T-Cell Epitope Prediction.
An epitope is a part of an immunogenic protein that can be recognized by the immune system. The peptides that can be recognized by the T-cell receptors after a particular antigen has been intracellularly processed, bound to at least one MHC molecule and expressed on the surface of the antigen presenting cell as a MHC-peptide complex, are called a T-cell epitope. Individuals who have at least one MHC molecule able to most avidly bind to allergenic amino acid sequences from an allergen, and at the same time have the appropriate T-cell clone that can recognize this MHC-peptide complex, are expected to be genetically prone to allergic reactions against that allergen. This possibility can be examined in silico by utilizing modern computational techniques that are based on sophisticated mathematics and statistics. The design principles of these techniques are different and therefore variations in their predictions are expected. The available software programs that have been developed on this basis are able to combine the increasing amount and complexity of the available experimental data that have been organized in immunoinformatics databases to predict potential allergen T-cell epitopes. All relevant T-cell epitope prediction methods can be accessed online as a freeware.


[Gastroscopic photo report of achalasia in the dog].
Five dogs with achalasia were examined pre- and post-operatively. Photos were taken of the diseased oesophagus, cardia, cardia with retroversion and the cardia following surgery. The normal structures are also shown.


Mechanisms in metal genotoxicity: the significance of in vitro approaches.
A survey of the literature published on the ability of metal salts to produce, in vitro, gene mutations, structural chromosome aberrations, sister-chromatid exchanges, to interfere with the chromosome distribution or to induce mammalian cell transformation demonstrates that the carcinogenicity of inorganic compounds is clearly associated with their genotoxicity. The induction of structural aberrations, SCEs and forward gene mutations represents the most sensitive and specific assay to assess the carcinogenic potential of metal salts.


BK channel inactivation gates daytime excitability in the circadian clock.
Inactivation is an intrinsic property of several voltage-dependent ion channels, closing the conduction pathway during membrane depolarization and dynamically regulating neuronal activity. BK K(+) channels undergo N-type inactivation via their β2 subunit, but the physiological significance is not clear. Here, we report that inactivating BK currents predominate during the day in the suprachiasmatic nucleus, the brain's intrinsic clock circuit, reducing steady-state current levels. At night inactivation is diminished, resulting in larger BK currents. Loss of β2 eliminates inactivation, abolishing the diurnal variation in both BK current magnitude and SCN firing, and disrupting behavioural rhythmicity. Selective restoration of inactivation via the β2 N-terminal 'ball-and-chain' domain rescues BK current levels and firing rate, unexpectedly contributing to the subthreshold membrane properties that shift SCN neurons into the daytime 'upstate'. Our study reveals the clock employs inactivation gating as a biophysical switch to set the diurnal variation in suprachiasmatic nucleus excitability that underlies circadian rhythm.


Flexural Properties and Hardness of CAD-CAM Denture Base Materials.
To compare flexural strength, elastic modulus, and surface hardness of computer aided design and computer aided manufacturing CAD-CAM milled, 3D-printed, and heat-polymerized denture base resins. A total of 120 specimens were fabricated from heat-polymerized acrylic resin (HP), milled resin (Avadent and IvoCad), and 3D-printed resin (ASIGA, FormLabs, and NextDent). The specimens were divided into 6 groups according to the type of denture base material (n = 20/material) (10/flexural properties and 10/hardness). Flexural strength and elastic modulus of the specimens were evaluated by 3-point bending test and surface hardness by Vickers hardness test. To test flexural properties, the specimens were fabricated according to ISO 20795-1:2013 standards (64 × 10 × 3.3 ± 0.2 mm). The dimensions for hardness test were 15 × 10 × 2.5 ± 0.2 mm. Scanning electron microscope was used to evaluate the surface morphology of the fractured specimens. The means and standard deviations were calculated, followed by one-way ANOVA and Tukey post-hoc test (α = 0.05). Milled resins showed significantly higher values for flexural strength, elastic modulus, and surface hardness, followed by HP and then 3D-printed resins (p < 0.001). Within milled groups, flexural strength of AvaDent was significantly higher than IvoCad (p < 0.001), while elastic modulus and hardness didn't show significant difference. Within 3D-printed resins, ASIGA showed the highest flexural strength and elastic modulus, insignificantly with FormLabs (p = 0.595) and significantly with NextDent (p = 0.008). ASIGA also showed significantly the highest hardness among the 3D-printed groups. No significant difference was found between FormLabs and NextDent in flexural strength (p = 0.357), elastic modulus (p = 1.00), or surface hardness (p = 0.987). CAD-CAM milled resins had greater flexural properties and hardness compared to heat-polymerized acrylic resin and 3D-printed resins. Although 3D-printed samples showed the lowest values of tested properties, the flexural strength and modulus were above clinically acceptable values.


Unique immunomodulation by electro-acupuncture in humans possibly via stimulation of the autonomic nervous system.
Cumulative evidence suggests that immunologic responses are under the regulation of the autonomic nervous system. Since acupuncture has recently been reported to modulate the autonomic nervous system, we investigated the possibility that acupuncture eventually modulates the immune system. In the present study, electro-acupuncture was applied in young volunteer subjects. As for the proportions of granulocytes and lymphocytes in the blood, there were three groups: (1) granulocytosis and lymphocytopenia; (2) granulocytopenia and lymphocytosis; and (3) normal pattern. Interestingly, with the administration of acupuncture, the status of subjects with relatively low levels of granulocytes and high levels of lymphocytes shifted to Group 1, whereas that of subjects with high levels of granulocytes and low levels of lymphocytes shifted to Group 2. In other words, acupuncture tended to normalize the pattern of leukocytes. We confirmed that acupuncture induced parasympathetic nerve stimulation, resulting in a decrease in the heart rate. These results suggest possible mechanisms underlying how acupuncture ameliorates the condition of patients with many chronic diseases.


Effect of whole-body microtitanium-treated garments on metabolic cost of exercise following strenuous hill running.
To determine the effect size of wearing sports garments treated with microscopic titanium particles (AQUA TITAN) during recovery from strenuous running on the restoration of running economy during subsequent exercise. A double-blind crossover was used to determine the effect of AQUA TITAN on running metabolic cost in 10 healthy men. Participants performed 40 min of treadmill running comprising 2×(10 min at 5% and 10 min at -10% grade), followed by random allocation to skin-tight nylon-polyurethane AQUA TITAN treated or non-treated placebo garments covering the torso, limbs, and feet. Garments were worn continuously throughout the next 48-h, during which time participants rested (day 2) then completed a graded treadmill run to determine metabolic outcome (day 3). Body-weight normalised running metabolic cost was evaluated by indirect calorimetry and the effect size referenced against the smallest meaningful change in economy (0.9%) for improvement in distance running performance. The fatigue effect while wearing control garments on metabolic cost at 48-h was small (2.2% 95%CL ±1.2%). In contrast, AQUA TITAN garments most certainly reduced running metabolic cost (-3.1% ±0.9%) vs. control. Additionally, AQUA TITAN increased the respiratory exchange ratio (0.011 ±0.005) and lowered minute ventilation at intensities below the ventilatory threshold (-4.0% ±0.9%). AQUA TITAN garments worn during recovery from strenuous exercise improved subsequent running economy to a magnitude likely to restore endurance performance. Future research should verify the magnitude of garment effects on performance outcomes, and on identifying the acute or passive neural, musculotendinous or metabolic mechanisms responsible.


First-principles study on the electronic and optical properties of AlSb monolayer.
Using density functional theory and many-body perturbation theory, we systematically investigate the optoelectronic properties of AlSb monolayer, which has been recently synthesized by molecular beam epitaxy [ACS Nano 2021, 15, 5, 8184-8191]. After confirming the dynamical stability of the monolayer, we analyze its electronic properties at different levels of theory without (PBE, HSE03, HSE06) and with (G[Formula: see text]W[Formula: see text], GW[Formula: see text], and GW) electron-electron interaction. The results show that AlSb monolayer is a semiconductor with a direct quasiparticle band gap of 1.35 eV while its electronic structure is dominated by spin-orbit coupling. Also, we study the optical properties of the monolayer by solving the Bethe-Salpeter equation. In this regard, the effects of spin-orbit coupling, electron-electron correlation, and electron-hole interaction on the optical spectrum of the monolayer are evaluated. Based on the highest level of theory, the first bright exciton is found to be located at 0.97 eV, in excellent agreement with the experimental value (0.93 eV). Moreover, the exciton binding energy, effective mass, and Bohr radius are obtained 0.38 eV, 0.25 m[Formula: see text], and 6.31 Å, respectively. This work provides a better understanding of the electronic, optical, and excitonic properties of AlSb monolayer and may shed light on its potential applications.


Heterologous expression of a cryptic gene cluster from a marine proteobacterium Thalassomonas actiniarum affords new lanthipeptides thalassomonasins A and B.
The aim of this study was to utilize a cryptic biosynthetic gene cluster (BGC) of a marine proteobacterium Thalassomonas actiniarum for production of new lanthipeptides by heterologous expression system. Based on genome mining, a new BGC of class I lanthipeptide was found in the genome sequence of a marine proteobacterium T. actiniarum. Molecular cloning was performed to construct an expression vector derived from commercially available plasmid pET-41a(+). Heterologous production of new lanthipeptides named thalassomonasins A and B was performed using the host Escherichia coli BL21(DE3) harbouring the expression vector. The structure of thalassomonasin A was determined by the interpretation of NMR and MS data. As a result, thalassomonasin A was determined to be a lanthipeptide with three units of lanthionine. The bridging pattern of the lanthionine rings in thalassomonasin A was determined by interpretation of NOESY data. The structure of thalassomonasin B was proposed by MS/MS experiment. We succeeded in heterologous production of new class I lanthipeptides using a BGC of a marine proteobacterium T. actiniarum. To the best of our knowledge, this is the first report of heterologous production of lanthipeptides derived from proteobacterial origin. There are many cryptic biosynthetic gene clusters (BCGs) of this class of lanthipeptides in proteobacterial genomes. This study may lead to the production of new lanthipeptides by utilizing the BCGs.


Fusion of Sindbis virus with model membranes containing phosphatidylethanolamine: implications for protein-induced membrane fusion.
The pH-induced fusion of Sindbis virus with model lipid membranes containing phosphatidylethanolamine has been studied using a quantitative fluorescence technique. The headgroup and acyl chain domains of the lipids have been altered systematically to determine their effect on fusion. Unsaturated phosphatidylethanolamines (PE) have been found to promote fusion, either by themselves, or in combination with phosphatidylcholines (PC). Cholesterol added to a mixture of unsaturated PE and PC was also shown to increase the extent of viral fusion. The results of these studies have been interpreted in terms of a tentative model for the molecular aspects of the target membrane which are necessary for viral fusion. In this model, the target membrane must have a sufficiently-sized domain containing poorly hydrated lipids which are capable of existing in a non-bilayer arrangement.


Efficient expression of haloarchaeal nucleoside diphosphate kinase via strong porin promoter in moderately halophilic bacteria.
Enzymes from extremely halophilic archaea require high concentration of salts for their proper folding and consequently are expressed as an unfolded and inactive form in Escherichia coli. Moderate halophile, which accumulates protein stabilizers, i.e., compatible solutes, is an attractive host cell for the recombinant production of heterologous proteins, since such protein stabilizers may help folding of expressed proteins. Here, we succeeded in efficient expression and purification to homogeneity of recombinant haloarchaeal nucleoside diphosphate kinase (HsNDK) in moderate halophile using newly isolated strong porin promoter.


Identification of persons at high risk for type 2 diabetes mellitus: do we need the oral glucose tolerance test?
The standard method of identifying persons at high risk for type 2 diabetes mellitus involves detection of impaired glucose tolerance, which requires a costly and inconvenient 2-hour oral glucose tolerance test. Because clinical trials have indicated that diabetes is preventable by using behavioral or pharmacologic interventions, less expensive methods of identifying high-risk persons are needed. To determine whether multivariable models are superior to glucose tolerance tests for identifying persons at high risk for diabetes mellitus. Prospective cohort study. San Antonio, Texas. 1791 Mexican Americans and 1112 non-Hispanic whites without diabetes at baseline who were randomly selected from census tracts. Medical history; body mass index; blood pressure; fasting and 2-hour plasma glucose levels; fasting serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels; and triglyceride level. For prediction of 7.5-year incidence of type 2 diabetes, the area under the receiver-operating characteristic (ROC) curve for a multivariable model involving readily available clinical variables was significantly (P < 0.001) greater than the area under the ROC curve for the 2-hour glucose value alone (84.3% vs. 77.5%). Impaired glucose tolerance represents a single point on the latter curve. Adding the 2-hour glucose measurement to the multivariable model increased the area under its ROC curve, but only from 84.3% to 85.7%. Persons at high risk for diabetes mellitus are better identified by using a simple prediction model than by relying exclusively on the results of a 2-hour oral glucose tolerance test. Although adding the 2-hour glucose variable to the model enhanced prediction, the resulting slight improvement entails greater cost and inconvenience.


Impact of attenuated-signal plaque observed by intravascular ultrasound on vessel response after drug-eluting stent implantation.
The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation. Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals. At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229). The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.


Conjugated dimers of horseradish peroxidase as neuroanatomical tracers.
Horseradish peroxidase dimer (HRP-HRP) and monomer (HRP) were compared in their ability to act as neuroanatomical tracers. Dimers exhibited less diffusion at the site of injection. At 48-72 h survival periods, there were no appreciable differences in the retrograde neuronal labeling produced by these two compounds. However, at 7 days survival, there was little retrograde labeling due to the presence of monomer while dimer labeling was still intense.


Medium modification to enhance the formation of bioactive metabolites in shake flask cultures of Antrodia cinnamomea by adding citrus peel extract.
Antrodia cinnamomea has recently become a well-known medicinal mushroom in Taiwan. Bioactive compounds found in A. cinnamomea include: polysaccharide, sesquiterpene lactone, steroids and triterpenoids. The aim of this study was to evaluate the feasibility of adding citrus peel extract to enhance the formation of bioactive metabolites in the submerged culture of A. cinnamomea. With the exception of grapefruit, citrus peel extracts tested were proved to be beneficial to mycelial growth and to the production of intracellular polysaccharide. Lemon was the most effective for enhancing bioactive metabolite production. With an addition of 2% (v/v), the mycelium biomass concentration and intracellular polysaccharide content rose from 11.96 g DW/L of the control and 123.6 mg/g DW to 21.96 g DW/L and 230.8 mg/g DW, respectively, on day 8. The production of triterpenoids also increased from 86.7 to 282.9 mg/L. Moreover, this study also demonstrates that although the addition of peel extract could cause the lengthening of the exponential phase and reduce the specific growth rate, the production rate of biomass, intracellular polysaccharide and triterpenoids was still enhanced significantly.


Pandemic tele-smart: a contactless tele-health system for efficient monitoring of remotely located COVID-19 quarantine wards in India using near-field communication and natural language processing system.
Efficient remote monitoring of the patient infected with coronavirus without spread to healthcare workers is the need of the hour. An effectual and faster communication system must be established wherein the healthcare workers at the remote quarantine ward can communicate with healthcare professionals present in specialty hospitals. Incidentally, there is a need to establish a contactless smart cloud-based connection between a specialty hospital and quarantine wards during pandemic situation. This paper proposes an initial contactless web-based tele-health clinical decision support system that integrates near-field communication (NFC) tags and a smart cloud-based structuring tool that enables the quick diagnosis of patients with COVID-19 symptoms and monitors the remotely located quarantine wards during the recent pandemic. The proposed framework consists of three-stages: (i) contactless health parameter extraction from the patient using an NFC tag; (ii) converting medical report into digital text using optical character recognition algorithm and extracting values of relevant medical-parameters using natural language processing; and (iii) smart visualization of key medical parameters. The accuracy of the proposed system from NFC reader until analysis using a novel structuring algorithm deployed in the cloud is more than 94%. Several capabilities of the proposed web-based system were compared with similar systems and tested in an authentic mock clinical setup, and the physicians found that the system is reliable and user friendly.


The Cognitive Architecture of Spatial Navigation: Hippocampal and Striatal Contributions.
Spatial navigation can serve as a model system in cognitive neuroscience, in which specific neural representations, learning rules, and control strategies can be inferred from the vast experimental literature that exists across many species, including humans. Here, we review this literature, focusing on the contributions of hippocampal and striatal systems, and attempt to outline a minimal cognitive architecture that is consistent with the experimental literature and that synthesizes previous related computational modeling. The resulting architecture includes striatal reinforcement learning based on egocentric representations of sensory states and actions, incidental Hebbian association of sensory information with allocentric state representations in the hippocampus, and arbitration of the outputs of both systems based on confidence/uncertainty in medial prefrontal cortex. We discuss the relationship between this architecture and learning in model-free and model-based systems, episodic memory, imagery, and planning, including some open questions and directions for further experiments.


SSc in 2011: From mechanisms to medicines.
Findings from ongoing studies of imatinib in systemic sclerosis (SSc) were eagerly awaited in 2011, but results from these clinical trials have so far been disappointing. However, progress in the understanding of the mechanisms that underlie SSc pathogenesis could provide clues to novel targets for 2012 and beyond.


Fluorescence Imaging of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer.
Non-small cell lung cancer (NSCLC) is a complex disease often driven by activating mutations or amplification of the epidermal growth factor receptor (EGFR) gene, which expresses a transmembrane receptor tyrosine kinase. Targeted anti-EGFR treatments include small-molecule tyrosine kinase inhibitors (TKIs), among which gefitinib and erlotinib are the best studied, and their function more often imaged. TKIs block EGFR activation, inducing apoptosis in cancer cells addicted to EGFR signals. It is not understood why TKIs do not work in tumours driven by EGFR overexpression but do so in tumours bearing classical activating EGFR mutations, although the latter develop resistance in about one year. Fluorescence imaging played a crucial part in research efforts to understand pro-survival mechanisms, including the dysregulation of autophagy and endocytosis, by which cells overcome the intendedly lethal TKI-induced EGFR signalling block. At their core, pro-survival mechanisms are facilitated by TKI-induced changes in the function and conformation of EGFR and its interactors. This review brings together some of the main advances from fluorescence imaging in investigating TKI function and places them in the broader context of the TKI resistance field, highlighting some paradoxes and suggesting some areas where super-resolution and other emerging methods could make a further contribution.


Reliability and validity of a smartphone-based assessment of gait parameters across walking speed and smartphone locations: Body, bag, belt, hand, and pocket.
The assessment of spatiotemporal gait parameters is a useful clinical indicator of health status. Unfortunately, most assessment tools require controlled laboratory environments which can be expensive and time consuming. As smartphones with embedded sensors are becoming ubiquitous, this technology can provide a cost-effective, easily deployable method for assessing gait. Therefore, the purpose of this study was to assess the reliability and validity of a smartphone-based accelerometer in quantifying spatiotemporal gait parameters when attached to the body or in a bag, belt, hand, and pocket. Thirty-four healthy adults were asked to walk at self-selected comfortable, slow, and fast speeds over a 10-m walkway while carrying a smartphone. Step length, step time, gait velocity, and cadence were computed from smartphone-based accelerometers and validated with GAITRite. Across all walking speeds, smartphone data had excellent reliability (ICC2,1≥0.90) for the body and belt locations, with bag, hand, and pocket locations having good to excellent reliability (ICC2,1≥0.69). Correlations between the smartphone-based and GAITRite-based systems were very high for the body (r=0.89, 0.98, 0.96, and 0.87 for step length, step time, gait velocity, and cadence, respectively). Similarly, Bland-Altman analysis demonstrated that the bias approached zero, particularly in the body, bag, and belt conditions under comfortable and fast speeds. Thus, smartphone-based assessments of gait are most valid when placed on the body, in a bag, or on a belt. The use of a smartphone to assess gait can provide relevant data to clinicians without encumbering the user and allow for data collection in the free-living environment.


Characteristics of immune function of full-term infants with different feeding patterns at the age of 3 months: a prospective cohort study.
To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex. A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes. Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils (P<0.05) and significantly higher expression and proportion of HLA-DR, a surface activation marker of CD8+ T cells, and proportion of lymphocytes (P<0.05). The male infants had a significantly lower white blood cell count and a significantly higher proportion of eosinophils compared with the female infants (P<0.05). Sex has no significant effect on the proportion of lymphocyte subsets in 3-month-old full-term infants, but feeding patterns are associated with the proportion of CD28+ T cells (lymphocyte functional subset) and HLA-DR+ T cells (lymphocyte activation subset), suggesting that feeding patterns have a certain effect on the development of immune function in 3-month-old full-term infants.


Evaluation of carbohydrate antigen 50 in human serum using magnetic particle-based chemiluminescence enzyme immunoassay.
A magnetic particles (MPs)-based chemiluminescence enzyme immunoassay (CLEIA) with high sensitivity, specificity, rapidity, and reproducibility was proposed for the evaluation of tumor marker, carbohydrate antigen 50 (CA50) in human serum. The immunomagnetic particles coated with anti-fluorescein isothiocyanate (FITC) antibody was used as dispersed solid phase for the immunoassay, which was based on a sandwich immunoreaction of FITC-labeled anti-CA50 antibody, CA50 antigen, and alkaline phosphatase (ALP)-labeled anti-CA50 antibody, and was based on a subsequent chemiluminescence reaction of ALP with 4-methoxy-4-(3-phosphate-phenyl)-spiro-(1,2-dioxetane-3,2'-adamantane) (AMPPD) solution. The CL emission intensity was directly proportional to the amount of analyte present in a sample solution. The effects of several physicochemical parameters, including the concentration of FITC-labeled anti-CA50 antibody, the dilution ratio of ALP-labeled anti-CA50 antibody, the volume of MPs and substrate, the immunoreaction time and other relevant variables upon the immunoassay were studied and optimized. The proposed method exhibited advantages in a lower minimum detectable concentration of 1.0 U mL(-1) with comparison to the commercially available immunoradiometric assay (IRMA), and showed a larger linear range of 0 to 300 U mL(-1), as well as less total assay time of only 50 min with comparison to both IRMA and microplate CLEIA. The coefficient of variation was less than 7 and 11% for intra- and inter-assay precision, respectively. This method has been successfully applied to the evaluation of CA50 in human serum with recoveries from 82 to 112%, and showed a good correlation with the commercially available CA50 IRMA.


A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers.
Psychosocial factors influencing smoking cessation were studied in current smokers prior to quitting. Two questionnaires were sent in 1975 and 1981 to adult members of the Finnish Twin Cohort. The 1975 response rate was 89%, and 89% of those eligible replied again in 1981. Analysis was done on data from one twin pair member only. Three groups were identified: 3617 never smokers, 2654 persistent smokers, and 823 quitters (i.e. current smokers in 1975, former smokers in 1981). Univariate and multivariate comparisons of baseline psychosocial variables for quitters and persistent smokers were performed in men aged 20-34 and 35-54 and women aged 20-39. Among women and young men quitters were better educated and scored lower on neuroticism. Young male quitters also slept longer, had been less often unemployed and drank less alcohol and coffee. Among middle-aged men quitters were more often married, slept longer, and had higher life satisfaction. The possibility that the influence of psychosocial factors on chronic disease may be mediated in part through changes in smoking behavior is discussed.


Accuracy and reliability of a wireless vital signs monitor for hospitalized patients in a low-resource setting.
The purpose of this study was to evaluate the accuracy and reliability of neoGuard in comparison to a conventional bedside monitor on patients in a low-resource clinical setting. This was a single-arm methods comparison study involving the use of a wearable vital signs monitor (neoGuardTM) versus a conventional bedside monitor (Edan iM8). The study was conducted at Jinja Regional Referral Hospital, a tertiary care hospital situated in Eastern Uganda. Thirty patients (10 male, 20 female) were enrolled from the adult recovery ward at JRRH. Participants were eligible for the study if they were at least 18 years of age, had 2 sets of normal vital sign measurements obtained 1 h apart, and were able and willing to provide informed consent. The primary outcome measures were (i) bias (mean deviation) and (ii) limits of agreement [95% CI]. Bland-Altman plots were generated to illustrate the level of agreement between the neoGuardTM technology and the Edan iM8 monitor. Bland-Altman analysis was performed for 24 participants; datasets from six participants were excluded due to missing or invalid measurements. Findings showed a moderate level of agreement for measurement of SpO2, PR, and RR, with >80% of subject means falling within the predefined acceptability limits. However, there was also notable variation in accuracy between subjects, with large standard deviations observed for measurement of all four parameters. While the level of agreement for measurement of temperature was low, this is partly explained by limitations in the comparison method.


Triacontanol modulates salt stress tolerance in cucumber by altering the physiological and biochemical status of plant cells.
Cucumber is an important vegetable but highly sensitive to salt stress. The present study was designed to investigate the comparative performance of cucumber genotypes under salt stress (50 mmol L-1) and stress alleviation through an optimized level of triacontanol @ 0.8 mg L-1. Four cucumber genotypes were subjected to foliar application of triacontanol under stress. Different physiological, biochemical, water relations and ionic traits were observed to determine the role of triacontanol in salt stress alleviation. Triacontanol ameliorated the lethal impact of salt stress in all genotypes, but Green long and Marketmore were more responsive than Summer green and 20252 in almost all the attributes that define the genetic potential of genotypes. Triacontanol performs as a good scavenger of ROS by accelerating the activity of antioxidant enzymes (SOD, POD, CAT) and compatible solutes (proline, glycinebetaine, phenolic contents), which lead to improved gas exchange attributes and water relations and in that way enhance the calcium and potassium contents or decline the sodium and chloride contents in cucumber leaves. Furthermore, triacontanol feeding also shows the answer to yield traits of cucumber. It was concluded from the results that the salinity tolerance efficacy of triacontanol is valid in enhancing the productivity of cucumber plants under salt stress. Triacontanol was more pronounced in green long and marketer green than in summer green and 20252. Hence, the findings of this study pave the way towards the usage of triacontanol @ 0.8 mg L-1, and green long and marketer genotypes may be recommended for saline soil.


Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.
This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The "has-miR-424-5p/lncRNA PVT1" was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.


A comparison of two microcomputer-based programs for bibliographic retrieval and formatting.
We evaluated two representative microcomputer-based programs for organizing a biomedical literature filing system. With a bibliography of 100 anesthetic references, a series of benchmark tests was developed to measure the speed and accuracy of typical searching, sorting, and formatting tasks. Each program performed the searching tasks accurately and at about the same speed. One program performed sorting without errors, provided the field order of the template used to enter references was unchanged. Both programs used "punctuation files," that is, templates for controlling author presentation; punctuation to suit style requirements of individual journals; and order of particular fields, such as publisher and year of publication. Each program was able to format journal, book, and chapter references correctly, but the resulting output required some refining in a word processor. Both require a major time commitment to learn and to create custom punctuation files for journals not included in the predesigned punctuation files. Once mastered, both programs are quite competent at organizing reprints and formatting journal references.


The long noncoding RNA CIRBIL is a regulator of steroidogenesis in mice.
Infertility affects roughly 8-12 % of couples worldwide, and in above 50 % of couples, male factors are the primary or contributing cause. Many long noncoding RNAs (lncRNAs) are detected in the testis, but their functions are not well understood. CIRBIL was 862 nucleotides in length and was found to be localized mostly in the cytosol of Leydig cell, a small portion was positioned inside the seminiferous tubules. Loss of CIRBIL in mice resulted in male subfertility, characterized by smaller testis and increased germ cell apoptosis. Deletion of CIRBIL significant decreased the number of sperm and impaired the integrity of sperm head and tail. In CIRBIL KO mice, testosterone levels in serum and expression of testosterone biosynthesis genes (STAR and 3β-HSD) were both reduced. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were primarily enriched in steroid synthesis process in CIRBIL-binding proteins. Protein-protein (PPI) interaction networks revealed that both cis- and trans-regulated target genes of CIRBIL were associated with testosterone synthesis. Collectively, our results strongly suggest that CIRBIL is a regulator of steroid hormone synthesis.


Optic disk neovascularization in hemoglobin SC disease.
A 37-year-old black man had a clinically documented case of optic disk neovascularization associated with hemoglobin SC disease. Through medical evaluation, we ruled out other disorders associated with proliferative retinopathy. Extensive areas of retinal nonperfusion were associated with vasoproliferative retinopathy at the junction of the perfused and nonperfused retina; and a delicate network of neovascularization extended from the optic disk into the vitreous gel in one eye.


Ribosomal Protein S6 Phosphorylation: Four Decades of Research.
The phosphorylation of ribosomal protein S6 (rpS6) has been described for the first time about four decades ago. Since then, numerous studies have shown that this modification occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues. However, despite a large body of information on the respective kinases and the signal transduction pathways, the physiological role of rpS6 phosphorylation remained obscure until genetic manipulations were applied in both yeast and mammals in an attempt to block this modification. Thus, studies based on both mice and cultured cells subjected to disruption of the genes encoding rpS6 and the respective kinases, as well as the substitution of the phosphorylatable serine residues in rpS6, have laid the ground for the elucidation of the multiple roles of this protein and its posttranslational modification. This review focuses primarily on newly identified kinases that phosphorylate rpS6, pathways that transduce various signals into rpS6 phosphorylation, and the recently established physiological functions of this modification. It should be noted, however, that despite the significant progress made in the last decade, the molecular mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology are still poorly understood.


The complete amino acid sequence of growth hormone of an elasmobranch, the blue shark (Prionace glauca).
The complete amino acid sequence of growth hormone (GH) from a phylogenetically ancient fish, the blue shark (Prionace glauca), was determined. The shark GH isolated from pituitary glands by U. J. Lewis, R. N. P. Singh, B. K. Seavey, R. Lasker, and G. E. Pickford (1972, Fish. Bull. 70, 933-939) was purified by reversed-phase high-performance liquid chromatography. The hormone was reduced, carboxymethylated, and subsequently cleaved in turn with cyanogen bromide and Staphylococcus aureus protease. The intact protein was also cleaved with lysyl endopeptidase and o-iodosobenzoic acid. The resulting peptide fragments were separated by rpHPLC and submitted to sequence analysis by automated and manual Edman methods. The shark GH consists of 183 amino acid residues with a calculated molecular weight of 21,081. Sequence comparisons revealed that the elasmobranch GH is considerably more similar to tetrapod GHs (e.g., 68% identity with sea turtle GH, 63% with chicken GH, and 58% with ovine GH) than teleostean GHs (e.g., 38% identities with salmon GH and 42% with bonito GH) except for eel GH (61% identity), and substantiates the earlier finding derived from the immunochemical and biological studies (Hayashida and Lewis, 1978) that the primitive fish are less diverged from the main line of vertebrate evolution leading to the tetrapod than are the modern bony fish.


Elimination of Solanum nigrum ilarvirus 1 and Apple Hammerhead Viroid from Apple Cultivars Using Antivirals Ribavirin, Rimantadine, and Zidovudine.
Apple hammerhead viroid (AHVd) was detected in the apple cultivar 'Šampion' and in mixed infection with Solanum nigrum ilarvirus 1 (SnIV-1) in the cultivars 'Selena' and 'Jonagored Supra', using a high-throughput sequencing method. Experiments were conducted to eliminate both pathogens in apples using meristem tip cultures in combination with the antivirotics ribavirin, rimantadine, and zidovudine. Elimination of both pathogens was verified by repeated RT-PCR and qRT-PCR assays after 7-11 months. Elimination of SnIV-1 from all cultivars was successful with each of the three antivirotics at concentrations of 20, 40, and 80 mg L-1. Elimination of AHVd was also achieved, although less effectively and only with ribavirin in the concentration range of 20-160 mg L-1.


Three-dimensional rGO/CNT/g-C3N4 macro discs as an efficient peroxymonosulfate activator for catalytic degradation of sulfamethoxazole.
Over the past few years, advanced oxidation processes (AOPs) have shown promising efficiencies for wastewater remediation. Carbocatalysis, in particular, has been exploited widely thanks to its sustainable and economical properties but has an issue of recovery and reusability of the catalysts. To address this, three-dimensional (3D) binary and ternary graphene-based composites in the form of macro discs were created to activate peroxymonosulfate (PMS) for catalytic oxidation of sulfamethoxazole (SMX). Graphene oxide served as the base, while graphitic carbon nitride (g-C3N4) and/or single-walled carbon nanotubes (SWCNTs) were added. Among the various discs synthesized, rGNTCN discs (ternary composite) were proven to be the most efficient by completely degrading SMX in 60 min owing to their large surface area and nitrogen loading. The catalytic system was further optimized by varying the reaction parameters, and selective radical quenching and electron paramagnetic resonance tests were performed to identify the active radical, revealing the synergistic role of both radical and non-radical pathways. This led to the development of possible SMX degradation pathways. This research not only provides insights into ternary carbocatalysis but also gives a novel breakthrough in catalyst recovery and reusability by transforming nanocatalysts into macro catalysts.


Residual proliferative capacity in F9 teratocarcinoma stem cell cultures treated with alpha-difluoromethylornithine, an inducer of parietal endoderm differentiation.
We have previously shown that inhibition of polyamine biosynthesis by treatment with 5 mM alpha-difluoromethylornithine (DFMO) causes growth arrest and induces differentiation of F9 teratocarcinoma stem cells. The resulting phenotype is similar to that of parietal endoderm, and these differentiated cells possess no apparent proliferative capacity. In the present study, however, it is demonstrated that some of the DFMO-treated cells are not terminally differentiated. Upon a change to DFMO-free growth medium these cells eventually start to proliferate. Using a colony forming efficiency assay, it is estimated that less than 1 out of 200,000 cells retains its proliferative capacity after 6-10 days of DFMO treatment. These cells exhibit no apparent resistance to DFMO, and their population doubling time is similar to that of untreated control F9 cells. Consequently, the possible existence of a small, quiescent, cell population possessing proliferative potential must be taken into account when designing therapeutic protocols for DFMO.


Investigation of an on-line detection method combining near infrared spectroscopy with local partial least squares regression for the elution process of sodium aescinate.
An on-line detection method combining near infrared (NIR) spectroscopy with local partial least squares regression (PLSR) was investigated for the elution process of sodium aescinate. A 2 mm pathlength flow cell which transmitted NIR radiation through two fiber optic probes was placed in bypass of the macroporous resin column to collect real-time spectra of the sodium aescinate eluate. To compare the predictive accuracy, both local and global PLSR were employed to build mathematical models between NIR spectra and reference values. Meanwhile, Mahalanobis distance was introduced to select the appropriate local model for the prediction of unknown samples. Experimental results demonstrated that local PLSR was superior to global PLSR in both calibration performance and predictive accuracy. Moreover, the on-line detection method was proven to be feasible in real application and thereby would be of great value for monitoring the elution process of sodium aescinate in real time as well as determining the start and end points of eluate collection.


Effect of Mesenchymal Stem Cells Overexpressing BMP-9 Primed with Hypoxia on BMP Targets, Osteoblast Differentiation and Bone Repair.
Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs+BMP-9) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs+BMP-9 and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated. Hypoxia was induced with cobalt chloride (CoCl2) in MSCs+BMP-9, and the expression of BMP components and targets was evaluated. The paracrine effects of hypoxia-primed MSCs+BMP-9 on cell viability and migration and osteoblast differentiation were evaluated using conditioned medium. The bone formation induced by hypoxia-primed MSCs+BMP-9 directly injected into rat calvarial defects was also evaluated. The results demonstrated that hypoxia regulated BMP components and targets without affecting BMP-9 amount and that the conditioned medium generated under hypoxia favored cell migration and osteoblast differentiation. Hypoxia-primed MSCs+BMP-9 did not increase bone repair compared with control MSCs+BMP-9. Thus, despite the lack of effect of hypoxia on bone formation, the enhancement of cell migration and osteoblast differentiation opens windows for further investigations on approaches to modulate the BMP-9-HIF-1α circuit in the context of cell-based therapies to induce bone regeneration.


Linear response curves from an ELISA assay: measurement of anti-myelin IgG and IgM during experimental allergic neuritis.
An ELISA method for generating linear dose-response curves for measuring anti-myelin IgG and IgM is described. Linearity is achieved without logarithmic transformations. This test is used to measure plasma levels of anti-myelin antibodies in rabbits with EAN. Results are expressed as relative concentrations of antibody in arbitary mass units with 95% confidence limits fitted by inverse prediction. In the 8 animals studied, appearance of anti-myelin antibody always preceded onset of clinical signs and neither anti-myelin IgG nor IgM could be detected in any animal pre-inoculation. Five out of 8 animals displayed steady and progressive increases in anti-myelin IgG with the remaining 3 animals showing plateaus in IgG levels 21-30 days post-inoculation. Increases in anti-myelin IgG were generally parallelled by increases in disease severity. However, 2 animals showed recovery and relapse from EAN with no change in plasma levels of anti-myelin IgG. Patterns of production of anti-myelin IgM varied with some animals displaying early peaks while others showed gradual increases.


The Value of Targeting Complement Components in Asthma.
Asthma is an important respiratory illness. Though pharmacological and biological treatment is well established and is staged according to endotypes and their responses to treatment, novel avenues are being explored. Our focus is complement. In this viewpoint, we evaluate the approach to target complement in this complex hypersensitivity reaction that develops chronicity and has a personal-as well as a societal-cost.


Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.
The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.


Comparative transcriptomics to reveal the mechanism of enhanced catalytic activities of Aspergillus niger whole-cells cultured with different inducers in hydrolysis of citrus flavonoids.
A new Aspergillus niger whole-cell catalyst was cultured for the cascade hydrolysis of hesperidin (HES) to produce high-value hesperetin-7-O-glucoside (HG) and hesperetin with high conversion (above 90%). Moreover, the inducers used were shown to be useful for cell growth and to induce cells to produce specific enzymes. Remarkably, the type of inducers determined whether the cells can hydrolyze HES. The product composition was also controllable by adjusting different inducers. Transcriptome analysis suggested that both naringin-vs-blank group and saccharose-vs-blank group had obviously difference in gene expression. The naringin-vs-blank group was mainly up-regulated differentially expressed genes (DEGs), while saccharose-vs-blank group was mainly down-regulated DEGs. The Gene Ontology (GO) analysis showed that whether naringin or saccharose was added as an inducer would greatly affect the catalytic activity of cells. Furthermore, 3 genes related to rhamnosidase, 14 genes related to glucosidase and 5 genes related to hydrolase activity were found. These genes were not only involved in rhamnosidase and glucosidase activities, but also spliceosome and the sucrose and starch metabolic pathways. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the results of transcriptome sequencing were reliable. This study gave a new approach to hydrolyze HES, and new perspectives to understand the mechanisms associated with the hydrolysis of whole-cell catalyst.


The proximal N-terminal amino acid residues are required for the coupling activity of the bovine heart mitochondrial factor B.
Treatment of the recombinant bovine factor B with trypsin yielded a fragment (amino acid residues 62-175) devoid of coupling activity. Removal of the N-terminal Trp2-Gly3-Trp4 peptide resulted in a significant loss of coupling activity in the FB(DeltaW)(2)(-W)(4) deletion mutant. Sucrose density gradient centrifugation demonstrated co-sedimentation of recombinant factor B with the ADP/ATP carrier, which is present in preparations of H(+)-translocating F(0)F(1)-ATPase, but not in preparations of complex V. The N-terminally truncated factor B mutant FB(DeltaW)(2)(-W)(4) did not co-sediment with the ADP/ATP carrier. Recombinant factor B co-sedimented with partially purified membrane sector F(0), extracted from F(1)-stripped bovine submitochondrial particles with n-dodecyl-beta-d-maltoside. Factor B inhibited the passive proton conductance catalyzed by F(0) reconstituted into asolectin liposomes. A factor B mutant, bearing a photoreactive unnatural amino acid pbenzoyl-l-phenylalanine (pBpa) substituted for Trp2, cross-linked with F(0) subunits e and g as well as the ADP/ATP carrier. These results suggest that the N-terminal domain and, in particular, the proximal N-terminal amino acids are important for the coupling activity and protein-protein interactions of bovine factor B.


Autosomal dominant congenital cataract associated with chromosomal translocation [t(3;4)(p26.2;p15)].
We studied a family in which congenital cataracts were found in a father and son who had a reciprocal translocation between the short arms of chromosomes 3 and 4 [t(3;4)(p26.2;p15)]. The father's parents and brother had normal chromosomes and no evidence of cataracts. While results of these studies do not prove a causal relationship, they do strongly suggest that the areas near the break points involved in the translocation (3p26.2 and 4p15) would be good sites for further investigations into the genetic basis of this type of cataract.


Monitoring of hydrocarbon emissions in a petroleum refinery.
In a petroleum refinery the hydrocarbon emissions which are mostly fugitive in nature are emitted from process, offsites and periodic accidental releases such as: materials storage & handling, process, equipment leaks, solvent evaporation, combustion sources, waste treatment etc. In India, the monitoring of such emissions in a refinery are limited as also the standards are not set for its limit in ambient air. Hence there is an urgent need for generating a database for such emissions. Recently in India, MoEF/CPCB has set some guidelines under CREP rules for monitoring such emissions in a refinery. A detailed monitoring of the hydrocarbon emissions from different sources in a typical 10.5 MMTPA Indian refinery is undertaken during 1999-2001 and the results are presented. It is observed that the storage tank emissions alongwith process leaks form the major contributor towards fugitive hydrocarbon emissions.


Transportation needs and mobility patterns of persons experiencing homelessness following shelter decentralization.
The provision and siting of homeless emergency shelters have community-wide implications for addressing the needs of people experiencing homelessness (PEH). In Utah, Salt Lake County's transition from a large, centralized emergency shelter sited in a free transit zone to a decentralized scattered-site model outside of a no-cost transit zone provided the context to evaluate how transportation access and mobility patterns of PEH were affected as they were displaced from a centralized service network in a downtown core. We conducted 19 in-depth, semi-structured interviews with PEH aged 18 + who were staying in one of three distributed resource centers who had also previously stayed at the former centralized shelter. Thematic analysis of the interviews resulted in three categories, each with distinct sub-categories: 1) Pre-decentralization transportation and mobility, 2) Post-decentralization transportation and mobility, and 3) Recommendations to improve transportation access for PEH, including lowering or eliminating financial barriers to transportation and expanding transit and shuttle van frequency and route radius. Study findings demonstrate that there is a significant need for community planners to collaborate on the siting of homeless shelters to provide more affordable, flexible, and equitable access to transportation networks.


A phase II study of gemcitabine plus oral etoposide in the treatment of patients with advanced nonsmall cell lung carcinoma.
The authors have designed a non-cisplatin-based chemotherapy regimen for the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). This regimen capitalizes on the mild toxicity of gemcitabine, a novel nucleoside analog. A total of 46 chemotherapy-naive patients with histologically confirmed Stage IIIB or IV NSCLC were enrolled. Eligible patients were treated with gemcitabine 1000 mg/m(2) on Days 1, 8, and 15, plus oral etoposide 50 mg daily for 14 days, which was increased to 21 days if there was no World Health Organization (WHO) Grade 3 or 4 toxicity in the 1st 2 cycles (each cycle was 28 days long). All patients were included for analysis of response and survival according to an intention-to-treat principle. The overall response rate was 43.5% (95% confidence interval [CI], 30. 7-60.2%). There was 1 complete response (2.2%) and 19 partial responses (41.3%). The median survival was 48.0 weeks (95% CI, 38. 1-75.9 weeks) and the 1-year survival rate was 45% (95% CI, 29-62%). The median time to progression for all patients was 39.2 weeks (95% CI, 35.7-49.7 weeks). World Health Organization (WHO) Grade 3 and 4 anemia, neutropenia, and thrombocytopenia was reported in 29%, 32%, and 18% of patients, respectively. Two patients had reactivation of hepatitis B viral infection that resulted in WHO Grade 4 hepatic dysfunction. Other nonhematologic toxicities were uncommon. This non-cisplatin-based regimen of gemcitabine and oral etoposide achieved a high response and survival rate. Toxicity appeared to be less severe than that associated with existing cisplatin-based regimens. A randomized study of this regimen versus a cisplatin-based regimen is indicated.


Sex-specific effects of heme oxygenase-2 deficiency on renovascular hypertension.
Heme oxygenase-2 (HO-2) is the main isoform responsible for the breakdown of heme and release of carbon monoxide in the vasculature. Vascular-derived carbon monoxide protects against excessive vasoconstriction due to agents such as angiotensin II (Ang II) and in states of deficiency of nitric oxide. The current study was designed to determine the role of HO-2 in the development of renovascular hypertension using HO-2 knockout mice. Polyurethane cuffs were placed around the left renal artery of male and female HO-2 wild-type (WT), heterozygous (HET), and knockout (KO) mice between 16 and 24 weeks of age to induce renovascular hypertension. After 3 weeks, blood pressure was measured for 5 days, after which time both clipped and unclipped kidneys were harvested. No differences were observed in the blood pressure of sham mice between the different genotypes of both sexes. Cuffing of the left renal artery resulted in a significant increase in blood pressure in all genotypes of both sexes. In male mice, the increase in blood pressure was significantly greater in HET and KO mice as compared to WT mice (P < .05). This effect was not observed in female mice. Renovascular hypertension resulted in a significant increase (P < .05) in cardiac hypertrophy in male mice, which was not different between the genotypes. In female mice, HET and KO mice exhibited significantly greater (P < .05) cardiac hypertrophy as compared with WT mice. These results demonstrate a sex-specific effect of HO-2 deficiency on the development of renovascular hypertension and its effects on the heart in response to the increase in blood pressure.


Various arrangements of mobile genetic elements among CC147 subpopulations of Klebsiella pneumoniae harboring blaNDM-1: a comparative genomic analysis of carbapenem resistant strains.
Certain clonal complexes (CCs) of Klebsiella pneumoniae such as CC147 (ST147 and ST392) are major drivers of blaNDM dissemination across the world. ST147 has repeatedly reported from our geographical region, but its population dynamics and evolutionary trajectories need to be further studied. Comparative genomic analysis of 51 carbapenem-nonsusceptible strains as well as three hypervirulent K. pneumoniae (hvKp) recovered during 16-months of surveillance was performed using various bioinformatics tools. We investigated the genetic proximity of our ST147 strains with publicly available corresponding genomes deposited globally and from neighbor countries in our geographic region. While IncL/M plasmid harboring blaOXA-48 was distributed among divergent clones, blaNDM-1 was circulated by twenty of the 25 CC147 dominant clone and were mostly recovered from the ICU. The NDM-1 core structure was bracketed by a single isoform of mobile genetic elements (MGEs) [ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403] and was located on Col440I plasmid in 68.7% of ST392. However, various arrangements of MGEs including MITESen1/MITESen1 composite transposon or combination of MITESen1/ISSen4/IS903B/IS5/ISEhe3 on IncFIb (pB171) were identified in ST147. It seems that ST392 circulated blaNDM-1 in 2018 before being gradually replaced by ST147 from the middle to the end of sample collection in 2019. ST147 strains possessed the highest number of resistance markers and showed high genetic similarity with four public genomes that harbored blaNDM-1 on the same replicon type. Mainly, there was a convergence between clusters and isolated neighboring countries in the minimum-spanning tree. A conserved arrangement of resistance markers/MGEs was linked to methyltransferase armA which was embedded in class 1 integron in 8 isolates of ST147/ST48 high-risk clones. Our findings highlight the dynamic nature of blaNDM-1 transmission among K. pneumoniae in Iran that occurs both clonally and horizontally via various combinations of MGEs. This is the first analysis of Iranian ST147/NDM + clone in the global context.


Association of multifocal Hodgkin's lymphoma and tuberculosis infection: A challenging entity.
The association of Hodgkin's lymphoma and Tuberculosis is a rare entity, resulting in misdiagnose or delay in diagnosis of both diseases, since they share similar signs and symptoms, laboratory tests results and imaging procedures. We report the case of a 63 years old man who consulted for a clinical presentation of pulmonary and cervico-thoracic lymph nodes tuberculosis confirmed at the histopathological examination. The evolution after 5 months of antituberculous treatment was marked by the increase in size of the cervical nodes with a papular skin rash, diffuse abdominal pain and more weight loss. The FDG-PET-scan showed multiple confluent hypermetabolic lymphadenopathies on the whole upper body with cervical skin extension, next to hypermetabolic splenomegaly and focal liver hypermetabolism; next to a bilateral pleural effusion. The histopathological examination of the cervical lymph node specimen concluded to a Hodgkin lymphoma classified as Ann Arbor stage III. The chemotherapy protocol was started, while completing his antituberculous treatment. The patient passed away a few weeks later due to a septic shock. We present this case to supplement the rare literature data concerning the association of Hodgkin's lymphoma and Tuberculosis, defining how they impact the prognosis of one another, in order to comfort the importance of tuberculosis screening in lymphoma patients, especially in endemic areas.


Validamycin A Induces Broad-Spectrum Resistance Involving Salicylic Acid and Jasmonic Acid/Ethylene Signaling Pathways.
Validamycin A (VMA) is an aminoglycoside antibiotic used to control rice sheath blight. Although it has been reported that VMA can induce the plant defense responses, the mechanism remains poorly understood. Here, we found that reactive oxygen species (ROS) bursts and callose deposition in Arabidopsis thaliana, rice (Oryza sativa L.), and wheat (Triticum aestivum L.) were induced by VMA and were most intense with 10 μg of VMA per milliliter at 24 h. Moreover, we showed that VMA induced resistance against Pseudomonas syringae, Botrytis cinerea, and Fusarium graminearum in Arabidopsis leaves, indicating that VMA induces broad-spectrum disease resistance in both dicots and monocots. In addition, VMA-mediated resistance against P. syringae was not induced in NahG transgenic plants, was partially decreased in npr1 mutants, and VMA-mediated resistance to B. cinerea was not induced in npr1, jar1, and ein2 mutants. These results strongly indicated that VMA triggers plant defense responses to both biotrophic and necrotrophic pathogens involved in salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) signaling pathways and is dependent on NPR1. In addition, transcriptome analysis further revealed that VMA regulated the expression of genes involved in SA, JA/ET, abscisic acid (ABA), and auxin signal pathways. Taken together, VMA induces systemic resistance involving in SA and JA/ET signaling pathways and also exerts a positive influence on ABA and auxin signaling pathways. Our study highlights the creative application of VMA in triggering plant defense responses against plant pathogens, providing a valuable insight into applying VMA to enhance plant resistance and reduce the use of chemical pesticides.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Ischemic Optic Neuropathy Following Spine Surgery: Case Control Analysis and Systematic Review of the Literature.
Case-control analysis and systematic literature review. To illustrate the prognosis and perioperative risk factors associated with this condition. Ischemic optic neuropathy (ION) is the most common pathological diagnosis underlying postoperative vision loss. It comes in two primary forms-anterior (AION)-affecting the optic disc or posterior (PION) affecting the optic nerve proximal to the disc. Spine surgery remains one of the largest sources of acute perioperative visual loss. We performed a 1:4 case-control analysis (by age and year of surgery) for patients with ION and those who didn't develop ION following spine surgery at our institution. A systematic literature search of Medline, Embase, Scopus from inception to September 2017 as also performed. We identified 12 cases from our institution. Comparison to 48 matched controls revealed fusion, higher number of operative levels, blood loss, and change in hemoglobin, hematocrit to be significantly associated with ION. Majority were diagnosed with PION (83%, 10/12) and had bilateral presentation (75%, 9/12). Only 30% patients (3/10) demonstrated improvement in visual acuity while the rest remained either unchanged (40%, 4/10) or worsened (20%, 2/10) at last follow-up. Literature review identified 182 cases from 42 studies. Posterior ischemic optic neuropathy (PION) was found in 58.7% (114/194) of cases, anterior ischemic optic neuropathy (AION) in 17% (33/19) and unspecified ION in 24% (47/194). PION was associated with higher odds of severe visual deficit at immediate presentation (odds ratio [OR]: 6.45, confidence interval [CI]: 1.04-54.3, P = 0.04) and last follow-up. PION is the most common cause of vision loss following spine surgery and causes more severe visual deficits compared with AION. Prone spine surgery especially multi-level fusions with longer operative time, higher blood loss, and intraoperative hypotension are most associated with the development of this devastating complication. 3.


Children with profound intellectual and multiple disabilities: the effects of functional movement activities.
To determine the effect of functional movement activities within the MOVE (Mobility Opportunities Via Education) curriculum on the independence of children with profound intellectual and multiple disabilities. Forty-four children with profound intellectual and multiple disabilities. Centres for special education. A quasi-experimental pretest-posttest with control group design. The children in the control group (n=12) participated in the regular programme at the centre of special education. The children within the experimental group (n=32) were additionally supported by the MOVE curriculum. Both group comparisons and individual analyses were conducted. The level of independence of the experimental group increased significantly in performing movement skills; the control group did not increase significantly. At an individual level, 20 children (63%) of the experimental group improved in comparison with the control group, in which four children (33%) improved. Results showed that the children receiving functionally focused activities achieved the greatest improvements in independence when performing movement activities.


Electrocautery effect on intestinal vascularisation in a murine model.
The use of electrocautery devices is associated with complications such as perforation or fistulisation when used near intestinal structures. This is likely due to its effect on vascularisation of the bowel wall. To test this hypothesis we established a murine model to quantify the effect of electrocautery injury on the intestinal microvascularisation. Sprague-Dawley rats were subjected to five electrocautery injuries on the small bowel in coagulation mode (30 W intensity) and in cut mode (40 W, 80 W and 200 W intensities) for durations of 1, 2 and 5 s. 5 mg/kg of fluorescein was injected intravenously, the injured bowel segments harvested and the rat sacrificed. The segments were analysed to measure the fluorescence of injured bowel compared to adjacent unharmed tissue. A significant decrease in bowel wall microvascularisation occurred with increasing intensity (coag 30 W/cut 40 W versus cut 200 W 1 s: p < 0.05) and duration of electrocautery injury (cut 40 W 1/2 s versus 5 s: p < 0.05). There was a 40% perforation rate when decreased bowel wall microvascularisation was 25% or more. Despite similar electrocautery injury, a significantly greater microvascularisation decrease was observed in jejunum compared to ileum (p < 0.05). We successfully established a murine model to quantify the decrease of bowel wall microvascularisation associated with electrocautery use. Unsurprisingly, the decrease in microvascularisation is greater with higher intensity and duration of electrocautery and is associated with more perforations in the experimental model. The jejunum seems more vulnerable to electrocautery injury than the ileum. These observations support caution when using electrocautery devices near intestinal structures.


Effectiveness of nurse home-visiting for disadvantaged families: results of a natural experiment.
To evaluate the effects of a postnatal home-visiting programme delivered by community health nurses to socially disadvantaged mothers in South Australia. The intervention group of 428 mothers lived in metropolitan Adelaide and the comparison group of 239 mothers lived in regional towns where the programme was not yet available. All participating mothers met health service eligibility criteria for enrolment in the home-visiting programme. Participants in both groups were assessed at baseline (mean child age=14.4 weeks SD=2.3), prior to programme enrolment, and again when the children were aged 9, 18 and 24 months. State-wide community child health service. 667 socially disadvantaged mothers enrolled consecutively. 487 mothers (73%) completed the 24-month assessment. Two-year postnatal home-visiting programme based on the Family Partnership Model. Parent Stress Index (PSI), Kessler Psychological Distress Scale and the Ages and Stages Questionnaire. Mixed models adjusting for baseline differences were used to compare outcomes in the two groups. The mothers in the home-visiting group reported greater improvement on the PSI subscales assessing a mother's perceptions on the quality of their relationship with their child (1.10, 95% CI 0.06 to 2.14) and satisfaction with their role as parents (0.46, 95% CI -0.15 to 1.07) than mothers in the comparison group. With the exception of childhood sleeping problems, there were no other significant differences in the outcomes across the two groups. The findings suggest that home-visiting programmes delivered by community health nurses as part of routine clinical practice have the potential to improve maternal-child relationships and help mothers adjust to their role as parents. Australian and New Zealand Clinical Trials Registry ACTRN12608000275369.


Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and triple-negative breast cancer in Polish women.
XRCC2 and XRCC3 genes involved in homologous recombination repair (HRR) of DNA and in the maintenance of the genome integrity play a crucial role in protecting against mutations that lead to cancer. The aim of the present work was to evaluate associations between the risk of triple-negative breast cancer (TNBC) and polymorphisms in the genes, encoding for two key proteins of HRR: XRCC2 Arg188His (c. 563 G>A; rs3218536, Genbank Accession Number NT 007914) and XRCC3 Thr241Met (c. 722 C>T; rs861539, Genbank Accession Number NT 026437). The polymorphisms of the XRCC2 and XRCC3 were investigated by PCR-RFLP in 70 patients with TNBC and 70 age- and sex-matched non-cancer controls. In the present work, a relationship was identified between XRCC2 Arg188His polymorphism and the incidence of triple-negative breast cancer. The 188His allele and 188His/His homozygous variant increased cancer risk. An association was confirmed between XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms and TNBC progression, assessed by the degree of lymph node metastases and histological grades. In conclusion, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of triple-negative breast cancer in female population.


Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer.
Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray [Gy]) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.


SPCS: a spatial and pattern combined smoothing method for spatial transcriptomic expression.
High-dimensional, localized ribonucleic acid (RNA) sequencing is now possible owing to recent developments in spatial transcriptomics (ST). ST is based on highly multiplexed sequence analysis and uses barcodes to match the sequenced reads to their respective tissue locations. ST expression data suffer from high noise and dropout events; however, smoothing techniques have the promise to improve the data interpretability prior to performing downstream analyses. Single-cell RNA sequencing (scRNA-seq) data similarly suffer from these limitations, and smoothing methods developed for scRNA-seq can only utilize associations in transcriptome space (also known as one-factor smoothing methods). Since they do not account for spatial relationships, these one-factor smoothing methods cannot take full advantage of ST data. In this study, we present a novel two-factor smoothing technique, spatial and pattern combined smoothing (SPCS), that employs the k-nearest neighbor (kNN) technique to utilize information from transcriptome and spatial relationships. By performing SPCS on multiple ST slides from pancreatic ductal adenocarcinoma (PDAC), dorsolateral prefrontal cortex (DLPFC) and simulated high-grade serous ovarian cancer (HGSOC) datasets, smoothed ST slides have better separability, partition accuracy and biological interpretability than the ones smoothed by preexisting one-factor methods. Source code of SPCS is provided in Github (https://github.com/Usos/SPCS).


Mosquito abundance in relation to extremely high temperatures in urban and rural areas of Incheon Metropolitan City, South Korea from 2015 to 2020: an observational study.
Despite concerns regarding increasingly frequent and intense heat waves due to global warming, there is still a lack of information on the effects of extremely high temperatures on the adult abundance of mosquito species that are known to transmit vector-borne diseases. This study aimed to evaluate the effects of extremely high temperatures on the abundance of mosquitoes by analyzing time series data for temperature and mosquito abundance in Incheon Metropolitan City (IMC), Republic of Korea, for the period from 2015 to 2020. A generalized linear model with Poisson distribution and overdispersion was used to model the nonlinear association between temperature and mosquito count for the whole study area and for its constituent urban and rural regions. The association parameters were pooled using multivariate meta-regression. The temperature-mosquito abundance curve was estimated from the pooled estimates, and the ambient temperature at which mosquito populations reached maximum abundance (TMA) was estimated using a Monte Carlo simulation method. To quantify the effect of extremely high temperatures on mosquito abundance, we estimated the mosquito abundance ratio (AR) at the 99th temperature percentile (AR99th) against the TMA. Culex pipiens was the most common mosquito species (51.7%) in the urban region of the IMC, while mosquitoes of the genus Aedes (Ochlerotatus) were the most common in the rural region (47.8%). Mosquito abundance reached a maximum at 23.5 °C for Cx. pipiens and 26.4 °C for Aedes vexans. Exposure to extremely high temperatures reduced the abundance of Cx. pipiens mosquitoes {AR99th 0.34 [95% confidence interval (CI) 0.21-0.54]} to a greater extent than that of Anopheles spp. [AR99th 0.64 (95% CI 0.40-1.03)]. When stratified by region, Ae. vexans and Ochlerotatus koreicus mosquitoes showed higher TMA and a smaller reduction in abundance at extreme heat in urban Incheon than in Ganghwa, suggesting that urban mosquitoes can thrive at extremely high temperatures as they adapt to urban thermal environments. We confirmed that the temperature-related abundance of the adult mosquitoes was species and location specific. Tailoring measures for mosquito prevention and control according to mosquito species and anticipated extreme temperature conditions would help to improve the effectiveness of mosquito-borne disease control programs.


Linking rhizoplane pH and bacterial density at the microhabitat scale.
Ion-selective microelectrodes and a novel micro-sampling technique were used to investigate the relationship in field soil between Brassica napus rhizoplane pH and bacterial density at a spatial scale approximating a microhabitat. Bacterial densities were observed to increase with decreasing pH, rhizoplane pH measurements varied by up to 1 pH unit over a distance of 1 mm and the mean pH of the rhizoplane at the root base varied by more than 1 pH unit between plants. These findings highlight the appropriateness of investigating the interactions between bacterial communities and their environment at the micro-spatial scale and the utility of the micro-sampling method.


Septate junctions in insects: comparison between intercellular and intramembranous structures.
Septate junctions have been studied in the hind-gut of Periplaneta americana, Incisitermes schwartzi and Thermobia domestica. The topographical disposition of intercellular septa revealed by lanthanum impregnation corresponds well with that of particle rows seen in freeze fracture preparations. However, there is no precise correspondence between the undulations of septa and the disposition of particles within a single row. The spacing of particles is variable and generally less than that of the undulation periodicity of septa. On the other hand, the disposition of septa, and of the rows of particles that correspond to them, appears to be variable: sometimes rectilinear and in close parallel, these may curve or form series of 'finger-print' loops. Moreover, the septa are evidently not deployed as continuous ribbons around the cell since intrruptions are freuqently observed. In addition to their mechanical role in intercellular cohesion, septate junctions apparently ensure a more or less complete closure of the intercellular space (i.e. provide a permeability barrier) and thus play a role comparable with that of tight junctions in epithelia of vertebrates.


Transcriptional entrainment between master-slave genes via sister chromatid exchanges.
The paper discusses a mechanism for the coordination of a differentiation path through activation of slave genes by transcriptional complexes (excitons) organised by master genes. Entrainment occurs when master-slave genes form partnerships of closely apposed entities. Sister chromatid exchanges provide the action necessary for successful entrainment. Although concerned mainly with normal hematopoietic (stem) cells, the model applies also to certain leukemic cells, regarding in particular retrodifferentiation back to the stem state followed by attenuation of malignancy.


Three infection clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19), Shanghai, China, January to February 2020.
We report three clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19) between January and February 2020 in Shanghai, China. Investigators interviewed suspected COVID-19 cases to collect epidemiological information, including demographic characteristics, illness onset, hospital visits, close contacts, activities' trajectories between 14 days before illness onset and isolation, and exposure histories. Respiratory specimens of suspected cases were collected and tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The interval between the onset of illness in the primary case and the last contact of the secondary case with the primary case in our report was 1 to 7 days. In Cluster 1 (five cases), illness onset in the five secondary cases was 2 to 5 days after the last contact with the primary case. In Cluster 2 (five cases) and Cluster 3 (four cases), the illness onset in secondary cases occurred prior to or on the same day as the onset in the primary cases. The study provides empirical evidence for transmission of COVID-19 during the incubation period and indicates that pre-symptomatic person-to-person transmission can occur following sufficient exposure to confirmed COVID-19 cases. The potential pre-symptomatic person-to-person transmission puts forward higher requirements for prevention and control measures.


Thermal inactivation of jack bean urease.
Thermal inactivation of oligomeric enzymes results in complex structural changes. This work deals with thermal inactivation of a native hexamer, jack bean urease. In order to find the mechanism and kinetics of thermal inactivation corresponding well with the modification of tertiary and quaternary structure of this enzyme, several types of experiments were carried out in the temperature range of 65-85 °C. Inactivation data exhibited the characteristic biphasic character. Dynamic light scattering experiments revealed a significant increase of the mean hydrodynamic radius of urease with temperature and time. A significant contribution to understanding the mechanism of inactivation was provided by native gel electrophoresis data of inactivated samples. Simultaneous fit of inactivation data verified a two-step mechanism composed of reversible unfolding/folding reaction followed by a relatively fast aggregation of the denatured urease form. A complex reaction scheme containing numerous oligomeric forms was thus described by a relatively simple model which suitably represents the main types of reactions involved in the urease activity loss.


Development and validation of a new in vitro assay for selection of probiotic bacteria that express immune-stimulating properties in chickens in vivo.
Oral administration of immunoprobiotic bacteria may support animal health. Species specificity of such microorganisms requires appropriate selection. An in vitro assay for the selection of immunoprobiotic lactic acid bacteria was developed in chicken. The assay allowed testing of large numbers of individual strains. Immune stimulation in vitro correlated well with the in vivo situation in two experiments and no false negative results occurred. Therefore this assay is an appropriate selection tool for immunomodulating properties of lactic acid bacteria in chicken.


A combination of the cytokinesis-block micronucleus cytome assay and centromeric identification for evaluation of the genotoxicity of dicamba.
The purpose of this study was to further investigate the cytotoxic and genotoxic effects of dicamba and Banvel(®) employing the cytokinesis-block micronucleus cytome (CBMN-cyt) assay estimated by the analysis of the nuclear division index (NDI), the frequency of micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs). Besides, for mechanism of MN induction CREST anti-kinetochore antibody analysis was performed. The activities of both compounds were tested within the range of 50-500 μg/ml on Chinese hamster ovary (CHO-K1) cells. Overall, dicamba and Banvel(®) produced a NDI dose-dependent decrease but the response was statistically significant only in cultures treated with Banvel(®) at a 100-500 μg/ml concentration range. A dose-dependent induction of MN was observed after dicamba- and Banvel(®)-treatments within the 50-400 μg/ml and 50-500 μg/ml concentration-ranges, respectively. Induction of NPBs and NBUDs was significantly enhanced by both test compounds. The NPBs/MN ratio values found for dicamba and Banvel(®) were 0.04-0.11 and 0.05-0.18, respectively. Results clearly demonstrated that dicamba and Banvel(®) exerted both cyto- and genotoxic damage on CHO-K1 cells. Furthermore, the CBMN-cyt assay employed confirmed our previous investigations concerning the cellular and DNA damaging capabilities of dicamba and highlights that both clastogenic and aneugenic mechanisms are implicated in the MN induction.


Protein oxidation as a novel biomarker of bladder decompensation.
To measure the degree to which partial bladder outlet obstruction (PBOO) results in oxidative bladder damage, which subcellular components of the bladder are affected and whether these changes correlate with bladder function. In all, 32 rabbits were divided into four groups. Each group underwent PBOO for 1, 2, 4, and 8 weeks, respectively. Bladder tissue from each group was homogenized and separated into subcellular fractions via differential centrifugation. The carbonyl content within the subcellular fractions, including the nuclear, mitochondrial, and microsomal pellets, was then quantified by dot blot analysis. Total bladder oxidation increased with duration of obstruction across all subcellular fractions. The largest increase in total oxidation occurred between 4 and 8 weeks. Protein oxidation density in the nuclear and microsomal fractions both showed increases at 2 weeks obstruction, decreases at 4 weeks, and then large increases at 8 weeks. The increase in protein oxidation density between 4 and 8 weeks obstruction was most pronounced in the microsomal fraction. Overall bladder protein oxidation increased with the duration of obstruction and increased at a greater rate during the transition to decompensation. Furthermore, the subcellular fraction that exhibited the most oxidation was the microsomal pellet. The amount of protein oxidation correlated with the functional changes in the bladder.


Open approach for ileocolic resection in Crohn's disease in the era of minimally invasive surgery: indications and perioperative outcomes in a referral center.
Minimally invasive surgery (MIS) is the first-line approach for ileocolic resection in Crohn's disease (CD), and it is safe and feasible, even with severe penetrating CD or redo surgery. While MIS indications are continually broadening, challenging CD cases might still require an open approach. This study aimed to report rate and indications for an upfront open approach in ileocolic resection for CD. Comprehensive perioperative data for all consecutive patients undergoing ileocolic resection for CD between 2014 and 2021 in a high-volume referral center for CD and MIS, were collected retrospectively. Indications for an upfront open approach were reviewed separately by two authors according to the preoperative visit. Among 319 ileocolic resections for CD, 45 (14%) were open and 274 (86%) MIS. Two or more of the below indications were present in 40 patients (89%) in the open group, while only in 6 patients (2%) in the MIS group (p < 0.0001). Indications for upfront open approach were severe penetrating disease (58%), adhesions at previous surgery (47%), history of abdominal sepsis (33%), multifocal and extensive disease (24%), abdominal wall involvement (22%), concomitant open procedures (9%), small bowel dilatation (9%), and anesthesiologic contraindications (4%). MIS was never performed in a patient with abdominal wall involvement, concomitant open procedure, and anesthesiologic contraindication to MIS. This study can help guide patients, physicians, and surgeons. An abdominal wall involvement or the presence of two of the above indications predicts a high surgical complexity and may be considered as a no-go for the MIS approach. These criteria should prompt surgeons to strongly consider an upfront open approach to optimize the perioperative planning and care of these complex patients.


Cadmium induced testicular pathophysiology: prophylactic role of taurine.
The aim of the present study was to investigate the role of taurine against cadmium induced testicular pathophysiology. Cadmium (in the form of Cadmium chloride, CdCl(2)) administration at a dose of 4 mg/kg body weight for 6 days significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities along with the reduction in the plasma testosterone level. In addition, reductions in testicular sperm count as well as loss in sperm motility were also observed in Cd-intoxication. Cd increased the intracellular concentration of reactive oxygen species and testicular Cd accumulation. Besides, increased levels of lipid peroxidation, protein carbonylation, glutathione disulfide and DNA fragmentation as well as decreased levels of the activities of the antioxidant enzymes, total thiols and reduced glutathione were also found to be associated with this toxicity. Taurine pretreatment at a dose of 100 mg/kg body weight for 5 days, on the other hand, could prevent all the Cd-induced testicular pathophysiology and oxidative insult related studied parameters. Taurine treatment, in addition also increased the in vivo ferric reducing antioxidant power linearly up to a dose of 100 mg/kg body weight. Histological examination of testicular sections from experimental animals supported these results. The effect of a well established antioxidant, vitamin C has been included in the study as a positive control. Combining all, data suggest that being an antioxidant, taurine plays a beneficial role against Cd-induced adverse effects on the male reproductive system.


Resistance of recent measles virus wild-type isolates to antibody-mediated neutralization by vaccinees with antibody.
The neutralization capacity of sera from Luxembourgian adolescent vaccinees and from Nigerian women with measles-induced immunity to a number of measles virus strains was compared. Although both cohorts were matched for their hemagglutination inhibition and standard neutralization titers, 12 of the 22 late convalescent sera, and only 6 of 24 vaccinees neutralized all viruses. Similarly, only 2 of 20 viruses were not neutralized by at least 75% of late convalescent sera, in comparison to 10 of 20 viruses that resisted neutralization by at least 75% of the vaccinees. The more resistant viruses were not limited to a certain clade. One Nigerian virus was resistant to neutralization by 30% of the late convalescent women and by 75% of vaccinees. These results suggest that qualitative differences in neutralizing antibodies may reduce further protection of infants by passively acquired immunity against wild-type viruses when vaccinated girls become mothers.


Clinical assessment of elderly people with cancer.
As the elderly population increases, the diagnosis of cancer will become more common than it is today, and difficult decisions about treatment will need to be made by various health-care providers. An important issue not only for patients but also for the whole health-care system is that only those who will benefit from therapy are treated. Individuals for whom treatment will add neither quantity nor quality to their lifespan should not be subjected to potentially harmful treatment. Many assessment scales are validated in elderly people but not used in elderly patients with cancer. Comprehensive geriatric assessment provides an overarching method of assessment before, during, and after treatment. The benefits and shortcomings of other assessment scales are discussed in this review, showing settings in which their use might be appropriate in the developing specialty of geriatric oncology.


Comparison of mechanical properties of 3-dimensional printed and thermoformed orthodontic aligners.
Orthodontic treatment using clear aligners has experienced exponential growth since its introduction in the late 1990s. Three-dimensional (3D) printing has also grown in popularity among orthodontists, and companies have begun to produce resins to directly print clear aligners. This study aimed to examine the mechanical properties of commercially available thermoformed aligners and direct 3D-printed aligners under laboratory conditions and a simulated oral environment. Samples were prepared (approximately 2.5 × 20 mm) from 2 thermoformed materials, EX30 and LD30 (Align Technology Inc, San Jose, Calif), as well as 2 direct 3D-printing resins, Material X (Envisiontec, Inc; Dearborn, Mich) and OD-Clear TF (3DResyns, Barcelona, Spain). Wet samples were subjected to phosphate-buffered saline at 37°C for 7 days, whereas dry samples were stored at 25°C. Tensile and stress relaxation tests were carried out on an RSA3 Dynamic Mechanical Analyzer (Texas Instruments, Dallas, Tex) and Instron Universal Testing System (Instron, Norwood, Mass) to calculate elastic modulus, ultimate tensile strength, and stress relaxation. The elastic modulus of dry and wet samples was 103.2 ± 17.3 MPa and 114.4 ± 17.9 MPa (EX30), 61.3 ± 9.18 MPa and 103.5 ± 11.4 MPa (LD30), 431.2 ± 16.0 MPa and 139.9 ± 34.6 MPa (Material X), and 38.4 ± 14.7 MPa and 38.3 ± 8.4 MPa (OD-Clear TF), respectively. The ultimate tensile strength of dry and wet samples was 64.41 ± 7.25 MPa and 61.43 ± 7.41MPa (EX30), 40.04 ± 5.00 MPa and 30.09 ± 1.50 MPa (LD30), 28.11 ± 3.75 MPa and 27.57 ± 4.09 MPa (Material X), and 9.34 ± 1.96 MPa and 8.27 ± 0.93 MPa (OD-Clear TF), respectively. Residual stress of wet samples at 2% strain for 2 hours was 59.99 ± 3.02% (EX30), 52.57 ± 12.28% (LD30), 6.98 ± 2.64% (Material X), and 4.39 ± 0.84% (OD-Clear TF). There was a significant difference in elastic modulus, ultimate tensile strength, and stress relaxation among the samples tested. Moisture, specifically a simulated oral environment, appears to have a greater effect on the mechanical properties of direct 3D-printed aligners when compared with thermoformed aligners. This is likely to impact the ability of 3D-printed aligners to generate and maintain adequate force levels for tooth movement.


Spectrofluorimetric analysis of cefuroxime in pharmaceutical dosage forms.
A fluorimetric method has been developed for the quantitative analysis of cefuroxime, based upon the formation of a fluorescent derivative formed by alkaline hydrolysis with 1.0 M sodium hydroxide and heating at 100 degrees C for 60 min. The fluorescent product gave excitation and emission maxima at 380 and 436 nm, respectively. The method was performed in aqueous solution adjusted to pH 10.5 by addition of phosphate buffer solution. The calibration curve was found to be linear in the range of concentrations 0.050-1.70 micrograms ml-1. The lower limit of detection was 1.0 x 10(-2) micrograms ml-1. The method was applied to authentic pharmaceutical preparations containing cefuroxime sodium or cefuroxime axetil, the 1-(acetyloxy) ethyl ester of the drug, and was found to be satisfactory. Cefuroxime sodium was also determined in physiological solutions used to prepare intravenous infusions of this antibiotic.