Plasmid-determined epistatic susceptibility to kasugamycin.
The effect of two representative plasmids, R100 and F8-gal, on the susceptibility of Escherichia coli to kasugamycin was studied. R(+) and F(+) cells were found to be more susceptible to this antibiotic than R(-) and F(-) cells, respectively. Retransfer and curing experiments of these plasmids show that this increased susceptibility of host cells to kasugamycin was conferred by either of the plasmids. At the early stage of growth of R100(+) cells in the presence of kasugamycin, R(-) segregants overgrew the population and then they were replaced by kasugamycin-resistant mutants of the R(+) cells which became the majority cell line of the population. The former phenomenon is assumed to be due to the increased susceptibility of R100(+) cells to kasugamycin, and the latter is probably related to the finding that R100 enhances the spontaneous mutation of host cells to resistance to kasugamycin. The practical and experimental significance of these findings are discussed.


NN'-dicyclohexylcarbodiimide (DCCD) reduces pancreatic NaHCO3 secretion without changing pancreatic tissue ATP levels.
To study the mechanism responsible for pancreatic NaHCO3 secretion, the inhibitor NN'-dicyclohexylcarbodiimide (DCCD) was administered to six secretin-infused, anaesthetized pigs. Pancreatic juice was collected from a catheter in the main pancreatic duct. Secretion rate was measured at several arterial pH values in each animal, both before and after DCCD. 15 (14-30) mumol kg-1 body wt DCCD, intra-arterially, reduced pancreatic NaHCO3 secretion from 296 (234-398) to 181 (134-237) mumol min-1 at arterial pH 7.43 (7.42-7.47). Similar fractional reductions of secretion occurred at lower arterial pH. Pancreatic tissue ATP concentration, 1.8 (1.4-2.0) mumol g-1 wet wt, was not changed by DCCD. DCCD, less than or equal to 10(-4) mol l-1, did not change Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. It is concluded that DCCD reduced pancreatic NaHCO3 secretion by a mechanism not involving ATP depletion nor inhibition of Na,K-ATPase nor carbonic anhydrase activities in pancreatic cells. Because DCCD inhibits proton pumps, DCCD may have reduced NaHCO3 secretion through interfering with a proton pump involved in extruding H+ from HCO-3 secreting cells to interstitial fluid in the pancreas.


Recent advances and prospects of computational methods for metabolite identification: a review with emphasis on machine learning approaches.
Metabolomics involves studies of a great number of metabolites, which are small molecules present in biological systems. They play a lot of important functions such as energy transport, signaling, building block of cells and inhibition/catalysis. Understanding biochemical characteristics of the metabolites is an essential and significant part of metabolomics to enlarge the knowledge of biological systems. It is also the key to the development of many applications and areas such as biotechnology, biomedicine or pharmaceuticals. However, the identification of the metabolites remains a challenging task in metabolomics with a huge number of potentially interesting but unknown metabolites. The standard method for identifying metabolites is based on the mass spectrometry (MS) preceded by a separation technique. Over many decades, many techniques with different approaches have been proposed for MS-based metabolite identification task, which can be divided into the following four groups: mass spectra database, in silico fragmentation, fragmentation tree and machine learning. In this review paper, we thoroughly survey currently available tools for metabolite identification with the focus on in silico fragmentation, and machine learning-based approaches. We also give an intensive discussion on advanced machine learning methods, which can lead to further improvement on this task.


Grief and Bereavement in Parents After the Death of a Child in Low- and Middle-Income Countries.
While great strides have been made in improving childhood mortality, millions of children die each year with significant health-related suffering. More than 98% of these children live in low- and middle-income countries (LMICs). Efforts have been made to increase access to pediatric palliative care (PPC) services to address this suffering in LMICs through policy measures, educational initiatives, and access to essential medicines. However, a core component of high-quality PPC that has been relatively neglected in LMICs is grief and bereavement support for parents after the death of their child. This paper reviews the current literature on parental grief and bereavement in LMICs. This includes describing bereavement research in high-income countries (HICs), including its definition, adverse effect upon parents, and supportive interventions, followed by a review of the literature on health-related grief and bereavement in LMICs, specifically around: perinatal death, infant mortality, infectious disease, interventions used, and perceived need. More research is needed in grief and bereavement of parents in LMICs to provide them with the support they deserve within their specific cultural, social, and religious context. Additionally, these efforts in LMICs will help advance the field of parental grief and bereavement research as a whole.


In situ extracorporeal shock wave lithotripsy for acute renal colic due to obstructing ureteral stones.
The purpose of the present study was to evaluate in situ extracorporeal shock wave lithotripsy (ESWL) for the treatment of obstructing ureteral stones causing acute renal colic. In situ ESWL with an EDAP LT-02 piezo-electric lithotriptor was used in a prospective study to treat 67 patients with obstructing ureteral stones causing acute renal colic. Patients were treated without anesthesia on an out-patient basis or during a one-day hospital stay. The overall one month stone-free rate was 94% (94% for proximal stones and 95% for distal stones). The overall success rate after a single ESWL session was 81%. Treatment was well tolerated in 90% (60/67) of patients. There was one case of non-obstructive pyelonephritis and one of ureteral edema. These rates compare well with published reports for delayed treatment in patients without renal colic. Immediate ESWL for cases of acute renal colic due to obstructing ureteral stones is an effective treatment strategy that warrants wider consideration.


[Immune system and rheumatic diseases in the elderly].
Impairments of the immune system play an important role in all immun-mediated rheumatic diseases. Recently, the following news were reported: · Early aging of the immune system with thymus insufficiency has now been reported for both patients with rheumatoid arthritis and axial spondyloarthritis, without prethymic lack of progenitors at least in rheumatoid arthritis.. · For giant cell arteritis, the most frequent vasculitis in the elderly, an increased expression of IL-17A in temporal artery biopsies coincides with good prognosis and reponse to glucocorticoids.. · Concerning immunosenescence in systemic lupus erythematosus, BAFF appears to have an important role for relapses after B-cell depletion.. For the future it can be anticipated that the use of unified classification criteria for rheumatic diseases (as with the new 2012 EULAR / ACR classification criteria for polymyalgia rheumatica) will ensure better comparability of immunological studies also in the elderly.


Comparison of transjugular and surgical portosystemic shunts on the outcome of liver transplantation.
To analyze the effect of previous transjugular intrahepatic portosystemic shunt (TIPS) vs surgical portosystemic shunt (SPS) on the outcome of orthotopic liver transplantation (OLT). A case series of 38 patients who underwent OLT: 25 with a previous TIPS and 13 with a previous SPS. A liver transplant center and interventional radiology service in a private, tertiary referral medical center. Eighteen men and seven women who had a TIPS before OLT were compared with nine men and four women who had an SPS before OLT. Operative transfusion requirements, operative time, length of hospital stay, postoperative liver chemistry studies, and graft and patient survival. Compared with patients who had an SPS, patients who had a TIPS had significantly less median transfusion requirements for packed red blood cells (5 vs 12 U), fresh-frozen plasma (0 vs 8 U), and thrombocytes (0 vs 1 U). The median operative time (9 vs 13 hours), length of intensive care unit stay (3 vs 5 days), and length of hospital stay (12 vs 24 days) were also significantly less in patients who had a TIPS. The 2-year actuarial patient survival rate was 92% in both groups. In patients undergoing OLT, TIPS is associated with reduced operative transfusion requirements, operative time, and length of intensive care unit and hospital stays compared with SPS. In the potential liver transplant candidate with refractory complications of portal hypertension, TIPS is preferred to SPS.


Upregulation of glutamate metabolism by BYHWD in cultured astrocytes following oxygen-glucose deprivation/reoxygenation in part depends on the activation of p38 MAPK.
Recent studies have demonstrated that Buyang Huanwu Decoction (BYHWD) decreased glutamate levels subsequent to cerebral ischemia. Glutamate transporter-1 (GLT-1) and glutamine synthetase (GS), which are located in astrocytes, mainly contribute to glutamate transportation, thus reducing glutamate concentration. BYHWD has previously been demonstrated to upregulate GLT-1 and GS following ischemia in vivo. However, whether BYHWD can directly influence astrocytic GLT-1/GS levels remains unknown. In the present study, the effect of BYHWD containing serum (BYHWD-CS) on GLT-1/GS levels in astrocytes following oxygen-glucose deprivation/reoxygenation (OGD/R) was investigated. The results revealed that BYHWD-CS enhanced the expression levels of GLT-1 and GS in cultured astrocytes, which reduced glutamate concentration in the culture medium. Meanwhile, increased p38 mitogen-activated protein kinase (p38 MAPK) was phosphorylated (activation form) by BYHWD-CS in cultured astrocytes, and the specific p38 inhibitor SB203580 blocked the increase of GLT-1/GS accompanied by decreased cell viability. Furthermore, SB203580 suppressed the effect of BYHWD-CS on the level of glial fibrillary acidic protein (an astrocytic marker), thus confirming that astrocytes are directly involved in the protective role of BYHWD after OGD/R. These findings suggest that BYHWD upregulates GLT-1 and GS via p38 MAPK activation, and protects cultured astrocytes from death caused by OGD/R (typical in vitro model), which complemented the role of astrocytes in the protective effect of BYHWD.


Cytogenetic tests for animal production: state of the art and perspectives.
Cytogenetic tests are effective tools for monitoring the health status of livestock and improving their genetic value. Cytogenetic screening allows for the detection of animals carrying chromosomal aberrations and to avoid using them as breeders. Progress in karyotype monitoring, with new molecular probes and automation, has greatly increased the productivity of this procedure. Several genotoxicity tests are available to detect the possible presence and effects of pollutants or drugs. Among these, the micronucleus test and the Comet assay are the most convenient in terms of costs and benefits. Finally, analysis of telomeres, the end of chromosomes and markers of genomic instability, may be developed into a new marker of stress and genetic value.


Localization of plant lipids for light microscopy using p-phenylenediamine in tissues of Arachis hypogaea L.
p-Phenylenediamine (pPD) can be used en bloc to preserve and differentiate cell lipids in aldehyde-fixed peanut plant tissues treated with osmium tetroxide during dehydration in 70% ethanol. Semithin plastic sections for light microscopy need no further staining and can be mounted in Histoclad after drying on a slide. Brown staining above background differentiates lipid-containing structures. Nonspecific staining can be distinguished in control preparations extracted en bloc with lipid solvents.


Stiffness of the gerbil basilar membrane: radial and longitudinal variations.
Experimental data on the mechanical properties of the tissues of the mammalian cochlea are essential for understanding the frequency- and location-dependent motion patterns that result in response to incoming sound waves. Within the cochlea, sound-induced vibrations are transduced into neural activity by the organ of Corti, the gross motion of which is dependent on the motion of the underlying basilar membrane. In this study we present data on stiffness of the gerbil basilar membrane measured at multiple positions within a cochlear cross section and at multiple locations along the length of the cochlea. A basic analysis of these data using relatively simple models of cochlear mechanics reveals our most important result: the experimentally measured longitudinal stiffness gradient at the middle of the pectinate zone of the basilar membrane (4.43 dB/mm) can account for changes of best frequency along the length of the cochlea. Furthermore, our results indicate qualitative changes of stiffness-deflection curves as a function of radial position; in particular, there are differences in the rate of stiffness growth with increasing tissue deflection. Longitudinal coupling within the basilar membrane/organ of Corti complex is determined to have a space constant of 21 microm in the middle turn of the cochlea. The bulk of our data was obtained in the hemicochlea preparation, and we include a comparison of this set of data to data obtained in vivo.


Cardiovascular Safety of β3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome.
Mirabegron, the first β3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because β3-adrenoceptors are expressed in cardiovascular (CV) tissues, there are concerns that OAB treatment with β3-adrenoceptor agonists may affect the heart and vasculature. To provide a summary of CV effects of β3-adrenoceptor agonists in clinical studies. A systematic literature search from inception until November 2014 was performed on studies in PubMed and Medline. Twenty papers, published between 1994 and 2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135 (1). More detailed CV data from mirabegron studies were available in online regulatory documents filed with the US Food and Drug Administration and the UK National Institute for Health and Care Excellence. The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB. In this review we looked at the cardiovascular (CV) effects of β3-adrenoceptor agonists used for the treatment of overactive bladder (OAB). The CV safety of mirabegron (the only clinically approved β3-adrenoceptor agonist) appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, the current first-line therapy for OAB.


The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection.
B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection. A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly. The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it. Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.


Non-coding RNA Regulated Cross-Talk Between Mitochondria and Other Cellular Compartments.
Mitochondria are the main hubs for cellular energy production. Metabolites produced in mitochondria not only feed many important biosynthesis pathways but also function as signaling molecules. Mitochondrial biosynthesis requires collaboration of both nuclear and mitochondrial gene expression systems. In addition, mitochondria have to quickly respond to changes inside and outside the cells and have their own functional states reported to the nucleus and other cellular compartments. The underlying molecular mechanisms of these complex regulations have not been well understood. Recent evidence indicates that in addition to small molecules, non-coding RNAs may contribute to the communication between mitochondria and other cellular compartments and may even serve as signals. In this review, we summarize the current knowledge about mitochondrial non-coding RNAs (including nucleus-encoded non-coding RNAs that are imported into mitochondria and mitochondrion-encoded non-coding RNAs that are exported), their trafficking and their functions in co-regulation of mitochondrial and other cellular processes.


Dried extracts of Encholirium spectabile (Bromeliaceae) present antioxidant and photoprotective activities in vitro.
The antioxidant and photoprotective activities of dried extracts from the leaves of Encholirium spectabile were investigated. It was also evaluated the total phenolic and flavonoid contents by the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using of 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching and compared with ascorbic acid, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) used as reference compounds. The photoprotective effect was evaluated by the spectrophotometric method. The most significant total phenolic and flavonoid contents was of 188.50 ± 27.50 mg of gallic acid equivalent/g and 129.70 ± 4.59 mg of catechin equivalent/g, respectively, for chloroform fraction (Es-CHCl3). The Es-CHCl3 also presented the best antioxidant activity (IC50 25.35 ± 4.35 μg/ml) for DPPH scavenging. The ethanol extract (Es-EtOH), Es-CHCl3 and the fraction ethyl acetate (Es-AcOEt) showed characteristic absorption bands in regions UVB and UVA in a concentration-dependent manner. Es-CHCl3 presented the highest sun protection factor SPF (8.89 ± 2.11). It shows the possibility to use this extract as sunscreen in pharmaceutical preparations.


27-Hydroxycholesterol, The Estrogen Receptor Modulator, Alters DNA Methylation in Breast Cancer.
27-hydroxycholesterol (27-HC) is the first known endogenous selective estrogen receptor modulator (SERM), and its elevation from normal levels is closely associated with breast cancer. A plethora of evidence suggests that aberrant epigenetic signatures in breast cancer cells can result in differential responses to various chemotherapeutics and often leads to the development of resistant cancer cells. Such aberrant epigenetic changes are mostly dictated by the microenvironment. The local concentration of oxygen and metabolites in the microenvironment of breast cancer are known to influence the development of breast cancer. Hence, we hypothesized that 27-HC, an oxysterol, which has been shown to induce breast cancer progression via estrogen receptor alpha (ERα) and liver X receptor (LXR) and by modulating immune cells, may also induce epigenetic changes. For deciphering the same, we treated the estrogen receptor-positive cells with 27-HC and identified DNA hypermethylation on a subset of genes by performing DNA bisulfite sequencing. The genes that showed significant DNA hypermethylation were phosphatidylserine synthase 2 (PTDSS2), MIR613, indoleamine 2,3-dioxygenase 1 (IDO1), thyroid hormone receptor alpha (THRA), dystrotelin (DTYN), and mesoderm induction early response 1, family member 3 (MIER). Furthermore, we found that 27-HC weakens the DNMT3B association with the ERα in MCF-7 cells. This study reports that 27-HC induces aberrant DNA methylation changes on the promoters of a subset of genes through modulation of ERα and DNMT3B complexes to induce the local DNA methylation changes, which may dictate drug responses and breast cancer development.


Effect of ovsynch versus prostaglandin F2α protocol on estrus response, ovulation rate, timing of ovulation and pregnancy per artificial insemination in Sahiwal cows.
Sahiwal cow is Bos indicus which is an important dairy breed of tropical and sub-tropical region. Research on reproduction is rare in this breed. The objectives of the present study were to determine the effect of Ovsynch (OVS) versus prostaglandin F2α (PG) protocol on estrus response and its intensity, ovulation rate, timing of ovulation and pregnancy per artificial insemination (AI) in Sahiwal cows. Experimental cows (n = 80) were of mixed parity, lactating, suckled, ≥120 days postpartum with body condition score 3.08 ± 0.34 and 375-475 kg of body weight which were randomly assigned to receive either OVS (n = 46) or PG (n =34) protocol. Cows were inseminated twice at 12 and 24 h after second gonadotropin releasing hormone in the OVS group, and 72 and 84 h after administration of prostaglandin F2α in PG group, respectively. The results revealed that estrus response did not differ (P > 0.05) and was 87% in OVS and 78% in PG cows. Ovulation rate did not differ (P > 0.05) and was 50% in both, OVS and PG cows. The pregnancy per AI did not differ (P > 0.05) and was 43% in OVS compared to 31% in PG cows. It is concluded that estrus response, ovulation rate and pregnancy per AI of OVS protocol is the same as PG in Sahiwal cows.


[Adenocarcinomas with mesonephric features in gynecologic tract: a clinicopathological analysis of seven cases].
Objective: To investigate and compare the histologic characteristics of adenocarcinomas with mesonephric features located in different parts of the gynecologic tract. Methods: Two cases of mesonephric adenocarcinomas (MA) of the cervix and 5 cases of mesonephric-like adenocarcinomas (MLA) of the uterus and ovary were collected in Women's Hospital, School of Medicine, Zhejiang University from January 2018 to October 2020. Hematoxylin-eosin staining, immunohistochemistry and KRAS mutation testing were performed together with review of literature. Results: MA of the cervix as well as MLA of the uterus and ovary had similar morphologic features, showing an admixture of glandular, tubular, papillary and solid growth patterns. However, both MA cases were located in cervical stroma, which demonstrated residual mesonephric ducts present at the periphery. All four uterine MLA cases extensively involved the endometrium and myometrium. The ovarian MLA case was associated with endometriosis. No residual mesonephric ducts were present in the MLA cases. Immunohistochemically, GATA3 was positive in all seven MA/MLA cases. TTF1 was expressed only in 4/5 MLA cases. ER and PR were negative and p53 was wild-type in all cases. KRAS mutation was detected in all five cases. During the 6-32 months of follow-up, one patient developed recurrence and the others were tumor-free. Conclusions: In the gynecologic tract, both MA in cervix and MLA in uterus and ovary have similar morphologic features, immunohistochemical expression and KRAS mutation. However, distinct from MA that originates from mesonephric remnant, MLA is closely related to Mullerian epithelium.


Cellulosic Biomass-Reinforced Polyvinylidene Fluoride Separators with Enhanced Dielectric Properties and Thermal Tolerance.
Safety issues are critical barriers to large-scale energy storage applications of lithium-ion batteries (LIBs). Using an ameliorated, thermally stable, shutdown separator is an effective method to overcome the safety issues. Herein, we demonstrate a novel, cellulosic biomass-material-blended polyvinylidene fluoride separator that was prepared using a simple nonsolvent-induced phase separation technique. This process formed a microporous composite separator with reduced crystallinity, uniform pore size distribution, superior thermal tolerance, and enhanced electrolyte wettability and dielectric and mechanical properties. In addition, the separator has a superior capacity retention and a better rate capability compared to the commercialized microporous polypropylene membrane. This fascinating membrane was fabricated via a relatively eco-friendly and cost-effective method and is an alternative, promising separator for high-power LIBs.


Effects of fatty acid substitution on the release of enzymes by osmotic shock.
The release of enzymes by osmotic shock from Escherichia coli strain 30E, an unsaturated fatty acid auxotroph, was examined in culture supplemented with either cis- or trans-unsaturated fatty acids. Cultures grown in oleate-supplemented medium release a large fraction of the total cyclic phosphodiesterase, acid hexose phosphatase, and 5'-nucleotidase following osmotic shock. Cultures grown in elaidate-supplemented medium release much less of these same enzymes after shock treatment. Cultures grown with either supplementation show total release of these enzymes upon conversion to spheroplasts, demonstrating that the enzymes are in the periplasmic space in both cases. Cultures grown with either oleate or elaidate as fatty acid source were washed and suspended in medium containing the other isomer. The change from oleate to elaidate resulted in a rapid decrease in ability of the cells to release the three enzymes after osmotic shock so that within a 25% increase in cell mass the culture responded to osmotic shock as would a culture grown overnight in elaidate-supplemented medium. The reverse experiment resulted in a gradual increase in the ability of the cells to respond to osmotic shock. The outer membrane of E. coli is altered by the incorporation of elaidate, as indicated by electron microscopic data.


Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell culture membrane.
A large number of studies have demonstrated that mechanical perturbation modulates cellular metabolism; however, the systematic characterization of the molecular and cellular transduction mechanisms underlying mechanically induced metabolic modulation has been impeded, in part, by the limitations of the mechanical device. The objective of this investigation was to develop an in vitro experimental system that would provide independent control of the spatial and temporal biaxial strain distribution imposed on a flexible transparent tissue culture membrane that permits attachment, proliferation, and maintenance of the phenotypic expression of cultured embryonic osteoblasts. Such a device would permit a systematic investigation of the cellular response to specific, independently controlled parameters of mechanical deformation. Using a prototype device designed to impose a dynamic sinusoidal spatially isotropic biaxial strain profile, we confirmed experimentally that the strain was biaxially uniform and isotropic (radial = circumferential strain over the entire culture membrane) to within 14% (SD/mean) for the range of the peak strains tested (2.3-9.4%). Additionally, the uniformity was maintained at 1 Hz for at least 5 days of continuous operation. This experimental verification of the theoretically predicted isotropic strain profile suggests that the design principle is sound. Embryonic osteoblasts cultured on the flexible substrate proliferated and exhibited a temporal pattern of phenotypic expression (extracellular matrix accumulation and mineralization) comparable with that observed on polystyrene of tissue culture grade.


Deletion of the major Escherichia coli multidrug transporter AcrB reveals transporter plasticity and redundancy in bacterial cells.
Multidrug Transporters (MDTs) are major contributors to the acquisition and maintenance of Antimicrobial Resistance (AMR), a growing public health threat of broad concern. Despite the large number of MDTs, the overwhelming majority of the studies performed thus far in Gram-negative bacteria emphasize the supremacy of the AcrAB-TolC complex. To unveil the potential role of other MDTs we studied the behavior of a null AcrB Escherichia coli strain when challenged with chloramphenicol, a bacteriostatic antibiotic. We found that such a strain developed an extremely high-level of resistance to chloramphenicol, cross resistance to quinolones and erythromycin and displayed high levels of expression of the single component MFS transporter MdfA and multiple TolC-dependent transporters. The results suggest that the high versatility of the whole ensemble of transporters, the bacterial Effluxome, is an essential part of a strategy of survival in everchanging, at times noxious, environments. The concept of a functional Effluxome presents an alternative to the existing paradigms in the field and provides novel targets for the search for inhibitors of transporters as adjuvants of existing antibiotics.


IgA myeloma associated with decreased anion gap and renal failure.
The anion gap in myeloma patients had been well studied. IgG myeloma usually has decreased anion gap, whereas IgA myeloma always presents with normal anion gap. We report an unusual presentation of IgA myeloma with decreased anion gap and renal failure due to superimposing of acetazolamide-related bicarbonate loss.


Why Sexually Selected Weapons Are Not Ornaments.
The elaboration and diversification of sexually selected weapons remain poorly understood. We argue that progress in this topic has been hindered by a strong bias in sexual selection research, and a tendency for weapons to be conflated with ornaments used in mate choice. Here, we outline how male-male competition and female choice are distinct mechanisms of sexual selection, and why weapons and ornaments are fundamentally different types of traits. We call for research on the factors contributing to weapon divergence, the potential for male-male competition to drive speciation, and the specific use of weapons in the context of direct fights versus displays. Given that weapons are first and foremost fighting structures, biomechanical approaches are an especially promising direction for understanding weapon design.


The Use of Topiramate for Weight Loss Causing Acute Glaucoma: A Case Report and Literature Review.
Topiramate is a sulfa-containing drug which is able to disrupt the ocular blood barrier. Recently it has gained more popularity, being used in many clinical conditions. Nowadays, the cases of glaucoma induced by topiramate have increased due to the use of this drug to induce weight loss. We here described a 29-year-old female presented with a one-day history of blurred vision in both eyes and headache. She was using a weight loss formula containing topiramate 100 milligrams. Ophthalmologic exam revealed an important myopic shift of -7.00 spherical diopters at presentation with intraocular pressure (IOP) of 32 mmHg and a shallow anterior chamber in both eyes. After discontinuous of topiramate and use of cycloplegic eyedrops, myopic shift improved and IOP controlled after two days. The anterior chamber was significantly deeper in both eyes after two weeks. It is theorized that topiramate can provoke a ciliochoroidal effusion and, therefore, can cause an anterior displacement of lens-iris diaphragm with a secondary angular closure. The treatment must include cycloplegic and discontinuation of the drug. Sulfa-containing drugs lead to an indirect mechanism of angle closure, frequently bilateral and, as mentioned above, with a different treatment approach. If unrecognized and untreated, it can provoke high morbidity with possibility of bilateral permanent visual loss.


Duplication of gallbladder: a rare anomaly of biliary tract- A case report.
Incomplete duplication of gall bladder or vesica fellea divisa is one of the rare anomalies of gallbladder. Until now, 25 cases have been reported; of which four were proceeded with laparoscopic cholecystectomy. In our case, we diagnosed this nadir anomaly laparoscopically, posing a technical challenge since no radiological clue was observed beforehand. Successful laparoscopic resection of duplicated gall bladders was performed followed by Magnetic Resonance CholangioPancreaticography.


Asthma and menstruation: the relationship between psychological and bronchial hyperreactivity.
The aim of this study was to investigate a possible interrelation between bronchial hyperreactivity and psychological hyperreactivity. In order to record changes in both bronchial and psychological reactions throughout the menstrual cycle, 10 women out-patients with moderate asthma were followed up for six months, and their physical and psychological status as well as their reactions to life-events and environmental influences were assessed through self-reporting measures and weekly psychotherapeutic sessions. Psychotherapy was used both as a supplement to the medical treatment and as a method of data collection. A relationship between lowered resistance to stress, lowered resistance to infections and increased bronchial hyperreactivity is suggested as background aetiological factors for the exacerbation of asthma around menstruation.


Stacking triple genes increased proanthocyanidins level in Arabidopsis thaliana.
Anthocyanins and proanthocyanidins are two important plant secondary metabolites, and they contribute to plant survival and human health. In particular, proanthocyanidins could also prevent ruminants from the damage of pasture bloat. However, the improvement of proanthocyanidins content remain unsatisfied. In this study, we attempted to improve proanthocyanidins level by gene stacking in Arabidopsis thaliana as prove-of-concept. Two proanthocyanidin pathway genes from tea plant, CsF3'5'H and CsANR2, were co-expressed in the wild type and PAP1 over-expression Arabidopsis. Over-expression of CsF3'5'H slightly affected anthocyanins level in leaves and proanthocyanidins in mature seed when expressed alone in the pap1-D line. Over-expression of CsANR2 led to an obvious decrease in anthocyanins in leaves of both wild type and pap1-D lines, but increase in proanthocyanidin level in mature seeds. Over-expression of CsANR2 in pap1-D lines lead to production of DMACA-reactive soluble proanthocyanidins in leaves, but not in wild type or pap1-D lines. Anthocyanins level was decreased in the leaves of CsF3'5'H, CsANR2 and pap1-D co-expression lines, but proanthocyanidins were increased remarkably in both leaves and mature seeds in the co-expression line. It is concluded that co-expression of CsANR2 and PAP1 in Arabidopsis produce soluble proanthocyanidins in leaves, and co-expression of CsF3'5'H, CsANR2 and PAP1 lead to a significant increase in proanthocyanidins in mature seeds. The transcript levels of endogenous CHS, DFR, ANS and ANR genes in Arabidopsis were up-regulated in the triple genes co-expression line. Based on these studies, it is possible to develop new plant germplasm with improved proanthocyanidins by co-expressing of multiple genes.


Metal organic framework derived porous carbon materials excel as an excellent platform for high-performance packaged supercapacitors.
Designing and synthesizing new materials with special physical and chemical properties are the key steps to assembling high performance supercapacitors. Metal organic framework (MOF) derived porous carbon materials have drawn great attention in supercapacitors because of their large specific surface area, high chemical/thermal stability and tunable pore structure. Thus, the recent development of porous carbon as an electrode material for supercapacitors is reviewed. The types, design and synthesis strategies of porous carbon are systematically summarized. This review will be divided into three main parts: (1) the design and synthesis of MOF precursors and templates for MOF-derived porous carbon materials; (2) the application of different types of MOF-derived carbon in supercapacitors; and (3) the design of typical structures of porous carbon composites for supercapacitors. Finally, the problems and challenges confronted when using porous carbon are assessed and elaborated, and some suggestions on future research directions are proposed.


Embryo-endometrial proteases during early mammalian development.
In mammals, extensive remodeling of uterine endometrial matrix occurs during reproductive cycle and blastocyst implantation. This is regulated by a variety of molecules such as hormones, growth factors, cytokines and proteases. In this article, we review the current state of knowledge available on various proteases and their inhibitors functionally involved in the embryo-endometrial tissues and present some data on endometrial proteases in hamsters and rats during estrous cycle and early pregnancy. We demonstrate the presence of at least four gelatinolytic activities in endometrial samples, belonging to gelatinase-A and -B categories and their dependence on calcium/zinc ions for enzyme activity and, their interrelationships between zymogen and active forms. We believe that the embryo-endometrial proteases are essential for hatching of blastocysts and for the dynamic remodeling of endometrial tissues, occurring during the critical peri-implantation period.


The Indirect Role of Executive Functions on the Relationship between Cardiorespiratory Fitness and School Grades.
The aim of this study was to investigate the indirect effects of cardiorespiratory fitness on scholastic performance through executive functions. More precisely, we examined the contribution of the different domains of executive functions, and whether this relationship was specific to certain school topics. Children 8-12 yr old completed nine cognitive tests and the multistage fitness test. Structural equation modeling techniques were used to analyze the role of different domains of executive functions (inhibition, working memory, cognitive flexibility, and a common factor to all tasks) in the relationship between cardiorespiratory fitness and school grades in three domains: (i) mathematics; (ii) grammar, spelling, and vocabulary; and (iii) text comprehension and expression. Covariate analyses included age and socioeconomic status. The results of this study showed that an indirect effect of the various domains of executive functions explained, in part, the relationship between cardiorespiratory fitness and (i) mathematics (β = 0.12, SE = 0.03, P < 0.001), and between cardiorespiratory fitness and (ii) grammar, spelling, and vocabulary (β = 0.12, SE = 0.03, P < 0.001). No relationship between cardiorespiratory fitness and (iii) text comprehension and expression was observed. Although executive functions correlated with school grades, cognitive flexibility drove the indirect effect when all executive function domains were simultaneously taken into account. These results show the role that executive functions play in understanding the relationship between cardiorespiratory fitness and scholastic performance. Importantly, not all executive function domains contributed equally because cognitive flexibility played a leading role in this wide age range. Furthermore, the relationship between cardiorespiratory fitness and scholastic performance was strongest for mathematics and for low-level language topics but nonsignificant for higher-level language topics, providing a more modulated view of the effect of cardiorespiratory fitness on language.


[Problems in treating early cases of head and neck cancer].
The term "early case" is defined as a Stage I case, i.e. a T1N0M0 case in this paper. Cases of Tis are also included. During the 10-year-period from 1971 to 1980, the rate of early cases to the entire cases was the greatest for the larynx, followed by the nasal cavity, tongue, oropharynx and hypopharynx and cervical esophagus. The purposes of this paper are to review retrospectively the patients with early carcinoma of these organs who were treated in our hospital during the last 23 years, to discuss the no-recurrence rate and function following varying treatments and to propose some improvements in treatment. Carcinomas of the nasal cavity and the maxillary sinus are successfully treated with transoral surgeries with/without chemo-radiotherapy. A Nd-YAG laser is very useful for the surgery. For carcinomas of the oropharynx and oral cavity, surgical removal with/without (chemo-) radiotherapy yielded good results, whereas radiotherapy with/without chemotherapy presented with frequent failures. Extensive surgical removals, however, resulted in significant functional disorders. Currently, we have been using CO2 laser. For those lesions confined to the mucosa, a simple laser excision is applied. For those lesions with extension to the submucous tissue, we first remove the visible and palpable tumor by means of laser and, then, post-laser chemoradiotherapy is applied. The function after these treatments is excellent. For carcinomas of the hypopharynx and cervical esophagus, surgical treatments associated with total laryngectomy yielded better results than those without total laryngectomy. Total laryngectomy, however, causes serious problems in speech communication. Recently, we have tried partial pharyngo-esophagectomy followed by (chemo-)radiotherapy. This seems to be a promising modality. Supraglottic carcinoma was best treated with total laryngectomy. Partial laryngectomy was also successful when conducted by well-trained surgeons. Small lesions were successfully treated with radiation. We feel partial laryngectomy with the use of CO2 laser should be the first choice in many cases. Endolaryngeal laser can be applied to small lesions. For glottic carcinoma, radiotherapy is indicated in most head and neck cancer clinic over the world, and so had been in our hospital until a few years ago. Recently, we have adopted endolaryngeal laser surgery. Laser is advantageous over radiotherapy because it takes less treatment time, it has no side effect or carcinogenicity and it saves radiotherapy as a future treatment for possible recurrence or second primary.(ABSTRACT TRUNCATED AT 400 WORDS)


The technique of laparoscopic and robotic extended cholecystectomy for gallbladder cancer.
The application of minimally invasive surgery for gallbladder cancer (GBC) is yet controversial. This article discusses the techniques of laparoscopic and robotic extended cholecystectomy. A 69-year-old male diagnosed with cT1-2N0 GBC underwent laparoscopic surgery, and a 55-year-old male with cT2N1 GBC underwent robotic surgery after preoperative chemotherapy. Nonanatomical partial hepatectomy with lymphadenectomy was performed. Liver parenchymal dissection was performed using Cavitron Ultrasonic Surgical Aspirator laparoscopically and Maryland bipolar dissector and Harmonic scalpel robotically. The operation time was 180 and 220 minutes, and the estimated blood loss was 140 and 130 mL, respectively. The final pathologies were pT1bN0 and pT2aN1, for which patients received adjuvant chemotherapy. There was no evidence of recurrence at 33 and 18 months without complications. Both laparoscopic and robotic extended cholecystectomy can be safely performed with the robotic surgical system as an effective alternative for GBC requiring liver resection with radical lymphadenectomy.


Rapid Quantification of N-Methyl-2-pyrrolidone in Polymer Matrices by Thermal Desorption-GC/MS.
Analysis of a residual solvent in polymeric materials has become an important issue due to the increased regulations and standards for its use. N-Methyl-2-pyrrolidone (NMP) is a solvent widely used in many industries and restricted as one of the chemicals under EU REACH regulations due to its potential harmful effects. In this study, thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) is applied for the quantitative analysis of NMP with the use of a polymer-coated sample cup. By using the polymer-coated sample cup, the vaporization of NMP was prevented during waiting time before TD-GC/MS analysis. The calibration curve for the TD method showed good linearity (correlation coefficient, r2 = 0.9998) and precision values (below 5.3% RSD). NMP recovery rates in different polymer matrices (PS, PMMA and PVC) were in the range of 98.8 to 106.6% with RSD values below 5.0%. The quantification result (600 mg NMP/kg PVC) for the blind NMP carrying sample in a PVC matrix by TD-GC/MS was higher than that (532 mg NMP/kg PVC) by solvent extraction-GC/MS method.


The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells.
Histone deacetylase (HDAC) inhibitors are showing promise as treatment for a variety of human cancers, but their precise mechanism of action has not been elucidated. We examined the effects of the HDAC inhibitor butyrate on colon cancer cells, focusing on its effect on the cell cycle promoter cyclin B(1). In HT-29 cells, sodium butyrate-mediated growth inhibition is associated with a marked decrease in cyclin B(1) mRNA levels. The decrease in cyclin B(1) occurred in a delayed fashion (at 24 h), is completely blocked by concomitant treatment with protein synthesis inhibitors, and appears to be dependent on changes in transcription. Cyclin B(1) repression is linked to the differentiation process in colon cancer cells, not merely with growth arrest. The mechanism of cyclin B(1) repression by butyrate requires prolonged histone hyperacetylation and is at least partly dependent on p21 expression. In fact, p21/WAF-1 appears to directly repress a minimal cyclin B(1) promoter (-90 bp), a process that can be mediated by the amino-terminal portion of the p21 protein. These findings highlight key molecular mechanisms by which HDAC inhibitors mediate their beneficial effects on human cancer cells.


[Chemotherapy of scirrhous gastric cancer].
Cancer chemotherapy plays a central role in the treatment of recurrent or unresectable scirrhous gastric cancers classified mainly as Borrmann type 4. Though we have no specifically effective drugs for scirrhous gastric cancer, 5-FU and its derivative, MMC, anthracyclines, CDDP, CQ and ACNU are known to be relatively effective single agents against this tumor. In an attempt to enhance the effect of single agents, several combined chemotherapy regimens have been devised and tested. These regimens included 5-FU + MMC, UFT + MMC, UFT + CDDP, MTX.5-FU, FAM, FAP, EAP and ELF regimen. At present, combined therapies using 5-FU and MTX or CDDP may be the most attractive of these combined regimens.


The effect of nanotubular titanium surfaces on osteoblast differentiation.
The biological response of fetal rat calvarial cells on a TiO2 nanotubular surface (Ti-NT) was evaluated by cell viability assay, alkaline phosphatase (ALP) activity and reverse transcription polymerase chain reaction (RT-PCR) analysis. The cell viability assay showed no significant difference between the Ti-NT and smooth titanium surfaces (Ti-S). Ti-NT had better cellular responses with regard to the ALP activity and bone-associated markers, such as bone sialoprotein and osteocalcin mRNA than Ti-S. These results suggest that Ti-NT stimulate the differentiation into osteoblasts of fetal rat calvarial cells, potentially contributing to rapid osseointegration.


When Disclosure Fails to Substantiate Abuse: Child and Perpetrator Race Predict Child Sexual Abuse Substantiation.
We examined the effects of child race, perpetrator race, and abuse disclosure status (within the context of a formal forensic interview) on abuse substantiation outcomes. Specifically, we coded child sexual abuse disclosure, abuse substantiation, and race of 315 children (80% girls, M age = 10, age range = 2-17; 75% White, 9% Black, 12% Biracial, 3% Hispanic, 1% Asian) who underwent a child forensic interview in a Midwestern child advocacy center. Supporting hypotheses, abuse substantiation was more likely in cases involving (a) abuse disclosure (vs. no disclosure), (b) White children (vs. children of color), and (c) perpetrators of color (vs. White perpetrators). Also supporting hypotheses, the effect of abuse disclosure on increased abuse substantiation was greater for White children than for children of color. This research suggests that even when children of color disclose their experiences of sexual abuse, they nonetheless face barriers to abuse substantiation.


Synthesis and photophysics of selective functionalized π-conjugated, blue light emitting, highly fluorescent C7-imidazo indolizine derivatives.
A new family of novel highly fluorescent π-conjugated, C7-imidazole based indolizine derivatives has been prepared in good to excellent yields, catalysed by l-proline in acetonitrile. These are π-conjugated, C7-imidazole based indolizine derivatives covering the emission wavelength range 423-449 nm in acetonitrile with high quantum yields at 25 °C. A thorough photophysical study of all the compounds has been carried out to understand the π-conjugated electronic effect of the imidazole moiety fused at the C7 position on the indolizine motif. In addition, a comparative photophysical study of three selective fluorophores was also carried out in a wide variety of solvents at 25 °C. Finally, the molecular orbitals of the two representative compounds were investigated through DFT calculations to illustrate the pi-conjugate effect.


Cost-effectiveness of intravenous acetaminophen and ketorolac in adolescents undergoing idiopathic scoliosis surgery.
Enhanced recovery after surgery protocols increasingly use multimodal analgesia after major surgeries with intravenous acetaminophen and ketorolac, despite no documented cost-effectiveness of these strategies. The goal of this prospective cohort study was to model cost-effectiveness of adding acetaminophen or acetaminophen + ketorolac to opioids for postoperative outcomes in children having scoliosis surgery. Of 106 postsurgical children, 36 received only opioids, 26 received intravenous acetaminophen, and 44 received acetaminophen + ketorolac as analgesia adjuncts. Costs were calculated in 2015 US $. Decision analytic model was constructed with Decision Maker® software. Base-case and sensitivity analyses were performed with effectiveness defined as avoidance of opioid adverse effects. The groups were comparable demographically. Compared with opioids-only strategy, subjects in the intravenous acetaminophen + ketorolac strategy consumed less opioids (P = .002; difference in mean morphine consumption on postoperative days 1 and 2 was -0.44 mg/kg (95% CI -0.72 to -0.16); tolerated meals earlier (P < .001; RR 0.250 (0.112-0.556)) and had less constipation (P < .001; RR 0.226 (0.094-0.546)). Base-case analysis showed that of the 3 strategies, use of opioids alone is both most costly and least effective, opioids + intravenous acetaminophen is intermediate in both cost and effectiveness; and opioids + intravenous acetaminophen and ketorolac is the least expensive and most effective strategy. The addition of intravenous acetaminophen with or without ketorolac to an opioid-only strategy saves $510-$947 per patient undergoing spine surgery and decreases opioid side effects. Intravenous acetaminophen with or without ketorolac reduced opioid consumption, opioid-related adverse effects, length of stay, and thereby cost of care following idiopathic scoliosis in adolescents compared with opioids-alone postoperative analgesia strategy.


Expression and functional influence of cellular retinoic acid-binding protein II in renal cell carcinoma.
Retinoic acid (RA) and its derivates possess antiproliferative and tumor-suppressive abilities and are successfully used in the treatment of various malignancies. However, in metastatic renal cell carcinoma (RCC), its application did not meet first expectations. As the exact mechanisms of RA action and especially the role of the cellular retinoic acid-binding proteins (CRABP) still remain unclear, we studied the expression of CRABP-II and its potential influence on RA response in RCC. We used the real-time RT-PCR methodology to investigate CRABP-II expression in 12 RCC samples and corresponding normal kidney tissue. Moreover, CRABP-II was cloned and overexpressed in CAKI-2 RCC cells. CRABP-II (un)transfected CAKI-2 cells were stimulated with all-trans RA (ATRA) and 9-cis RA, and their antiproliferative effects were evaluated using 3H-thymidine-proliferation assays. Using RPS9 and RPLP0 to normalize its expression, the median tumor/kidney ratio for CRABP-II expression was 0.16 and 0.12, respectively. Using proliferation assays, CRABP-II overexpressing CAKI-2 cells did not exhibit a significant change in RA sensitivity, but appeared to be less sensitive toward RA-stimulation compared to CAKI-2 cells expressing naturally low levels of CRABP-II (maximum difference, 59% at 3 microM ATRA). We were able to demonstrate a downregulation of CRABP-II expression in primary RCC tumor samples compared to the corresponding normal kidney tissue. However, CRABP-II overexpression in CAKI-2 RCC cells did not significantly influence RA associated antiproliferative actions. Further experiments are necessary to define the exact role of CRABP-II and its downregulation in RCC including its influence and dependence on other molecules involved in RA signalling and metabolism.


Transient Pain Following Orthodontic Fixed Appliances Induces Sensitization of Gingival and Periodontal Tissues.
To evaluate the transient effects of orthodontic treatment on the mechanical detection threshold (MDT) and mechanical pain threshold (MPT) of the buccal attached gingiva and the pressure pain threshold (PPT) of the buccal attached gingiva and of the teeth in two directions (perpendicular and parallel). A total of 20 patients (15 females and 5 males) aged 18 to 30 years participated in the study. Perceived pain on a 0- to 10-cm visual analog scale (VAS) and MDT, MPT, and PPT scores were evaluated at two time points at the masseter muscle, gingiva, teeth, and hand (control) prior to orthodontic treatment (T₀) and 24 hours after the first archwire placement (T₁). Mean values and SEMs were calculated for all continuous variables. The differences between T₀ and T₁ of MDT, MPT, and PPT were analyzed by means of a paired Student t test. The pain intensity as assessed on the VAS was 4.2 ± 1.8 cm. No significant changes in MDT or MPT were found at the hand and buccal attached gingiva (P > .06). The PPTs at the buccal attached gingiva of teeth 21, 23, 24, and 34, at teeth 21, 23, 24, and 34 (perpendicular) and at teeth 21 and 23 (parallel) were lower (ie, more sensitive) at T₁ compared with T₀ (P < .04). This study indicates for the first time that pain following insertion of an archwire causes sensitization to blunt-pressure stimuli both in the attached gingiva and in the periodontal ligament. Quantitative assessment of mechanical sensitivity may provide more insights into procedural pain and allow for better monitoring and evaluation of the effects of orthodontic treatment in the future.


Double stochastic resonance over an asymmetric barrier.
In a recent experiment [Müller, Phys. Rev. A 79, 031804(R) (2009)] reported a splitting of the stochastic resonance peak, which they attributed to the asymmetry of an effective double-well restoring potential in their optomechanical read-out device. We show here that such an effect, though smaller than reported, is indeed consistent with a characterization of stochastic resonance as a synchronization phenomenon, while it proves elusive in terms of spectral quantifiers.


Living with uncertainty: genetic imprints of climate shifts in East Pacific anchovy (Engraulis mordax) and sardine (Sardinops sagax).
In the upwelling zone of the northeastern Pacific, cold nutrient-rich conditions alternate with warm nutrient-poor intervals on timescales ranging from months to millennia. In this setting, the abundances of Pacific sardine (Sardinops sagax) and northern anchovy (Engraulis mordax) fluctuate by several orders of magnitude, with sardine dominating during warm conditions and anchovy dominating during cool conditions. Two population models can explain the response of these fishes to adverse conditions. Under the basin model, species distributions contract to a central (optimal) range during population crashes. Expectations of this model may include a single range-wide population with a decline in genetic diversity on both sides of a central refuge. In contrast, the self-recruitment model invokes a series of local oceanographic domains that maintain semi-isolated subpopulations. During adverse conditions, some subpopulations cannot complete the life cycle within the local environment and are extirpated. Expectations of this model include some degree of population genetic structure and no clear gradient in genetic diversity. We examined mitochondrial DNA cytochrome b sequences to assess these competing models for anchovy (N = 196; 539 bp) and sardine (N = 107; 425 bp). The mitochondrial DNA gene genealogies are shallow but diverse for both species. Haplotype frequencies are homogeneous among subpopulations, but genetic diversities peak for both species along Baja California and adjacent southern California. Mismatch distributions and Tajima's D-values reveal distinctive signatures of population bottlenecks and expansions. Sardine haplotypes coalesce at approximately 241,000 years bp, with an initial female effective population size Nf0 = 0 followed by exponential growth to Nf1 = 115 million. Anchovy haplotypes coalesce at approximately 282,000 years bp, with an initial population size of Nf0 = 14,000, followed by exponential growth to Nf1 = 2.3 million. These results indicate a founder event for sardine and a severe population decline for anchovy in the California Current during the late Pleistocene. Overall, these data support the basin model on decadal timescales, although local recruitment may dominate on shorter timescales.


A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides.
We performed a meta-analysis of the efficacy and toxicity of single daily dosing (SDD) vs. multiple daily dosing of aminoglycosides and summarized the results of the four previously published meta-analyses on this subject. Our analysis showed that the overall clinical response rate favored SDD therapy (mean difference, +3.06%; 95% confidence limit [CL], +0.17% to +5.95%; P = .04). However, we found no significant difference in the overall microbiological response rates (mean difference, +1.25%; 95% CL, -0.40% to +2.89%) or in the clinical response rates (mean difference, +0.62%; 95% CL, -2.48% to +3.71%) when patients who received adjunctive antimicrobial therapy were excluded from the analysis. No significant differences were found in the incidences of nephrotoxicity, ototoxicity, or vestibular toxicity; the summary differences in the rates of these toxicities were -0.18% (95% CL, -2.17% to +1.81%), +1.38% (95% CL, -0.99% to +3.75%), and -3.05% (95% CL, -10.69% to +4.59%), respectively. These results are similar to those of the previously published meta-analyses.


Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds.
Fungal infections have become an important medical condition in the last decades, but the number of available antifungal drugs is limited. In this scenario, the search for new antifungal drugs is necessary. The protocol reported here details a method to screen peptides for their antifungal properties. It is based on the broth microdilution susceptibility test from the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines with modifications to suit the research of antimicrobial peptides as potential new antifungals. This protocol describes a functional assay to evaluate the activity of antifungal compounds and may be easily modified to suit any particular class of molecules under investigation. Since the assays are performed in 96-well plates using small volumes, a large-scale screening can be completed in a short amount of time, especially if carried out in an automation setting. This procedure illustrates how a standardized and adjustable clinical protocol can help the bench-work pursuit of new molecules to improve the therapy of fungal diseases.


Oxygen and nitrogen plasma hydrophilization and hydrophobic recovery of polymers.
PLASMA HYDROPHILIZATION AND SUBSEQUENT HYDROPHOBIC RECOVERY ARE STUDIED FOR TEN DIFFERENT POLYMERS OF MICROFABRICATION INTEREST: polydimethylsiloxane (PDMS), polymethylmethacrylate, polycarbonate, polyethylene, polypropylene, polystyrene, epoxy polymer SU-8, hybrid polymer ORMOCOMP, polycaprolactone, and polycaprolactone/D,L-lactide (P(CL/DLLA)). All polymers are treated identically with oxygen and nitrogen plasmas, in order to make comparisons between polymers as easy as possible. The primary measured parameter is the contact angle, which was measured on all polymers for more than 100 days in order to determine the kinetics of the hydrophobic recovery for both dry stored and rewashed samples. Clear differences and trends are observed both between different polymers and between different plasma parameters.


Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Their Variations as a Basis for a Prediction Model in Advanced NSCLC Patients Receiving Anlotinib.
A phase III randomized multicenter trial (ALTER0303) reported anlotinib to be significantly beneficial to patient survival. An array of inflammatory biomarkers, such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), are associated with the response to treatment in numerous types of cancer. However, we found few studies investigating the predictive value of NLR or PLR in advanced NSCLC treatment with anlotinib. Thus, our objective was to examine the relationship between NLR and PLR and treatment effect, as well as to individuate patient stratification and selection. NLR and PLR as well as their variations were calculated in 152 advanced NSCLC patients receiving anlotinib as a third or further-line treatment at Ningbo Medical Center Lihuili Hospital between July 2018 and December 2020. The best cut-off values of NLR and PLR for predicting the treatment response were selected. Survival curves were plotted using the Kaplan-Meier method, while univariable and multivariable Cox regression were used to identify and determine dependent and independent predictors of survival. , Low disease control rate (DCR) was related with a high pre-NLR (P = 0.007), high pre-PLR (P = 0.004), and elevated post-NLR (P = 0.010). Multivariate analysis determined high pre-PLR (>205.63) and elevated post-NLR to be independently associated with poor PFS or OS. Patients whose risk score was 2 resulting from the prediction model based on pre-PLR and post-NLR had a 4.52 times higher risk of death compared to patients whose risk score was 0 (HR: 4.516, 95% CI: 2.502-8.152, P ≤ 0.001). Pre-PLR and post-NLR were independent prognostic indicators in patients with advanced NSCLC receiving anlotinib as a third or further-line treatment. Patients whose risk value score was 0 had a higher therapy effectiveness and better survival.


[The species specificity of fish and mammalian gonadotropic hormones].
Protein spectra of the hypophyses of fishes from various taxonomic groups obtained by disc electrophoresis in polyacrylamide gel exhibit high species specificity. By means of biological testing on the loach Misgurnus fossilis, zones of gonadotropic activity were obtained which differ in various species by the electrophoretic mobility. The mammalian gonadotropins obtained reveal lower electrophoretic mobility. The gonadotropins investigated significantly differ in their biological effect.


Transcriptional dynamics of pluripotent stem cell-derived endothelial cell differentiation revealed by single-cell RNA sequencing.
Pluripotent stem cell-derived endothelial cell products possess therapeutic potential in ischaemic vascular disease. However, the factors that drive endothelial differentiation from pluripotency and cellular specification are largely unknown. The aims of this study were to use single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape and cellular dynamics of directed differentiation of human embryonic stem cell-derived endothelial cells (hESC-EC) and to compare these cells to mature endothelial cells from diverse vascular beds. A highly efficient directed 8-day differentiation protocol was used to generate a hESC-derived endothelial cell product (hESC-ECP), in which 66% of cells co-expressed CD31 and CD144. We observed largely homogeneous hESC and mesodermal populations at Days 0 and 4, respectively, followed by a rapid emergence of distinct endothelial and mesenchymal populations. Pseudotime trajectory identified transcriptional signatures of endothelial commitment and maturation during the differentiation process. Concordance in transcriptional signatures was verified by scRNA-seq analysis using both a second hESC line RC11, and an alternative hESC-EC differentiation protocol. In total, 105 727 cells were subjected to scRNA-seq analysis. Global transcriptional comparison revealed a transcriptional architecture of hESC-EC that differs from freshly isolated and cultured human endothelial cells and from organ-specific endothelial cells. A transcriptional bifurcation into endothelial and mesenchymal lineages was identified, as well as novel transcriptional signatures underpinning commitment and maturation. The transcriptional architecture of hESC-ECP was distinct from mature and foetal human EC.


Production of protein arrays by cell-free systems.
Protein arrays make possible the functional screening of large numbers of immobilized proteins in parallel. To facilitate the supply of proteins and to avoid their deterioration on storage, we describe our protein in situ array (PISA) method for production of protein arrays in a single step directly from PCR DNA, using cell-free transcription and translation. In PISA, the in vitro-generated proteins are immobilized, as they are formed, on the surface of wells, beads, or slides coated with a protein-capturing reagent. In our preferred method, proteins are tagged with a double-hexahistidine sequence that binds strongly to Ni-NTA-coated surfaces. Advantages of PISA include avoiding bacterial expression and protein purification and making functional protein arrays available as required from genetic information.


Early recovery of albumin synthesis after liver transplantation.
The delay necessary for an orthotopic transplanted liver to recover in normal activity has never been defined. This is of great importance whenever liver transplantation is considered in patients with severe liver insufficiency. This delay was studied in dogs using albumin synthesis and BSP clearance as tests of liver function. Albumin synthesis was normal as early as 2 h following graft revascularization while BSP clearance was not yet normal by this time. It is suggested that transplanted livers will be rapidly able to corect metabolic disorders and above all coagulation problems in patients with terminal hepatic failure.


N-terminal pyroglutamate formation in CX3CL1 is essential for its full biologic activity.
CX3CL1 (fractalkine) is a unique member of the CX3C chemokine family and mediates both adhesion and cell migration in inflammatory processes. Frequently, the activity of chemokines depends on a modified N-terminus as described for the N-terminus of CCL2 modified to a pGlu- (pyroglutamate) residue by QC (glutaminyl cyclase) activity. Here, we assess the role of the pGlu-modified residue of the CX3CL1 chemokine domain in human endothelial and smooth muscle cells. For the first time, we demonstrated using MS that QC (QPCT, gene name of QC) or its isoenzyme isoQC (iso-glutaminyl cyclase) (QPCTL, gene name of isoQC) catalyse the formation of N-terminal-modified pGlu-CX3CL1. Expression of QPCT is co-regulated with its substrates CCL2 and CX3CL1 in HUVECs (human umbilical vein endothelial cells) and HCASMCs (human coronary artery smooth muscle cells) upon stimulation with TNF-α and IL-1β whereas QPCTL expression is not affected. By contrast, inhibition of the NF-κB pathway using an IKK2 inhibitor decreased the expression of the co-regulated targets QPCT, CCL2, and CX3CL1 Furthermore, RNAi-mediated inhibition of QPCT expression resulted in a reduction in CCL2 and CX3CL1 mRNA. In HCASMCs, N-terminal-modified pGlu1-CX3CL1 induced a significant stronger effect on phosphorylation of ERK (extracellular signal regulated kinase) 1/2, Akt (protein kinase B), and p38 (p38 mitogen-activated protein kinase) kinases than the immature Gln1-CX3CL1 in a time- and concentration-dependent manner. Furthermore, pGlu1-CX3CL1 affected the expression of CCL2, CX3CL1, and the adhesion molecule ICAM1/CD54 (intercellular adhesion molecule-1) inducing in higher expression level compared with its Gln1-variant in both HCASMCs and HUVECs. These results strongly suggest that QC-catalysed N-terminal pGlu formation of CX3CL1 is important for the stability or the interaction with its receptor and opens new insights into the function of QC in inflammation.


Chronic Wound Biofilms: Pathogenesis and Potential Therapies.
Chronic wounds are a growing medical problem that cause high rates of morbidity and mortality, costing the healthcare industry in the United States millions of dollars annually. Chronic wound healing is hampered by the presence of bacterial infections that form biofilms, in which the bacteria are encased in exopolysaccharide (EPS) and are less metabolically active than their free-living counterparts. Bacterial biofilms make chronic wounds more refractory to treatment and slow tissue repair by stimulating chronic inflammation at the wound site. Bacterial species communicate through a mechanism known as quorum sensing (QS) to regulate and coordinate the gene expression that is important for virulence-factor production, including biofilm formation. This review focuses on the relationships between chronic wounds, biofilms, and QS in the virulence of chronic-wound pathogens.


Inhibition of the Mitochondrial Permeability Transition for Cytoprotection: Direct versus Indirect Mechanisms.
Mitochondria are fascinating organelles, which fulfill multiple cellular functions, as diverse as energy production, fatty acid β oxidation, reactive oxygen species (ROS) production and detoxification, and cell death regulation. The coordination of these functions relies on autonomous mitochondrial processes as well as on sustained cross-talk with other organelles and/or the cytosol. Therefore, this implies a tight regulation of mitochondrial functions to ensure cell homeostasis. In many diseases (e.g., cancer, cardiopathies, nonalcoholic fatty liver diseases, and neurodegenerative diseases), mitochondria can receive harmful signals, dysfunction and then, participate to pathogenesis. They can undergo either a decrease of their bioenergetic function or a process called mitochondrial permeability transition (MPT) that can coordinate cell death execution. Many studies present evidence that protection of mitochondria limits disease progression and severity. Here, we will review recent strategies to preserve mitochondrial functions via direct or indirect mechanisms of MPT inhibition. Thus, several mitochondrial proteins may be considered for cytoprotective-targeted therapies.


Multipole electron densities and atomic displacement parameters in urea from accurate powder X-ray diffraction.
Electron density determination based on structure factors obtained through powder X-ray diffraction has so far been limited to high-symmetry inorganic solids. This limit is challenged by determining high-quality structure factors for crystalline urea using a bespoke vacuum diffractometer with imaging plates. This allows the collection of data of sufficient quality to model the electron density of a molecular system using the multipole method. The structure factors, refined parameters as well as chemical bonding features are compared with results from the high-quality synchrotron single-crystal study by Birkedal et al. [Acta Cryst. (2004), A60, 371-381] demonstrating that powder X-ray diffraction potentially provides a viable alternative for electron density determination in simple molecular crystals where high-quality single crystals are not available.


An analysis of healthcare providers' online ratings.
Many websites allow consumers to evaluate their healthcare experience yet scant data exist that explore the type and content of reviews. To evaluate and describe online healthcare provider reviews. We analysed 16,703 ratings on 6101 providers from four US cities. Ratings spanned five categories and an overall provider score. We also performed text analyses of narrative commentary (n = 15,952). Providers had a high mean score for each category (3.7-4.0 out of 5). Higher overall scores were associated with higher staff (adjusted odds ratio (aOR) 3.0, 95% CI 2.9-3.0, P < 0.01) and punctuality scores (aOR 2.1, 95% CI 2.05-2.15, P < 0.01). Review frequency was inversely associated with scores, (aOR 0.94, 95% CI 0.92-0.96, P < 0.01). Analyses of narrative commentaries revealed more positive than negative terms (P < 0.01). Online ratings were largely positive. Future research must discern how online surveys affect patient referrals, provider reputations and patients' perceptions of quality of care.


Ghrelin inhibits sympathetic nervous activity in sepsis.
Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating alpha(2)-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We have also shown that a novel stomach-derived peptide, ghrelin, is downregulated in sepsis and that its intravenous administration decreases proinflammatory cytokines and mitigates organ injury. However, it remains unknown whether ghrelin inhibits sympathetic activity through central ghrelin receptors [i.e., growth hormone secretagogue receptor 1a (GHSR-la)] in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). Ghrelin was administered through intravenous or intracerebroventricular injection 30 min before CLP. Our results showed that intravenous administration of ghrelin significantly reduced the elevated NE and TNF-alpha levels at 2 h after CLP. NE administration partially blocked the inhibitory effect of ghrelin on TNF-alpha in sepsis. GHSR-la inhibition by the administration of a GHSR-la antagonist, [d-Arg(1),d-Phe(5), d-Trp(7,9),Leu(11)]substance P, significantly increased both NE and TNF-alpha levels even in normal animals. Markedly elevated circulating levels of NE 2 h after CLP were also significantly decreased by intracerebroventricular administration of ghrelin. Ghrelin's inhibitory effect on NE release was completely blocked by intracerebroventricular injection of the GHSR-1a antagonist or a neuropeptide Y (NPY)/Y(1) receptor antagonist. However, ghrelin's downregulatory effect on TNF-alpha release was only partially diminished by these agents. Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. Ghrelin's inhibitory effect on TNF-alpha production in sepsis is partially because of its modulation of the overstimulated sympathetic nerve activation.


Cochlear implant electrode array exposure: A delayed complication.
Exposure of the cochlear implant electrode array as a late complication has been reported rarely in the literature. A retrospective analysis revealed 4 patients presenting with exposure of their cochlear implant electrode arrays from 2 to 17 years after implantation. Data collected from these 4 patients were surgical implantation approach, type of implant, age at implant, interval between implant and complication, surgical correction of the problem, pathology at the time of correction, and length of follow-up after intervention. All 4 patients presented with otitis or mastoiditis. Each had undergone a transmastoid approach with facial recess and cochleostomy and full implant insertion. In 3 cases, the tympanic membrane had retracted to expose the electrode array. In 1 patient, the electrode array had eroded through the external canal, lateral to the facial recess. The exposed arrays were addressed surgically, including explantation/reimplantation for 1 patient. Cochlear implant electrode arrays can become exposed by relative migration of the array and the tympanic membrane. Implant surgeons and audiologists need to be aware of the possibility of this complication. Closure of the ear canal appears to be the most effective surgical intervention.


Disinfection of removable dentures using ozone.
Over time, removable dentures tend to become unsanitary and emit unpleasant odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused by denture plaque. Recently, various cleaning products designed to keep removable dentures sanitary have appeared on the market. It is known that denture plaque is mainly composed of Candida albicans (C. albicans), and that ozone seems to inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles (ozone concentration of about 10 ppm) was considered as clinically appropriate because of its strong disinfecting and deodorizing power, and high biological safeness. The effectiveness of this cleaner against C. albicans was investigated using. Results showed that C. albicans decreased to about 1/10 after 30 min and to 1/10(3) after 60 min.


The ART of Antiretroviral Therapy in Critically Ill Patients With HIV.
The management of patients with human immunodeficiency virus (HIV) can be a complicated specialty within itself, made even more complex when there are so many unanswered questions regarding the care of critically ill patients with HIV. The lack of consensus on the use of antiretroviral medications in the critically ill patient population has contributed to an ongoing clinical debate among intensivists. This review focuses on the pharmacological complications of antiretroviral therapy (ART) in the intensive care setting, specifically the initiation of ART in patients newly diagnosed with HIV, immune reconstitution inflammatory syndrome (IRIS), continuation of ART in those who were on a complete regimen prior to intensive care unit admission, barriers of drug delivery alternatives, and drug-drug interactions.


Continuous-wave mid-infrared laser operation of Tm3+:KY3F10 at 2.3 μm.
We report continuous-wave lasing demonstration of a Tm3+:KY3F10 crystalline gain medium at 2343 nm. A narrow-linewidth, tunable, continuous-wave Ti3+:sapphire laser was used to end pump a Tm3+:KY3F10 crystal with thulium doping of 8 at. %. With 1 W of pump power, the resonator with a 1% output coupler generated output powers of 31 and 122 mW in single-pumping and double-pumping configurations, respectively. Excitation efficiency of the laser was investigated for pump wavelengths in the 765-806 nm range. Four pump bands were identified in this wavelength range, with the two most efficient pump bands centered at 773 and 778 nm. The output of the laser could be tuned smoothly and continuously over a spectral width of 125 nm from 2260 to 2385 nm. The lifetime of the H43 level was further measured to be 16 μs, and the emission cross section was determined based on lasing threshold measurements.


Glomerular T cell and monocyte populations in patients with IgA nephropathy.
Renal tissues from 19 patients with the minimal or slight stage of IgA nephropathy were examined for evidence of glomerular T cell or monocyte infiltration using monoclonal antibodies to identify T cells (OKT3, OKT11), T cell subsets (OKT4, OKT8), and monocytes and null cells (OKM1) by indirect immunofluorescence. Renal tissues from 12 patients at the same stage of mesangial proliferative glomerulonephritis without IgA deposition were also investigated by these procedures. Light microscopic examination of the same renal tissues was also performed. Reactive glomerular mononuclear cells were found to be numerous in patients with IgA nephropathy. The most prominent type of glomerular cells was OKT8 positive. T cell subsets and OKM1 positive cells in glomeruli from patients with IgA nephropathy were significantly increased as compared to those from patients with mesangial proliferative glomerulonephritis. Focal segmental proliferation of mesangial cells was observed in glomeruli which showed an accumulation of OKT8 positive cells. It is concluded that the immuno-regulatory mechanism involving T cells and/or monocytes might be one of the exacerbating factors in patients with IgA nephropathy.


Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood.
Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.


[The syndromes of oculogyric crisis and paroxysmal perceptual alteration in chronic schizophrenic patients--a clinical inquiry into their pathophysiology].
The syndromes of oculogyric crisis (OGC) and paroxysmal perceptual alteration (PPA) in chronic schizophrenics have been investigated. The perceptual symptoms of PPA are characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.) and a disorder of somatic schema (one feels that one is floating, one's extremities are pulled and elongated, etc.). PPA in chronic schizophrenics occurs abruptly mainly in the evening, often precipitated by fatigue. During the attack patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood and inability to distract their thought from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. The syndrome of OGC occurs in a similar fashion as in PPA; the attack occurs mainly in the evening and is also associated with a variety of transient mood and thought disturbances similar to those in PPA. Four cases have been described in this study, who experienced both PPA and OGC simultaneously. Among 223 schizophrenic patients admitted to our hospital between April 1987 and September 1988, 18 cases with OGC, 5 cases with PPA, and 4 cases with both PPA and OGC were found. The mean +/- SD dose of neuroleptics (chlorpromazine equivalent) at the latest occurrence of these syndromes was 761 +/- 470 mg (N = 22, ranging from 195 to 2010 mg) for OGC and 773 +/- 587 mg (N = 9, ranging from 227 to 2010 mg) for PPA. The appearance of OGC in cases with 195 mg or more dose (chlorpromazine equivalent) of neuroleptics of OGC in cases with with 195 mg or more dose (chlorpromazine equivalent) of neuroleptics (NLP) is significantly higher (p less than 0.05) than that in cases with less than 195 mg of NLP. Similarly, the appearance of PPA in cases with 277 mg or more dose of NLP was higher (p less than 0.1) than that in cases with less than 277 mg of NLP. In paranoid schizophrenic patients the incidences of OGC and PPA were significantly lower (p less than 0.001 and p less than 0.05, respectively) than those in other types of schizophrenics. In disorganized schizophrenic patients the incidence of PPA was significantly lower (p less than 0.01) than those in undifferentiated, residual and schizoaffective types.(ABSTRACT TRUNCATED AT 400 WORDS)


Successful transplantation of kidneys bearing previously mismatched HLA A and B locus antigens.
Transplantation of kidneys bearing HLA antigens to which recipients have previously been exposed is generally avoided, and such prudence is a well-documented means of preventing early graft loss. Prior exposure and subsequent reactions can, however, take a wide variety of forms, and blanket avoidance may prevent many deserving patients from being transplanted. In our region, operating through a single tissue-typing laboratory, we follow a consistent policy of allowing retransplantation with kidneys bearing previous mismatches, provided no relevant antibody response has been detected. Twenty-one of 34 such transplants remain functioning at time periods ranging from 7 months to 7 years. Four were lost due to rejection within the 1st month, and the remaining 9 functioned for periods ranging from 2 months to 8 years. Three were lost for reasons other than rejection. Our antibody screening policy and our criteria for a negative crossmatch results in the exclusion of two-thirds of all repeat mismatch transplantations. The results indicate that in the remaining third, transplantation can be performed across a repeat mismatch with excellent long-term results, provided our defined crossmatch policy is adhered to strictly.


Involvement of T cell immunity in the transient thyroid inflammation induced by iodide in goitrous BALB/C and nude mice.
To evaluate the involvement of T cell immunity in the thyroiditis induced in goitrous mice by iodide administration, we analyzed the immunological changes happening in the thyroid glands and lymph nodes during goiter involution in balb/c and athymic nude mice of similar background. In both balb/c and nude mice, goiter involution was characterized by thyroid cell necrosis and inflammation. In balb/c mice, the inflammatory infiltrate was made of numerous Ia+ cells. Their number was unchanged during goiter development, but was significantly increased after 2 days of involution and remained high after 8 days. CD4+ and CD8+ T cells were also observed, some of which were clearly activated since they expressed the receptor for Interleukin-2 (IL-2R). The numbers of CD4+, CD8+ and IL-2R+ T cells were increased during goiter as compared to control mice, and they reached a maximum at day 1 of involution. In nude mice, unexpectedly, CD4+ and CD8+ T cells were also found in the thyroid. Their numbers, as well as the number of Ia+ cells, were significantly increased at the onset of involution, but they remained systematically lower than in the corresponding groups of balb/c mice. Iodide treatment of goitrous mice also induced modifications of the lymph nodes draining the thyroid: enlargement of the paracortical T zone, presence of germinal centers in cortical follicles, and increase of the density of IL-2R+ cells. Mesenteric lymph nodes taken as controls were unchanged. Thus, three observations suggest the involvement of T cell immunity in iodine-induced thyroid inflammation: 1. Infiltration of Ia+, CD4+, CD8+ and IL-2R+ cells. 2. Signs of stimulation in thyroid lymph nodes, 3. Significant differences between balb/c and nude mice, in which the inflammatory reaction is weaker.


Production of oxidants by ion irradiation of water/carbon dioxide frozen mixtures.
We present new experimental results on the formation of oxidants, such as hydrogen peroxide, ozone, and carbonic acid, under ion irradiation of icy mixtures of water/carbon dioxide at different ratios and temperatures (16 and 80 K). Pure water ice layers and mixtures with carbon dioxide were irradiated by 200 keV He+ ions. We found that the CO(2)/H(2)O ratio progressively decreased to a value of about 0.1, the H(2)O(2) production increased with increasing CO(2) abundance at both 16 and 80 K, and the CO and H(2)CO(3) production increased with increasing CO(2) abundance at 16 K. At 80 K, the synthesis of CO was less efficient because of the high volatility of the molecule that partially sublimed from the target. The production of carbonic acid was connected with the production of CO(3). O(3) was detected only after ion irradiation of CO(2)-rich mixtures. The experimental results are discussed with regard to the relevance they may have in the production of an energy source for a europan or a martian biosphere.


QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases.
Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-alpha inhibitor therapy. However, no agreement exists on the best strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID). The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette-Guérin (BCG) vaccinated. Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring. Use of the QuantiFERON-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON-TB Gold in-tube testing in a low prevalence bacillus Calmette-Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.


Ensemble-based control of evolutionary optimization algorithms.
This paper presents a study on how the intrinsic search parameters of an evolutionary optimization algorithm can be automatically controlled. It will be shown that only a small search parameter window ensures good optimization results. This evolutionary window, enclosing effective values for the mutation rate and temperature, can be adapted to by carefully steering the ensemble's fitness dispersion. A control sensor based on an entropy measure is introduced to achieve this goal. The efficiency of the proposed control method will be tested by optimizing artificial sequences such as the well-known low autocorrelated binary strings and natural sequences including RNA.


Females exhibit shorter paraspinal reflex latencies than males in response to sudden trunk flexion perturbations.
Females have a higher risk of experiencing low back pain or injury than males. One possible reason for this might be altered reflexes since longer paraspinal reflex latencies exist in injured patients versus healthy controls. Gender differences have been reported in paraspinal reflex latency, yet findings are inconsistent. The goal here was to investigate gender differences in paraspinal reflex latency, avoiding and accounting for potentially gender-confounding experimental factors. Ten males and ten females underwent repeated trunk flexion perturbations. Paraspinal muscle activity and trunk kinematics were recorded to calculate reflex latency and maximum trunk flexion velocity. Two-way mixed model analyses of variance were used to determine the effects of gender on reflex latency and maximum trunk flexion velocity. Reflex latency was 18.7% shorter in females than in males (P=0.02) when exposed to identical trunk perturbations, and did not vary by impulse (P=0.38). However, maximum trunk flexion velocity was 35.3% faster in females than males (P=0.01) when exposed to identical trunk perturbations, and increased with impulse (P<0.01). While controlling for differences in maximum trunk flexion velocity, reflex latency was 16.4% shorter in females than males (P=0.04). The higher prevalence of low back pain and injury among females does not appear to result from slower paraspinal reflexes.


[EEG controls in recurrences of supratentorial brain-specific tumors].
The purpose of this study was to find out the value of postoperative EEG controls in the early detection of recurrence of supratentorial gliomas (the majority being astrocytomas, stage II to IV). 29 cases with verified tumour recurrence were examined and in all but one the EEG showed a reactivation of the focus in accordance with the development of the glioma. At least one of the following parameters had to be established: a further spreading of the focal changes, a reduction in frequency, an increase in amplitudes and focal depression of amplitudes. At least 3 postoperative EEG controls were made in each case. The duration of tumour treatment was 3 to 59 months. In 3 cases temporary focus activation was found without evidence of tumour recurrence; in one of these cases the activation was preceded by an epileptic seizure. Epileptic seizures, thus, seem to have a focus activating effect. Focus activation as a result of radiotherapy or cytostatic treatment was not observed. On the basis of our findings it appears that regularly conducted postoperative EEG controls seem to be highly suited as a non-invasive and economical method for the early detection of recurrence of this type of tumour. In the case of malignant types of gliomas involving rapid growth EEG controls should be made monthly.


Emerging drugs for immune thrombocytopenia (ITP).
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoantibody production against platelets, increased platelet destruction, and, in some cases, impaired thrombopoiesis. The majority of affected patients have significant bleeding risks due to low platelet counts and require treatment. The etiology of ITP is an immunological labyrinth. Currently available treatment options are usually not only nonspecific, but are also associated with some risks. Areas covered: Several useful drugs for the treatment of ITP are currently available. Furthermore, ongoing trials with new drugs and preclinical development of additional drugs may help to improve and determine their value. Expert opinion: ITP is a heterogeneous complex requiring individualized treatment. None of the available drugs are specific, nor are they invariably safe and effective. Thus, the need for specific therapy is evident.


[The development of computer-assisted gastric function testing system].
This paper introduces a system consisting of the PC computer, sensing device, the card for electro-gastric signals amplifier and analog-digital converter. By using only one piece of 1.2 M 3" diskette, the system can realize the dialogue between human and the computer to sample, process, store and display the electro-gastric signals, and print the auxiliary analysis and diagnostic results for doctors to refer to. When the computer is more and more popular today, it is one of the convenient, painless and effective method to check up the gastric functional disease.


Similarity Metric Learning for 2D to 3D Registration of Brain Vasculature.
2D to 3D image registration techniques are useful in the treatment of neurological diseases such as stroke. Image registration can aid physicians and neurosurgeons in the visualization of the brain for treatment planning, provide 3D information during treatment, and enable serial comparisons. In the context of stroke, image registration is challenged by the occluded vessels and deformed anatomy due to the ischemic process. In this paper, we present an algorithm to register 2D digital subtraction angiography (DSA) with 3D magnetic resonance angiography (MRA) based upon local point cloud descriptors. The similarity between these local descriptors is learned using a machine learning algorithm, allowing flexibility in the matching process. In our experiments, the error rate of 2D/3D registration using our machine learning similarity metric (52.29) shows significant improvement when compared to a Euclidean metric (152.54). The proposed similarity metric is versatile and could be applied to a wide range of 2D/3D registration.