Endothelial adhesion molecules in breast cancer invasion into the vascular and lymphatic systems.
It is well recognised that intravasation of tumour cells into the vasculature and/or lymphatics is a key stage in the metastatic process. It is also clear that very little is known about the mechanisms underlying this event. In this review, we will focus on cell surface molecules that may be instrumental in mediating the attachment of tumour cells, and in particular breast carcinoma cells, to the lymphatic and microvascular endothelia and discuss the therapeutic and prognostic value in targeting these receptors in metastatic disease. A literature search was carried out from PubMed for indexed articles and reviews. Websites containing information on gene expression profiles were located using standard web browser search functions. For articles containing gene expression data, relevant information was frequently located in supplementary tables or in associated websites. The search yielded a very large number of indexed published articles and websites. Important major reports and studies were reviewed, screened and tracked for other relevant publications. The most important articles were analysed and discussed. The lack of knowledge as to the mechanism by which tumour cells intra-vasate into the vasculature and/or lymphatics is perhaps not surprising given the lack of suitable models with which to investigate tumour cell intravasation. However, recent advances in the identification of molecular markers of angiogenic and lymphangiogenic endothelium, the development of techniques to image tumour cells in vivo and a better understanding of the architecture of these vessels is beginning to offer hope that this least well understood event in the metastatic process is becoming more amenable to study.


Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma.
This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained significant. This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials.


Incidence of adenovirus and respiratory syncytial virus in chronic otitis media with effusion using the polymerase chain reaction.
The aim of this study is to investigate the role of adenovirus and respiratory syncytial virus in the cause of chronic otitis media with effusion by use of the polymerase chain reaction for detection. The polymerase chain reaction has proved to be more sensitive and specific than viral cultures and immunoassays in the detection of viruses in other specimens. Adenovirus and respiratory syncytial virus were chosen because these viruses have been the most commonly isolated viruses in middle ear effusions in studies using other techniques. The effusions (132 total) were sterilely collected from 88 children undergoing myringotomy and ventilation tube placement for chronic otitis media with effusion. Nine (6.8%) specimens were positive for adenovirus by the polymerase chain reaction, and 13 (9.9%) were positive for respiratory syncytial virus by the polymerase chain reaction. Only one specimen was positive for adenovirus and respiratory syncytial virus by viral culture and immunofluorescence, respectively. Our results show that the polymerase chain reaction can be used to detect adenovirus and respiratory syncytial virus in chronic middle ear effusions and that PCR is more sensitive than viral culture and immunofluorescence techniques.


A panel of extracellular vesicle long noncoding RNAs in seminal plasma for predicting testicular spermatozoa in nonobstructive azoospermia patients.
Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients? Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA. The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE. RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples. RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets. A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended. In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated. When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate. This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study. N/A.


Stability of genomic DNA fragment patterns in methicillin resistant Staphylococcus aureus (MRSA) during the course of intra- and interhospital spread.
The analysis of genomic DNA fragment patterns has revealed as a powerful tool for strain discrimination in Staphylococcus aureus; for use as an epidemiological marker, stability during the course of an outbreak is an essential prerequisite. Genomic DNA fragment patterns (SmaI restriction, pulsed-field electrophoresis) of four different epidemic MRSA strains were compared along with intra- and interhospital and country-wide spread over more than 12 months in Germany. Strain I was isolated from infections in 8 hospitals. In one hospital a subclone arised which differed from the original strain by 4 fragments. Strain II was spread among 4 hospitals, isolates from three of these hospitals exhibited a variability of one to three fragments in the 150-200 kb range. Two hospitals in the Hannover-area were affected by strain III; in 17 isolates of this strain a variability up to three fragments was found in the 170-200 kb range. Strain IV was isolated from 19 cases of infections in 3 hospitals in Berlin. The fragment patterns were completely stable. When S. aureus strains are typed by genomic DNA fragment patterns, a variability in a definite range of molecular masses during the course of an epidemic should be taken into consideration.


A biofilter integrated with gas membrane separation unit for the treatment of fluctuating styrene loads.
Biofiltration for volatile organic compound control in waste gas streams is best operated at steady contaminant loadings. To provide long-term stable operation of a biofilter under adverse contaminant feeding conditions, an integrated bioreactor system with a gas separation membrane module installed after a biofilter was proposed for styrene treatment. Styrene was treated effectively, with average styrene effluent concentrations maintained at less than 50 mg m(-3) and a total removal efficiency of over 96% achieved when the biofiltration column faced fluctuating loads. The maximum elimination capacity of the integrated bioreactor system was 93.8 g m(-3)h(-1), which was higher than that obtained with the biofiltration column alone. The combination of these two processes (microbial and chemical) led to more efficient elimination of styrene and buffering of the fluctuating loads. The factors on gas membrane separation, microbial characteristics in the integrated bioreactor and membrane fouling were also investigated in this study.


Janus-Nanojet as an efficient asymmetric photothermal source.
The combination of materials with radically different physical properties in the same nanostructure gives rise to the so-called Janus effects, allowing phenomena of a contrasting nature to occur in the same architecture. Interesting advantages can be taken from a thermal Janus effect for photoinduced hyperthermia cancer therapies. Such therapies have limitations associated to the heating control in terms of temperature stability and energy management. Single-material plasmonic nanoheaters have been widely used for cancer therapies, however, they are highly homogeneous sources that heat the surrounding biological medium isotropically, thus equally affecting cancerous and healthy cells. Here, we propose a prototype of a Janus-Nanojet heating unit based on toroidal shaped plasmonic nanoparticles able to efficiently generate and release local heat directionally under typical unpolarized illumination. Based on thermoplasmonic numerical calculations, we demonstrate that these Janus-based nanoheaters possess superior photothermal conversion features (up to [Formula: see text] K) and unique directional heating capacity, being able to channel up over 90% of the total thermal energy onto a target. We discuss the relevance of these innovative nanoheaters in thermoplasmonics, and hyperthermia cancer therapies, which motivate the development of fabrication techniques for nanomaterials.


Intracranial glossopharyngeal neurinomas. Report of two cases with special emphasis on computed tomography and magnetic resonance imaging findings.
Two patients with intracranial glossopharyngeal neurinoma are described. In both patients, neurologic signs and findings of conventional radiologic and computed tomography examinations suggested a diagnosis of acoustic neurinoma. Magnetic resonance imaging, however, definitely indicated that the mass had actually arisen from the lower cranial nerves. This was confirmed at operation. The superb sensitivity and specificity of magnetic resonance imaging in the diagnosis of posterior fossa extraaxial mass are emphasized.


Peptide products of the cleavage of bovine preprolactin by signal peptidase.
Cleavage of preprolactin (pPL) by detergent-solubilized signal peptidase produced mature prolactin and two small peptides derived from the signal peptide region of the pPL molecule. The production of both peptides was dependent on functional signal peptidase; the peptides were not generated at detergent concentrations that abolished signal peptidase activity. The amount of both peptides was proportional to the concentration of signal peptidase in the assay. The appearance of both peptides was insensitive to protease inhibitors, as was signal peptidase activity. The size, labeling characteristics, and amino acid sequence of the larger peptide, peptide 1, corresponded to those of the intact signal peptide of pPL. The smaller peptide, peptide 2, lacked the carboxy terminus of the signal peptide, and was, therefore, a fragment of intact signal peptide. These results demonstrate the endoproteolytic nature of signal peptidase.


Breakfast eating habit and its influence on attention-concentration, immediate memory and school achievement.
To study the relationship of breakfast to the attention -concentration, immediate recall memory, nutritional status and academic achievement of school children. Cross-sectional study. Two schools catering to middle class families in Hyderabad city. 379 urban 11 to 13 years old school children studying in 6th, 7th and 8th grades. Data collected in a single way blind procedure using Letter Cancellation test, immediate memory from the PGI Memory Scale, school marks of the previous year and nutritional status. Comparison between groups indicated significant differences in the letter cancellation (LC) total scores with the regular breakfast group achieving the highest mean scores compared to the no breakfast group (P< 0.05). Marks scored by the regular breakfast group in subjects - Science, English and total Percentage were significantly higher compared to those scored by the children in the no breakfast group. Regular breakfast eating habit and weight for age percent were significantly (P< 0.001) associated with immediate recall memory score explaining 4.3 percent variation. Regular habit of eating breakfast as opposed to irregular consumption or skipping breakfast altogether had beneficial influence on attention-concentration, memory and school achievement.


Immediate argon laser peripheral iridoplasty as treatment for acute attack of primary angle-closure glaucoma: a preliminary study.
This study aimed to examine the intraocular pressure (IOP)-lowering effects and safety of immediate argon laser peripheral iridoplasty (ALPI) as a first-line treatment for acute primary angle-closure glaucoma (PACG). A prospective cohort study. Ten consecutive patients with their first attack of PACG, with IOP of 40 mmHg or greater, were recruited into the study. On presentation, each patient received topical pilocarpine (4%) and timolol (0.5%) and immediate ALPI as primary treatment. The IOPs at 15, 30, and 60 minutes after ALPI were documented by applanation tonometry. When the corneal edema had settled, laser peripheral iridotomy was performed as a definitive treatment. The IOP, corneal edema, and complications from ALPI were measured. The mean IOP of this group of patients was reduced from 59.5+/-10.4 mmHg to 28.7+/-14.9 mmHg at 15 minutes, 21.7+/-13.1 mmHg at 30 minutes, and 16.0+/-9.4 mmHg at 60 minutes after ALPI. No complications from the laser procedure were encountered during the study period. In nine of the ten patients, the corneal edema cleared up 1 hour after ALPI. In the remaining patient, the cornea cleared up 2 hours after ALPI. From this preliminary study, immediate ALPI, without adjunctive systemic antiglaucoma treatment, appeared to be very effective in controlling the IOP and returning corneal clarity in acute PACG. Its safety also appeared reassuring and did not have the risks associated with conventional systemic therapies.


Drosophila development: novel signal elicits visceral response.
A Drosophila screen aimed at furthering understanding of how tissues develop from the mesoderm has identified a novel signalling molecule that is proposed to signal from somatic muscle progenitors to direct the development of adjacent visceral muscle.


A unique amino acid sequence of the B subunit of a heat-labile enterotoxin isolated from a human enterotoxigenic Escherichia coli.
The purified B subunit of heat-labile enterotoxin produced from a human strain, 240-3, of enterotoxigenic Escherichia coli (LTh(240-3] was carboxymethylated, succinylated, digested with chymotrypsin and subjected to high performance liquid chromatography (HPLC), and the amino acid compositions of the peptide peaks from the column were analyzed and compared with the data reported by Yamamoto and Yokota (J. Bacteriol. 155, 728.1983), who deduced the amino acid sequence of LTh(H10407) from the DNA sequence of a human strain H10407. Only one fraction differed in amino acid composition from that reported by them. This fraction was found to consist of peptides with the sequences Arg-Asn-Thr-Gln-Ile-Tyr and Arg-Ile-Ala-Tyr. Yamamoto and Yokota reported the sequence of the latter peptide as Arg-Ile-Thr*-Tyr, which corresponds to the peptide from 73rd to 76th from amino (N-) terminus. Thus amino acid residue 75 from the N-terminus of LTh-B(240-3) is alanine, not threonine. The B subunit of cholera toxin also has alanine at position 75. LTh(240-3) appeared similar to LTh(H10407) in an Ouchterlony test, vascular permeability test and GMI ganglioside ELISA. These data show that substitution of threonine for alanine at position 75 from the N-terminus does not affect the immunological and biological characteristics of LTh.


Decrease of serotonin transporters in blood platelets after epileptic seizures.
Serotonin transporter (SERT) was studied by [3H]-paroxetine binding in blood platelets from controls and epileptic patients with generalized convulsive seizures. The average KD and BMax were not different in the two cases. However, a significant decrease was found in the serotonin transporter density in the platelet membranes from patients having undergone an epileptic seizure less than 4 days before. This circumstance may indicate a homeostatic reaction to the epileptic attack.


Metal oxide nanoparticles inhibit nitrogen fixation and rhizosphere colonization by inducing ROS in associative nitrogen-fixing bacteria Pseudomonas stutzeri A1501.
The potential effects of engineered metal oxide nanoparticles (MONPs) on bacterial nitrogen fixation are of great concern. Herein, the impact and mechanism of the increasing-used MONPs, including TiO2, Al2O3, and ZnO nanoparticles (TiO2NP, Al2O3NP, and ZnONP, respectively), on nitrogenase activity was studied at the concentrations ranging from 0 to 10 mg L-1 using associative rhizosphere nitrogen-fixing bacteria Pseudomonas stutzeri A1501. Nitrogen fixation capacity was inhibited by MONPs in an increasing degree of TiO2NP < Al2O3NP < ZnONP. Realtime qPCR analysis showed that the expressions of nitrogenase synthesis-related genes, including nifA and nifH, were inhibited significantly when MONPs were added. MONPs could cause the explosion of intracellular ROS, and ROS not only changed the permeability of the membrane but also inhibited the expression of nifA and biofilm formation on the root surface. The repressed nifA gene could inhibit transcriptional activation of nif-specific genes, and ROS reduced the biofilm formation on the root surface which had a negative effect on resisting environmental stress. This study demonstrated that MONPs, including TiO2NP, Al2O3NP, and ZnONP, inhibited bacterial biofilm formation and nitrogen fixation in the rice rhizosphere, which might have a negative effect on the nitrogen cycle in bacteria-rice system.


Synthesis, Structural Characterization, and Water Vapor Sorption Behavior of Two Ligand Ratio-Dependent Supramolecular Networks, [Cd(2,2'-bpym)1.5(BDC)]·0.5(2,2'-bpym)·5H2O and [Cd(2,2'-bpym)0.5(BDC)(H2O)3].
Two ligand ratio-dependent supramolecular networks, [Cd(2,2'-bpym)1.5(BDC)]·0.5(2,2'-bpym)·5H2O (1) and [Cd(2,2'-bpym)0.5(BDC)(H2O)3] (2), (BDC2- = dianion of terephthalic acid and 2,2'-bpym = 2,2'-bipyrimidine) have been synthesized and structurally characterized by the single-crystal X-ray diffraction method. Structural determination reveals that compound 1 is a two-dimensional (2D) layered metal-organic framework (MOF) constructed via the bridges of Cd(II) ions with 2,2'-bpym and BDC2- ligands, and compound 2 is a zero-dimensional (0D) 2,2'-bpym-bridged di-Cd(II) monomeric complex. When the thermally dehydrated powders of 1 (at 100 °C) were immersed into water solution, most of the dehydrated powders of 1 underwent structural transformation back to rehydrated 1, but very little amounts of the dehydrated powders of 1 were decomposed to light-brown crystals of 2 or colorless crystals of a new coordination polymer (CP), [Cd(2,2'-bpym)(BDC)(H2O)]·3H2O (3), with its one-dimensional (1D) zigzag chain-like framework being constructed via the bridges of Cd(II) ions with the BDC2- ligand. Structural analysis reveals that all 3D supramolecular networks of 1-3 are further constructed via strong intermolecular interactions, including hydrogen bonds and π-π stacking interactions. Compounds 1 and 2 both exhibit significant water vapor hysteresis isotherms, and their cyclic water de-/adsorption behavior accompanied with solid-state structural transformation has been verified by de-/rehydration TG analyses and powder X-ray diffraction (PXRD) measurements.


Pharmacogenomic assessment of treatment options in gestational diabetes.
Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a "normal" gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.


Molecular switching fluorescence based high sensitive detection of label-free C-reactive protein on biochip.
A novel detection technique on biochip for the quantification of label-free C-reactive protein (CRP) based on molecular switching of fluorescence (MSF) is demonstrated by total internal reflection fluorescence microscopy. It alters fluorescence intensity of fluoreseinamine isomer 1 (FAI) upon binding with its specific ligand, O-phosphorylethanolamine (PEA). In the MSF-based detection, FAI was used as an ink, printed on a 3-glycidoxypropyl-trimethoxysilane (GPTS)-coated glass coverslip. With the addition of GPTS conjugated PEA solution to the FAI-printed coverslip, the fluorescence intensity was remarkably decreased. Addition of CRP increased fluorescence intensity linearly in the range of 800 aM to 500 fM (R=0.997). The MSF-based biochip assay for the estimation of CRP in human sera showed ∼200 times increased detection sensitivity in less than a third of the time to obtain results using a conventional enzyme-linked immunosorbent assay. This biochip detection is a promising new technique for the quantification of CRP molecules from trace amounts of clinical samples.


Electrophysiological evidence of the Riche-Cannieu anastomosis in the hand and its diagnostic implications; 2 case reports.
Anomalous anastomoses between the nerves of the hand are not as rare as thought to be. Amongst these, the Riche-Cannieu anastomosis (RCA) is a connection between the ulnar nerve and median motor nerve in the palm. Presence of this can sometimes be misdiagnosed as a severe median mononeuropathy at the wrist/carpal tunnel syndrome (CTS).We describe two cases that were referred for evaluation of CTS and were found to have incidental RCA. Electrophysiological studies showed typical findings consistent with RCA and coexistent mild CTS. Patients in whom median sensory and motor latency prolongations suggest CTS, the presence of an anastomosis should be suspected if the median motor amplitudes are worse than the median sensory amplitudes. The electrophysiological study should be extended to avoid erroneous interpretation of low median motor amplitudes as severe CTS and to prevent unnecessary surgical intervention.


Association between Tulathromycin Treatment for Bovine Respiratory Disease and Antimicrobial Resistance Profiles among Gut Commensals and Foodborne Bacterial Pathogens Isolated from Feces of Beef Steers.
This study was conducted to evaluate the association between a therapeutic dose of tulathromycin for bovine respiratory disease in beef steers and the antimicrobial and multidrug resistance profiles of the gastrointestinal tract commensals Escherichia coli and Enterococcus spp. and the foodborne pathogens Salmonella enterica and Campylobacter spp. isolated from fecal samples. Individual fecal samples were collected on days 0, 14, and 28 from 70 beef steers that were housed in a single pen and had been treated or not treated with tulathromycin. Samples were cultured for bacterial isolation, and isolates were tested for antimicrobial susceptibility with the broth microdilution method to determine the MICs of clinically relevant antimicrobials used in both human and veterinary medicine. Generalized linear mixed effects models were fitted to estimate the prevalence of the bacterial species and the prevalence of resistant isolates over time and between treated and nontreated cattle and of multidrug-resistant isolates. Model-adjusted mean prevalences of E. coli, Enterococcus spp., S. enterica, and Campylobacter spp. were 99.5, 85.9, 1.5, and 17.7%, respectively. The prevalence of erythromycin-resistant Enterococcus spp. was significantly higher on day 14 (59.7%) than on day 28 (22.2%). A higher prevalence of erythromycin-resistant Enterococcus spp. was found in samples from treated (59.3%) than in samples from nontreated (27.6%) animals. Multidrug resistance (three or more antimicrobial classes) was observed in 8.4% of E. coli isolates and 62.7% of Enterococcus isolates. The administration of tulathromycin was significantly associated with an increased prevalence of erythromycin-resistant Enterococcus spp. isolates.


Ultrasonography for the Prediction of High-Volume Lymph Node Metastases in Papillary Thyroid Carcinoma: Should Surgeons Believe Ultrasound Results?
Lymph node metastasis (LNM) often occurs in papillary thyroid carcinoma (PTC); the efficacy of ultrasound for predicting high-volume lymph node metastases (LNMs) in patients with PTC remains unexplored. The medical records of 2073 consecutive PTC patients were reviewed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to evaluate the efficacy of ultrasound. Risk factors for LNM/high-volume LNMs and lymph node involvement on ultrasound (usLNM) were identified by univariate and multivariate analyses. Of all the patients, 936 (45.2%) patients had LNMs, and 254 (12.3%) patients had high-volume LNMs. The sensitivity of ultrasound for detecting LNM/high-volume LNMs was 27.9% and 63.8%, respectively; the specificity was 93.1% and 90.3%, respectively. The NPV for ultrasound in detecting high-volume LNMs was 94.7%. In multivariate analysis, male sex (OR = 2.108, p < 0.001), tumor diameter > 1.0 cm (OR = 2.304, p < 0.001) and usLNM (+) (OR = 12.553, p < 0.001) were independent clinical risk factors for high-volume LNMs. Tumor diameter > 1 cm (OR = 3.036, p < 0.001) and male sex (OR = 1.642, p < 0.001) were independent clinical risk factors for usLNM; a skilled sonographer (OR = 1.121, p = 0.358) was not significantly associated with usLNM. Lymph node involvement found by ultrasound has great predictive value for high-volume LNMs; the NPV is very high for patients without lymph node involvement on ultrasound. The ultrasound results do not appear to be influenced by the experience of the sonographer.


Active site mutants of Escherichia coli citrate synthase. Effects of mutations on catalytic and allosteric properties.
We report properties of five active site mutants of Escherichia coli citrate synthase, in which histidine 264, aspartate 362, and phenylalanine 383 were replaced by alanines, and arginines 387 and 407 by leucines. All mutants have much lower turnover numbers than wild type enzyme; the strongest effect was with the arginine 387 mutant, perhaps because the substrate, oxaloacetate, binds in a different orientation. The arginine 407 mutant has lost most of its ability to distinguish alpha-ketoglutarate, a competitive inhibitor, from oxaloacetate. The mutations of histidine 264 and aspartate 362 affect steady-state kinetics as would be anticipated from current models for citrate synthase catalysis, and resemble mutations of these residues, in pig heart and E. coli enzyme, reported by others. Mutations of residues 264, 362, and 383 also affect allosteric properties. With the phenylalanine 383 mutant, acetyl-CoA saturation is strongly sigmoid, even in the presence of the activator, KCl, implying a marked shift of the allosteric equilibrium toward the T state. The histidine 264 mutant appears to be shifted toward R state and shows weaker binding of the allosteric inhibitor, NADH; thus this mutation also affects the allosteric site, 25-30 A away.


Practices and perceptions of food safety among seniors who prepare meals at home.
Given senior citizens' vulnerability for food-borne illness, a need exists to determine the necessity and focus for education. Focus groups at senior centers reveal that the seniors (N=74) who prepare more than five meals a week at home use both inappropriate and appropriate practices to cook, cool, and thaw foods. Seniors rely of the distant past for knowledge and identify barriers to altering practices but state that information from educators about the health effects of inappropriate practices will convince them to change. For future food safety education, seniors recommend programs, videotapes, television, newspapers, radio, church bulletins, and written educational pieces.


Recovery after hyperpyrexia during beta-haemolytic streptococcal septicaemia.
A patient with septicaemia caused by a beta-haemolytic streptococcus developed a high fever during which his temperature reached 44 degrees C (112 degrees F). Although body temperatures above 42 degrees C are unusual, in this case the high temperature was rapidly brought under control and the infection was successfully treated. The patient made a full recovery with no long-term sequelae.


Self-cured resin modified by quaternary ammonium methacrylates and chlorhexidine: Cytotoxicity, antimicrobial, physical, and mechanical properties.
To evaluate the addition of dimethylaminohexadecyl methacrylate (DMAHDM) and chlorhexidine diacetate on cytotoxicity, antimicrobial activity, physical, and mechanical properties of a self-cured resin. 132 disk-shaped and 48 rectangular specimens were divided into four experimental groups as described: Control Group (CG - no addition), dCHX (1%), DMAHDM (5%), and DMAHDM+dCHX (5%+1%). The biofilm viability, flexural strength (FS - ISO 20795-1:2013), surface roughness (SR), and color stability (ΔE) were analyzed after being stored for 4 weeks in distilled water and immersed for 72h in coffee. Cytotoxicity was measured after 24h, 3, and 7 days of elution using an MTT test on L929 cells (ISO 10993-5:2009). SR and ΔE were measured by a contact profilometer and a spectrophotometer using the CIELab parameter. Data were submitted to ANOVA and Bonferroni's/Tukey's tests (p≤0.05). Significant antimicrobial activity against Streptococcus mutans and Candida albicans was detected in all groups when compared to the CG (p<0.05). Only the dCHX group, in 24h of elution, demonstrated no cytotoxicity effects. There was a statistical difference for FS on the tested groups (p<0.05). No differences were detected in the initial roughness' measurements among the groups (p>0.05). However, after storage and immersion in coffee, the groups containing DMAHDM presented with rougher surfaces and significantly lower color stability compared to the control (p<0.05). The addition of dCHX and DMAHDM in self-cured resin presented antimicrobial properties; however, cytotoxicity, physical, and mechanical properties were compromised.


Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?
Cancer chemotherapy is still a serious challenge. Chemo-resistance and destructive side effects of chemotherapy drugs are the most critical limitations of chemotherapy. Chemo-resistance is the leading cause of chemotherapy failure. Chemo-resistance, which refers to the resistance of cancer cells to the anticancer effects of chemotherapy drugs, is caused by various reasons. Among the most important of these reasons is the increase in the efflux of chemotherapy drugs due to the rise in the expression and activity of ABC transporters, the weakening of apoptosis, and the strengthening of stemness. In the last decade, a significant number of studies focused on the application of nanotechnology in cancer treatment. Considering the anti-cancer properties of zinc, zinc oxide nanoparticles have received much attention in recent years. Some studies have indicated that zinc oxide nanoparticles can target the critical mechanisms of cancer chemo-resistance and enhance the effectiveness of chemotherapy drugs. These studies have shown that zinc oxide nanoparticles can reduce the activity of ABC transporters, increase DNA damage and apoptosis, and attenuate stemness in cancer cells, leading to enhanced chemo-sensitivity. Some other studies have also shown that zinc oxide nanoparticles in low doses can be helpful in minimizing the harmful side effects of chemotherapy drugs. In this article, after a brief overview of the mechanisms of chemo-resistance and anticancer effects of zinc, we will review all these studies in detail.


Monoclonal antibody internalization by tumor cells: an experimental model for potential radioimmunotherapy applications.
The monoclonal IgM 3G5, which reacts with the surface membranes of rat insulinoma cells RINm5F, was purified by HPLC and labeled with 125I using Protag-125; bovine IgG (bIgG) was similarly radiolabeled, and used as a control. 125I-3G5 was incubated with RINm5F cells either at 4 degrees C or at 37 degrees C. 125I-3G5 bound onto RINm5F cells growing in Petri dishes remained approx. constant over 44 h when incubated at 4 degrees C, whereas at 37 degrees C radioactivity was released back in the medium starting at 3 h (plateau at approx. 20 h). At the end of incubation at 37 degrees C, activity in the medium included a high percentage of free 125I (15.69 vs 2.62% for bIgG, and 1% for 3G5 at 4 degrees C). In a cell suspension experiment, cell-bound 125I-3G5 also remained constant over a 24 h incubation at 4 degrees C, whereas at 37 degrees C it decreased to 37.5% of its initial value (64.1% at 4 h). Concomitant microautoradiography showed diffuse radioactive deposits within the RINm5F cells following incubation with 125I-3G5 (but not 125I-bIgG) at 37 degrees C. These results indicate that 3G5-IgM reacts with a surface antigen on the RINm5F cells, but is rapidly internalized by the cells: within the cells, this antibody undergoes some metabolic processing which results in the release of free 125I outside the cells.


Lithium treatment versus hospitalization in bipolar disorder and major depression patients.
Preventing hospitalization of major affective disorder patients is a fundamental clinical challenge for which lithium is expected to be helpful. We compared hospitalization rates and morbidity of 260 patients with DSM-5 bipolar or major depressive disorder in the 12 months before starting lithium versus 12 months of its use. We evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, lithium dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses. Within 12 months before lithium, 40.4 % of patients were hospitalized versus 11.2 % during lithium treatment; other measures of morbidity also improved. Benefits were similar with bipolar and major depressive disorders. Independently associated with hospitalization during lithium treatment were: receiving an antipsychotic with lithium, suicide attempt during lithium treatment, lifetime substance abuse, and psychiatric hospitalization in the year before starting lithium, but not diagnosis. Participants and observation times were limited. The study was retrospective regarding clinical history, lacked strict control of treatments and was not blinded. This naturalistic study adds support to the effectiveness of lithium treatment in preventing hospitalization in patients with episodic major mood disorders.


Regulation and deregulation of human IgE synthesis.
The IgE antibody system is among the most sophisticated of immune defense mechanisms. IgE molecules bind specifically and avidly to receptors localized on the surface of tissue mast cells and circulating basophils. These cells can produce and release several potent mediators after antigen interaction with a small number of surface-bound IgE molecules. The enormous amplification power of the IgE antibody system not only provides an important defense mechanism against parasites, but is also responsible for a number of clinical disorders. The human pathological condition most commonly associated with hyperproduction of IgE is atopy, the familial allergic disorder of immediate-type hypersensitivity to environmental allergens. In this paper Sergio Romagnani summarizes current understanding of the mechanisms involved in IgE regulation. Such studies are of primary importance in defining alterations responsible for the pathological conditions characterized by hyperproduction of IgE.


MR findings of malignant melanoma of the vagina.
We report the MR findings in two cases of malignant melanoma of the vagina, one arising at the cervicovaginal junction which mimicked squamous cell carcinoma of the cervix and the other recurred in the vagina after previous resection. Two cases of malignant melanoma had high signal intensity on T1-weighted images and enhanced after gadopentetate dimeglumine administration.


Dermatoscopy of Granulomatous Disorders.
Although diagnosis of cutaneous granulomatous disorders (CGDs) is usually suspected based on morphologic findings, localization, and anamnestic data, clinical differentiation from each other and from similar dermatoses may be challenging. Recently, dermatoscopy has been demonstrated to be a useful tool for assisting the recognition of several CGDs. This article provides a current overview of the dermatoscopic features of the main noninfectious and infectious CGDs, including sarcoidosis, necrobiosis lipoidica, granuloma annulare, rheumatoid nodules, and leishmaniasis. Other, less common, CGDs are briefly addressed, including granulomatous rosacea, acne agminata, and leprosy.


Clinical trials in dental primary care: what research methods have been used to produce reliable evidence?
To identify controlled clinical trials done exclusively in dental primary care and to classify the research according to design. Details of any procedures used to recruit general dental practitioners and any special organisational arrangements were also collected. A scoping literature review. Dental primary care defined as general dental practice, community and school dental settings. Published randomised controlled trials using randomised or quasi randomised approaches and controlled clinical trials were considered for inclusion in the review. Reports were excluded if they did not describe either a randomised controlled trial or a controlled trial. Studies were excluded if the setting was not primary dental care or the intervention was for non-dental conditions. Conference abstracts without a full report and trials published in a language other than English were also excluded. Experimental and quasi-experimental designs, clinical areas and different kinds of strategies used to recruit dentists, any organisational arrangements made to support research in dental primary care. The search of the Cochrane Oral Health Group Controlled Trials Register found 174 articles. Forty-three randomised controlled trials met the inclusion criteria. Trials to evaluate the effects of interventions for types of anaesthesia, periodontal diseases, smoking cessation techniques, dental materials, organisational aspects of dental care, patient anxiety, post extraction healing rates, antibiotics were identified. All were done in general dental practice. Trials in school and community settings were also included. Practice-based research needs to be encouraged to provide dental primary care with relevant evidence upon which effective treatment can be based. This review shows there are few trials done in dental primary care to inform clinical practice, most of which have been reported since 1997. The range of trial designs shows that this method of evaluation can be used to evaluate dental primary care interventions and this is promising for those with an interest in improving dental patient outcomes. More research on how to recruit dentists into clinical trial research must be done.


Classification of men arrested for driving while intoxicated, and treatment implications. A cluster-analytic study.
Statistical analysis of blood alcohol concentration at time of arrest, quantity-frequency level of drinking and scores on an impairment index and the N Scale of the Eysenck Personality Inventory differentiated 7 types among 1500 men arrested for driving while intoxicated.


History of the discoveries of the first human retroviruses: HTLV-1 and HTLV-2.
HTLV-1 was discovered in the US in 1979, and published in 1980. This was rapidly followed by four additional reports in early 1981 describing additional isolates, characterization of some of the HTLV-1 proteins, serological assays for specific antibodies indicative of HTLV-1 infection, and evidence for integrated DNA proviruses in infected cells. None of this early work was dependent upon or influenced by the subclassification of some T-cell malignancies as ATL (in Japan). Instead, I was stimulated by prior work from many investigators in the US and Europe on retroviruses which caused leukemia in animals and our discoveries were made possible by our technical approaches developed in the 1970s involving especially sensitive assays for RT as a surrogate marker for a retrovirus and our discovery of Il-2 which made it possible to culture human T cells. However, following our reports the same virus was isolated in Japan, and both groups provided evidence that HTLV-1 caused ATL, a subclassification of T-cell malignancies first recognized in Japan.


Doppler echocardiography: theory, instrumentation, technique, and application.
A Doppler examination is a valuable adjunct to a complete echocardiographic examination. It has the capability of measuring normal and abnormal velocities of blood flow noninvasively. For the first time, this procedure allows noninvasive quantitation of stenotic gradients, intracardiac pressures, and blood flow as well as semiquantitative assessment of regurgitant lesions. With this procedure, the operator must progress through a learning curve in order to gain a complete understanding of the examination techniques, the limitations of the instruments, and the Doppler physics principles before applications can be made to clinical practice. Evaluation of other aspects of Doppler echocardiography, such as color-flow mapping and assessment of diastolic events, portends great promise for the role of this procedure in the future.


Vincristine-induced bladder neuropathy.
We report a case of detrusor areflexia caused by vincristine neurotoxicity and documented by urodynamic testing. Vincristine commonly induces peripheral neuropathy but rarely causes voiding dysfunction. Neurourological evaluation aided in monitoring and understanding this problem.


Spatial accessibility to vaccination sites in a campaign against rabies in São Paulo city, Brazil.
It is estimated that the city of São Paulo has over 2.5 million dogs and 560 thousand cats. These populations are irregularly distributed throughout the territory, making it difficult to appropriately allocate health services focused on these species. To reasonably allocate vaccination sites, it is necessary to identify social groups and their access to the referred service. Rabies in dogs and cats has been an important zoonotic health issue in São Paulo and the key component of rabies control is vaccination. The present study aims to introduce an approach to quantify the potential spatial accessibility to the vaccination sites of the 2009 campaign against rabies in the city of São Paulo and solve the overestimation associated with the classic methodology that applies buffer zones around vaccination sites based on Euclidean (straight-line) distance. To achieve this, a Gaussian-based two-step floating catchment area method with a travel-friction coefficient was adapted in a geographic information system environment, using distances along a street network based on Dijkstra's algorithm (short path method). The choice of the distance calculation method affected the results in terms of the population covered. In general, areas with low accessibility for both dogs and cats were observed, especially in densely populated areas. The eastern zone of the city had higher accessibility values compared with peripheral and central zones. The Gaussian-based two-step floating catchment method with a travel-friction coefficient was used to assess the overestimation of the straight-line distance method, which is the most widely used method for coverage analysis. We conclude that this approach has the potential to improve the efficiency of resource use when planning rabies control programs in large urban environments such as São Paulo. The findings emphasize the need for surveillance and intervention in isolated areas.


Spontaneous and mitomycin-C induced sister-chromatid exchanges. Comparison of in vivo and in vitro systems.
Frequencies of sister-chromatid exchanges (SCE) were measured in vitro in mouse fibroblasts and in vivo in mouse bone-marrow cells. SCE levels in these cell systems were measured in response to varying concentrations of bromode-oxyuridine (BrdU) and mitomycin-C (MMC). Although BrdU was found to induce SCE in both cellular systems, baseline SCE levels were 2- to 3-fold higher in vitro than in vivo. SCE induction was found to be a linear function of MMC concentration in vivo and in vitro; however the slope of the vivo curve was 5-fold higher. The interaction of BrdU substituted DNA and MMC was examined by administering a fixed dose of MMC with increasing concentrations of BrdU. The induced SCE frequencies appeared to be additive. In addition to measuring drug-induced SCE, the BrdU differential staining technique allows concomitant measurement of the inhibition of cellular replication by the test drugs.


Protonation and water exchange kinetics in sandwich polyoxometalates.
Density functional theory is used to explore the locus and consequences of protonation in [Zn4(HO)2(PW9O34)2]10-. The results are used to explain recent observations regarding the contrasting pH effects on the water-ligand exchange in [Mn4(H2O)2(P2W15O56)2]16- and [Co4(H2O)2(P2W15O56)2]16-, and the general effect of protonation on solvent exchange in metal oxides is discussed.


Social Determinants of Health Amplify the Association Between Ethnicity and COVID19: A Retrospective-Cohort study.
People in racial and ethnic minority groups have been shown to be at increased risk for a variety of diseases, including COVID-19. However, the role that social needs play in this increased risk has not yet been quantified. Investigating these roles can elicit a greater understanding of how social needs influence the manner in which this disease is contracted and spread. A retrospective analysis was conducted of 1,969 Lynn Community Health Center patients. Patients that visited the center between February 1st and July 1st, 2020, tested for COVID-19, and screened for social determinants of health (SDOH) risk factors. Demographics were compared between COVID-19 positive and negative patients. Confounding by age on the association between ethnicity and COVID-19 status was evaluated. A stratified analysis was performed to evaluate the effect modification of SDOH on the relationship between race, ethnicity, and COVID-19 status. Hispanic patients had 2.93 times the odds of a positive COVID-19 test compared to non-Hispanics (95% CI: 2.37 - 3.64, p<0.0001). With at least one SDOH risk factor, Hispanics had 4.71 times the odds of a positive COVID-19 test relative to non-Hispanics (95% CI: 3.10 - 7.14). With no SDOH risk factors, Hispanics had 2.45 times the odds of a positive COVID-19 test relative to non-Hispanics (95% CI: 1.91 - 3.16). No significant associations were found for race. Ethnicity had a significant impact on COVID-19 status in our population, where the effect of ethnicity on COVID-19 status was amplified for those with SDOH risk factors.


Application of ex vivo (1)H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases.
Renal cell carcinoma (RCC) is the most prevalent malignancy of the kidney. Its survival rates are very low since most of patients develop metastases beyond the kidney at the time of diagnosis. Early detection is currently by far the most promising approach to reduce RCC mortality. Metabolic alterations have been suggested to have a crucial role in cancer development. Metabonomics can present a holistic picture of the metabolites alterations and provide biomarkers that could revolutionize disease characterization and detection. Ex vivo (1)H NMR spectra of tumors and the paired adjacent tissues obtained from living patients with RCC were recorded and analyzed using multivariate statistical techniques combined with quantitative statistical analyses. In the present study, we showed that the metabonomes of RCC, either with or without metastases, differ markedly from those of their adjacent tissues. Besides, the RCC patients with metastases can be distinctly differentiated from those without metastases. Metabolic perturbations arising from malignant transformations were also systematically characterized. Compared to the adjacent tissues, RCC tumors had elevated levels of lactate, glutamate, pyruvate, glutamine, and creatine, but decreased levels of acetate, malate, and amino acids including valine, alanine, and aspartate. Systemic changes in metabolite concentrations are most likely the result of cells switching to glycolysis to maintain energy homeostasis. The results suggest that metabonomics may also facilitate the discovery of novel cancer biomarkers and allows the stratification of tumors under different pathophysiological conditions, which might be a valuable future tool for RCC detection and possibly other cancers.


Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes.
Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (approximately 1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators.


No evidence for specificity between host and parasite genotypes in experimental Strongyloides ratti (Nematoda) infections.
A key requirement for several theories involving the evolution of sex and sexual selection is a specificity between host and parasite genotypes, i.e. the resistance of particular host genotypes to particular parasite genotypes and the infectivity of particular parasite genotypes for particular host genotypes. Determining the scope and nature of any such specificity is also of applied relevance, since any specificity for different parasite genotypes to infect particular host genotypes may affect the level of protection afforded by vaccination, the efficacy of selective breeding of livestock for parasite resistance and the long-term evolution of parasite populations in response to these control measures. Whereas we have some evidence for the role of specificity between host and pathogen genotypes in viral and bacterial infections, its role in macroparasitic infections is seldom considered. The first empirical test of this specificity for a vertebrate-nematode system is provided here using clonal lines of parasite and inbred and congenic strains of rat that differ either across the genome or only at the major histocompatibility complex. Although significant differences between the resistance of host genotypes to infection and between the fitness of different parasite genotypes are found, there is no evidence for an interaction between host and parasite genotypes. It is concluded that a specificity between host and parasite genotypes is unlikely in this system.


RB1 loss in castration-resistant prostate cancer confers vulnerability to LSD1 inhibition.
Genomic loss of RB1 is a common alteration in castration-resistant prostate cancer (CRPC) and is associated with poor patient outcomes. RB1 loss is also a critical event that promotes the neuroendocrine transdifferentiation of prostate cancer (PCa) induced by the androgen receptor (AR) signaling inhibition (ARSi). The loss of Rb protein disrupts the Rb-E2F repressor complex and thus hyperactivates E2F transcription activators. While the impact of Rb inactivation on PCa progression and linage plasticity has been previously studied, there is a pressing need to fully understand underlying mechanisms and identify vulnerabilities that can be therapeutically targeted in Rb-deficient CRPC. Using an integrated cistromic and transcriptomic analysis, we have characterized Rb activities in multiple CRPC models by identifying Rb-directly regulated genes and revealed that Rb has distinct binding sites and targets in CRPC with different genomic backgrounds. Significantly, we show that E2F1 chromatin binding and transcription activity in Rb-deficient CRPC are highly dependent on LSD1/KDM1A, and that Rb inactivation sensitizes CRPC tumor to the LSD1 inhibitor treatment. These results provide new molecular insights into Rb activity in PCa progression and suggest that targeting LSD1 activity with small molecule inhibitors may be a potential treatment strategy to treat Rb-deficient CRPC.


A review on biological recycling in agricultural waste-based biohydrogen production: Recent developments.
Hydrogen has become a research highlight by virtue of its clean energy production technology and high energy content. The technology of biohydrogen production from biological waste via fermentation has lower costs, provides environment-friendly methods regarding energy balance, and creates a pathway for sustainable utilization of massive agricultural waste. However, biohydrogen production is generally limited by lower productivity. Many studies have been conducted aimed at improving biohydrogen production efficiency. Hence, this review is intended to describe improving routes for biohydrogen production from agricultural waste and highlights recent advances in these approaches. In addition, the critical factors affecting biohydrogen production, including the pretreatment method, substrate resource, fermentation conditions, and bioreactor design, were also comprehensively discussed along with challenges and future prospects.


Description of a novel Babesia sp. genotype from a naturally infected Eurasian lynx (Lynx lynx) in Anatolia, Turkey, with remarks on its morphology and phylogenetic relation to other piroplasmid species.
There are very limited data on Babesia species infecting lynx species worldwide, and almost nothing is known about babesias in the Eurasian lynx, the most widely distributed wild feline species in the Palearctic geography. This study describes a novel Babesia sp. genotype in a free-living Eurasian lynx in Turkey, named tentatively as 'Babesia sp. lynx', and its integrated genetic and morphological features. Phylogenetic analyses of piroplasmids with the novel Babesia sp. genotype in the current study indicated that this genotype falls into the 'carnivore clade A' of Babesia sensu stricto (true babesias), at the level of different genes (mainly 18S rRNA, ITS1, ITS2, and cyt b) and is monophyletic with the Babesia sp. Ankara genotype, previously observed in Turkey. Additionally, the constructed phylogenetic trees showed that the Babesia sp. lynx genotype infecting the Eurasian lynx is closely related to certain domestic and wild carnivore babesias, mainly Babesia rossi, Babesia presentii, and Babesia pisicii, at the level of different genes. This study also genetically barcoded the lynx infected with the Babesia sp. lynx and Haemaphysalis erinacei, and specimens collected from the animal revealed significant genetic variations between the sample Ha. erinacei and Babesia sp. Ankara-related Ha. erinacei that persists with sympatric populations in Central Anatolia. The lynx infected with the Babesia sp. lynx genotype was also found to be coinfected with Hepatozoon felis, an adeleorinid tick-borne protozoan parasite infecting wild and domestic felids, confirming for the first time its presence in a lynx species. Therefore, this study is the first to describe a potential novel Babesia sp. using its both morphological and phylogenetic characteristics in a lynx species. Adding the Babesia sp. lynx genotype to the phylogeny of feline piroplasmids significantly expands our knowledge of feline babesias in the Palearctic geography and their putative coevolution with their vertebrate hosts.


Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol.
Azathioprine and mercaptopurine remain first line immunomodulatory treatments for inflammatory bowel disease. Toxicity and non-response are significant issues. Co-prescription of allopurinol with reduced-dose (25-33%) azathioprine or mercaptopurine may overcome these problems. We present the outcome of co-prescription in a large single-centre cohort. Patients on thiopurine/allopurinol co-prescription were identified. Indication for and outcome on combination treatment were established. Blood parameters and metabolite results were compared on single agent and combination treatment. Toxicity associated with combination treatment was sought. 110 patients on combination treatment were identified. Clinical remission was achieved in 60/79 (76%) of patients in whom the effect of thiopurine could be studied in isolation. 20/25 patients with hepatotoxicity tolerated combination treatment and normalised their liver function tests. 24/28 patients with atypical side effects tolerated co-therapy. 13/20 non-responders responded to combination treatment. In patients started on combination treatment as first line therapy, 15/23 achieved clinical remission. Thioguanine nucleotides were significantly higher and methylated metabolites significantly lower on combination therapy. Mean cell volume was higher and total white cell and neutrophil counts lower on combination treatment. 13 adverse events occurred, including 6 specific to co-therapy (3 rash, 2 abnormal liver function tests, 1 dosing error). All were minor and self-limiting. This is the largest published experience of the use of allopurinol to optimise outcomes on thiopurine treatment. Combination therapy permitted successful treatment of a significant number of patients who would otherwise have been labelled as thiopurine failures. A few self-limiting side effects were encountered.


The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids.
High thymidylate synthase (TS) level in cancer tissue is considered to result in resistance to pemetrexed therapy for advanced stages of nonsquamous non-small cell lung cancers. To further investigate the mechanism of pemetrexed resistance and potential prognostic outcomes in lung cancer, we established pemetrexed-resistant lung adenocarcinoma cell sublines from CL1 harboring a mutated TP53 gene (R248W) and A549 harboring wild-type TP53. We found the TS expression is upregulated in both pemetrexed-resistant sublines and the reduced TS level achieved through shRNA inhibition resulted in higher pemetrexed sensitivity. We also demonstrated that the acquisitions of pemetrexed resistance enhances epithelial-mesenchymal transition (EMT) in vivo with a mice animal model and in vitro with CL1 and A549 sublines, which was associated with upregulation of ZEB1 which, in turn, downregulates E-cadherin and upregulates fibronectin. When ERK1/2 phosphorylation was reduced by an inhibitor (U0126) or siRNA inhibition, both pemetrexed-resistant sublines reduced their migration and invasion abilities. Therefore, the ERK-mediated pathways induce apoptosis with pemetrexed treatment, and may in turn mediate EMT when cancer cells are resistant to pemetrexed. We further demonstrated that the growth of pemetrexed-resistant tumors could be inhibited by vinblastine in vivo and vincristine in vitro. Our data indicate that pemetrexed resistance could be relieved by non-cross-resistant chemotherapeutic drugs such as vinca alkaloids and might be independent to TP53 status. Furthermore, the phosphorylation of ERK was reduced by vincristine. This finding provides a new insight for overcoming pemetrexed resistance and metastasis by application of vinca alkaloids.


Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator.
The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate.


Noncardiac pulmonary edema, newer environmental aspects. An update.
Accidental spread of potentially toxic gases, fumes, and particulate chemicals has been reported recently in various cities throughout the country and appears to be on the increase throughout the world in the past few years. Moreover, cerebral trauma, septic shock (ARDS), and environmental pulmonary edema from drug intoxication have been commonly encountered. Newer modalities of treatment include selective [corrected] fiber optic bronchoscopy, constant positive airway pressure mask, administration of surfactant, pentoxifylline, and use of newer experimental agents such as nitrous oxide, antitumor necrosis factor (ATNF), and extracorporeal carbon dioxide with low-frequency positive pressure (ECCO2R-LFPPV). The future holds promise for probable reductions in both morbidity and mortality rates of this ubiquitous occupational and environmental health problem, which is of global importance.


An Epstein Barr virus-related cross reactive autoimmune response in multiple sclerosis in Norway.
In studies of patients in Norway with multiple sclerosis (MS), we have found cross reactive autoantibodies related to the Epstein Barr virus nuclear antigen-1 (EBNA-1). The MS patients had elevated IgG antibody to EBNA-1, as measured by reactivity with a synthetic glycine/alanine peptide, P62, which represents the glycine/alanine repeat in EBNA-1. The mean titer of anti-P62 in patients with acute relapse at the time of assay was significantly higher than in the remaining patients. Patients with remitting/relapsing MS also had elevated autoantibody to a lymphocyte protein, p542, cross reactive with EBNA-1 through a glycine/serine epitope. High titered anti-EBNA-1 antibodies from some MS, as well as from some SLE sera, were shown to cross react with 80-82 kDa and 60 kDa proteins in neuroglial cells.


Long-term recovery behavior of brain tissue in hydrocephalus patients after shunting.
The unpredictable complexities in hydrocephalus shunt outcomes may be related to the recovery behavior of brain tissue after shunting. The simulated cerebrospinal fluid (CSF) velocity and intracranial pressure (ICP) over 15 months after shunting were validated by experimental data. The mean strain and creep of the brain had notable changes after shunting and their trends were monotonic. The highest stiffness of the hydrocephalic brain was in the first consolidation phase (between pre-shunting to 1 month after shunting). The viscous component overcame and damped the input load in the third consolidation phase (after the fifteenth month) and changes in brain volume were stopped. The long-intracranial elastance (long-IE) changed oscillatory after shunting and there was not a linear relationship between long-IE and ICP. We showed the long-term effect of the viscous component on brain recovery behavior of hydrocephalic brain. The results shed light on the brain recovery mechanism after shunting and the mechanisms for shunt failure.


HIV 2 infection among blood donors and other subjects in France. The "Retrovirus" Study Group of the French Society of Blood Transfusion.
During a 3 year period, from August 1985 to August 1988, 18 HIV 2-infected blood donors were detected in France as a result of systematic HIV 1 screening. These sera were characterized as HIV 2 by specific Western blot and synthetic peptides. Within the same period, 40 other HIV 2 infected subjects were identified by our study group, independently of blood donations. Thirty of these 58 subjects living in France originate from West Africa (8 blood donors), 3 (I blood donor) are Portuguese men who had lived in West Africa and 25 (9 blood donors) are of French origin; among these, 16 have had a known close contact with West Africa. When HIV 2-infected subjects were asymptomatic, cross reactivity between antibodies to HIV 2 and HIV 1 proteins was generally observed with the two-step ELISA assays using total HIV 1 proteins; it was poor with the competitive assays and variable with the assays using recombinant proteins. When the subjects had signs of immunodeficiency, cross reactivity decreased. The data confirm that HIV 2 is not widespread in France and that most of HIV 2-infected but asymptomatic subjects are recognized by several HIV 1 ELISA assays. Accordingly, systematic screening for HIV 2 with an additional test cannot be recommended at the present time, but a combined HIV 1 and HIV 2 test will be useful when available.


Taurine prevents free fatty acid-induced hepatic insulin resistance in association with inhibiting JNK1 activation and improving insulin signaling in vivo.
We infused the 48 h intralipid plus heparin (IH) to normal rats to elevate plasma free fatty acids (FFAs). Co-infusion of taurine was designed for the purpose of studying the effects of taurine on insulin sensitivity, oxidative stress, c-Jun NH-terminal kinase (JNK)1 activity and insulin signaling in livers of prolonged IH-infused rats. Cannulated rats were infused for 48 h intravenously with either saline or IH, with or without taurine. Hyperinsulinemic-euglycemic clamps with [6-3H] glucose infusion were performed to assess hepatic insulin sensitivity. IH infusion increased plasma 8-isoprostaglandin and hepatic malondialdehyde (MDA). IH also increased JNK1 activity and insulin receptor substrate 1/2 (IRS-1/2) serine phosphorylation, reduced insulin-stimulated IRS-1/2 tyrosine phosphorylation and Akt serine 473 phosphorylation, and induced hepatic insulin resistance. Taurine co-infusion with IH prevented the rise in 8-isoprostaglandin and MDA, inhibited the activation of JNK1, and improved insulin signaling and insulin resistance in liver. The present study has demonstrated that taurine, as an antioxidant, prevented hepatic oxidative stress and ameliorated hepatic insulin resistance. And this effect may be associated with the inhibition of JNK1 activation and the improvement of insulin signaling. This study suggests the therapeutic value of taurine in protecting from hepatic insulin resistance caused by elevated FFAs.


Photosynthetic adaptation strategy of Ulva prolifera floating on the sea surface to environmental changes.
For 8 consecutive years, a green tide has originated in the southern Yellow Sea and spread to the Qingdao offshore area. The causative species, Ulva prolifera, always forms a very thick thallus mat that is capable of drifting long distances over long periods. During this process, although the thalli face disturbance by complex environmental factors, they maintain high biomass and proliferation. We hypothesized that some form of photosynthetic adaptation strategy must exist to protect the thalli. Therefore, we studied the different photosynthetic response characteristics of the surface and lower layers of the floating thallus mats, and investigated the physiological and molecular-level adaptation mechanisms. The results showed that: (1) U. prolifera has strong photosynthetic capability that ensures it can gain sufficient energy to increase its biomass and adapt to long-distance migration. (2) Surface layer thalli adapt to the complex environment by dissipating excess energy via photosynthetic quantum control (energy quenching and energy redistribution between PSII/PSI) to avoid irreversible damage to the photosynthetic system. (3) Lower layer thalli increase their contents of Chlorophyll a (Chl a) and Chlorophyll b (Chl b) and decrease their Chl a/Chl b ratio to improve their ability to use light energy. (4) U. prolifera has strong photosynthetic plasticity and can adapt to frequent exchange between the surface and lower layer environments because of wave disturbance. Pigment component changes, energy quenching, and energy redistribution between PSII/PSI contribute to this photosynthetic plasticity.


Dichotomy of superconductivity between monolayer FeS and FeSe.
The discovery of high-temperature (T c) superconductivity in monolayer FeSe on SrTiO3 raised a fundamental question: Whether high T c is commonly realized in monolayer iron-based superconductors. Tetragonal FeS is a key material to resolve this issue because bulk FeS is a superconductor with T c comparable to that of isostructural FeSe. However, difficulty in synthesizing tetragonal monolayer FeS due to its metastable nature has hindered further investigations. Here we report elucidation of band structure of monolayer FeS on SrTiO3, enabled by a unique combination of in situ topotactic reaction and molecular-beam epitaxy. Our angle-resolved photoemission spectroscopy on FeS and FeSe revealed marked similarities in the electronic structure, such as heavy electron doping and interfacial electron-phonon coupling, both of which have been regarded as possible sources of high T c in FeSe. However, surprisingly, high-T c superconductivity is absent in monolayer FeS. This is linked to the weak superconducting pairing in electron-doped multilayer FeS in which the interfacial effects are absent. Our results strongly suggest that the cross-interface electron-phonon coupling enhances T c only when it cooperates with the pairing interaction inherent to the superconducting layer. This finding provides a key insight to explore heterointerface high-T c superconductors.


The Association between Serum Chemerin and Peritoneal Membrane Transport Function in Patients Undergoing Incident Peritoneal Dialysis: A Prospective Cohort Study.
Some biomarkers in drained dialyzate or peritoneal membrane have been found related to the dialyzate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays important roles in inflammation, adipogenesis, and metabolism. We intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test after PD for 4-6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay. The patients' CVDs were recorded during the follow-up period. 151 eligible patients with a mean age of 46.59 ± 13.52 years were enrolled, and the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 ng/mL vs. 27.37 ng/mL, p = 0.000), and there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42 vs. 21%, p = 0.009). Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of the peritoneal membrane, and serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.


Anti-TB drug resistance in Tanga, Tanzania: A cross sectional facility-base prevalence among pulmonary TB patients.
To determine the prevalence and risk factors associated with drug resistance tuberculosis (TB) at facility-base level in Tanga, Tanzania. A total of 79 Mycobacterium tuberculosis (MTB) isolates included in the study were collected from among 372 (312 new and 60 previously treated) TB suspects self-referred to four TB clinics during a prospective study conducted from November 2012 to January 2013. Culture and drug susceptibility test of the isolates was performed at the institute of medical microbiology and epidemiology of infectious diseases, University hospital, Leipzig, Germany. Data on the patient's characteristics were obtained from structured questionnaire administered to the patients who gave informed verbal consent. Unadjusted bivariate logistic regression analysis was performed to assess the risk factors for drug resistant-TB. The significance level was determined at P < 0.05. The overall proportions of any drug resistance and MDR-TB were 12.7% and 6.3% respectively. The prevalence of any drug resistance and MDR-TB among new cases were 11.4% and 4.3% respectively, whereas among previously treated cases was 22.2% respectively. Previously treated patients were more likely to develop anti-TB drug resistance. There was no association between anti-TB drug resistances (including MDR-TB) with the risk factors analysed. High proportions of anti-TB drug resistance among new and previously treated cases observed in this study suggest that, additional efforts still need to be done in identifying individual cases at facility-base level for improved TB control programmes and drug resistance survey should continuously be monitored in the country.


A novel Delftia plant symbiont capable of autotrophic methylotrophy.
A facultative methylotrophic bacterium, strain Lp-1, which was isolated from root nodules of lupine (Lupinus polyphyllus L.) on the medium with methanol as a carbon and energy source, exhibited high similarity of the 16S rRNA gene sequences to Delftia strains (94‒99.9%). The cells of Delftia sp. Lp-1 were motile gram-negative rods dividing by binary fission. Predominant fatty acids were C16:0 (34.2%), C16:1ω9 (14.5%), and C18:1ω7c (17.3%). Phosphatidylethanolamine, phosphatidylcholine, and phosphatidylglycerol were the dominant phospholipids. Q8 was the major ubiquinone. Optimal growth occurred at 24‒26°C and pH 7.1‒7.3; growth was inhibited by 1% NaCl. The organism oxidized methanol with the classical methanol dehydrogenase and used the ribulose bisphosphate pathway of C1 metabolism. Analysis of translated amino acid sequence of the large subunit of the MxaF methanol dehydrogenase revealed 85.5‒94% similarity to the sequences of such autotrophic methylotrophs of the class Alphaproteobacteria as Angulomicrobium, Starkeya, and Ancylobacter, indicating the possible acquisition of the mxaF gene via horizontal gene transfer. Delftia sp. Lp-1 (VKM B-3039, DSM 24446), the first methylotrophic member of the genus Delftia, was shown to be a plant symbiont, stimulating plant growth and morphogenesis, increasing the level of photosynthetic pigments and specific leaf weight. It possesses the nifH gene of nitrogen fixation, is capable of phosphate solubilization, synthesis of auxins and siderophores, and is antagonistic to plant pathogenic fungi and bacilli.


Continuous peripheral nerve blocks in the ambulatory setting: an update of the published evidence.
To review the evidence recently published involving the use of continuous peripheral nerve blocks (cPNBs) in the ambulatory setting. New evidence exists involving the risks and benefits of cPNB in ambulatory patient populations such as pediatric ambulatory and postmastectomy patients. In addition, new related equipment is now available to facilitate ambulatory cPNB. Recent advancements in equipment for cPNB facilitate the usage in the ambulatory setting. Research-supported ambulatory cPNB indications have expanded to include pediatric subpopulations and major breast surgery, while further evidence mounts for its efficacy in patient populations with previously demonstrated benefits, such as foot, ankle and shoulder surgery.


Echocardiographic imaging of the left ventricle by peripheral intravenous injection of echo contrast agent.
With the use of a new echo contrast agent (ECA) that consists of a suspension with microbubbles (100% less than 3.9 micron in a moving system), we were able to opacify the left ventricle by peripheral intravenous injection in 124 of 130 patients (95%) without shunt connection. In 12 patients with aortic valve disease we measured the opacification of the right and left ventricles videodensitometrically by means of increasing doses. Dose 1 (8.7 ml ECA) and dose 4 (50 ml ECA) led to no significant difference in intensity in the right ventricle (168 +/- 32 vs 184 +/- 16 units, respectively; p greater than 0.05); however, opacification of the left ventricle was significantly more evident after dose 4 (60 +/- 60 vs 88 +/- 62 units, respectively; p less than 0.05). On the basis of the farthest distance reached by the regurgitant microbubbles from the aortic valve, the severity of regurgitation was graded on a four-point scale; the results were compared with those of aortography. A significant correlation (r = 0.98, n = 9) was found between ECA grading and aortography in the evaluation of the severity of aortic insufficiency. In addition, flow characteristics in patients with mitral stenosis, aortic insufficiency, and the regurgitation jet in incompetent aortic prosthesis in connection with diastolic inflow over the mitral valve were described. Moreover, it was possible to differentiate between inflow of ECA into the left atrium via an atrial septal defect and across the pulmonary vascular bed. No adverse effects were reported by the patients. Left ventricular end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction were determined before and after intravenous injection of increasing doses of ECA by means of the area-length method of Sandler and Dodge. Even after dose 4 we observed no significant changes in left ventricular function. The values before and after injection were in the range of intra- and interobserver reproducibility. Only three patients reported a slight taste sensation. In nine patients with a history of allergies there were no side effects.


[Self-help on the internet. Chances and risks of communication in electronic networks].
The worldwide web is used for self-help purposes by an increasing number of patients with a variety of mental disorders. The benefits and dangers of applying the internet in psychiatry are discussed based on a case report concerning a female with post traumatic stress and multiple personality disorders who visited a chat-room in the internet with two of her 48 supernumerary identities. During one stage of her history, she displayed an excessive use of the internet which must be considered a symptom of mental disorder rather than a distinct disease entity, viz. "internet addiction".


Getting ahead of acute meningitis & encephalitis.
Learn how to distinguish between these common central nervous system infections and respond appropriately.


In vitro degradation of gastric mucin. Carbohydrate side chains protect polypeptide core from pancreatic proteases.
The polypeptide core of mucin glycoprotein subunits resists cleavage by proteases. To determine if the carbohydrate side chains of these subunits protect the underlying polypeptide core from proteolytic cleavage, we compared the effect of pancreatic proteases on hog gastric mucin before and after cleavage of its carbohydrate moieties by bacterial glycosidases from an anaerobic human fecal culture supernate. Hog gastric mucin was resistant to pancreatic proteases: less than 10% of the mucin protein became soluble in 80% vol/vol ethanol after 24-h incubation with trypsin, alpha-chymotrypsin, and elastase, and its elution pattern from Sephadex G-200 remained unchanged after elastase treatment, with 90% eluting at the void volume. By contrast, after removal of 50% of its carbohydrates, mucin was susceptible to pancreatic proteases: 50% of mucin protein became soluble in 80% vol/vol ethanol after 24-h incubation with alpha-chymotrypsin and elastase, and 24% of mucin protein became soluble in 80% vol/vol ethanol after 24-h incubation with trypsin; after elastase treatment, its elution from Sephadex G-200 was markedly retarded. We conclude that the carbohydrate side chains of hog gastric mucin glycoprotein protect the underlying polypeptide core from proteolysis and that degradation of the carbohydrate side chains by glycosidases from fecal bacteria renders the polypeptide core susceptible to pancreatic proteases.


Profile Likelihood-Based Confidence Intervals and Regions for Structural Equation Models.
Structural equation models (SEM) are widely used for modeling complex multivariate relationships among measured and latent variables. Although several analytical approaches to interval estimation in SEM have been developed, there lacks a comprehensive review of these methods. We review the popular Wald-type and lesser known likelihood-based methods in linear SEM, emphasizing profile likelihood-based confidence intervals (CIs). Existing algorithms for computing profile likelihood-based CIs are described, including two newer algorithms which are extended to construct profile likelihood-based confidence regions (CRs). Finally, we illustrate the use of these CIs and CRs with two empirical examples, and provide practical recommendations on when to use Wald-type CIs and CRs versus profile likelihood-based CIs and CRs. OpenMx example code is provided in an Online Appendix for constructing profile likelihood-based CIs and CRs for SEM.


Sulphinpyrazone and renal function following myocardial infarction.
The effects of sulphinpyrazone 800 mg daily on renal excretory function were studied in a double-blind placebo-controlled randomised trial of incremental and full doses of the drug in 28 patients with plasma urea concentration less than 10 mmol/l in the period 2-28 days following uncomplicated acute myocardial infarction. Sulphinpyrazone in both dosage regimens increased uric acid excretion and lowered plasma urate concentration. There was no evidence that the drug reduced glomerular filtration rate or damaged the renal tubules. These results suggest that sulphinpyrazone in the doses used in this study is not contraindicated in patients early after acute myocardial infarction even though they may have a moderate rise in the blood urea.


Patterns of axillary evaluation in older patients with breast cancer and associations with adjuvant therapy receipt.
Although axillary lymph node status has traditionally been a key factor in informing adjuvant breast cancer therapy recommendations, this information may be less relevant as our focus shifts more towards tumor biology, particularly in older patients where comorbidity influences treatment decisions and nodal staging and/or surgery may not improve outcomes. We examined patterns of axillary surgery and associations between axillary surgery and receipt of adjuvant treatment in older breast cancer patients. Women aged ≥ 65 years with clinically node-negative, stage I-II breast cancer treated between 2012 and 2013 were identified using the National Cancer Data Base. Using multivariable logistic regression, we examined associations between axillary surgery and age, adjusting for patient, clinical, and facility factors. We also examined receipt of adjuvant treatment by nodal surgery. Among 68,205 women, 40.1% were aged 65-70, 24.5% were 71-75, 17.4% were 76-80, and 18.0% were > 80. Overall, 91.2% had axillary surgery (67.8% sentinel lymph node biopsy, 11.7% axillary lymph node dissection, 11.7% unspecified/unknown axillary surgery); 88.0% of those aged ≥ 70 with lower risk, hormone receptor-positive tumors underwent axillary surgery. In adjusted analyses, compared to patients aged 65-70, increasing age was associated with lower odds of any axillary surgery (ages 71-75: OR 0.64, 95% CI 0.57-0.71; ages 76-80: OR 0.33, 95% CI 0.30-0.37; age > 80: OR 0.08, 95% CI 0.07-0.08). Axillary surgery was associated with higher odds of receipt of radiation after breast conservation and receipt of chemotherapy in human epidermal growth factor 2-positive disease. In a large nationwide dataset, the vast majority of older women with clinically node-negative breast cancer underwent axillary staging despite uncertainty about its impact on survival, particularly for those with lower-risk disease. Further study on how to tailor node assessment in older patients is warranted.


Dosimetric analysis of radiation-induced gastric bleeding.
Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD₅₀ (normal) = 56 Gy and TD₅₀ (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD₅₀ value for the cirrhosis patients points out their greater sensitivity. This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.


Distal radial approach: a review on achieving a high success rate.
The transradial approach is the standard for percutaneous coronary intervention (PCI). Moreover, to lead to the evolution of PCI, a new approach site was developed, namely the distal radial approach (dRA). The vessel diameter of the distal radial artery is smaller than that of the forearm radial artery; hence, use of 1 Fr size or a sheath with a thinner outer diameter is recommended. Ultrasound examination before the procedure provides useful information on this matter. There are two approaches to puncture: proximal site puncture of the distal radial artery and distal site puncture. Based on anatomical characteristics, the puncture angle is large on the former and small on the latter. Although a learning curve for the dRA puncture is needed, the use of ultrasound facilitates the process. Using a hemostatic device dedicated to the dRA simplifies observation after PCI. Hemostatic devices for the conventional radial approach or simple bandage with an elastic band can be useful. Usually, less hemostasis time is needed for the dRA compared with the conventional radial approach. Studies have shown high success rates of the dRA (approximately 88-99.5%). Advantages of the dRA are patient comfort, short hemostasis time, less restraint for the patients after PCI, and easy observation at the ward. Disadvantages are the learning curve required for the puncture and the small diameter of the distal radial artery. The dRA is a new approach site for PCI. Further research is warranted for the selection of suitable patients to undergo PCI through the dRA.


Homeobox C5 expression is associated with the progression of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
Aberrant expression of homeobox genes (HOX), normally required for the differentiation of a particular tissue, has been reported in several types of cancer, but poorly addressed in oral squamous cell carcinoma (OSCC). The present study investigated the expression of HOXC5 in OSCC and identified molecular biomarker whose expression is associated with the multistep oral carcinogenesis. The expression of HOXC5, proliferation cell nuclear antigen (PCNA), and Bcl-2 was examined by RT-PCR and Western blot analysis and confirmed by immunohistochemistry and transferase-mediated dUTP nick end-labeling (TUNEL) assay in a 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis model. Homeobox genes C5 was overexpressed in SCC tissues, but not in normal tissues by RT-PCR and Western blot analysis. Along with the progress of multistep carcinogenesis, the levels of HOXC5 expression of mRNA and protein significantly increased during the dysplasia (moderate to severe dysplasia) when compared with normal and hyperplasia. The levels of PCNA and Bcl-2 were sequentially increased from hyperplasia to dysplasia and SCC. By immunohistochemistry, HOXC5 expression was significantly increased in dysplasia, whereas PCNA expression was gradually increased during tongue carcinogenesis. TUNEL-positive cells were increased until dysplasia, but reduced in SCC. These results indicate that overexpression of HOXC5 is correlated with oral carcinogenesis and strongly contributed to the development of OSCC. HOXC5 may be a useful biomarker and has an emerging therapeutic target of OSCC.


Human Pluripotent Stem Cells: Applications and Challenges for Regenerative Medicine and Disease Modeling.
In recent years, human pluripotent stem (hPS) cells have started to emerge as a potential tool with application in fields such as regenerative medicine, disease modeling, and drug screening. In particular, the ability to differentiate human-induced pluripotent stem (hiPS) cells into different cell types and to mimic structures and functions of a specific target organ, resourcing to organoid technology, has introduced novel model systems for disease recapitulation while offering a powerful tool to provide a faster and reproducible approach in the process of drug discovery. All these technologies are expected to improve the overall quality of life of the humankind. Here, we highlight the main applications of hiPS cells and the main challenges associated with the translation of hPS cell derivatives into clinical settings and other biomedical applications, such as the costs of the process and the ability to mimic the complexity of the in vivo systems. Moreover, we focus on the bioprocessing approaches that can be applied towards the production of high numbers of cells as well as their efficient differentiation into the final product and further purification.


Effect of menthol on detrusor smooth-muscle contraction and the micturition reflex in rats.
To investigate the effects of menthol, an activator of the temperature-sensitive transient receptor potential family member TRPM8, on detrusor smooth-muscle contraction and the micturition reflex in rats. We evaluated the effect of intravesical infusion of 1 or 3 mM menthol by cystometry in conscious female Sprague-Dawley rats. Some of the animals were pretreated with 125 mg/kg capsaicin subcutaneously 4 days earlier. The parameters measured were voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), and pressure threshold for inducing micturition (PT). Strips of detrusor muscle were mounted in organ baths to study the effect of menthol on the contractile response to 0.01 mM carbachol. Intravesical infusion of 3 mM menthol reduced VV by 20%, VT by 19%, and PT by 31%. RV, VE, and MP were unaltered. Capsaicin pretreatment had no effect on baseline cystometric parameters, and 3 mM menthol caused similar reductions in VV (24%), VT (22%), and PT (30%), while having no effect on RV, VE, and MP. Menthol at 0.1, 0.3, and 1 mM inhibited carbachol-induced contractions by 10.7%, 36.7%, and 97.3%, respectively. Our results demonstrated that intravesical infusion of menthol facilitated the micturition reflex, and capsaicin pretreatment had no effect on this response. Menthol inhibited carbachol-induced contraction of the detrusor smooth muscle. This suggests that intravesically infused menthol cannot relax detrusor muscle, and acts on capsaicin-resistant afferents (probably through TRPM8 in urothelium or sensory nerve endings) to facilitate the micturition reflex.