Expression kinetics of the (proto) oncogenes c-myc and bcl-2 following photodynamic treatment of normal and transformed human fibroblasts with 5-aminolaevulinic acid-stimulated endogenous protoporphyrin IX.
In the same way as common tumour therapies can cause secondary tumour induction, photodynamic tumour therapy also shows a moderate mutagenicity. The oncogenes responsible for it can be distinguished from their proto-oncogenic precursors by an irreversible increase in their constitutive expression. Transient changes of the expression level of (proto) oncogenes can indicate the beginning of disturbances in the cell homeostasis: many of these genes have a normal function in proliferation or play a role in apoptosis. In this study, therefore, quantitative determination of the expression of the (proto) oncogenes c-myc and bcl-2 in normal and transformed human fibroblasts at different times following photodynamic treatment with 5-aminolaevulinic acid-stimulated endogenous protoporphyrin IX and low-dose irradiation has been carried out by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The aim is to investigate if irreversibly increased (proto) oncogene expression can be found, and if expression changes are involved in cell-cycle alterations (detected in a parallel study) and in initiation of apoptotic processes. The results show: (1) no mutagenic risk, since the over-expression of c-myc and bcl-2 is transient; (2) an interaction of bcl-2 and c-myc associated with an increase of the proliferative activity of the cell cycle of transformed cells; (3) a possible role of bcl-2 in counteracting processes that could be at least precursors for apoptosis induction; and (4) higher constitutive expression of both genes in transformed than in normal fibroblasts.


Hemolytic characteristics of three commercially available centrifugal blood pumps.
As compared with traditional extracorporeal roller-occlusion blood pumps, nonocclusive centrifugal pumps offer the benefits of requiring a smaller circuit surface area and, thus, a smaller prime volume. However, centrifugal blood pumps have been reported to generate unacceptable levels of hemolysis. We hypothesize that the newer generation centrifugal pumps have an incidence of hemolysis similar to the traditional roller head pumps and, thus, could be used for extracorporeal membrane oxygenation circuits. Randomized, prospective, bench study. University research laboratory. Three centrifugal blood pumps (Cobe Revolution, Jostra Rotaflow, and Medtronic BioMedicus) were compared with a roller occlusion blood pump (Cobe Century). Hemolysis generation was examined during 6 hrs of continuous use. Two test runs per group were randomly performed on three consecutive days for a total of six test runs for each of the four pumps (n = 24). Plasma free hemoglobin values were determined using a Spectra MaxPlus spectrophotometer. A normalized index of hemolysis was calculated to compare the individual trials. The Cobe Revolution and the Jostra Rotaflow compared favorably with the Cobe Century roller occlusion blood pump in the amount of hemolysis produced. These data are encouraging for the development of a low-prime, mobile neonatal extracorporeal membrane oxygenation circuit using centrifugal pump technology.


[The effect of auditory image moving in vertical plane upon posture responses of humans].
The influence of sound image motion on postural reactions was studied. The movement of sound source was created by successive switching of the loudspeakers situated over the arc in sagittal plane. Movement duration of sound stimulus was 1.6 s, 3.2 s and 4.8 s. The mean sway magnitudes decreased when the stimuli duration was 1.6 s and 3.2 s. Averaging of the wave-forms of center-of-pressure sway for signal with 4.8 s duration revealed that the sound image presentation induces body displacement in the direction opposite to that of sound image.


Integrating music-based interventions with Gamma-frequency stimulation: Implications for healthy ageing.
In recent years, music-based interventions (MBIs) have risen in popularity as a non-invasive, sustainable form of care for treating dementia-related disorders, such as Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). Despite their clinical potential, evidence regarding the efficacy of MBIs on patient outcomes is mixed. Recently, a line of related research has begun to investigate the clinical impact of non-invasive Gamma-frequency (e.g., 40 Hz) sensory stimulation on dementia. Current work, using non-human-animal models of AD, suggests that non-invasive Gamma-frequency stimulation can remediate multiple pathophysiologies of dementia at the molecular, cellular and neural-systems scales, and, importantly, improve cognitive functioning. These findings suggest that the efficacy of MBIs could, in theory, be enhanced by incorporating Gamma-frequency stimulation into current MBI protocols. In the current review, we propose a novel clinical framework for non-invasively treating dementia-related disorders that combines previous MBIs with current approaches employing Gamma-frequency sensory stimulation. We theorize that combining MBIs with Gamma-frequency stimulation could increase the therapeutic power of MBIs by simultaneously targeting multiple biomarkers of dementia, restoring neural activity that underlies learning and memory (e.g., Gamma-frequency neural activity, Theta-Gamma coupling), and actively engaging auditory and reward networks in the brain to promote behavioural change.


Free radicals in Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disorder comprising multisystem atrophies probably caused by multifactorial processes. The disease is characterized by typical neuropathology, impaired synaptic function and massive cell loss. The pathobiochemistry of this disorder involves oxidative stress, which accumulates free radicals leading to excessive lipid peroxidation and neuronal degeneration in certain brain regions. Moreover, radical induced disturbances of DNA, proteins and lipid membranes have been measured. The hypothesis has been proposed that cellular events involving oxidative stress may be one basic pathway leading to neurodegeneration in Alzheimer's disease. In this work we report evidence for increased oxidative stress and disturbed defense mechanisms in Alzheimer's disease, which may result in a self-propagating cascade of neurodegenerative events. Furthermore it is evident from experimental data, that aggregation of beta-amyloid and beta-amyloid toxicity is favourably caused by oxidative stress. Therefore, oxidative stress plays a key role in the conversion of soluble to unsoluble beta-amyloid, suggesting that oxidative stress is primary to the beta-amyloid cascade.


Chromosome-scale genomes of commercial timber trees (Ochroma pyramidale, Mesua ferrea, and Tectona grandis).
Wood is the most important natural and endlessly renewable source of energy. Despite the ecological and economic importance of wood, many aspects of its formation have not yet been investigated. We performed chromosome-scale genome assemblies of three timber trees (Ochroma pyramidale, Mesua ferrea, and Tectona grandis) which exhibit different wood properties such as wood density, hardness, growth rate, and fiber cell wall thickness. The combination of 10X, stLFR, Hi-Fi sequencing and HiC data led us to assemble high-quality genomes evident by scaffold N50 length of 55.97 Mb (O. pyramidale), 22.37 Mb (M. ferrea) and 14.55 Mb (T. grandis) with >97% BUSCO completeness of the assemblies. A total of 35774, 24027, and 44813 protein-coding genes were identified in M. ferrea, T. grandis and O. pyramidale, respectively. The data generated in this study is anticipated to serve as a valuable genetic resource and will promote comparative genomic analyses, and it is of practical importance in gaining a further understanding of the wood properties in non-model woody species.


Correction: Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods.
[This corrects the article DOI: 10.1039/C8RA06707D.].


Programmed cell death 4 in bacterially-challenged Apostichopus japonicus: Molecular cloning, expression analysis and functional characterization.
Programmed cell death 4 (PDCD4) plays a crucial role in modulating cellular signals, mainly via TOLL cascades during the immune response. In the present study, a novel PDCD4 homologue gene (denoted as AjPDCD4) was cloned from the sea cucumber Apostichopus japonicus using RACE. The full-length AjPDCD4 cDNA comprised a 366bp 5'-UTR, a 418bp 3'-UTR, and a 1353bp open reading frame encoding a 450 amino acid residue protein with two typical MA3 domains. Phylogenetic analysis revealed that AjPDCD4 belonged to the invertebrate PDCD4 family. Spatial expression analysis indicated that AjPDCD4 mRNA transcripts are expressed at a high level in the tentacles and at a low level in muscle compared with coelomocytes. Vibrio splendidus challenge and LPS exposure could both significantly down-regulate AjPDCD4 mRNA expression. More importantly, we found that ultraviolet (UV)-induced ROS production and DNA damage were greatly repressed in AjPDCD4-knockdown coelomocytes. Meanwhile, the expression levels of the NF-kappa B homologue, p105, were synchronously up-regulated in the same conditions. All of these results indicated that AjPDCD4 is involved in modulating DNA damage and ROS production in sea cucumber, perhaps by affecting the TLR pathway.


The negative coupling between serotonin and muscarinic receptor(s) for arachidonic acid and inositol phosphates release in brain cortex synaptoneurosomes. Effect of aging.
In the present study we have investigated the relationship between serotonergic receptor(s) (5-HTR) and muscarinic cholinergic receptor (mAChR) activation, leading to the arachidonic acid (AA) release and inositol phosphates (IPs) formation in adult and aged brain cortex synaptoneurosomes. It was observed that serotonin (5-HT) almost completely inhibits carbachol-stimulated AA release in adult brain. This negative coupling between 5-HTR and mAChR probably depends on the direct stimulation of the acylation reaction coupled with 5-HT1AR. In the aged brain this type of interaction does not occur because aging eliminates carbachol and 5-HT effect. On the other hand, in aged brain, both 5-HT and carbachol more actively stimulate IPs accumulation than in adult brain. Serotonin inhibits carbachol-stimulated IPs release to the level observed during 5-HT2R activation. Our study indicates for the first time, the negative coupling between 5-HTR and mAChR for AA liberation in adult brain and a lack of this kind of receptors interaction in senescent brain. In adult brain, 5-HT1AR-stimulated AA incorporation is responsible for this coupling. Moreover, serotonin through the stimulation of 5-HT2R, suppresses mAChR-dependent IPs liberation in adult and aged brain similarly. The interactions between these two neurotransmitter receptors lead to the modification of lipid mediators formation and may have important implications in alteration of signal transduction in adult and in aged brain.


Arbovirus infections in Sarawak, October 1968-February 1970: GETAH virus isolations from mosquitoes.
14 strains of Getah virus were isolated from a variety of mosquito species collected in Sarawak between October 1968 and February 1970. Ten strains were isolated from C. tritaeniorhynchus 7 of them at K. Tijirak. Single strains were isolated from C. gelidus, C. pseudovishnui, M. bonneae/dives and Aanopheles species. 6 of the isolates were obtained in October 1968 when Japanese encephalitis, Tembusu and Sindbis viruses were also very active. The available evidence suggest that Getah virus in Sarawak is maintained in a cycle similar to that of Japanese encephalitis virus and involves C. tritaeniorhynchus, C. gelidus and domestic pigs.


Proton NMR studies of vesicles incorporating glycophorin.
The effects of incorporation of glycophorin, the major sialoglycoprotein of the human erythrocyte membrane, on the lipid of small vesicles have been studied using proton NMR and electron microscopy. In contrast to the incorporation of other peptides, the major effect is apparently the clustering of vesicles without fusion. The relative mobility of lipids of the vesicle, monitored by changes in proton spin-lattice time, is only moderately effected by the presence of protein. The methylene protons of the lipid chains are subject to a somewhat greater restriction of motion following the incorporation of glycophorin than are the protons of the head group.


Translational regulation: versatile mechanisms for metabolic and developmental control.
It has become clear that many vital metabolic circuits and early developmental programs are regulated translationally. Until recently, the mechanisms underlying most of these observations were poorly understood. The past year has witnessed several important advances in the understanding of how the translational apparatus is controlled by different regulatory mechanisms.


The potential application of red mud and soil mixture as additive to the surface layer of a landfill cover system.
Red mud, the by-product of aluminum production, has been regarded as a problematic residue all over the world. Its storage involves risks as evidenced by the Ajka red mud spill, an accident in Hungary where the slurry broke free, flooding the surrounding areas. As an immediate remediation measure more than 5cm thick red mud layer was removed from the flooded soil surface. The removed red mud and soil mixture (RMSM) was transferred into the reservoirs for storage. In this paper the application of RMSM is evaluated in a field study aiming at re-utilizing waste, decreasing cost of waste disposal and providing a value-added product. The purpose was to investigate the applicability of RMSM as surface layer component of landfill cover systems. The field study was carried out in two steps: in lysimeters and in field plots. The RMSM was mixed at ratios ranging between 0 and 50% w/w with low quality subsoil (LQS) originally used as surface layer of an interim landfill cover. The characteristics of the LQS+RMSM mixtures compared to the subsoil (LQS) and the RMSM were determined by physical-chemical, biological and ecotoxicological methods. The addition of RMSM to the subsoil (LQS) at up to 20% did not result any ecotoxic effect, but it increased the water holding capacity. In addition, the microbial substrate utilization became about triple of subsoil (LQS) after 10months. According to our results the RMSM mixed into subsoil (LQS) at 20% w/w dose may be applied as surface layer of landfill cover systems.


Correlation between compression, tensile and tearing tests on healthy and calcified aortic tissues.
An anastomosis performed in calcified tissues tears up faster than in healthy tissues. This study develops and validates an in vitro non-destructive method to distinguish healthy from calcified aortic tissues. An uniaxial unconfined compression test is able to distinguish healthy from calcified aortas (p<0.01). The compressive E-modulus at a strain level of 10% is 227+/-34kPa for artificially calcified and 147+/-15kPa for healthy porcine aortic tissues. Calcified aortic tissues have a lower tensile strength than healthy porcine aortic tissues (p<0.05). The ultimate tensile strength is 1.34+/-0.18MPa and 1.55+/-0.31MPa for artificially calcified and healthy porcine aortic tissues respectively. Calcified aortic tissues have a lower resistance to tearing than healthy aortic tissues (p<0.05). The resistance to tearing is 1.78+/-0.33N/mm and 2.16+/-0.64N/mm for artificially calcified and healthy porcine aortic tissues respectively.


Improvement in organic solvent tolerance by double disruptions of proV and marR genes in Escherichia coli.
To investigate the involvement of osmoprotectant transporters in organic solvent tolerance in Escherichia coli and to construct an E. coli strain with high organic solvent tolerance. The organic solvent tolerance of ΔbetT, ΔproV, ΔproP or ΔputP single-gene knockout mutants of E. coli K-12 strain was examined. Among these mutants, the organic solvent tolerance of the ΔproV mutant remarkably increased compared with that of the parent strain. It has been known that a marR mutation confers tolerance on E. coli to organic solvents. A ΔproV and ΔmarR double-gene mutant was more tolerant to organic solvents than the ΔproV or ΔmarR single-gene mutant. The n-hexane amount accumulated in E. coli cells was examined after incubation in an n-hexane-aqueous medium two-phase system. The intracellular n-hexane level in the ΔproV and ΔmarR double-gene mutant was kept lower than those of the parent strain, ΔproV mutant and ΔmarR mutant. The organic solvent tolerance level in E. coli highly increased by dual disruption of proV and marR. This study suggests a new strategy for increasing the organic solvent tolerance level in E. coli to improve the usability of the whole-cell biocatalysts in two-phase systems employing organic solvents.


Effects of cataracts on flicker electroretinograms recorded with RETeval™ system: new mydriasis-free ERG device.
The purpose of this study was to evaluate the effects of cataracts on the flicker electroretinograms (ERGs) recorded with the RETeval™ system under mydriatic-free conditions. This was a retrospective study of 82 eyes of 60 patients with cataracts and 52 eyes of 38 patients who were pseudophakic. Flicker ERGs were recorded with the RETeval™ system (LKC Technologies, Gaithersburg, MD) under mydriatic-free condition with skin electrodes. Flicker ERGs were elicited by white light delivered at a frequency of 28.3 Hz and intensity of 8 Td-s. The implicit times and amplitudes of the ERGs recorded from the Grade 2 cataract, Grade 3 cataract, and pseudophakic groups were compared. The mean amplitude was significantly smaller in both cataract groups than the pseudophakic group (Grade 2 cataract vs pseudophakic group, P < 0.0001; Grade 3 cataract vs pseudophakic group, P < 0.0001; Grade 2 cataract vs Grade 3 cataract, P = 0.027). The mean implicit times was significantly longer in both cataract groups than the pseudophakic group (Grade 2 cataract vs pseudophakic group, P = 0.046; Grade 3 cataract vs pseudophakic group, P = 0.0004; Grade 2 cataract vs Grade 3 cataract, P = 0.0084). The results indicate that the presence of Grade 2 or more cataracts will affect both the amplitude and the implicit time of the flicker ERGs. The presence of cataracts should be taken into consideration when interpreting the flicker ERG recorded with RETeval™.


Tissue factor, its inhibitor, and the thrombogenicity of two new synthetic membranes.
The aim of the study was to compare the effect of new high-flux hemodialysis membranes made from polyacrylonitrile (AN69ST) and polysulfone (Helixone) on the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) playing a key role in hemostasis. Established thrombogenicity markers were also determined. In a clinical prospective randomized study, 10 patients were examined using either membrane at the start and at minutes 15, 60, and 240 of hemodialysis. Increases in the plasma TF levels reached significance at the end of hemodialysis with both membranes, with the Helixone also after 15 min. TFPI levels tended to rise significantly from minute 15 onward while not differing from baseline at the end of the procedure. Judging by the increase in thrombin-antithrombin III complexes, both membranes significantly activated coagulation at the end of hemodialysis. Platelet factor 4 levels, released during thrombocyte and endothelial stimulation, were elevated from the start of procedures. There were no significant differences between the AN69ST and the Helixone in any of the assessed markers. The AN69ST and Helixone membranes do not differ in their effects on TF and TFPI or even in established thrombogenicity markers.


Variation in Fukienogomphus prometheus (Lieftinck, 1939) reveals Stylurus takashii (Asahina, 1966) as a junior synonym, with discussion on the status of F. choifongae Wilson amp; Tam, 2006 (Odonata: Gomphidae).
We investigate variation of body pattern in Fukienogomphus prometheus (Lieftinck, 1939) and notice the similarity of its female to Stylurus takashii (Asahina, 1966), an enigmatic species whose male is still unknown. We then review the taxonomic history of S. takashii and compare its holotype female with the female F. prometheus. Our results show S. takashii is a junior synonym to F. prometheus. We elucidate the intraspecific variation of F. prometheus and provide information for its ecology and distribution in Taiwan. We also discuss the similarities between the adults of Fukienogomphus choifongae Wilson Tam, 2006 and F. prometheus which in future studies may prove to be conspecific and will require to synonymise the two names. Finally, we confirm the genus Stylurus Needham, 1897 is not distributed in Taiwan.


Biochemical basis for retinol deficiency induced by the I41N and G75D mutations in human plasma retinol-binding protein.
Retinol-binding protein (RBP) is the retinol-specific carrier protein present in plasma, where it circulates almost entirely bound to thyroxine-binding transthyretin (TTR). Recently, depressed plasma retinol and RBP levels in carriers of the I41N and G75D RBP point mutations have been reported. We show here that although recombinant human N41 and D75 RBPs can form complexes with retinol and TTR in vitro, the retinol-mutated RBP complexes are significantly less stable than human normal holo-RBP, as revealed by the markedly facilitated retinol release by mutated holo-RBPs to phospholipid membranes, in accordance with the location of mutated residues inside the RBP retinol-binding cavity. Taken together, the data are consistent with the I41N and G75D point mutations being the cause of an altered interaction of retinol with RBP, resulting in a remarkably reduced stability of the retinol-RBP complex, which in turn can lead to the lowering of plasma retinol and RBP levels.


Male sexual behavior induced by intracranial electrical stimulation.
Electrical brain stimulation in the anterior dorsolateral hypothalamus produced a marked increase in sexual capacity in some male rats. Several measures of sexual behavior, including the length of the postejaculatory refractory period, were significantly affected.


Sources and characteristics of carbonaceous aerosols at Agra "World heritage site" and Delhi "capital city of India".
Agra, one of the oldest cities "World Heritage site", and Delhi, the capital city of India are both located in the border of Indo-Gangetic Plains (IGP) and heavily loaded with atmospheric aerosols due to tourist place, anthropogenic activities, and its topography, respectively. Therefore, there is need for monitoring of atmospheric aerosols to perceive the scenario and effects of particles over northern part of India. The present study was carried out at Agra (AGR) as well as Delhi (DEL) during winter period from November 2011 to February 2012 of fine particulate (PM₂.₅: d < 2.5 μm) as well as associated carbonaceous aerosols. PM₂.₅ was collected at both places using medium volume air sampler (offline measurement) and analyzed for organic carbon (OC) and elemental carbon (EC). Also, simultaneously, black carbon (BC) was measured (online) at DEL. The average mass concentration of PM₂.₅ was 165.42 ± 119.46 μg m(-3) at AGR while at DEL it was 211.67 ± 41.94 μg m(-3) which is ~27% higher at DEL than AGR whereas the BC mass concentration was 10.60 μg m(-3). The PM₂.₅ was substantially higher than the annual standard stipulated by central pollution control board and United States Environmental Protection Agency standards. The average concentrations of OC and EC were 69.96 ± 34.42 and 9.53 ± 7.27 μm m(-3), respectively. Total carbon (TC) was 79.01 ± 38.98 μg m(-3) at AGR, while it was 50.11 ± 11.93 (OC), 10.67 ± 3.56 μg m(-3) (EC), and 60.78 ± 14.56 μg m(-3) (TC) at DEL. The OC/EC ratio was 13.75 at (AGR) and 5.45 at (DEL). The higher OC/EC ratio at Agra indicates that the formation of secondary organic aerosol which emitted from variable primary sources. Significant correlation between PM₂.₅ and its carbonaceous species were observed indicating similarity in sources at both sites. The average concentrations of secondary organic carbon (SOC) and primary organic carbon (POC) at AGR were 48.16 and 26.52 μg m(-3) while at DEL it was 38.78 and 27.55 μg m(-3), respectively. In the case of POC, similar concentrations were observed at both places but in the case of SOC higher over AGR by 24 in comparison to DEL, it is due to the high concentration of OC over AGR. Secondary organic aerosol (SOA) was 42% higher at AGR than DEL which confirms the formation of secondary aerosol at AGR due to rural environment with higher concentrations of coarse mode particles. The SOA contribution in PM₂.₅ was also estimated and was ~32 and 12% at AGR and DEL respectively. Being high loading of fine particles along with carbonaceous aerosol, it is suggested to take necessary and immediate action in mitigation of the emission of carbonaceous aerosol in the northern part of India.


Predictive factors for acute renal failure in crush injuries in the Sichuan earthquake.
The Sichuan earthquake caused a large number of crush injuries and many of them developed acute renal failure (ARF). A retrospective study was performed on victims with crush injuries of West China Hospital to investigate the predictive factors for acute renal failure (ARF) in crush injuries. Medical records of injured victims treated in West China Hospital within the first week after the Sichuan earthquake were retrospectively reviewed and 101 patients with crush injury were enrolled in the study. We divided them into an ARF group and a non-ARF group. The clinical data of included patients were extracted and analysed. Patients with ARF accounted for 42% of the included population. Patients younger than 20 made up the biggest age category (45%), and the entrapped time under the debris (22 [IQR 3.5-38]h) was longer than previous reports. In univariate analysis, male gender, multiple crush injuries, medical comorbidities, surgical interventions and infections were more frequent in patients with ARF than in those without ARF. Mean arterial pressure was higher in the ARF group. Besides, the risk of ARF was increased by creatine kinase >14,494.5IU/L most significantly, followed by time under the rubble >4h, aspartate transaminase >453.5IU/L, albumin <27.15g/L and white blood cell >11.8×10(9)/L. In multivariate analysis, male gender, time under the rubble, multiple crush injuries, surgical interventions, infections and creatine kinase level were independently associated with ARF in crush injuries. The entrapped time under the debris, multiple crush injuries, male gender, infections, and creatine kinase level are predictive factors for ARF in crush injuries.


Identification of identical binding polypeptides for cephalosporins and dipeptides in intestinal brush-border membrane vesicles by photoaffinity labeling.
The uptake of a photolabile derivative of the orally effective cephalosporin cephalexin, N-(4-azidobenzoyl)cephalexin, was investigated in brush-border membrane vesicles. The compound was taken up into the intravesicular space and inhibited the active uptake of cephalexin in a concentration-dependent manner. Therefore, this probe interacts with the transport system shared by alpha-aminocephalosporins and dipeptides. Photoaffinity labeling of brush-border membrane vesicles from rat small intestine with N-(4-azido[3,5-3H]benzoyl) derivatives of the cephalosporin cephalexin and the dipeptide glycyl-L-proline resulted in the covalent incorporation of radioactivity into membrane polypeptides with apparent molecular weights of 127,000, 100,000, 94,000 and 86,000, the polypeptide of molecular weight 127,000 being predominantly labeled. The specificity of labeling was demonstrated by a decrease in the labeling of the polypeptide of apparent molecular weight 127,000 in the presence of beta-lactam antibiotics and dipeptides, whereas glucose, taurocholate or amino acids had no effect on the labeling pattern. These data demonstrate an interaction of cephalosporins and dipeptides with a common membrane protein of molecular weight 127,000, which could be a component of the intestinal transport system(s) responsible for the uptake of orally effective cephalosporins and dipeptides.


Parsimonious clinical prediction model for the diagnosis of complicated appendicitis.
To develop a logistic regression model that combines clinical and radiological parameters for prediction of complicated appendicitis. 248 patients with histologically proven uncomplicated (n = 214) and complicated (n = 34) acute appendicitis were analyzed retrospectively. All patients had undergone a presurgical abdominal and/or pelvic computed tomography (CT) scan, assessed by two radiologists. A model using univariate and multivariate logistic regression analyses was developed, and the strength of association between independent predictors and complicated acute appendicitis was evaluated by adjusted odds radio. Clinical parameters were gender, age, anorexia, vomiting, duration of symptoms, right lower abdominal quadrant (RLQ) tenderness, rebound tenderness, body temperature, white blood cell (WBC) count, and neutrophil ratio. Radiological parameters were appendix diameter, appendicolith, caecal wall thickening, mesenteric lymphadenopathy, extraluminal air, abscess, fat stranding, and periappendicular fluid. Four features (body temperature>37.2 °C, vomiting, appendicolith, and periappendiceal fluid) were included in the logistic regression model, and yielded an area under the curve (AUC) of 0.87 (95% confidence interval (CI), 0.80-0.93), sensitive of 88%, and specificity of 74%. The logistic regression model makes an accurate and simple prediction of complicated appendicitis possible.


The variability of fetal breathing movements in normal human fetuses at term.
With the use of a B-scan phase-locked tracking system, 108 observations of fetal breathing were performed on 97 normal antenatal patients at term. One hundred thirty-three recorded segments of fetal breathing movements were obtained. Breath-to-breath variability was analyzed in 79 segments and expressed as a coefficient of variability. The mean coefficient of variability was 28.6% +/- 13.2%, and a histogram plot revealed a normal distribution. All fetuses had normal antepartum testing and all Apgar scores and neonatal courses were normal. The potential application of human fetal breathing variability as a test for fetal health is discussed.


Serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes in patients with testicular germ cell tumors.
The activities of serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes were determined in 252 patients with a history of testicular germ cell tumors (TGCT). Fifteen of 37 patients with TGCT lesions and seven of 215 without had raised levels of S-LDH (above 8.0 mukat/l (480 U/l)). Of the patients with TGCT lesions, four had only raised S-LDH-1 levels, one only raised S-LDH-2 (and normal S-LDH), two only raised S-LDH-3 (one with normal S-LDH), and 10 had five combinations of raised levels of S-LDH isoenzymes with a predominance of S-LDH-1. S-LDH and S-LDH-1 correlated significantly with the total tumor volume in the patients with TGCT lesions, especially pronounced in those with lesions from seminoma. Of 34 patients with TGCT metastases, 13 with raised S-LDH levels lived significantly shorter lengths of time than 21 with normal S-LDH. Similarly, 11 with raised S-LDH-1 (above 3.0 mukat/l (180 U/l) lived significantly shorter times than 23 with normal S-LDH-1. S-LDH is a valuable tumor marker in patients with TGCT, especially in those with seminoma. Routine determination of S-LDH isoenzymes in addition to S-LDH in patients with TGCT is not recommended. In patients with a history of TGCT and an unexplained elevation of S-LDH levels, a raised S-LDH-1 level indicates the presence of TGCT lesions.


A novel α-glucosidase inhibitory constituent from Uncaria gambir.
Bioactivity-guided fractionation of an aqueous methanolic extract of manufactured gambir product from Uncaria gambir with in vitro α-glucosidase inhibitory activity was performed to isolate a novel prenyl resorcinol derivative (1) together with seven known compounds, including two flavone glycosides (2, 3), three catechin analogues (4-6), and two simple phenolics (7, 8). Structures of the isolated compounds were determined by analysis of physical and spectroscopic data (NMR, UV, [α]D, and MS). All isolates were evaluated for in vitro α-glucosidase inhibitory activity. Among the compounds, novel compound 1, possessing an unprecedented spirocyclopropane ring in the molecule, showed the most potent α-glucosidase inhibitory activity in this assay. On the other hand, compounds 4 and 7 showed less potent inhibitory effects in this same bioassay, with half-maximal inhibitory concentration values of 17.3 ± 1.0 μM and 27.0 ± 0.9 μM, respectively.


Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis.
To clarify whether any particular β blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly due to a class effect. Systematic review and network meta-analysis of efficacy of different β blockers in heart failure. CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011). Randomized trials comparing β blockers with other β blockers or other treatments. The primary endpoint was all cause death at the longest available follow-up, assessed with odds ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers. 21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, β blockers provided credible mortality benefits in comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80). However, no obvious differences were found when comparing the different β blockers head to head for the risk of death, sudden cardiac death, death due to pump failure, or drug discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar irrespective of the individual study drug. The benefits of β blockers in patients with heart failure with reduced ejection fraction seem to be mainly due to a class effect, as no statistical evidence from current trials supports the superiority of any single agent over the others.


Poly[bis-(μ2-N,N-di-methyl-formamide-κ2 O:O)bis-(μ4-thio-phene-2,5-di-carboxyl-ato-κ4 O:O':O'':O''')dicobalt(II)].
The asymmetric unit of the title three-dimensional metal-organic hybrid compound, [Co2(C6H2O4S)2(C3H7NO)2] n , comprises two cobalt(II) cations, one residing on a twofold axis and the other on a centre of inversion, one thio-phene-2,5-di-carboxyl-ate (tdc2-) ligand and one coordinating di-methyl-formamide (DMF) solvent mol-ecule. Both of the cobalt(II) cations exhibit an octa-hedral coordination environment from the four carboxyl O atoms of the tdc2- anions in a μ 4-κ 1:κ 1:κ 1:κ 1 fashion and two O atoms from DMF. A pair of carboxyl O atoms and one DMF molecule connect the adjacent cobalt(II) cations into an infinite chain, leading to a rod-spacer framework with rhombus-window channels, yet no residual solvent-accessible voids are present because the coordinating DMF molecules are oriented into the potential channels.


The effect of epinephrine and benzalkonium chloride on cultured corneal endothelial and trabecular meshwork cells.
We evaluated the effect of dipivefrin hydrochloride, epinephrine hydrochloride, epinephrine borate and their respective vehicles with and without the preservative benzalkonium chloride, on the in vitro growth characteristics of human corneal keratocytes, endothelial cells and trabecular meshwork. Epinephrine hydrochloride and borate at low concentrations (0.0002%) significantly inhibited growth of both trabecular meshwork and corneal endothelial cells. Higher concentrations (0.02%) of these same drugs induced the same effect on the growth of keratocytes in vitro. Similar observations were made on the effect of dipivefrin hydrochloride on human corneal cells in vitro. Benzalkonium chloride alone was demonstrated to be responsible for the growth inhibitory effects on trabecular cells. The susceptibility of trabecular meshwork cells in culture to the commonly used ophthalmic preservative benzalkonium chloride is demonstrated.


Biodegradation of ketoprofen using a microalgal-bacterial consortium.
To test the toxicity of ketoprofen (a commonly-used NSAIDs) using two microalgal strains and Artemia sp. following the isolation of bacterial and microalgal strains and testing their ability to biodegrade and tolerate ketoprofen. Chlorella sp. was the most resistant to ketoprofen. A defined bacterial consortium (K2) degraded 5 mM ketoprofen as a sole carbon source both in the dark or continuous illumination. Ketoprofen did not undergo photodegradation. In the dark, biodegradation was faster with a lag phase of 10 h, 41% COD removal and 82 % reduction in toxicity. The consortium degraded up to 16 mM ketoprofen. The consortium was composed of four bacterial isolates that were identified. MS/MS analysis suggested a ketoprofen biodegradation pathway that has not been previously reported. Combining Chlorella sp. and the K2 consortium, ketoprofen was degraded within 7 days under a diurnal cycle of 12 h light/12 h dark. The feasibility of using a microalgal-bacterial system to treat pharmaceutical wastewater is promising for the reduction of the process cost and providing a safer technology for pharmaceutical wastewater treatment.


Observations on regional cerebral blood flow in cortical and subcortical structures during language production in normal man.
Regional cerebral blood flow (rCBF) was studied by single photon emission computerized tomography (SPECT) of inhaled xenon-133 in six normal volunteers during various language, articulatory, and control conditions. Language production increased rCBF in predominantly left-sided cortical and subcortical areas. The involved regions were anatomically related to a left frontal area (Broca's), to both caudate nuclei, to a left thalamic/pallidal area, and bilaterally in retrorolandic areas. The failure to demonstrate lateralized retrorolandic activity is thought to reflect the complexity of the tasks.


Cloning and mapping of the sporulation gene, spoT7, in Saccharomyces cerevisiae.
In order to isolate a DNA fragment able to complement a sporulation-deficient mutation in Saccharomyces cerevisiae, a simple screening procedure was devised which was based on the difference in osmotic sensitivity between protoplasts and spores. A plasmid (pHT7) containing a 13 kb DNA insert that complemented the spoT7 mutation was isolated from a yeast genomic library prepared in the vector YEp13. Gene spoT7 was linked to rna1 at 1.2 cM and to mak27 at 7.2 cM on the right arm of chromosome XIII. Mapping of the cloned gene following integration into the chromosome showed that the cloned gene was allelic to spoT7 and that a part of the RNA1 gene was also cloned into the same fragment. Gene spoT7 was localized on a 5 kb DNA fragment by further subcloning.


Symposium on semiprecision attachments in removable partial dentures. Extracoronal attachments.
An overview of several types of extracoronal attachments has been presented. They have been classified into rigid types, resilient types, and bar attachments. The uses of each classification were discussed, and the problems inherent with all types of extracoronal attachments were mentioned.


Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis.
We sought to describe characteristics and outcome in adults with isolated ventricular noncompaction (IVNC). Isolated ventricular noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven meshwork. Knowledge regarding diagnosis, morbidity and prognosis is limited. Echocardiographic criteria for IVNC include-in the absence of significant heart lesions-segmental thickening of the left ventricular myocardial wall consisting of two layers: a thin, compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep recesses. Thirty-four adults (age >16 years, 25 men) fulfilled the diagnostic criteria and were followed prospectively. At diagnosis, mean age was 42 + 17 years, and 12 patients (35%) were in New York Heart Association class III/IV. Left ventricular end-diastolic diameter was 65 + 12 mm and ejection fraction 33 + 13%. Apex and/or midventricular segments of both the inferior and lateral wall were involved in >80% of patients. Follow-up was 44 + 40 months. Major complications were heart failure in 18 patients (53%), thromboembolic events in 8 patients (24%) and ventricular tachycardias in 14 patients (41%). There were 12 deaths: sudden in six, end-stage heart failure in four and other causes in two patients. Four patients underwent heart transplantation. Automated cardioverter/defibrillators were implanted in four patients. Diagnosis of IVNC by echocardiography using strict criteria is feasible. Its mortality and morbidity are high, including heart failure, thrombo-embolic events and ventricular arrhythmias. Risk stratification includes heart failure therapy, oral anticoagulation, heart transplantation and implantation of an automated defibrillator/cardioverter. As IVNC is a distinct entity, its classification as a specific cardiomyopathy seems to be more appropriate.


Postprandial lipid metabolism in diabetes.
Postprandial lipemia is an inherent feature of diabetic dyslipidemia and highly prevalent in diabetic patients even with normal fasting triglyceride concentrations. Postprandial lipemia is characterized by long residence time of chylomicron and VLDL remnants in the circulation. Insulin resistance causes increased flux of free fatty acids, and thus enhanced VLDL apolipoprotein B (apo B) synthesis in the liver. Together with chylomicron and VLDL remnant competition for the common removal mechanisms the increased substrate input results in exaggerated and prolonged postprandial lipemia. Studies using both apo B-48 and retinyl esters as a marker for intestinally derived particles have shown that increased postprandial lipemia does not predict the presence or absence of coronary artery disease between non-insulin-dependent diabetes mellitus (NIDDM) subjects. Recent data have shown that postprandial triglyceride-rich remnants are atherogenic, and postprandial hypertriglyceridemia contributes to the metabolic disturbances transforming LDL and HDL subclasses into more atherogenic direction in diabetic subjects.


Possible involvement of hippocampal immediate-early genes in contextual fear memory deficit induced by cranial irradiation.
Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal plasticity during memory formation.


Temperature control of the motility of actin filaments interacting with myosin molecules using an electrically conductive glass in the presence of direct current.
The motility of actin filaments interacting with heavy meromyosin molecules was directly observed on indium tin oxide-coated glass (ITO-glass), over which a surface current flowed. Because the increase in surface current applied to ITO-glass increases the temperature, we focused on the temperature-dependence of the sliding velocity and the effect of the current flow on the orientation of filament motion. Using high precision fluorescence measurements, the displacement vectors of filaments were collected at intervals of 1/30 s. The direction of filament motion was independent to that of current flow up to 0.17 A (7.7 A/m of surface current density); however, the velocity increased by approximately 2-fold when the surface temperature increased from 25 °C to 37 °C. The moving actin filaments exhibited a broader velocity distribution at high temperature than at low temperature. Collectively, these data suggest that using ITO-glass with a surface current to generate a well-controlled temperature change may serve to evaluate temperature-dependent transient responses in protein activity under a microscope, without interference from electrical effects.


Contribution of stent underexpansion to recurrence after sirolimus-eluting stent implantation for in-stent restenosis.
We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR). Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES. Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10. These were compared with 16 patients (19 lesions) without recurrence as documented by angiography. Nine of 11 recurrent lesions had a minimum stent area (MSA) <5.0 mm2 versus 5 of 19 nonrecurrent lesions (P=0.003); 7 of 11 recurrent lesions had an MSA <4.0 mm2 versus 4 of 19 nonrecurrent lesions (P=0.02); and 4 of 11 recurrent lesions had an MSA <3.0 mm2 versus 1 of 19 nonrecurrent lesions (P=0.03). A gap between SESs was identified in 3 of 11 recurrences versus 1 of 19 nonrecurrent lesions. Stent underexpansion is a significant cause of failure after SES implantation treatment of ISR.


Cerebral Area Differential Redox Response of Neonatal Rats to Selenite-Induced Oxidative Stress and to Concurrent Administration of Highbush Blueberry Leaf Polyphenols.
Our goal was to delineate the mechanisms of selenite-induced oxidative stress in neonatal rats and investigate the potential of blueberry leaf polyphenols to counteract the induced stress. Vaccinium corymbosum leaf decoction (BLD) was analyzed by UPLC-MS and LC-DAD, along with its in vitro antioxidant activity (DPPH radical scavenging, FRAP, ferrous chelation). Newborn suckling Wistar rats were randomly divided into three groups: 'Se' and 'SeBLD' received 20 μmol Na2SeO3/kg BW subcutaneously (PN day 10); 'SeBLD' received 100 mg dry BLD/kg BW intraperitoneally (PN11 and 12) and Group 'C' received normal saline. Βiochemical analysis revealed tissue-specific effects of selenite. Brain as a whole was more resistant to selenite toxicity in comparison to liver; midbrain and cerebellum were in general not affected, but cortex was moderately disturbed. Liver lipid peroxidation, GSH, SOD, CAT, GPx were significantly affected, whereas proteolytic activity was not. BLD, which is rich in chlorogenic acid and flavonols (especially quercetin derivatives), exerted significant antioxidant protective effects in all regions. In conclusion, we provide for the first time an insight to the neonatal rat cerebral and liver redox response against a toxic selenite dose and blueberry leaf polyphenols.


Childhood transverse myelitis and its mimics.
Childhood transverse myelitis is an acute inflammatory disorder of the spinal cord with a risk of permanent disability. A timely and accurate diagnosis is imperative, and the radiologist needs to discern between a variety of extra-axial and spinal cord abnormalities that produce similar symptoms but require vastly differing treatments. This article presents the range of imaging characteristics seen in childhood transverse myelitis and the differentiation from its mimics.


In vivo selection of transduced hematopoietic stem cells and little evidence of their conversion into hepatocytes in vivo.
FMEV-type retroviral vector provides high transgene expression in hepatocytes and hematopoietic stem cells (HSCs). Here, we examined whether these vectors could provide a sufficient drug-resistance gene expression in HSCs and whether transduced HSCs could differentiate into hepatocytes in vivo. The CD45(+)/Lin(-) cells were transduced in vitro by FMEV-type vectors containing human O(6)-methylguanine-DNA methyltransferase (MGMT)/reporter genes and transferred into recipient mice. After the treatment with temozolomide and O(6)-benzylguanine (TMZ/BG) in vivo, we analyzed the transgene expression in peripheral blood cells by flow-cytometry. Immunohistochemistry was performed on the liver slices in partial hepatectomized recipient mice. After TMZ/BG treatment, transduced host cells were enriched in recipient mice. In the liver, we observed the efficient transgene expression in many small cells along sinusoids. However, only few large cells in hepatic lobules expressed albumin. They also expressed both a transgene and a recipient marker gene, suggesting the fusion of donor HSCs with recipient hepatocytes. This vector expressed a drug-resistance gene in HSCs highly enough to protect them from the drugs. But, the conversion of HSCs into hepatocytes in vivo might be a rare event in this model.


Is high relative humidity associated with childhood hand, foot, and mouth disease in rural and urban areas?
To examine the relationship between relative humidity and childhood hand, foot and mouth disease (HFMD) in Hefei, China, and to explore whether the effect is different between urban and rural areas. Retrospective ecological study. A Poisson generalized linear model combined with a distributed lag non-linear model was used to examine the relationship between relative humidity and childhood HFMD in a temperate Chinese city during 2010-2012. The effect of relative humidity on childhood HFMD increased above a humidity of 84%, with a 0.34% (95% CI: 0.23%-0.45%) increase of childhood HFMD per 1% increment of relative humidity. Notably, urban children, male children, and children aged 0-4 years appeared to be more vulnerable to the effect of relative humidity on HFMD. This article study indicates that high relative humidity may trigger childhood HFMD in a temperate area, Hefei, particularly for those who are young and from urban areas.


Intubation decision criteria in adult epiglottitis.
To identify contributive criteria in decision-making for intubation in acute epiglottitis, based on clinical and endoscopic data in adult patients, and to study clinical and biological characteristics and management. Diagnosis was established by flexible endoscopy showing epiglottic edema in association with general signs of sepsis in 28 patients consulting into two French hospitals between 2005 and 2016. Retrospective univariate and multivariate analysis between patients managed by intubation (Group I) or surveillance (Group S) was performed on clinical and endoscopic data. Ten patients were intubated (36%). On univariate analysis, 4 variables were suggestively associated with intubation. On multivariate analysis, associations remained suggestive for dyspnea (OR=50.6; 95% CI=[2.7; 940.1]) and supraglottic edema extension (OR=42.2; 95% CI=[2.2; 799.5]). The area under the curve identifying intubated patients on these 2 criteria was 90.8%, testifying to high discrimination. Intubation must always be considered in epiglottitis. Dyspnea and supraglottic extension of the edema seem to be the two main criteria to be considered in airway control decision-making.


Droplet-based microfluidics for binding assays and kinetics based on FRET.
Droplet microfluidic systems provide a controlled environment in which to perform rapid mixing, isolation of picoliter size fluid volumes and rapid variation of reaction conditions. Indeed, the ability to controllably form droplets with variable reagent composition at high speed lies at the heart of performance improvements when compared to conventional microfluidic devices operating under laminar flow conditions. Furthermore, it is important to realize that segmented-flow systems can generate droplets at rates in excess of 1 kHz. In theory, this means that millions of individual reactions or assays can be processed in very short times. In addition, since mixing is rapid and reagent transport occurs with no dispersion, microdroplet reactors are superior environments in which to study biological reactions, especially rapid kinetic reactions, when compared to diffusion-limited continuous-flow formats. Accordingly, droplet microfluidics is a promising technology to perform reactions and assays in a high-throughput manner, in which a hugely productive and efficient system for screening a desired component from thousands of samples is necessary.


[Psoriasis arthritis. An interdisciplinary challenge].
Psoriatic arthritis (PsA) is classified as a spondylarthropathy based on its clinical and serological characteristics. The clinical manifestations and the association with psoriasis or nail psoriasis have led, together with immunological characteristics, to a further differentiation. The pathophysiological and genetic understanding of this disease has advanced as a result of the development of new treatment strategies and targets in rheumatology and dermatology. Collaborative efforts and increasing multidisciplinary cooperation between rheumatologists and dermatologists have led to an increased awareness in early diagnosis and treatment. New treatment modalities have demonstrated significant efficacy in preventing radiologic progression resulting in amelioration of clinical symptoms, improvement of function and quality of life.


Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors.
Peroxisomes are cytoplasmic organelles which are important in mammals in modulation of lipid homeostasis, including the metabolism of long-chain fatty acids and conversion of cholesterol to bile salts (reviewed in refs 1 and 2). Amphipathic carboxylates such as clofibric acid have been used in man as hypolipidaemic agents and in rodents they stimulate the proliferation of peroxisomes. These agents, termed peroxisome proliferators, and all-trans retinoic acid activate genes involved in peroxisomal-mediated beta-oxidation of fatty acids. Here we show that the receptor activated by peroxisome proliferators and the retinoid X receptor-alpha (ref. 6) form a heterodimer that activates acyl-CoA oxidase gene expression in response to either clofibric acid or the retinoid X receptor-alpha ligand, 9-cis retinoic acid, an all-trans retinoic acid metabolite; simultaneous exposure to both activators results in a synergistic induction of gene expression. These data demonstrate the coupling of the peroxisome proliferator and retinoid signalling pathways and provide evidence for a physiological role for 9-cis retinoic acid in modulating lipid metabolism.


Iron-enhanced sand filters: Multi-year urban runoff (stormwater) quality performance.
Untreated urban runoff (stormwater) is a major pathway for contaminants, e.g., nutrients and metals, to receiving waters. Where eutrophication occurs, dissolved phosphorus (DP) treatment is often necessary to protect receiving waters, yet few practical methods exist. Iron-enhanced sand filters (IESFs) have successfully treated DP in laboratory and limited field studies. Yet, multi-year-IESF studies to understand reportedly variable performance are unavailable. Herein, nine IESFs were sampled from 2015 to 2018 (528 samples; 70 rainfall-runoff events). Analysis focused on influent/effluent concentrations and removal efficiencies alongside design and catchment parameters. Overall, IESFs significantly removed most total and dissolved metal analytes. Generally, phosphorus removal efficiencies correlated positively with influent concentrations and IESF:catchment area ratios, demonstrating the importance of proper sizing and siting. For all paired influent-effluent samples, respective median total phosphorus, orthophosphate, and DP removal efficiencies were 33 %, 41 %, and 13 %, and respective median effluent concentrations were 120, 25, and 75 (μg/L); with two malfunctioning sites omitted, these respective concentrations were 92, 11, and 47, which better matched relevant goals and (indirectly applicable) standards. Nonetheless, phosphorus removal efficiency and effluent concentrations varied significantly across IESFs and events. Seasonality appeared influential, yet variable influent concentrations confounded spatiotemporal removal efficiency comparisons. Thus, compared to removal efficiencies, effluent concentrations may be better indicators of receiving water risk/benefit and of equal importance for water quality crediting. Although 122 influent-effluent pairs were analyzed, a greater sample size would allow multivariate hypothesis tests with additional predictors. Overall, in this multi-site-year study, most IESFs performed at (n = 5) or near (n = 2) phosphorus effluent concentration and less-so, removal efficiency benchmarks. This research provides new quantitative knowledge on long-term IESF performance for real-world conditions and goals. Research recommendations include multivariate dimension reduction studies and comprehensive, effective information transfer to improve IESF understanding and performance and address practitioner needs, e.g., for refined design, operation, and assessment guidance.


Cell attachment and fibrinogen binding properties of platelet and endothelial cell thrombospondin are not affected by structural differences in the 70 and 18 kDa protease-resistant domains.
Structural differences between platelet and endothelial cell thrombospondin (TBSP) were found in two protease-resistant domains (70 and 18 kDa). The 70 kDa fragment is involved in the binding of TBSP to fibrinogen and the 18 kDa fragment in the attachment to various cultured cells. Despite these structural differences, platelet and endothelial cell TBSP bound with the same affinity to fibrinogen and mediated the attachment of smooth muscle cells but not of endothelial cells.


Bovine trophoblastic cell differentiation on collagen substrata: formation of binucleate cells expressing placental lactogen.
The differentiation of trophectoderm in ruminants is marked by the appearance of binucleate cells in cytotrophoblasts. Binucleate cells are produced by the acytokinesis of cytotrophoblasts and undergo endoreduplication. They secrete hormones such as placental lactogen, and exhibit migratory behavior to transfer their hormones into maternal circulations. In this study, we showed that a bovine trophoblastic cell line (BT-1) established from in vitro fertilized blastocysts differentiated into binucleate cells on collagen gel. BT-1 had cytotrophoblastic epithelial characteristics in that it expressed cytokeratin, E-cadherin and interferon-tau. It spontaneously formed multicellular spherical vesicles floating in the medium. We cultured these vesicles on type I collagen substrata. Most vesicles attached to the collagen substrata, and exhibited cell outgrowth and proliferation. We found that after more than 10 days, clusters of binucleate cells appeared in the cell colonies on the collagen gel, but not on the collagen film. These binucleate cells have features characteristic of those in vivo, including an increased nuclear DNA content and the expression of placental lactogen. BT-1 is a useful model with which to study trophoblast differentiation in ruminants.


Glycated Hemoglobin as an Integrator of Cardiovascular Risk in Individuals Without Diabetes: Lessons from Recent Epidemiologic Studies.
Prediabetes, or dysglycemia in the absence of diabetes, is a prevalent condition typically defined by a glycated hemoglobin (HgbA1c) of 5.7- < 6.5%. This article reviews current contemporary data examining the association between prediabetes and cardiovascular disease (CVD) as well as HgbA1c as a continuous measure of cardiovascular risk across the glycemic spectrum. Dysglycemia in the prediabetic range is associated with an increased risk of both subclinical and clinical CVD, including atherosclerotic CVD, chronic kidney disease, and heart failure. Several recent large, prospective studies demonstrate roughly linear risk with increasing HgbA1c, even below the threshold for prediabetes. "High-risk" patients with prediabetes have similar CVD risk as those with diabetes. HgbA1c below the threshold for diabetes stratifies CVD risk. Use of HgbA1c as a continuous measure, rather than simply dichotomized, may inform current and future prevention strategies. Given the high population attributable risk associated with prediabetes, targeted prevention strategies in this population warrant dedicated study.


Deficiency of neural cell adhesion molecule or its polysialylation modulates pharmacological effects of the AMPA receptor antagonist NBQX.
The neural cell adhesion molecule NCAM and its dynamically regulated posttranslational modification polysialic acid (PSA) are major determinants of cellular interactions during ontogeny. While NCAM in the absence of PSA stabilizes cell-cell interactions, the attachment of the large and polyanionic PSA negatively influences cell adhesion and promotes plasticity. Disease-associated changes in the polysialylation state of NCAM raise the question whether the PSA-NCAM system can affect CNS pharmacology. Here we investigated the pharmacological effects of the competitive AMPA antagonist NBQX in genetic mouse models either lacking NCAM and PSA (female NCAM knockout mice) or being drastically reduced in the level of PSA expression (female ST8SiaIV knockout mice). Studies were carried out with the respective wildtype littermate controls. In mice lacking NCAM and PSA, NBQX-induced ataxia proved to be more intense as compared with wild-type mice. On both mutant backgrounds, NBQX significantly elevated seizure thresholds during i.v. infusion of the chemoconvulsant pentylenetetrazole. In summary, the data demonstrate that the PSA-NCAM system impacts AMPA receptor pharmacology under in vivo conditions. The fact that comparable effects were observed in NCAM- and ST8SiaIV-knockout mice indicates that this impact is not due to a stabilizing effect of NCAM in the absence of PSA. Thus, disease-related changes in the polysialylation of NCAM are likely to be associated with effects on the efficacy and tolerability of AMPA receptor antagonists.


Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis.
Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms. We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior cingulate, orbitofrontal and posterior parietal cortices, inferior frontal and fusiform gyri, superior temporal sulcus, amygdala, and supplemental motor area. Next, we performed an unbiased data-driven voxelwise lesion symptom mapping (VLSM) analysis. Finally, we calculated the risk of ASD associated with positive findings from the above analyses. There were no significant ASD-related differences in tuber burden across the whole brain, within specific lobes, or within a priori regions derived from the ASD literature. However, using VLSM analysis, we found that tubers involving the right fusiform face area (FFA) were associated with a 3.7-fold increased risk of developing ASD. Although TSC is a rare cause of ASD, there is a strong association between tuber involvement of the right FFA and ASD diagnosis. This highlights a potentially causative mechanism for developing autism in TSC that may guide research into ASD symptoms more generally. ANN NEUROL 2023;93:577-590.


Rapid qualitative analysis of polar and nonpolar lipids in a single sample using "three-way" thin layer chromatography.
Plastic sheets, precoated with silica gel, are cut to give a square with a strip attached at the top right-hand corner. Lipid extract is applied to the square portion, just below the strip, and chromatographed in a solvent which moves nonpolar lipids on to the strip, leaving polar lipids at the origin. The strip is cut off and separation of the lipids on the strip and the remaining square portion of the plate is completed by conventional one- or two-dimensional chromatography, respectively. The application of this method and a multiple staining technique to the analysis of lipids in human bronchoalveolar lavage fluid is described.


Mutagens, N-nitroso compounds and their precursors in gastric juice from patients with and without precancerous lesions of the stomach.
This study examined whether elevated risk of gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in gastric juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found to increase with the pH of GJ from the three countries and was dependent on country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ were not affected by stomach histology and country of collection. NOC levels increased linearly with nitrite concentrations, but the slope of the regression line was greater for acidic GJ (pH < or = 4). These data together suggest that chemical nitrosation contributes at least as much as other nitrosation pathways to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold but this increase was not predictive of gastric cancer risk either by country or by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS-inducing potency) was significantly higher in GJ with original pH > 4 and highest in samples from Colombia. The results (a) provide no support that intragastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were significantly higher in achlorhydric subjects and highest in Colombian patients, these data together provide support for a role of intragastrically formed nitrite-derived direct mutagens in gastric cancer aetiology.


Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage.
Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.


Evaluation of Nationwide Trends in Nodal Sampling Guideline Adherence for Gastric Cancer: 2005-2017.
Surgical resection is the primary curative treatment for localized gastric cancer. A multitude of research supports surgical nodal sampling guidelines. Though there are known disparities in adherence to nodal sampling, it is unclear how hospital program-level disparities have changed over time. The purpose of this study is to evaluate trends in program-level disparities in adherence to gastric cancer nodal sampling guidelines. Patients who underwent resection of gastric cancer from 2005 to 2017 were identified in the National Cancer Database. Patients treated at academic programs were compared to those treated at nonacademic programs, and rates and trends of adherence to nodal sampling guidelines (defined as ≥15 lymph nodes) were determined. Adjusted multivariable analysis was used to determine likelihood of nodal sampling adherence while controlling for sociodemographic, clinical, hospital, and travel distance characteristics. A total of 55,421 patients were included with 27,201 (49.1%) of patients meeting adherence criteria for lymph node sampling. Academic programs treated 44.4% of the total cohort. Overall, lymph node sampling criteria were met in 59.2% of patients treated at high-volume academic programs and 37.0% of patients treated at low-volume nonacademic programs (incidence rate ratios 0.67, 95% confidence interval 0.63-0.72 versus high-volume academic programs). Adherence rates improved from 2005 to 2017 for both low-volume nonacademic programs (27.8% in 2005 to 50.1% in 2017) and high-volume academic programs (46.0% in 2005 to 69.8% in 2017, P < 0.001). Though adherence rates have improved from 2005 to 2017, high-volume academic programs were more likely to adhere to lymph node sampling guidelines for gastric cancer.


Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats.
Hepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE. A 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis. Cirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1β, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1β) (n = 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P = .035) and tracer dye uptake in the anterior and middle regions of the cortex (P = .006 and .003, respectively), their corresponding meninges (P = .086 and .006, respectively), and the draining lymph nodes (P = .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P = .024). Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.


Muscle transketolase in normal foetuses and Duchenne dystrophy.
The activity of the enzyme transketolase (EC 22.214.171.124) or the pentose phosphate metabolizing enzyme (PPME) was investigated in the quadriceps muscles of patients with Duchenne muscular dystrophy (DMD), polymyositis and spinal muscular atrophy (SMA) and in normal foetuses. The enzyme activity was significantly elevated in these muscle disorders with highest and lowest levels seen in DMD and SMA groups, respectively. The enzyme activity was increased early in DMD muscle and appeared to increase with progression of the disease. Normal foetal muscle contained high transketolase activity which is comparable to that seen in DMD patients.


Cold abscess of the chest wall as an unusual complication of BCG vaccination.
Bacillus-Calmette-Guérin (BCG) vaccination often results in local adverse effects; however, serious or long-term complications are rare. The involvement of sternum among skeletal BCG osteomyelitis is a rarely seen complication of BCG vaccination. Such a complication may confuse with a chest wall tumor and a surgical intervention may be needed for the definite diagnosis. A 9-month-old infant who had a parasternal cold abscess in the anterior chest wall and sternal osteomyelitis of tuberculosis in the late period of BCG vaccination of whom the etiological diagnosis was histopathologically confirmed after surgery is presented and the preoperative diagnostic problems are discussed.


Failed vacuum and preterm delivery risk in the subsequent pregnancy: a multicenter retrospective cohort study.
Second-stage cesarean delivery is associated with subsequent preterm delivery. Failed vacuum-assisted delivery is a subgroup of second-stage cesarean delivery in which the fetal head is engaged deeper in the pelvis and, thus, is associated with an increased risk of short-term maternal complications. This study aimed to investigate the maternal and neonatal outcomes of women at their subsequent delivery after a second-stage cesarean delivery with failed vacuum-assisted extraction vs after a second-stage cesarean delivery without a trial of vacuum-assisted extraction. This was a multicenter retrospective cohort study. The study population included all women in their subsequent pregnancy after a second-stage cesarean delivery who delivered in all university-affiliated obstetrical centers (n=4) in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who had second-stage cesarean delivery after a failed vacuum-assisted delivery were compared with women who had second-stage cesarean delivery without a trial of vacuum-assisted delivery. The primary outcome of this study was preterm delivery at <37 weeks of gestation. The secondary outcomes were vaginal birth rate and other adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression modeling. During the study period, 1313 women met the inclusion criteria, of whom 215 (16.4%) had a history of failed vacuum-assisted delivery at the previous delivery and 1098 (83.6%) did not. In univariate analysis, women with previously failed vacuum-assisted delivery had similar preterm delivery rates (<37, <34, <32, and <28 weeks of gestation), a successful trial of labor after cesarean delivery rates, uterine rupture, and hysterectomy. However, multivariable analyses controlling for confounders showed that a history of failed vacuum-assisted delivery is associated with a higher risk of preterm delivery at <37 weeks of gestation (adjusted odds ratio, 2.05; 95% confidence interval, 1.11-3.79; P=.02), but not with preterm delivery at <34 or <32 weeks of gestation. Among women with a previous second-stage cesarean delivery, previously failed vacuum-assisted delivery was associated with an increased risk of preterm delivery at <37 weeks of gestation in the subsequent birth.


Osmotic adjustment in cowpea plants: Interference of methods for estimating osmotic potential at full turgor.
Osmotic adjustment is a persisting controversy in studies on the effect of salt and water stress in cowpea crops. Our hypothesis is that the osmotic potential determination method interferes with the osmotic adjustment calculation. The objective of this study was to consider the osmotic adjustment comparing results obtained by pressure-volume (P-V) curves and osmometry. The experiment was conducted in a randomized block design, with six salt water concentrations 0, 20, 40, 60, 80, and 100 mmol L-1 of NaCl in a Fluvisol. The osmotic adjustment found through osmometry were lower than those found through P-V curves. The apoplastic water fraction of the cowpea had a dilution effect, denoting overestimation of the osmotic potential by the methodology based on osmometry. This may be the source of the different interpretations of osmotic adjustment in cowpea plants. Thus, osmotic adjustment should be calculated preferably using the osmotic potential determined by method of pressure-volume curves.


Stimuli-responsive biodegradable polyurethane nano-constructs as a potential triggered drug delivery vehicle for cancer therapy.
Polyurethanes (PUs) constitute an essential class of stimuli-responsive and biodegradable material, which has significantly contributed to the advancement of polymers utilization in the biomedical field. The bio-erodible PUs construct an active corridor for facilitating drug into tumor cells, which has significantly impacted the progression of nano-micellar delivery systems. The self-assembledcolloidal PUs pose distinctive features such as enhancing the solubility of hydrophobic chemotherapeutics, rapid cellular uptake, triggered erosion and drug release, bio-stimulus sensitivity, improvement in the targeting and proficiency ofbioactive. Cationic PUs can easily be condensed with genetic material to form polyplexes and have shown excellent transfection efficiency for potential gene therapy against various cancers. Their modifiable chemistry offers a tool to impart the desired multifunctionality such as biocompatibility, sensitivity to pH, redox, temperature, enzyme, etc. and ligand conjugation for active targeting. These diverse exceptional properties make them excellent nano-carrier for a variety of bioactive, including chemotherapeutic drugs, DNA, RNA, and diagnostic moieties to the target tissue or cells. The PUs based nano-devices have certainly uncovered the path to achieve ideal systems for controlled personalized therapy. The literature discussed in this review shed light on the research innovations carried out in the last ten years for the development of multifunctional PUs for triggered delivery of bioactive to treat various cancers.


Activation of multiple angiogenic signaling pathways in hemangiopericytoma.
Hemangiopericytoma (HPC) is a highly vascularized mesenchymal tumor. Local recurrence and distant metastasis are common features of HPC. Considering the remarkable hyper-vasculature phenotype of HPC, we assumed that dysregulated angiogenic signaling pathways were involved in HPC. The key components of angiogenic signaling pathways including VEGF-VEGF-R2, EphrinB2-EphB4 and DLL4-Notch were examined by real-time RT-PCR, Western blotting and immunostaining in 17 surgical specimens of HPC patients and in 6 controls. A significant upregulation of VEGF and VEGF-R2 associated with elevated levels of p-Akt and proliferating cell nuclear antigen (PCNA) was detected in HPC. Moreover, a dramatic increase in the mRNA and protein expression of EphB4 and its downstream factor p-Erk1/2 was found in HPC. A massive activation of core-components of DLL4-Notch signaling was detected in HPC. Double-immunofluorescent staining confirmed the expression of these upregulated key factors in the endothelial cells of tumor vessels. The present study identified the activation of multiple and crucial angiogenic signaling pathways, which could function individually and/or synergistically to stimulate angiogenesis in HPC and eventually contribute to tumor growth and progression. Our findings emphasize the importance to target multiple angiogenic signaling pathways when an anti-angiogenic therapy is considered for this highly vascularized tumor.


Platelets and vascular endothelial growth factor (VEGF): a morphological and functional study.
The growth of primary tumours beyond a critical mass is dependent on angiogenesis. The switch to the angiogenic phenotype involves changes in the local equilibrium of cytokines with either pro- or anti-angiogenic properties. Vascular Endothelial Growth Factor (VEGF) is one of the major positive regulators of tumour angiogenesis. Serum VEGF is, in cancer patients, correlated with worse prognosis. Recent evidence suggests that platelets are the main contributors of serum VEGF. We demonstrate, ultrastructurally and with immunofluorescence techniques, the alpha granule and membranous localisation of VEGF and provide further evidence for the role of platelets, both in healthy individuals as in patients with locally and advanced breast cancer, in the storage of circulating VEGF. We also demonstrate that, linear with tumoural progression, platelets accumulate more VEGF. Enhanced production in bone marrow platelet progenitors as well as endocytosis of circulating VEGF by platelets and/or megakaryocytes could explain the higher VEGF load in platelets from advanced cancer patients. This study provides further evidence for a role of platelets in transporting VEGF.


Antimüllerian hormone (AMH) and age as predictors of preimplantation genetic testing for aneuploidies (PGT-A) cycle outcomes and blastocyst quality on day 5 in women undergoing in vitro fertilization (IVF).
The objective of this study was to investigate whether women with diminished ovarian reserve who planned for PGT-A exhibit a lower number of blastocysts for biopsy, ploidy outcomes, and blastocyst quality on day 5, regardless of age. A retrospective analysis was performed between March 2017 and July 2020 at ART Fertility Clinics Abu Dhabi, including couples that were triggered for final oocyte maturation in an ovarian stimulated cycle planned for PGT-A. Patients were stratified into four AMH groups: < 0.65 ng/ml, 0.65-1.29 ng/ml, 1.3-6.25 ng/ml, and > 6.25 ng/ml; four age categories: ≤ 30, 31-35, 36-40, and > 40 years. A total of 1410 couples with a mean maternal age of 35.2 ± 6.4 years and AMH of 2.7 ± 2.6 ng/ml were included. In a multivariate logistic regression analysis, controlling for age, the chance of having at least one blastocyst biopsied/stimulated cycle (1156/1410), the chance of having at least one euploid blastocyst/stimulated cycle (880/1410), and the chance of having one euploid blastocyst once biopsy was performed (880/1156) were affected in all patients with AMH < 0.65 ng/ml [AdjOR 0.18[0.11-0.31] p = 0.008)], [AdjOR 0.18 [0.11-0.29] p < 0.001], and [AdjOR 0.34 [0.19-0.61] p = 0.015] as well as in patients with AMH 0.65-1.29 ng/ml (AdjOR 0.52 [0.32-0.84] p < 0.001), (AdjOR 0.49 [0.33-0.72] p < 0.001), and (AdjOR 0.57 [0.36-0.90] p < 0.001), respectively. In a multivariate linear regression analysis, AMH values did not affect blastocyst quality (- 0.72 [- 1.03 to - 0.41] p < 0.001). Irrespective of age, patients with diminished ovarian reserve (AMH < 1.3 ng/ml) have a lower chance of having at least one blastocyst biopsied and lower chance of having at least one euploid blastocyst per ovarian stimulated cycle. Blastocyst quality was not affected by AMH values.


[A case of cardiac lipoma in the ventricular septum].
Lipoma in the ventricular septum is very rare. Our review of the English literature revealed that our case is the sixth of removal of lipoma in the ventricular septum. A 60-year-old male was admitted because a mass in the ventricular septum was found incidentally in abdominal CT taken following type B hepatitis. CT scanning of the heart showed 2 cm diameter of tumor in the ventricular septum. The tumor had very low radiodensity, so it was thought to be identical to fat tissue. The tumor was more clearly visualized by MR imaging and the signal intensity was high on the T1-weighted image. The tumor was suspected to be lipoma. The intraoperative histological diagnosis showed the tumor was lipoma. The tumor adhered strictly on the myocardium of the septum, and it was located near the left anterior descending coronary artery. It could not completely resected, in these reasons. Postoperative course was uneventful, and echocardiogram taken 9 months after the operation showed no evidence of enlargement of the residual tumor. It is necessary to follow-up rigidly for the potential of enlargement of the residual tumor.


Involvement of corpus callosum in amyotrophic lateral sclerosis shown by MRI.
Abnormal high signal in the corticospinal tracts on MRI has been described in amyotrophic lateral sclerosis. We report a case with further high signal in fibres of the corpus callosum on proton density and T2-weighted spin-echo images, closely matching findings of earlier pathological reports.


Real-World Effectiveness of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve, Compensated Cirrhotic HCV Patients.
The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1-6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1-6. Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1-6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8 weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58 years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4-6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6 months prior to G/P initiation). Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1-6 from a large US claims database.


Building beauty: the genetic control of floral patterning.
Floral organ identity is controlled by combinatorial action of homeotic genes expressed in different territories within the emerging flower. This review discusses recent progress in our understanding of floral homeotic genes, with an emphasis on how their region-specific expression is regulated.


Genetic profile of the Ecuadorian Mestizo population (Ecuador-South America) by using the Power Plex 16 System Kit.
Allele frequency data for the 15 STR systems and Amelogenine were determined in a population sample of healthy Mestizo unrelated individuals. All loci met Hardy-Weinberg expectations and the high discrimination power of combined system showed the forensic efficiency of these genetic markers. There is a lack of information on Ecuadorian population from a genetic point of view and therefore no previous publications on the distribution of STRs on Mestizos is available. Mestizos are descendents of Spanish and Amerindian people, however, significant differences were found between the former and the populations from Spanish peninsula, that have been analyzed for these genetic markers.


Author Correction: Shadow pricing and the art of profiteering from outdated therapies.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Tuning T cell receptor sensitivity through catch bond engineering.
Adoptive cell therapy using engineered T cell receptors (TCRs) is a promising approach for targeting cancer antigens, but tumor-reactive TCRs are often weakly responsive to their target ligands, peptide-major histocompatibility complexes (pMHCs). Affinity-matured TCRs can enhance the efficacy of TCR-T cell therapy but can also cross-react with off-target antigens, resulting in organ immunopathology. We developed an alternative strategy to isolate TCR mutants that exhibited high activation signals coupled with low-affinity pMHC binding through the acquisition of catch bonds. Engineered analogs of a tumor antigen MAGE-A3-specific TCR maintained physiological affinities while exhibiting enhanced target killing potency and undetectable cross-reactivity, compared with a high-affinity clinically tested TCR that exhibited lethal cross-reactivity with a cardiac antigen. Catch bond engineering is a biophysically based strategy to tune high-sensitivity TCRs for T cell therapy with reduced potential for adverse cross-reactivity.


Translation initiation by non-AUG codons in Arabidopsis thaliana transgenic plants.
The efficiency of translation initiation at codons differing at one or two nucleotides from AUG was tested as initiation codons for the phosphinotricin-acetyltransferase gene in T-DNA plant transformation in Arabidopsis thaliana. With the exception of UUA codon that differs from AUG at two nucleotides and does not permit any detectable activity, all the other codons (AUC, GUG, ACG, and CUG) present a phosphinotrycin acetyltransferase activity that varies between 5 and 10% of the AUG activity. This low activity is sufficient to confer glufosinate resistance to some of the plants. These results indicate that, in plants as is the case in animals, non-AUG initiating codons may be used for translation initiation, namely when a low expression rate is needed.


Ras oncogenes in oral cancer: the past 20 years.
Oral squamous cell carcinoma (OSCC) of head and neck is associated with high morbidity and mortality in both Western and Asian countries. Several risk factors for the development of oral cancer are very well established, including tobacco chewing, betel quid, smoking, alcohol drinking and human papilloma virus (HPV) infection. Apart from these risk factors, many genetic factors such as oncogenes, tumor suppressor genes and regulatory genes are identified to involve in oral carcinogenesis with these risk factors dependent and independent manner. Ras is one of the most frequently genetically deregulated oncogene in oral cancer. In this review, we analyze the past 22years of literature on genetic alterations such as mutations and amplifications of the isoforms of the ras oncogene in oral cancer. Further, we addressed the isoform-specific role of the ras in oral carcinogenesis. We also discussed how targeting the Akt and MEK, downstream effectors of the PI3K/Akt and MAPK pathways, respectively, would probably pave the possible molecular therapeutic target for the ras driven tumorigenesis in oral cancer. Analysis of these ras isoforms may critically enlighten specific role of a particular ras isoform in oral carcinogenesis, enhance prognosis and pave the way for isoform-specific molecular targeted therapy in OSCC.


Oxidative stress and inflammation in the normal airways and blood of patients with lung cancer and COPD.
Respiratory conditions such as chronic obstructive pulmonary disease (COPD) are associated with a greater risk for lung cancer (LC). Oxidative stress and inflammation are involved in LC pathophysiology. Studies conducted so far have focused solely on lung tumor parenchyma and not the airways. We explored levels of local and systemic oxidative stress and inflammation within normal bronchial epithelium and blood of patients with lung cancer (n=52), with and without COPD, and in control subjects (COPD and non-COPD, n=21). In normal bronchial epithelium specimens (bronchoscopy) and blood from patients with similar smoking history (LC-COPD and LC) and control subjects (both COPD and non-COPD), redox balance and inflammatory markers were measured (ELISA and immunoblotting). All subjects were clinically evaluated. Absence of malignant cells within the bronchial specimens was always pathologically confirmed. Bronchial levels of protein carbonylation, MDA-protein adducts, antioxidants, TNF-α, interferon-γ, TGF-β, and VEGF and blood levels of superoxide anion, oxidatively damaged DNA and proteins, TNF-α, interferon-γ, TGF-β, VEGF, and neutrophils were significantly greater in all LC patients compared to control subjects. Systemic levels of oxidatively damaged DNA, superoxide anion, and TNF-α and bronchial levels of TGF-β and TNF-α showed high sensitivity and specificity for LC among patients. Regardless of the presence of an underlying respiratory condition (COPD), protein oxidation, oxidatively damaged DNA, and inflammation were remarkably increased in the normal airways and blood of patients with LC. Furthermore, the potential predictive value for LC development of these molecular events warrants attention and should be explored in future larger longitudinal studies.


Effects of the dipeptides comprising leucine and lysine on lifespan and age-related stress in Caenorhabditis elegans.
The aging process is affected by various stressors. An increase in oxidative stress is related to the impairment of physiological functions and enhancement of glycative stress. Food-derived bioactive peptides have various physiological functions, including antioxidant activities. Dipeptides comprising Leu and Lys (LK and KL, respectively) have been isolated from foods; however, their physiological properties remain unclear. In this study, we investigated the antioxidant/antiglycation activity of dipeptides and their antiaging effects using Caenorhabditis elegans (C. elegans). Both dipeptides showed antioxidant activities against several reactive oxygen species (ROS) in vitro. In particular, the scavenging activity of LK against superoxide radicals was higher than KL did. Moreover, dipeptides suppressed advanced glycation end products (AGEs) formation in the BSA-glucose model. In the lifespan assays using wild-type C. elegans, both LK and KL significantly prolonged the mean lifespan by 20.9% and 11.7%, respectively. In addition, LK decreased intracellular ROS and superoxide radical levels in C. elegans. Blue autofluorescence, an indicator of glycation in C. elegans with age, was also suppressed by LK. These results suggest that dipeptides, notably LK, show an antiaging effect by suppressing oxidative and glycative stress. Our findings suggest that such dipeptides can be used as a novel functional food ingredient. Food-derived dipeptide Leu-Lys (LK) and Lys-Leu (KL) exert antioxidant and antiglycation activity in vitro. Treatment with LK prolonged the mean lifespan and maximum lifespan of C. elegans more than that of KL. Intracellular ROS and blue autofluorescence levels (indicator of aging) were suppressed by LK.


Surgery for benign thyroid disease causing tracheoesophageal compression.
Even though the incidence of multinodular goiter is decreasing in the United States, still we see a large number of neglected goiters causing pressure effects on the surrounding structures. Both tracheal and esophageal displacement cause compression symptoms. However, tracheal compression may lead to acute airway distress. Eighteen per cent of our patients presented with acute airway problems, requiring emergency admission or intubation. Surgical intervention has been our preferred approach whenever there are signs or symptoms of tracheoesophageal compression. Fifty-five per cent of patients had only tracheal compression, while 18 per cent had only esophageal compression. Twenty-seven per cent had compression of both trachea and esophagus. Eighty-five per cent of patients had some symptoms of compression, while only 15% were asymptomatic despite large goiters. Compression symptoms and acute problems were noticed more frequently in patients with substernal goiters. Our preoperative work-up regularly included complete history, physical examination, indirect laryngoscopy, and airway radiography. Barium studies were performed if patients had dysphagia. Computed tomography scans were utilized if there was mediastinal extension. Pulmonary flow volume studies were used to locate the site of compression. However, decisions relative to surgical intervention were based primarily on clinical judgment. Since the postoperative morbidity is minimal in surgery for thyroid abnormalities, we strongly recommend early surgical intervention in patients with tracheoesophageal compression caused by enlarged thyroids.