.
An investigator-initiated clinical study was carried out to evaluate the therapeutic potency of SR-0379 for the treatment of leg ulcers in patients with Werner syndrome. A multicenter, open-label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR-0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end-point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end-points, the DESIGN-R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR-0379 was evaluated during the study period. The reduction rate of ulcer size treated with 0.1% SR-0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN-R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events. Treatment with SR-0379 was safe, well-tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118-1123.


High-performance liquid chromatographic analysis of polyhydroxyflavones using solid-phase borate-complex extraction.
A high-performance liquid chromatographic method using a solid-phase borate-complex extraction pretreatment was studied for the selective quantitation of polyhydroxyflavones in vegetables, red wine and human blood plasma. Homogenate, extract and intact samples were applied to phenylboric acid cartridges to retain polyhydroxyflavones on the solid-phase by forming the borate-complex, followed by elution of the retained analytes with an acidic solvent. Reversed-phase chromatography with diode array detection allowed the simultaneous separation of rutin, myricetin, fisetin, morin, quercetin and kaempferol without significant interference from other components, indicating high selectivity of the solid-phase borate-complex extraction. The absolute recoveries of quercetin, fisetin and rutin were superior to those of kaempferol, myricetin and morin, suggesting a difference in the complex formation efficiency between 1,2- and 1,3-diol structures. When using fisetin as an internal standard, polyhydroxyflavones were quantified in the concentration range 0.10-30.0 microg/ml. In replicate spiking experiments with standards, the mean relative recoveries ranged between 75.7 and 104.6%, and the intra-and inter-assay C.V.s ranged between 0.8 and 10.2% for onion, wine and plasma samples. The proposed method will be applicable to nutritional and pharmacokinetic experiments of polyhydroxyflavones.


Design, synthesis and biological evaluation of sugar-derived Ras inhibitors.
The design and synthesis of novel Ras inhibitors with a bicyclic scaffold derived from the natural sugar D-arabinose are presented. Molecular modelling showed that these ligands can bind Ras by accommodating the aromatic moieties and the phenylhydroxylamino group in a cavity near the Switch II region of the protein. All the synthetic compounds were active in inhibiting nucleotide exchange on p21 human Ras in vitro, and two of them selectively inhibited Ras-dependent cell growth in vivo.


Facile, novel two-step syntheses of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines.
Three scaffolds of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines were synthesized via Ugi/de-protection/cyclization methodology. Benzimidazole forming ring closure was enabled under microwave irradiation in the presence of 10% TFA/DCE. The methodology demonstrates the utility of 2-(N-Boc-amino)-phenyl-isocyanide for the generation of new molecular diversity.


Comparison of Ibuprofen with Ketorolac on the Control of Renal Colic Pain: A Meta-Analysis of Randomized Controlled Studies.
The comparison of ibuprofen with ketorolac remains controversial for the pain control of renal colic. We therefore conduct this meta-analysis to compare the analgesic efficacy of ibuprofen with ketorolac for renal colic. We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2022 for randomized controlled trials (RCTs) assessing the analgesic efficacy of ibuprofen in comparison with ketorolac for renal colic. This meta-analysis was performed using the random-effect or fixed-effect model based on the heterogeneity. Four RCTs were included in the meta-analysis. In patients with renal colic pain, intravenous ibuprofen and ketorolac produced comparable pain scores at 15 min (MD=-0.46; 95% CI=-1.24 to 0.31; P=0.24), 30 min (MD=-0.81; 95% CI=-1.75 to 0.31; P=0.09), 60 min (MD=-0.63; 95% CI=-1.40 to 0.13; P=0.10) and 120 min (MD=-0.74; 95% CI=-2.18 to 0.70; P=0.31), as well as adverse events (OR=0.95; 95% CI=0.61 to 1.49; P=0.83). Ibuprofen can obtain the comparable analgesic efficacy to ketorolac for renal colic pain.


An efficient synthesis of nucleotides via the phosphoramidite method using a triflic acid salt of an imidazole-related compound as a promoter.
N-Phenylimidazolium triflate and N-methylbenzimidazolium triflate, new imidazole-related compound/triflic acid-complex type of promoters in the phosphoramidite method, has been developed. These reagents are, particularly, useful for internucleotide-bond formation with lowly reactive reactants and have allowed an efficient, high-yield synthesis of oligodeoxyribonucleotides both in a solution phase and on a solid supports.


Relation between left ventricular shape and Doppler filling parameters in patients with left ventricular dysfunction secondary to coronary artery disease.
Left ventricular (LV) shape is an independent predictor of exercise capacity in patients with systolic LV dysfunction. Recent studies suggest that end-systolic LV shape is related to the generation of restoring forces during contraction that facilitate filling at lower LV pressure during subsequent diastole. To test the hypothesis that preservation of a more elliptical LV shape would be associated with a distribution of diastolic inflow characterized by increased early relative-to-late filling, 32 outpatients with coronary artery disease and ejection fraction < 40% underwent quantitative 2-dimensional and Doppler echocardiography. LV volumes, ejection fraction, and eccentricity index were measured as were standard Doppler indexes of LV filling. Simple and multiple linear regression models were used to examine relations between LV shape and Doppler measurements. LV eccentricity at end-systole correlated strongly with the Doppler atrial filling fraction (r = -0.670; p < 0.001) and the ratio of early-to-late flow velocity integrals (r = 0.648; p < 0.001). No other 2-dimensional echocardiographic variable was significantly correlated with any other Doppler index of LV filling. Thus, LV shape at end-systole appears to be an important determinant of diastolic filling patterns. In patients with systolic LV dysfunction, preservation of a more elliptical chamber is associated with a diastolic inflow pattern characterized by increased early relative-to-late diastolic filling.


Co+2, Ni+2 and Cu+2 incorporated Bi2O3 nano photocatalysts: Synthesis, DFT analysis of band gap modification, adsorption and photodegradation analysis of rhodamine B and Triclopyr.
This study deals with the fabrication of metal ion (M = Co+2, Ni+2, and Cu+2) doped- Bi2O3 photocatalysts by solution combustion method. All the synthesized materials were characterized and analysed with the help of XRD, FESEM, EDX, HRTEM, UVDRS, Zeta potential, PL, and LCMS techniques for the structural, morphological, surface charge, optical and degradation pathways characteristics. Synthesized compounds were used for the decontamination (adsorption and degradation) of two organic pollutants namely Rhodamine B and Triclopyr. Adsorption aspects of the pollutants were studied in terms of different isotherm, kinetic and thermodynamic models. Adsorption phenomenon was best fitted with the Freundlich (R2 = 0.992) and Langmuir isotherm (R2 = 0.999) models along with pseudo second order model of kinetics for RhB and TC, respectively. Moreover, the thermodynamic parameters indicated exothermic and endothermic adsorption (ΔH ° (-7.19 kJ/mol) for RhB) and (ΔH ° (52.335 kJ/mol) for TC), respectively. Evaluated negative values of ΔG ° indicated spontaneous adsorption with most favourable at 298 K and 318 K for both the pollutants (RhB and TC) respectively. Modification with metal ions significantly improved the removal efficiency of pure Bi2O3 photocatalyst and followed the trend Co+2/Bi2O3 > Ni+2/Bi2O3 > Cu+2/Bi2O3 > Bi2O3. DFT calculations demonstrate that amongst the doped materials, only Co+2/Bi2O3 is characterized by an indirect band gap; which exhibited efficacious photocatalytic activity. Besides, the highest degradation efficiency was obtained in the case of Co+2/Bi2O3 (2 mol %); being 99.80% for RhB in 30 min and 98.50% for TC in 60 min, respectively. The doped nanostructures lead to higher absorption of visible light and more separation of light-induced charged carriers. Effect of pH of the reaction medium and role of reactive oxygen species was also examined. Finally, a probable mechanism of charge transfer and degradation of the pollutants was also presented.


Malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma): an electron microscopic study.
A comparative ultrastructural analysis of malignant soft tissue tumors (malignant fibrous histiocytoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma) revealed similar ultrastructural features in this group of tumors. However, by electron microscopy these tumors can be differentiated on the basis of cytoplasmic and extracytoplasmic features (myosin filaments, lipid droplets, and perinuclear intermediate filaments, for example). This is even true of less well differentiated tumors and tumor cells. These findings support and amplify the concept of a common histogenesis for tumors of mesenchymal origin. Paradoxical features observed by light microscopy warrant further study by electron microscopy if the correct diagnosis is to be made in atypical cases, such as apparent malignant fibrous histiocytoma with cross striations.


The influence of the polar head-group of synthetic cationic lipids on the transfection efficiency mediated by niosomes in rat retina and brain.
The development of novel non-viral delivery vehicles is essential in the search of more efficient strategies for retina and brain diseases. Herein, optimized niosome formulations prepared by oil-in water (o/w) and film-hydration techniques were characterized in terms of size, PDI, zeta potential, morphology and stability. Three ionizable glycerol-based cationic lipids containing a primary amine group (lipid 1), a triglycine group (lipid 2) and a dimethylamino ethyl pendent group (lipid 3) as polar head-groups were part of such niosomes. Upon the addition of pCMS-EGFP plasmid, nioplexes were obtained at different cationic lipid/DNA ratios (w/w). The resultant nioplexes were further physicochemically characterized and evaluated to condense, release and protect the DNA against enzymatic digestion. In vitro experiments were performed to evaluate transfection efficiency and cell viability in HEK-293, ARPE-19 and PECC cells. Interestingly, niosome formulations based on lipid 3 showed better transfection efficiencies in ARPE-19 and PECC cells than the rest of cationic lipids showed in this study. In vivo experiments in rat retina after intravitreal and subretinal injections together with in rat brain after cerebral cortex administration showed promising transfection efficiencies when niosome formulations based on lipid 3 were used. These results provide new insights for the development of non-viral vectors based on cationic lipids and their applications for efficient delivery of genetic material to the retina and brain.


The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing.
The ability to program different atrioventricular (AV) delay intervals for paced and sensed atrial events is incorporated in the design of some newer dual chamber pacemakers. However, little is known regarding the hemodynamic benefit of differential AV delay intervals or the magnitude of difference between optimal AV delay intervals for paced and sensed P waves in individual patients. In this study, Doppler-derived cardiac output was used to examine the optimal timing of paced and sensed atrial events in 24 patients with a permanent dual chamber pacemaker. The hemodynamic effect of utilizing separate optimal delay intervals for sensed and paced events compared with utilizing the same fixed AV delay interval for both was determined. The optimal delay interval during DVI (AV sequential) pacing and VDD (atrial triggered, ventricular inhibited) pacing at similar heart rates was 176 +/- 44 and 144 +/- 48 ms (p less than 0.002), respectively. The mean difference between the optimal AV delay intervals for sensed (VDD) and paced (DVI) P waves was 32 ms and was up to 100 ms in some individuals. The difference between optimal AV delay intervals for sensed and paced atrial events was similar in patients with complete heart block and those with intact AV node conduction. At the respective optimal AV delay intervals for sensed and paced P waves, there was no significant difference in the cardiac output during VDD compared with DVI pacing. However, cardiac output significant declined during VDD pacing at the optimal AV delay interval for a paced event and during DVI pacing at the optimal interval for a sensed event.(ABSTRACT TRUNCATED AT 250 WORDS)


Thoracic radiotherapy in patients with lymphoma and restenosis after coronary stent placement.
The aim of this study was to assess the incidence of restenosis after coronary stenting in patients with lymphoma treated with thoracic radiation. Patients with Hodgkin lymphoma treated with thoracic radiation have an increased incidence of coronary artery disease (CAD). The incidence of restenosis after percutaneous coronary interventions is completely unknown. This study included 12,626 consecutive patients with CAD treated with coronary stenting during a 10-year period. Within this cohort, three subgroups of patients were assessed: patients with lymphoma and previous thoracic radiation (15 patients), patients with lymphoma without thoracic radiation (7 patients) and patients without lymphoma or previous thoracic radiation (control group; 12,604 patients). Coronary stenting was performed after a median [25th; 75th percentiles] of 8 years [4; 17] after thoracic radiation. The primary end point of the study was restenosis at 6-month coronary angiography. Six-month coronary angiography was performed in 14 patients (93%) in the group with lymphoma and radiation, 6 patients (86%) in the group with lymphoma without radiation and 10,032 patients (80%) in the control group (P = 0.38). Angiographic restenosis was found in 12 patients (85.7%) in the group with lymphoma and radiation, 1 patient (16.7%) in the group with lymphoma without radiation and 2,555 patients (25.5%) in the control group (P < 0.001). Multiple logistic regression identified thoracic radiation as an independent predictor of coronary restenosis (odds ratio 21.7, 95% confidence interval, 4.7-100.9, P < 0.001). Patients with lymphoma treated with thoracic radiation have an increased risk of restenosis after coronary artery stenting.


Early diagnosis of bilateral sub-deltoid bursitis using clinic-based ultrasonography in a patient receiving infliximab therapy for ulcerative pouchitis.
Infliximab, a monoclonal chimeric antibody to tumour necrosis factor (TNF)α, is a novel therapy used in the management of chronic refractory pouchitis that is unresponsive to conventional medical therapy. This report describes a case of non-infective bursitis following infliximab therapy and documents the role of musculoskeletal ultrasound in detecting soft tissue fluid collections and in guiding aspiration. A high index of suspicion is required when assessing new or worsening musculoskeletal pain in patients receiving infliximab and involvement of a rheumatologist at an early stage is essential in order to appropriately diagnose and manage this condition.


Multifocal renal oncocytoma.
A case of multifocal oncocytoma of the kidney is reported. A review of the literature revealed only 2 other cases with multifocal tumors. The occurrence of these multicentric tumors should discourage the attempt of performing partial renal resection as recently advocated by some authors.