Cellular immune responses in the acute exacerbation of hepatitis B e antigen-positive type B chronic hepatitis.
The compositions of lymphocytes in peripheral blood and liver biopsies from 29 patients with hepatitis B e antigen-positive type B chronic hepatitis were studied by an indirect peroxidase-labeled antibody method using monoclonal antibodies to surface antigens on pan T cells (Leu-1 +), cytotoxic/suppressor T cells (Leu-2a +), helper/inducer T cells (Leu-3a +), natural killer/killer cells (Leu-7 +), and B cells (Leu-10 +). In the peripheral blood during the acute exacerbation of chronic hepatitis B, the percentage of cytotoxic/suppressor T cells was decreased, and the ratio of helper/inducer to cytotoxic/suppressor cells was elevated corresponding to the peak of serum transaminase. In contrast, in liver biopsies obtained during acute exacerbation, numerous lymphocytes infiltrated sites of liver cell necrosis and were predominantly cytotoxic/suppressor cells. When compared with the liver biopsies obtained about 2 months after the peak of serum transaminase, cytotoxic/suppressor cells were significantly increased in those obtained during the acute exacerbation period. No significant change of the percentage of natural killer/killer cells was observed in either the peripheral blood or the liver during the acute exacerbation. These findings suggest that T cell cytotoxicity plays an important role in the mechanisms of liver cell damage in acute exacerbation of chronic hepatitis B.


Factors associated with unprotected anal intercourse among men who have sex with men: results from a respondent driven sampling survey in Nanjing, China, 2008.
Unprotected anal intercourse (UAI) is a well-documented risk factor for acquiring HIV, but not well-studied in China. We studied demographic and behavioral correlates for UAI among men who have sex with men (MSM) in a respondent-driven-sampling (RDS) survey in Nanjing, China. Four hundred and thirty MSM (including ten seeds) participated in this study, rendering an adjusted rate of UAI as 62.3 % (95 % CI 56.4-68.4 %). Adjusted HIV and syphilis prevalence rates were 6.6 % (95 % CI 3.0-10.4) and 12.6 % (95 % CI 8.1-18.3), respectively. HIV- and syphilis-positive cases were more likely to have engaged in UAI. Being unwilling to use condoms, meeting partners in non-conventional venues, having multiple male sex-partners in the past 6 months, having sex with regular and casual male partners in the past 6 months, and consumption of alcohol before sex were all positively associated with UAI. Based on the observed high prevalence of UAI among MSM in Nanjing, we can conclude that implementation of strategies to motivate MSM with high-risk behaviors to use condoms is urgently required in Nanjing.


Effects of timolol maleate eye drops on experimentally dilated cardiomyopathy and healthy rabbits.
Dilated cardiomyopathy (DCM) is the most frequently diagnosed cardiomyopathy in rabbits. Timolol maleate (nonselective beta-blockers), which reduces the heart rate (HR) and blood pressure, has been used for glaucoma. However, this effect has not been assessed in a rabbit DCM model. This study aimed to evaluate the circulatory effects of 0.5% timolol maleate eye drops on rabbit DCM models. Rabbits were randomly divided into healthy (n = 8) and DCM rabbits (n = 8). Rabbit DCM models were established through intravenous administration of daunorubicin (4 mg/kg/week), an anthracycline anticancer drug, for 6 weeks. We measured the HR, mean arterial pressure (MAP), and echocardiography before (pre) and at 10, 30, 60, and 120 minutes after timolol maleate administration. Timolol maleate 0.5% eye drops significantly reduced the HR at 10, 30, and 60 minutes in DCM models and 10 minutes in healthy rabbits; however, there were no alterations in MAP. There was a significant fraction shortening elevation at 10 and 120 minutes in DCM models; moreover, there were marked ejection fraction elevations at all measurement points in only DCM models. Timolol maleate eye drops exert several effects on the circulatory system in rabbit DCM models and healthy rabbits.


Use of modified Delphi introduces the risk of chronological bias during clinical research interventions.
A study aimed at reducing the time spent on the phone obtaining insurance preauthorisation in a neurosurgical clinic was successfully completed. However, the researchers were unable to reject the null hypothesis because of a combination of chronological bias and the Hawthorne effect. To increase nurse researchers' awareness of the potential to introduce a chronological bias as a confounder in clinical research and suggest potential alternative approaches to study design. The researcher shared the study's purpose, design and outcome measure with the participants before collecting the baseline data. This enabled the participants to alter their practice before the intervention was implemented (a chronological bias) and change their behaviour surrounding the outcome (the Hawthorne effect). The use of the Delphi method became a catalyst for change before the collection of baseline data, the combination of chronological bias and the Hawthorne effect affecting the study's results. Nurse researchers seeking to improve practice should collect baseline data before informing participants and consider the risks and benefits of blinding (concealment) surrounding the outcome.


Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes.
The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are autosomal dominant disorders sharing the following characteristics: slowly growing and sparse scalp hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum, thin upper lip with vermilion border, and protruding ears. In addition, individuals with TRPS generally share skeletal and bone anomalies, including shortening of the phalanges and metacarpals (mild to severe brachydactyly), cone-shaped epiphyses, hip dysplasia, and short stature. The etiology of the different types of TRPS can result from either single base pair mutations, or the complete deletion of the TRPS1 gene, which encodes a zinc-finger transcription factor located on chromosomal band 8q24.1. We have identified nine heterozygous mutations, five novel and four recurrent, in unrelated families diagnosed with TRPS. The five novel mutations identified show 1- or 2-bp deletions and a single base substitution, whereas all of the recurrent mutations are single base substitutions. Seven of the nine mutations result in a premature stop codon, leading to a truncated, nonfunctional TRPS1 protein. The final two mutations are missense mutations in the GATA DNA binding zinc finger, which is believed to be important for the protein's normal function.


ClsGAN: Selective Attribute Editing Model based on Classification Adversarial Network.
Attribution editing has achieved remarkable progress in recent years owing to the encoder-decoder structure and generative adversarial network (GAN). However, it remains challenging to generate high-quality images with accurate attribute transformation. Attacking these problems, the work proposes a novel selective attribute editing model based on classification adversarial network (referred to as ClsGAN) that shows good balance between attribute transfer accuracy and photo-realistic images. Considering that the editing images are prone to be affected by original attribute due to skip-connection in encoder-decoder structure, an upper convolution residual network (referred to as Tr-resnet) is presented to selectively extract information from the source image and target label. In addition, to further improve the transfer accuracy of generated images, an attribute adversarial classifier (referred to as Atta-cls) is introduced to guide the generator from the perspective of attribute through learning the defects of attribute transfer images. Experimental results on CelebA demonstrate that our ClsGAN performs favorably against state-of-the-art approaches in image quality and transfer accuracy. Moreover, ablation studies are also designed to verify the great performance of Tr-resnet and Atta-cls.


Mechanism of non-steroidal anti-inflammatory drug-gastropathy.
Non-steroidal anti-inflammatory drugs are recognized to cause gastrointestinal damage impairing the defense ability of gastric mucosal barrier. A variety of mechanisms due to non-steroidal anti-inflammatory drugs direct irritant (topical) action and to their main pharmacological (systemic) effect, is involved in the pathogenesis of non-steroidal anti-inflammatory drugs induced gastropathy. The systemic activity comprises the inhibition of cyclo-oxygenase, but an increasing body of evidence suggests that cyclo-oxygenase-independent mechanisms are involved in the development of gastric injury. In line with this concept, neither cyclo-oxygenase-1 nor cyclo-oxygenase-2 deficient mice develop spontaneous gastrointestinal ulcers and pharmacological inhibition of cyclo-oxygenase-1 or cyclo-oxygenase-2 with selective inhibitors doesn't elicit gastrointestinal damage; suggesting that both isoforms of cyclo-oxygenase enzymes have to be inhibited to induce ulcers. Moreover non-steroidal anti-inflammatory drugs administration in rats, induces the systemic release of tumor necrosis factor-alpha and drives gastric epithelial cells to apoptosis activating the pro-apoptotic cascade of caspases. In response to non-steroidal anti-inflammatory drugs, neutrophils are recruited into the gastric microcirculation through a process that requires activation of adhesion molecules. Although there is virtually no information regarding the regulation of expression of gastric endothelial cell adhesion molecules in response to non steroidal anti-inflammatory drugs, the nuclear factor-kB may represent a potential modulator. Supporting this view, selective proteasome inhibitors inhibit nuclear translocation of nuclear factor-kB induced by tumor necrosis factor-alpha in human endothelial cells in vitro and reduce indomethacin-induced gastric mucosal injury in vivo.


Virulence of Pasteurella multocida in atrophic rhinitis of gnotobiotic pigs infected with Bordetella bronchiseptica.
Bordetella bronchiseptica and Pasteurella multocida have been impLicated in the aetiology of atrophic rhinitis of pigs but the precise cause and pathogenesis of field outbreaks have still to be clarified. The virulence of 11 strains of P multocida was investigated by intraperitoneal injection of culture filtrates in BALB/C mice, or by infection of gnotobiotic piglets given B bronchiseptica five days previously. Three of four type D strains of P multocida were lethal for mice and caused severe turbinate lesions and shortening of the snout with B bronchiseptica in gnotobiotic pigs; large numbers of P multocida and B bronchiseptica persisted for 64 days in the nasal cavity of these pigs. The fourth strain caused moderately severe turbinate lesions in gnotobiotic pigs infected with B bronchiseptica; small numbers of P multocida were found in these pigs and the lesions were attributed mainly to B bronchiseptica. Filtrates from seven strains of P multocida (four type A and three type D) were not lethal for mice and these strains with B bronchiseptica caused moderately severe turbinate lesions in gnotobiotic pigs; five of them colonised the nasal cavity reasonably well for 35 days but the lesions were attributed mainly to B bronchiseptica. The turbinate bones had regenerated by 64 days in pigs given type A strains of P multocida whereas the lesions persisted in pigs given type D strains. Antibodies to P multocida were detected in sera from infected gnotobiotic pigs by acid agglutination but not by indirect haemagglutination tests; neutralising activity to the mouse lethal toxin was detected in serum from one of five piglets at 64 days. The lethal toxin was inactivated at 56 degrees C for 30 minutes, by incubation with protease K for two hours and by 0.2 per cent formalin for 18 hours at 37 degrees C but not by trypsin; it was precipitated by 30 to 40 per cent saturation with ammonium sulphate and remained in the supernatant after centrifugation at 150,000 g. It was concluded that infection with virulent, type D strains of P multocida and B bronchiseptica could explain severe outbreaks of atrophic rhinitis; large numbers of both organisms persisted in the nasal cavity of gnotobiotic pigs with severe lesions; and that a soluble, heat-labile toxin may be an important virulence determinant in the type D strains of P multocida that cause severe atrophic rhinitis.


Adverse effect of Pneumocystis Jirovecii infection associated with rituximab therapy for autoimmune disease are more frequently reported in older vs. younger patient.
Rituximab is a chimeric anti-CD20 antibody commonly used to treat patients with autoimmune diseases. Such diseases mainly affect young people, but older patients may also be concerned. So far, very little data exist concerning the safety of rituximab in older patients with autoimmune diseases. This study was intended to describe the adverse reaction profile of rituximab in patients over 75 years of age treated for autoimmune diseases and to compare such profile to those observed in patients below 75 years of age. Adverse reactions related to rituximab were reported to the French Pharmacovigilance Network. From such reports, a descriptive analysis as well as a disproportionality analysis were performed to identify safety signals. 1096 reports of rituximab-related adverse reactions reported in France between 2006 and 2019, were included in the study, such as 127 in the older group (>75 years) and 969 in the younger group (<75 years). Infusion reactions were less frequently reported than other adverse drug reaction in older patients (11 vs. 27%, P<0.001). By contrast, a higher rate of opportunistic infection due to Pneumocystis jirovecii was reported in the older subject group (3.9 vs. 0.6%, P<0.001), along with neutropenia (22.8 vs. 9.3%, P<0.0001). These results were confirmed by the disproportionality analysis. Pneumocystis jirovecii infection was significatively more reported in older patients treated by Rituximab which probably reflects a higher incidence in this population. The use of anti-pneumocystis prophylaxis should be considered in this population.


Sequence variations in the transcriptional regulatory region and intron1 of HLA-DQB1 gene and their linkage in southern Chinese ethnic groups.
Sequence polymorphism in the transcriptional regulatory region extending to intron1 (DQRRI1) of HLA-DQB1 gene, and their haplotypic distributions were investigated in southern Chinese populations. We cloned and sequenced a 1.1-kb segment containing the transcriptional regulatory region, exon1, and partial intron1 of HLA-DQB1 gene of 37 individuals from nine different ethnic groups in southern China. A high-density map of 162 polymorphisms, including 152 single nucleotide polymorphisms (SNPs) and 10 insertion-deletion polymorphisms, was revealed. By comparing these data with SNPs deposited in dbSNP database in National Center for Biotechnology Information and polymorphisms that have been reported, 66 polymorphisms were firstly reported. A total of 16 different haplotypes were detected based on these 162 polymorphisms. The distribution of 16 alleles of DQRRI1 as well as their linkage with DQB1 exon2 alleles was also investigated based on the population study and phylogenetic analysis. Tight linkage between these two regions were discovered, as each of DQB1*02, DQB1*03, DQB1*04, DQB1*05, and DQB1*06 alleles was seen to be linked with specific DQRRI1 allele. Our study showed different pattern of transcriptional regulatory region, exon1, and intron1 of different DQB1 alleles.


Audit of a pathway for childhood idiopathic constipation.
Constipation is a common condition in developed and industrialised nations. Although its exact prevalence is unknown it is estimated that between five and thirty per cent of the U.K. population suffer with it, depending on the criteria used for diagnosis (Candelli, 2001). Constipation that cannot be explained by any underlying abnormalities is known as idiopathic constipation.


Influences of doping and annealing on the structural and photoluminescence properties of Y2O3 nanophosphors.
This paper reports the structural and optical properties of rare earth doped and codoped yttrium oxide nanophosphors. Dysprosium (Dy(3+)) and Terbium (Tb(3+)) doped and codoped yttrium oxide (Y2O3) phosphors were prepared by combustion synthesis method and subsequently annealed to high temperature to eliminate the hydroxyl group (-OH) and to get more crystallinity. The formation of compounds was confirmed by the X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR). The diffuse reflectance spectra (DRS) of doped and codoped Y2O3 powder phosphors were measured and it is observed that the absorption edge of the doped samples is shifted towards blue region with respect to undoped sample. The bandgap of the prepared samples were evaluated with the help of Kubelka-Munk function using Diffuse Reflectance Spectra (DRS) and an increase in bandgap was observed with the decrease in crystallite size. A strong characteristics emission from Tb(3+) and Dy(3+) ions was identified and the influence of doping concentration and annealing temperature on photoluminescence properties was systematically studied. Transfer of energy was observed in dysprosium-terbium codoped Y2O3 nanophosphor at room temperature from Dy(3+) ions to Tb(3+) ions.


Interpretation of elevated FSH in the regular menstrual cycle.
In reproductive medicine, abnormal elevation of serum follicle stimulating hormone (FSH) concentrations during the luteofollicular transition is associated with low response in infertility treatment. Increasing levels of serum FSH in the early follicular phase is a characteristic of reproductive ageing and has become very popular for the determination of diminished ovarian oocyte reserve. In the case of elevated FSH in premenopausal women, many more (patho)physiological mechanisms other than ageing may be responsible and should be considered also. FSH concentrations may vary considerably due to a number of factors. Next to intra-, inter- and between different assays variation there is hourly-, cycle day dependent-, intercycle and life time variation. Furthermore, physiological conditions such as during puberty, in hereditary dizygotic twinning, after use of oral contraceptives and during lactation also elevated FSH levels can be found. Pathological conditions associated with significant increases in FSH are after unilateral ovariectomy, during recovery from hypothalamic amenorrhea and with excessive smoking. It should be kept in mind, that with the interpretation of an abnormal high FSH value, just as with any other abnormal laboratory results, one should be aware, that there may be a variety of underlying causes other than the one where was aimed at.


Is the 9 kDa thylakoid membrane phosphoprotein functionally and structurally analogous to the 'H' subunit of bacterial reaction centres?
Although the amino acid sequence of the 9 kDa (phospho)protein of chloroplasts has been determined, the function of this thylakoid membrane protein in photosynthetic electron transport and the reason for its physiological control remains unclear. In this paper, I briefly review the evidence which indicates that the phosphorylation of the 9 kDa protein results in a partial inhibition of photosynthetic oxygen evolution by increasing the stability of the semiquinone bound to QA the primary, plastoquinone-binding site of photosystem II (PS II). I propose that in its dephosphorylated state, the 9 kDa thylakoid membrane protein may serve PS II to ensure efficient photochemical charge separation by aiding the transfer of reducing equivalents out of the reaction centre to the attendant plastoquinone pool. This function is analogous to that proposed for the H-subunit of the reaction centre of photosynthetic eubacteria. Whether these two proteins have evolved from a common ancestral reaction centre protein is discussed in the light of a comparison of their amino acid sequences and predicted secondary structures.


Research and therapy with induced pluripotent stem cells (iPSCs): social, legal, and ethical considerations.
Induced pluripotent stem cells (iPSCs) can self-renew indefinitely in culture and differentiate into all specialized cell types including gametes. iPSCs do not exist naturally and are instead generated ("induced" or "reprogrammed") in culture from somatic cells through ectopic co-expression of defined pluripotency factors. Since they can be generated from any healthy person or patient, iPSCs are considered as a valuable resource for regenerative medicine to replace diseased or damaged tissues. In addition, reprogramming technology has provided a powerful tool to study mechanisms of cell fate decisions and to model human diseases, thereby substantially potentiating the possibility to (i) discover new drugs in screening formats and (ii) treat life-threatening diseases through cell therapy-based strategies. However, various legal and ethical barriers arise when aiming to exploit the full potential of iPSCs to minimize abuse or unauthorized utilization. In this review, we discuss bioethical, legal, and societal concerns associated with research and therapy using iPSCs. Furthermore, we present key questions and suggestions for stem cell scientists, legal authorities, and social activists investigating and working in this field.


Toxicity of fungicides to terrestrial non-target fauna - Formulated products versus active ingredients (azoxystrobin, cyproconazole, prothioconazole, tebuconazole) - A case study with Enchytraeus crypticus (Oligochaeta).
Despite the high usage of pesticides in current agricultural practices, its effects to humans and to the environment (non-target species) are a continuous concern. Soil dwelling organisms are among the first in line of exposure to pesticides, however their risks are often based on the pure active ingredient (a.i.) and not on the commercial formulated products (FPs) actually applied in the fields. In the present study, we investigated the effects of two fungicide FPs versus its a.i. (s): Amistar® XTRA and the respective a.i. (s) azoxystrobin and cyproconazole, and Prosaro® 250 EC and the respective a.i. (s) prothioconazole and tebuconazole, to the non-target soil oligochaete Enchytraeus crypticus. The standard Enchytraeid Reproduction Test was used to assess effects on survival and reproduction. Results showed that Amistar was more toxic than Prosaro, particularly for reproduction (EC50 = 161 mg Amistar/kg soil, EC50 = 350 mg Prosaro/kg soil). For both FPs, reproductive effects were mainly related to one of its a.i. (s) (azoxystrobin [EC50 = 37 mg azosxystrobin/kg soil] for Amistar, and tebuconazole [EC50 = 41 mg tebuconazole/kg soil] for Prosaro), while lethal effects were not predicted by the toxicity of its a.i. (s) (particularly in the case of Prosaro, which was more toxic than its a.i. (s)). These findings highlight the need to further explore the toxicity data of the FPs compared to the a.i. (s), aiming to predict a more realistic environmental hazard of pesticides.


Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme.
Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal. The cancer stem cell hypothesis offers a new view on the possible mechanisms dictating the heterogeneous nature of this disease and contributes to our understanding of glioma resistance and recurrence. Revealing cell division characteristics of initiating cell populations within GBM may represent novel treatment targets and/or the effective repurposing of existing therapies. In this review, we discuss the potential role of targeting the cyclin-dependent kinases (CDKs) driving this specific population. We also describe developments using multi-omic approaches that may aid in stratifying patient populations for CDK inhibitor therapy.


Changes in growth conditions alter the male strobilus gene expression pattern in Cryptomeria japonica.
Two-year old saplings grown from cuttings of Cryptomeria japonica D. Don initiate strobilus development following treatment with gibberellic acid under long-day photoperiods. At 25 degrees C with a 14-h photoperiod in a phytotron, male strobili initiated normally; however, they remained green and fell from the saplings prematurely. To examine the change in male strobilus development at the molecular level, three genes expressed specifically in male strobili were analyzed. Two were MADS box genes homologous to the B-function genes in angiosperms, CjMADS1 and CjMADS2, and the third was Cry j I, which encodes an allergen protein, and this gene is expressed mainly in microspores. Under phytotron growing conditions, the homeotic genes were expressed constantly, which reflected the extended early developmental stage of male strobili. On the other hand, Cry j I expression was detected after a long delay just before strobilus development ceased. These results indicate that the expression of the genes related to male reproductive development in C. japonica is regulated by a factor(s) that is sensitive to environmental signals.


Lipoprotein(a)--An independent causal risk factor for cardiovascular disease and current therapeutic options.
It is widely accepted that elevated levels of lipoprotein(a) (Lp(a)) are associated with an increased risk for cardiovascular diseases. Several studies have identified Lp(a) as independent cardiovascular risk factor. Consequently, therapeutic concepts are targeting at lowering Lp(a) serum levels. To date, in Europe no pharmaceutical treatment to lower levels of Lp(a) is available. Current developments of pharmaceutical agents like the apolipoprotein-(B-100)-antisense mipomersen, inhibitors of PCSK9 and apolipoprotein-(a)-antisense have shown promising results in lowering Lp(a). Presently, the only available therapy to effectively reduce levels of Lp(a) is regular extracorporeal lipoprotein apheresis. Different apheresis methods show a similar lowering effect of about 60-70 % by a single session. Apart from one small-scale study there has been no randomized, controlled study which could prove that lowering Lp(a) will result in a risk reduction for cardiovascular disease. This review looks into the current scientific evidence of.


The role of Kupffer cells in rat liver regeneration revealed by cell-specific microarray analysis.
Liver regeneration after partial hepatectomy is a process with various types of cells involved. The role of Kupffer cells (KCs) in liver regeneration is still controversial. In this study we isolated KCs from regenerating liver and conducted cell-specific microarray analysis. The results demonstrated that the controversial role of KCs in liver regeneration could be explained with the expression patterns of TGF-α, IL-6, TNF, and possibly IL-18 during liver regeneration. IL-18 may play an important role in negative regulation of liver regeneration. The functional profiles of gene expression in KCs also indicated that KC signaling might play a negative role in cell proliferation: signaling genes were down regulated before cell division. Immune response genes in KCs were also down regulated during liver regeneration, demonstrating similar expression profiles to that of hepatocytes. The expression patterns of key genes in these functional categories were consistent with the temporal functional profiles.


The rat epithalamus. I. Correlative scanning-transmission electron microscopy of supraependymal nerves.
Transmission and scanning electron microscopy of the rat epithalamus shows a regional variation in the distribution of supraependymal nerves (SN) which correlates well with supraependymal yellow fluorescence reported by Richards et al. (1974). The medial habenular nucleus, the intercommissural and suprahabenular recesses, the habenular commissure and the fibrae periventriculares thalami have the greatest density of SN/100micron of ependymal surface. The floor of the suprahabenular and intercommisural recesses is covered by non-ciliated ependyma. The significance of these findings is discussed with respect to (1) a direct functional relationship of SN with ependyma, and (2) a possible participation of the non-ciliated ependyma of the suprahabenular and intercommissural recesses in secretory activity whereby the CSF serves as a vehicle for neuroendocrine communication.


Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us.
The interactions of fatty acids with proteins have been studied by a variety of conventional approaches for decades. However, only limited aspects of fatty acid-protein interactions have been elucidated, even with the integration of information gleaned from the many techniques. Judgments must be made about what information is most reliable, particularly when derivatives of fatty acids are substituted for natural fatty acids. In recent years, the application of techniques of structural biology has brought about dramatic advances in this important area of lipid research. High-resolution crystallographic and NMR structures of several proteins with bound fatty acids reveal the complete tertiary structure of the protein and molecular details of fatty acid-protein interactions. The examples presented include most of the known structures of (non-enzymatic) proteins that bind fatty acids. The proteins are found in very different compartments of cells and organisms: the plasma compartment (human serum albumin); the cytosolic compartment of mammalian cells (fatty acid- binding proteins); the cytosol of plant cells (nonspecific lipid-transfer protein); the nucleus of mammalian cells (peroxisome proliferator-activated receptor and hepatic nuclear factor 4); and a bacterial membrane (halorhodopsin). This review discusses the structural features of these proteins and their binding pocket(s) and compares the specific modes of their interactions with fatty acids.


Charge migration fragmentation in the negative ion mode of cyclopentenone and cyclopentanone intermediates in the biosynthesis of jasmonates.
Jasmonates are formed from 12-oxo-10,15(Z)-phytodienoic acid (12-OPDA) in plants and also from 12-oxo-10-phytoenoic acid (12-OPEA) in fungi. Collision-induced dissociation (CID) of [M-H]- generates characteristic product anions at m/z 165 [C11 H17 O]- . Our goal was to investigate the structure and mode of formation of this anion by CID of 12-OPDA, 12-OPEA, and 12-oxophytonoic acid (12-OPA). We investigated the CID of the [M-H]- , [M-H-CO2 ]- , and [M-H-H2 O]- anions using electrospray ionization and MS/MS analysis of 12-OPDA, 12-OPEA, and 12-OPA, and compared the results with the data obtained with the corresponding compounds labeled with 2 H at C-6 and C-7 and with structural and side chain analogs. CID of [6,6,7,7-2 H4 ]12-OPEA and [6,6-2 H2 ]12-OPDA ([M-H]- and [M-H-CO2 ]- ) showed that one or two 2 H atoms were transferred to anions at m/z 165 as judged by the signal intensities of m/z 165 + 1 or 165 + 2, respectively. CID of [6,6-2 H2 ]- and [6,6,7,7-2 H4 ]-12-OPA ([M-H]- and [M-H-CO2 ]- ) yielded the loss of H2 from the cyclopentanone and displayed the transfer of one 2 H atom in analogy to 12-OPEA. In contrast, CID of [6,6,7,7-2 H4 ]12-OPEA and [6,6,7,7-2 H4 ]12-OPA [M-H-H2 O]- demonstrated the transfer of two 2 H atoms (m/z 165 + 2). All spectra obtained by CID of [6,6,7,7-2 H4 ]12-OPDA and [6,6,7,7-2 H4 ]12-oxo-9(13),15(Z)-phytodienoic acid showed that one or two additional 2 H atoms could be transferred to this anion at m/z 167 of [6,6-2 H2 ]12-OPDA due to isotope scrambling. CID of 12-OPDA and 12-OPEA generates cyclopentanone enolate anions at m/z 165 by charge-driven hydride transfer as a common mechanism and by bond cleavage between C-7 and C-8 of the carboxyl side chains with either gain or loss of a hydrogen atom.


Relationships among vasculature, mitotic activity, and endothelial nitric oxide synthase (eNOS) in bovine antral follicles of the first follicular wave.
To determine the relationships among vasculature, mitotic activity, and expression of endothelial nitric oxide synthase (eNOS) of antral follicles in Bos indicus, bovine ovaries were obtained on day 6 of the estrous cycle from 10 crossbred (Brahman to Thai native cows) after a synchronized estrus with prostaglandin F2α analogue. Ovaries were fixed, paraffin-embedded, and used for immunofluorescence detection of factor VIII (a marker of endothelial cells). Immunostaining of eNOS and proliferating cell nuclear antigen (PCNA) were performed with specific monoclonal antibodies. Vasculature and positive staining of eNOS and PCNA were quantitatively evaluated with the image analysis. Follicles were classified by size (small, medium, and large) and by structure as healthy and atretic follicles (n = 82). The expression of factor VIII and eNOS were detected greater in the blood vessels of the theca layers of the healthy follicles than those in atretic follicles. The labeling indices (LIs) in granulosa and theca cells were greater (P < 0.05) in the healthy small and medium follicles than in the healthy large follicles. Vasculature, capillary area density, and capillary number density were positively correlated with eNOS expression and the LIs of granulosa and theca cells but were negatively correlated with the healthy follicle size. During the growing phase of antral follicle in Bos indicus, relationships among vasculature, mitotic activity, and eNOS were observed predominantly in healthy antral follicles. Thus, these data highlight the importance of vasculature, cell proliferation, and eNOS expression of growing and atretic follicles in the first follicular wave.


Phonological alexia with optic and tactile anomia: a neuropsychological and anatomical study.
We describe a patient with phonological alexia caused by a small hemorrhage in the posterior-inferior portion of the left temporal lobe. The lesion induced a highly selective impairment of phonological reading without concomitant oral language deficits other than anomia for objects presented in the visual and tactile modalities. We propose that an intact dorsal pathway from inferior visual association areas to Wernicke's area via the angular gyrus could mediate reading by the lexical route, while damage to a ventral pathway disrupted the patient's ability to read nonwords. We suggest further that although visually and tactually presented objects could be recognized and both verbally and nonverbally identified, they could not be named because of a disconnection from the area of word representations.


Serum lipids and lipoproteins in patients treated with antiepileptic drugs.
The concentration levels of serum lipids and lipoproteins were measured in three groups of children and adolescents treated with antiepileptic drugs: carbamazepine (14 patients), phenobarbital (20 patients), and valproic acid (20 patients). Patients treated with these drugs revealed significant changes in lipids and lipoproteins, but when the authors reevaluated the three groups of children 1 year after the end of treatment, a complete return to normal of all parameters was observed. These data demonstrate that the changes induced by these drugs are transient and reversible.


The 3' Untranslated Regions of Ebola Virus mRNAs Contain AU-Rich Elements Involved in Posttranscriptional Stabilization and Decay.
The 3' untranslated regions (UTRs) of Ebola virus (EBOV) mRNAs are enriched in their AU content and therefore represent potential targets for RNA binding proteins targeting AU-rich elements (ARE-BPs). ARE-BPs are known to fine-tune RNA turnover and translational activity. We identified putative AREs within EBOV mRNA 3' UTRs and assessed whether they might modulate mRNA stability. Using mammalian and zebrafish embryo reporter assays, we show a conserved, ARE-BP-mediated stabilizing effect and increased reporter activity with the tested EBOV 3' UTRs. When coexpressed with the prototypic ARE-BP tristetraprolin (TTP, ZFP36) that mainly destabilizes its target mRNAs, the EBOV nucleoprotein (NP) 3' UTR resulted in decreased reporter gene activity. Coexpression of NP with TTP led to reduced NP protein expression and diminished EBOV minigenome activity. In conclusion, the enrichment of AU residues in EBOV 3' UTRs makes them possible targets for cellular ARE-BPs, leading to modulation of RNA stability and translational activity.


Reconstruction of Electric Discharge Patterns and Electrogenesis Mechanism in African Sharptooth Catfish Clarias gariepinus (Clariidae, Siluriformes).
Electrical discharges (EDs) in the African sharptooth catfish Clarias gariepinus were studied. Irregular monopolar EDs, lasting for 8-10 ms and longer, and more complex EDs, lasting for 20-50 ms and characterized by specific indentation of the discharge pattern, were recorded in pairs of individuals exhibiting both aggressive and defensive behavior. The pattern of long discharges was reconstructed by adding short EDs with different latencies and amplitudes. The conditions for the formation of long EDs with asynchronous activity of electromotor neurons and the possibility of coordinated operation of the electric generator and electroreceptor systems in catfish were considered, since an increase in the duration of EDs lowers the threshold of their perception.


The primary structures of rat ribosomal proteins: the characterization of the cDNAs for S21 and L39, corrections in the sequences of L7 and L18a, and the identification of L33.
cDNAs for rat ribosomal proteins S21 and L39 were characterized. S21 has 83 amino acids and a molecular weight of 9,121; L39 has 50 amino acids and a molecular weight of 6,271. There are 8 to 9 copies of the S21, and 9 to 11 copies of the L39 genes. The mRNA for S21 is about 500 nucleotides in length and for L39 it is about 450. Rat S21 and L39 are related to ribosomal proteins from other species. Corrections have been made in the amino acid sequences of L7 and L18a. The rat ribosomal protein designated L33 from its coordinates on two-dimensional gels has been found, from its amino acid sequence, to be identical to S24.


Knowledge mapping of nano drug delivery systems across blood - Brain barrier from 1996 to 2022: A bibliometric analysis.
The blood-brain barrier (BBB) is a natural physiological barrier that protects the central nervous system from foreign substances and limits the delivery of drugs to the brain. Nanotechnology has opened up new possibilities for drug delivery in the brain. Over several decades, various Nanoparticle Drug Delivery Systems (NDDS) that can cross the BBB have been developed for targeted delivery in the brain. To gain a comprehensive understanding of the current research hotspots and trends of NDDS across the BBB, this paper employs bibliometric analysis of articles published in the core database of Web of Science (WOS) from 1996 to 2022. A search for relevant research literature on NDDS that can cross the BBB was conducted in the Web of Science database, covering the period from 1996 to 2022. The Bibliometrix R-4.0 software package was used to analyze data related to the countries of publication, research institutions, journals, citations, and keywords. The analysis aimed to identify the co-occurrence of keywords in the documents, including their titles and abstracts. Additionally, cooperative network analyses of authors, institutions, and countries of publication were conducted. A total of 436 articles were analyzed, originating from 174 journals and 13 books, with the majority published in Q1 and Q2 journals. Contributors from 53 countries or regions participated in the publication of these articles, with China, the United States, and India having the highest number of articles by correspondent authors, and China, the United States, and Germany being the most cited countries. Fudan University, Hacettepe University, and Sichuan University were the top three institutions with the most publications. Among the 436 articles analyzed, 1337 keywords and 1450 keywords plus were identified. Factor analysis grouped the keywords plus into two categories: drug delivery systems, polymeric nanoparticles, gold nanoparticles, transferrin, and others, and drug, delivery, efficiency, expression, and mechanism. The research on NDDS that can cross the BBB is gradually receiving attention, and the recognition and cooperation in this field have increased.


Adsorption of lead ions by activated carbon doped sodium alginate/sodium polyacrylate hydrogel beads and their in-situ recycle as sustainable photocatalysts.
In this study, sodium alginate (SA), sodium polyacrylate (PAAS) and powdered activated carbon (PAC) were cross-linked by calcium ions [(Ca(II)] to form SA/PAAS/PAC (SPP) hydrogel beads. The hydrogel-lead sulfide (SPP-PbS) nanocomposites were successfully synthesized by in-situ vulcanization after the lead ions [(Pb(II)] adsorption. SPP showed an optimal swelling ratio (600% at the pH value of 5.0) and superior thermal stability (206 °C of heat-resistance index). The adsorption data of Pb(II) was compatible with the Langmuir model, and the maximum adsorption capacity of SPP was 391.65 mg/g after optimizing the mass ratio of SA to PAAS (3:1). The addition of PAC not only enhanced the adsorption capacity and stability, but also promoted photodegradation. The significant dispersive capacity of PAC and PAAS resulted in PbS nanoparticles with particle sizes of around 20 nm. SPP-PbS showed good photocatalysis and reusability. The degradation rate of RhB (200 mL, 10 mg/L) was 94% within 2 h and maintained above 80% after 5 cycles. The treatment efficiency of SPP was more than 80% in actual surface water. The results of quenching experiments and electron spin resonance (ESR) experiments revealed that the superoxide radicals (O2-) and holes (h+) were the main active species in the photocatalytic process.


Enabling successful transition-Evaluation of a transition to adult care program for pediatric liver transplant recipients.
This study aimed to evaluate the transition to adult care program instituted for liver transplant recipients (LTRs) at a large tertiary pediatric hospital in Melbourne, Australia. Evaluation included the change in a Global Assessment Measure (GAM) before and after the transition program, satisfaction with the program, and measures of transition success including rejection rates and attendance at appointments post-transfer. We hypothesized that the introduction of our structured transition program would improve disease understanding, health system understanding, and self-care. We also hypothesized that those who had undergone the transition program would have lower failure to attend rates and lower rates of rejection than historical controls. A LTR transition program was instituted at our service from 2013 to 2015. The program involved initial assessment of competencies with a Global Assessment Measure (GAM), followed by the introduction of a personalized goal setting program addressing issues identified in dedicated transition clinics. Assessment of competencies was compared between the commencement of the program and immediately prior to transfer. Patient satisfaction with the transition process was assessed at an interview 6-12 months after transfer to the adult service. Rejection rates and failure to attend rates were compared between the intervention group and a group of LTRs who did not receive the intervention. Twenty-eight LTRs participated in the study; 20 received the transition intervention and 8 served as controls. Within the intervention group, all domains of transition competency and reported anxiety regarding transferring had significantly improved at the conclusion of the intervention and all reported satisfaction with the transition program with most (81%) reporting readiness to transfer. There were no significant differences in rejection rates or failure to attend rates between those who did and did not receive the transition intervention. A longitudinal holistic transition program has the potential to positively impact the competencies and readiness of LTRs to successful transition and transfer to adult care.


The evidence rejects the expertise hypothesis: reply to Gauthier & Bukach.
In Robbins, R. & McKone, E. (2006). No face-like processing for object-of-expertise in three behavioural tasks. Cognition this issue, we showed face-like holistic/configural processing does not occur for objects-of-expertise on standard paradigms including inversion, part-whole, part-in-configurally-transformed-whole, and the standard composite task. In this reply to the discussion by Gauthier, I., & Bukach, C. (2006). Should we reject the expertise hypothesis? Cognition, this issue, we focus on several issues: the fact that they do not dispute our review of previous data; the strength of null effects obtained from multiple studies and paradigms; the evidence for domain-specificity of the neural substrate supporting face processing; the difference between the expertise hypothesis (as a theory about the origin of face processing) and studies of how experience affects object processing in general; and the problems with G&B's proposed alteration to the standard composite paradigm. We argue that overwhelming evidence suggests the expertise hypothesis should be put to rest so that researchers can focus on what the origin of "special" processing for faces actually is, and investigate the many interesting changes to object recognition that do occur with experience.


Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation, t(13;22)(q22;q11).
A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.


Unique mitogenomic features in the scleractinian family pocilloporidae (scleractinia: astrocoeniina).
The complete DNA sequences of three mitochondrial (mt) genomes were obtained from the scleractinian corals, Stylophora pistillata, Pocillopora damicornis, and Madracis mirabilis, and were compared to the published mt genomes to elucidate phylogenetically unique features of the family Pocilloporidae. The entire mt genomes of pocilloporid corals ranged from 16,951 to 17,425 bp with the A+T contents of their sense strands ranging from 68.4% to 70.2%. The gene order of protein-coding genes was identical to those of other scleractinian corals. The novel atp8 gene, first described in confamilial Seriatopora corals, was also confirmed using reverse transcription-polymerase chain reaction (RT-PCR), Northern blot, and sequence analyses in other genera of the Pocilloporidae. The intergenic spacer between atp6 and nad4, containing distinct repeated elements, conserved sequence blocks and domains, and functional structures, possesses typical characteristics of a putative control region for the four coral genera. A duplicated trnW, detected in the region close to the cox1 gene and which shares the highly conserved primary and secondary structures of its original counterpart, was discovered in both Seriatopora and Stylophora. These molecular characteristics are unique and provide the phylogenetic information for future evaluation of the status of the family Pocilloporidae in the evolutionary history of scleractinian corals.


Prediction of the mode of interaction between monoterpenes and the nitroreductase from Enterobacter cloacae by docking simulation.
Monoterpenes from the essential oils of several plants have been shown to enhance the bactericidal activities of nitrofurantoin and furazolidone against the bacteria of Enterobacteriaceae family. In this study, computer-aided molecular modeling and docking techniques have been employed to simulate the theoretical mode of interaction between monoterpenes and Enterobacter cloacae nitroreductase. Enhancement of nitro drug potency in the presence of monoterpenes may be the result of modulation of nitroreductase activity. Binding nitroreductase with monoterpenes may decrease the efficient conversion of toxic reactive intermediates to final products lacking bactericidal activity.


Spontaneous parkinsonisms and striatal impairment in neuroleptic free youth at ultrahigh risk for psychosis.
Spontaneous movement abnormalities, occurring independent of medication status, are thought to reflect basal ganglia pathology in patients at ultrahigh risk (UHR) for psychosis. To date, the research literature has primarily focused on movements associated with elevated striatal dopamine (i.e., hyperkinesia) while little is known about motor symptoms associated with low levels of subcortical dopamine (i.e., spontaneous parkinsonisms; SPs). As SPs (e.g., bradykinesia) may be governed by distinct neural mechanisms, this line of research can provide a clearer picture of the etiological processes in the prodrome. AIMS: To examine SPs and striatal structural correlates in youth at risk for psychosis. A total of 81 (35 UHR, 46 healthy controls) adolescents were administered a structured clinical interview, structural MRI scan, and handwriting kinematic analysis capable of assessing SPs that are not detectable by traditional observer-based inventories. The UHR group exhibited significant decreased velocity scaling (indicative of SPs), t(79) = -2.65, P ≤ 0.01, as well as decreased ipsilateral t(68) = -3.16, P ≤ 0.001 and contralateral t(68) = -3.32, P ≤ 0.001 putamen volume compared with the healthy control group. Further, decreased velocity scaling was significantly associated with smaller ipsilateral putamen r(68) = 0.23, P ≤ 0.05, 95% confidence interval (CI) (-0.005, 0.44), left r(68) = 0.23, P ≤ 0.05, 95% CI (-0.005, 0.44) and right r(68) = 0.21, P ≤ 0.05, 95% CI (-0.03, 0.42) caudate volume, as well as increased positive r(79) = - 0.20, P = 0.05, 95% CI (-0.40, - 0.02) and negative r(79) = - 0.27, P ≤ 0.05, 95% CI (-0.46, -0.06) symptoms across the sample. These findings represent the first evidence for hypokinetic movement abnormalities in the UHR period, indicating that pathophysiological processes in UHR patients may also involve hypodopaminergia. The results implicate a dopamine-induced imbalance contributing to frontal-subcortical circuit dysfunction in the psychosis prodrome.


Two case reports-Use of relative motion orthoses to manage extensor tendon zones III and IV and sagittal band injuries in adjacent fingers.
Case report. Injuries to adjacent fingers with differing extensor tendon (ET) zones and/or sagittal band pose a challenge to therapists as no treatment guidelines exist. This report highlights how the relative motion flexion/extension (RMF/RME) concepts were combined into one orthosis to manage a zone IV ET repair (RME) and a zone III central slip repair (RMF) in adjacent fingers (Case 1); and how a single RME orthosis was adapted to limit proximal interphalangeal joint motion to manage multi-level ET zone III-IV injuries and a sagittal band repair in adjacent fingers (case 2). Adapted relative motion orthoses allowed early active motion and graded exercises based on clinical reasoning and evidence. Outcomes were standard TAM% and Miller's criteria. 'Excellent' and 'good' outcomes were achieved by twelve weeks post surgery. Both cases returned to unrestricted work at 6 and 7 weeks. Neither reported functional deficits at discharge. Outcomes in 2 cases involving multiple digit injuries exceeded those previously reported for ET zone III-IV repairs. Relative motion orthoses can be adapted and applied to multi-finger injuries, eliminating the need for multiple, bulky or functionally-limiting orthoses. 4.


The Beta-Hydroxybutyrate Suppresses the Migration of Glioma Cells by Inhibition of NLRP3 Inflammasome.
Activation of inflammasome leads to the formation of an inflammatory microenvironment which plays an important role in the process of cancer development. Beta-hydroxybutyrate (BHB) is a ketone body that has recently been reported to exert anti-inflammatory effects via inhibition of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Here, we investigated the potential influence of BHB on the in vitro migration of C6 glioma cells and the activation of NLRP3 inflammasome. Our results indicated that administration of BHB suppressed C6 cells migration and NLRP3 inflammasome activation, reducing the levels of activated cysteinyl aspartate-specific proteinase 1 (caspase-1) and mature Interleukin 1β (IL-1β). Fully activation of NLRP3 inflammasome was induced by lipopolysaccharide (LPS) prime plus adenosine triphosphate (ATP) stimulation in C6 cells, which promoted in vitro migration of C6 cell. BHB also counteracted the LPS/ATP-promoted cell migration by suppressing the activation of caspase-1 and the maturation of IL-1β. The enhancement of phospho-signal transducer and activator of transcription 3 (p-STAT3), degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) as well as the overexpression of fibroblast growth factor 2 (FGF2) resulting from LPS/ATP treatment, and subsequent IL-1β maturation could also be compensated by BHB. Our results suggested that BHB inhibits the activation of NLRP3 inflammasome in C6 glioma cells and consequently suppressed the C6 cell migration. These findings also implicated that by inhibiting NLRP3 inflammasome, BHB reduced the inflammatory microenvironment which provided ancillary therapeutic benefits for the intervention of glioma.


Operant responding for oral ethanol in the alcohol-preferring P and alcohol-nonpreferring NP lines of rats.
Rats of the P (n = 4) and NP (n = 5) lines were housed in operant chambers with food available ad lib, but all liquid was obtained by responding on either of two levers according to a FR5 schedule. Presses on one lever produced water from an automated dipper, while the other lever gave access to a dipper containing ethanol in concentrations ranging from 2 to 30% (v/v). P rats worked to obtain the ethanol at all concentrations offered and preferred the ethanol over water. The highest ethanol intake averaged 7.7 +/- 0.5 g/kg body weight/day at the 15% concentration and at least 5.8 +/- 0.9 g/kg/day for the 20-30% range. The NP rats responded more for the 2 and 5% concentrations of ethanol than for water, but responded predominantly for water when the ethanol concentrations were 10% and higher. In a second experiment, NP rats drank water rather than 10% ethanol by free-choice, even though the ethanol was mixed with a preferred flavor and the water with a nonpreferred flavor. The findings indicate that ethanol is rewarding to P rats in concentrations up to 30% (v/v) but is not rewarding to NP rats when the concentration is 10% and above.


Machine learning for predicting levetiracetam treatment response in temporal lobe epilepsy.
To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach. Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome. A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained. This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy. Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.


Contraception in women with epilepsy: pharmacokinetic interactions, contraceptive options, and management.
Contraceptive counseling is a critical component of the management of the female patient with epilepsy because of the increased risk of pregnancy associated with epilepsy and the multitude of interactions between antiepileptic drugs (AEDs) and hormonal contraception. Steroid hormones and many of the AEDs are substrates for the cytochrome P450 enzyme system, in particular, the 3A4 isoenzyme. As a result, concomitant use of hormonal contraceptives and AEDs may pose a risk for unexpected pregnancy, seizures, and drug-related adverse effects. The risk of combined oral contraceptive (COC) failure is slightly increased in the presence of cytochrome P450 3A4 enzyme-inducing AEDs. Several AEDs induce the production of sex hormone binding globulin (SHBG) to which the progestins are tightly bound, resulting in lower concentrations of free progestin that may also lead to COC failure. There is no increase in the risk of COC failure in women taking nonenzyme-inducing AEDs. Oral contraceptives significantly increase the metabolism of lamotrigine, posing a risk of seizures when hormonal agents are initiated and/or toxicity during pill-free weeks. There is no evidence that COCs increase seizures in women with epilepsy. While higher dose COCs are one contraceptive option for women on enzyme-inducing AEDs, a variety of other options are available. Injectable contraception (depot medroxyprogesterone acetate) appears effective with AED use, but the potential for bone mineral density loss is a concern. Intrauterine devices (IUDs) and barrier methods do not rely on hormonal components for contraceptive efficacy, and are therefore appropriate to recommend for use in women using enzyme-inducing medications. This chapter reviews the evidence regarding the pharmacokinetic interaction between AEDs and oral contraceptive hormones, the known or potential interactions with alternative contraceptive methods, and provides practical advice for management of contraceptive needs in reproductive-age women.


Naturally occurring carbohydrate antibodies: interference in solid-phase immunoassays.
Antibody assays utilizing carbohydrate matrices (agarose, cellulose) for protein insolubilization are subject to non-specific and specific interfering factors. This report examines factors which diminish the quality of particle-based solid-phase radioimmunoassays (SPRIAs) for antigen-specific human IgG. Interfering factors are divided into (a) constant non-specific binding which is similar with all human sera and appears related to simple adherence of IgG to agarose and cellulose, and (b) absorbable binding which varies considerably among sera in agarose and cellulose-based assays, and results from the presence of IgG antibody specific for the carbohydrate matrix. Constant non-specific binding is predictably 1-3% Bmax (maximum binding) in all human and rabbit sera. In contrast, the absorbable binding levels vary widely: 0.75-29% Bmax in 58% (study 1, n = 50) and 40% (study 2, n = 200) of normal individuals for agarose, and 3-30% Bmax in 70% of the population for microcrystalline cellulose. IgG anti-agarose antibodies were found in 13 of 16 rabbit sera examined. Ultracentrifugation and immune-complex studies demonstrated that aggregated or immune-complexed IgG does not contribute to the absorbable IgG binding. Inhibition with acid hydrolyzed soluble agarose and provided evidence for a specific IgG anti-agarose antibody that causes variable background binding. Pre-absorption of sera with agarose prior to analysis in the agarose-based SPRIA removed greater than 90% of anti-agarose antibodies and eliminated false positive results. These studies suggest rabbit and perhaps other heterologous antibodies prepared by protein-agarose affinity column chromatography may contain significant levels of naturally occurring antibodies against agarose or cellulose. These naturally occurring carbohydrate antibodies may interfere in solid-phase carbohydrate-based immunologic methods and immunoassays.


Bromobimanes--fluorescent labeling agents for histochemical detection of sulfur containing neuropeptides in semithin sections.
Sulfur containing neuropeptides could be demonstrated in semithin sections of invertebrate nervous tissue, especially of gastropods, by using the bromobimanes as fluorescent labeling agents for thiol groups. Semithin sections showed a brilliant fluorescence of labeled peptides and should be used if an excellent resolution is important. The three bromobimanes (MB: monobromobimane, DB: dibromobimane, MQ: monobromotrimethylammoniobimane) gave positive results under our experimental conditions. Dibromobimane (DB) was selected because the application is more convenient. In gastropods, the bromobimane technique seems to be the most specific and sensitive one compared to the classical neurosecretory staining methods. Neuropeptides with sulfur containing amino acids could be demonstrated in perikarya, axons, and axon swellings easily. We suppose that there are neurons--not stainable by the classical methods--which can be identified as peptidergic ones by the bromobimane technique. A slight reduction of fluorescence intensity (fading) was observed. So, the fading rate was determined for dibromobimane reaction products; a decrease in the fluorescence intensity of 50% was only reached after 1 h using a Neofluar objective 10/0.30. Nevertheless, we suppose that a comparative quantification of the labeled neuropeptides should be possible if special parameters are considered.


[Role of genetic processes in modification variability. Prophecy of B.L. Astaurov].
In his pioneering work on mutation tetraptera in Drosophila melanogaster, B.L. Astaurov discovered spontaneous modifications based on variability in gene expression. This new approach to the phenomenon of modifications should be considered as the first stimulus to development of the general theory of variability. Contemporary classification of variability based predominantly on phenomenology encounters many contradictions. The same specific molecular mechanisms may be responsible, for example, for both hereditary and nonhereditary variability depending on the taxonomic status. Some mechanisms responsible for both mutations and modifications or for mutations, recombination, and ontogenetic variability have been considered from this viewpoint. It may well be more productive to consider different types of variability with respect to the main genetic processes: replication and expression of genetic material.


Community Health Worker Perspectives on Recruitment and Retention of Recent Immigrant Women in a Randomized Clinical Trial.
This study explores the recruitment and retention strategies used by community health workers who enrolled Korean Americans in a church-based, randomized trial to promote mammogram and Papanicolaou tests and retained them for 6 months. We conducted 4 focus groups with 23 community health workers. Data were analyzed using a thematic analysis. Themes were identified in relation to recruitment: personal networks, formal networks at churches, building on trust and respect, and facilitating a nonthreatening environment. Themes were identified for retention: trust and peer support. Qualified, well-trained community health workers can recruit and retain hard-to-reach immigrant women in a randomized trial by using multiple culturally sensitive strategies.


Effect of pupil size and astigmatism on contrast acuity with monofocal and bifocal intraocular lenses.
We conducted a bicenter study to evaluate the effect of pupil size and corneal astigmatism on best corrected contrast acuity (BCCA) in patients with the True Vista bifocal intraocular lens (IOL) and compared the results with those in a matched group of monofocal patients. Best corrected contrast acuity was measured using the Regan Charts (96%, 50%, 25%, 11%) at four pupil sizes (2.0, 2.5, 3.5, 6.0 mm) in three groups (Group 1: corneal astigmatism 0-0.50 D [n = 11]; Group 2: 0.75-1.50 D [n = 11]; Group 3: 1.75-2.50 D [n = 4]). In monofocal eyes, BCCA between these astigmatic groups did not differ significantly at any contrast step or at any pupil size tested. However, BCCA decreased slightly with increasing pupil size in each group, and differences between 2.00 mm and 6.0 mm pupils were significant at each contrast level. In all bifocal groups, BCCA decreased significantly with increasing pupil size and also decreased with increasing corneal astigmatism; differences were significant at most pupil sizes and contrasts tested. In Group 1, BCCA was lower in eyes with bifocal IOLs than in eyes with monofocal IOLs at 25% and 11% contrast with a 2.5, 3.5, and 6.0 mm pupil; with a 2.0 mm pupil it did not differ significantly. In Groups 2 and 3, BCCA in eyes with bifocal IOLs was lower at all contrast steps and all pupil sizes tested. Our results indicate that corneal astigmatism in excess of 0.50 D reduces quality of vision in eyes with bifocal IOLs, while eyes with monofocal IOLs are not affected.(ABSTRACT TRUNCATED AT 250 WORDS)


Circulating erythroid progenitors in normal and anemic rabbits.
The position of circulating blood erythroid progenitors in the erythroid maturation sequence was determined in rabbits. The erythroid progenitors in blood appeared to be the same as the earliest class of erythroid progenitors detectable in bone marrow on the basis of time course studies of colony formation by blood and marrow cells in vitro. This result was confirmed by the ability of circulating erythroid progenitors to respond to the early erythroid regulator burst-promoting activity with an increase in colony number and 59Fe incorporation into heme. Induction of anemia with phenylhydrazine resulted in large increases in early erythroid progenitor frequency in blood and an influx of more mature progenitors (intermediate BFU-E and CFU-E). Circulating erythroid progenitors in rabbits may be an interesting model for the study of human disorders of erythropoiesis.


Genetic association of polymorphisms at the intergenic region between PRDM1 and ATG5 with hepatitis B virus infection in Han Chinese patients.
Chronic hepatitis B virus (HBV) infection is related to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and the interplay between the virus and host immune response leads to different outcomes of the infection. PR domain zinc finger protein 1 (PRDM1) and autophagy-related protein 5 (ATG5) are involved in immune response and HBV infection. An intergenic region between PRDM1 and ATG5 (PRDM1-ATG5 region) has been identified, and single-nucleotide polymorphisms (SNPs) in this region were shown to be involved in immune regulation. This study investigated the functionally relevant rs548234, rs6937876, and rs6568431 polymorphisms at the PRDM1-ATG5 region in a Han Chinese population (403 patients with chronic HBV infection [171 chronic hepatitis, 119 cirrhosis, and 113 HCC], 70 infection resolvers, and 196 healthy controls). The frequencies of the rs6568431 allele A in HBV patients (P = .005) and genotype CA in infection resolvers (P = .005) were significantly higher than in healthy controls. In the dominant model, HCC patients had significantly higher frequencies of rs548234 genotypes CC + TC than cirrhosis patients (P = .009). Rs548234 was an independent factor for HCC in comparison with either cirrhosis (P = .005) or all chronic HBV infection without HCC (P = .018). Functional annotation showed evidence of the role of the SNPs in gene regulation. In conclusion, through this study it is revealed for the first time that rs6568431 may be associated with susceptibility to HBV infection and that rs548234 may be associated with HCC risk in chronic HBV infection, supporting the presence of HBV-related disease-causing regulatory polymorphisms in the PRDM1-ATG5 intergenic region.


Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness.
The aim of this study was to evaluate myocardial function using pulsed and color-coded tissue Doppler imaging (TDI) and vascular wall elasticity using whole-body impedance cardiography (ICG) in patients with newly diagnosed Type 2 diabetes mellitus (DM2), and to compare the measurements with those of healthy controls. Systolic (SBP) and diastolic (DBP) blood pressure and glycosylated hemoglobin (HbA1c) were measured in 49 men (mean age 52.3+/-5.6 years, duration of DM2 1.8 years), and 15 healthy male control subjects (48.3+/-7.4 years). Mitral annular peak systolic (Svm), early (Evm), and late (Avm) diastolic velocities as well as myocardial peak systolic (Sv), early (Ev) and late diastolic (Av) velocity from middle segments of the anterior, inferior and lateral wall and the inferior septum were measured by TDI. ICG at rest was used to measure cardiac index (CI) and pulse wave velocity (PWV). The patients had higher body mass index (BMI 29.1+/-3.7 vs. 25.2+/-2.4 kg/m(2), p=0.000) and SBP (142+/-15 vs. 120+/-7 mmHg, p=0.005) than the controls, CI was comparable (2.8+/-0.5 vs. 2.8+/-0.6l/min/m(2)). The patients had lower age adjusted myocardial Sv (3.8+/-1.1 vs. 4.8+/-1.1cm/s, p=0.002) and Ev (4.6+/-1.6 vs. 6.2+/-1.7 cm/s, p=0.011), and also mitral annulus peak early diastolic velocity (Evm 7.8+/-1.9 vs. 10.4+/-2.6 cm/s, p=0.001). In diabetic patients PWV (14.2+/-2.7 vs. 10.0+/-1.7 m/s, p=0.002) was higher. Age (r=-0.39, p=0.001), BMI (r=-0.44, p=0.000) and PWV (r=-0.52, p=0.000) correlated significantly with Evm. PWV correlated with age (r=0.50, p=0.000), SBP (r=0.67, p=0.000), and HBA1c (r=0.36, p=0.010). In stepwise regression analysis, PWV (beta=-0.39, p=0.000) was the major determinant of Evm. Myocardial function is impaired in asymptomatic patients with newly detected DM2 consistent with diabetic heart muscle disease. Arterial stiffness is strongly related to myocardial dynamics, and both may have the same pathophysiologic background.


The Ethics of induction of Labor at 39 Weeks in Low-Risk Nulliparas in Research and Clinical Practice.
The ARRIVE trial published in 2018 suggested that induction of labor can be considered a "reasonable option" for low-risk nulliparous women at 39 or more weeks of gestation. These results led some professional societies to endorse the option for elective induction of labor at 39 weeks in low-risk nulliparas, and this has begun to change obstetrical practice. The ARRIVE trial provided valuable information supporting the benefits of induction but is insufficient to serve as the primary justification for widespread elective induction of labor at 39 weeks in low-risk nulliparas due to concerns about external validity. Thus, French ARRIVE was designed to test the hypothesis in a different setting that elective induction of labor at 39 weeks in low-risk nulliparas leads to a lower cesarean delivery rate compared to expectant management. This ongoing trial has been criticized as "pseudo-scientific," and telling "women where, when and how to give birth." We reject these allegations and critically examine the ethical framework that should govern clinical and research interventions including elective induction of labor at 39 weeks in low-risk nulliparas. This article aims to discuss the ethical issues that emerge from randomized trials of elective induction of labor at 39 weeks in low-risk nulliparas, as well as the ethics of the clinical practice itself. Analysis of existing evidence shows the importance of further research on induction of labor at 39 weeks in low-risk women. Certain aspects of research ethics in this area, in particular the consent of pregnant women in a context where autonomy remains fragile, calls for vigilance. We also emphasize that childbirth is not only a medical object but also a social phenomenon that cannot be regarded only from the perspective of a health risk to be managed by clinical research. Further research on this issue is needed to allow pregnant women to make informed decisions, and the results should be integrated with social issues. The perspective of women is required in constructing, evaluating, and implementing medical interventions in childbirth such as induction of labor at 39 weeks.


Familial transmission of preauricular fistula in a seven generation Indian pedigree.
Familial occurrence of fistula auris congenita (ear pits) is described in a Muslin kindred of Indian origin. The pedigree was traced through seven generations. The abnormality appeared in sixty individuals comparising equal number of males and females. No sexual dimorphism was indicated in the expression of the trait, which occurred bilaterally as a small pit just anterior to the crus at the root of the ascending helix. The abnormality was found to be inherited through an autosomal dominant gene with incomplete penetrance. The expression of the trait does not show any dosage effect.


Facile syntheses of BODIPY derivatives for fluorescent labeling of the 3' and 5' ends of RNAs.
As inexpensive and readily available fluorophores for 3' and 5' end labeling of RNA molecules, symmetrical BODIPY (boron dipyrromethene: 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) derivatives having a primary amino group were designed, and their facile synthetic route was established. Novel BODIPY derivatives exhibited photophysical properties comparable to commercially available BODIPY FL EDA (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl ethylenediamine). To confirm utility of new derivatives, specific labeling of the 3' and 5' ends of in vitro transcribed RNAs was carried out. Furthermore, the 3' end of the 5' fragment of the bimolecular Tetrahymena ribozyme was labeled, and its catalytic activity was investigated.


Identifying weak interdomain interactions that stabilize the supertertiary structure of the N-terminal tandem PDZ domains of PSD-95.
Previous studies of the N-terminal PDZ tandem from PSD-95 produced divergent models and failed to identify interdomain contacts stabilizing the structure. We used ensemble and single-molecule FRET along with replica-exchange molecular dynamics to fully characterize the energy landscape. Simulations and experiments identified two conformations: an open-like conformation with a small contact interface stabilized by salt bridges, and a closed-like conformation with a larger contact interface stabilized by surface-exposed hydrophobic residues. Both interfaces were confirmed experimentally. Proximity of interdomain contacts to the binding pockets may explain the observed coupling between conformation and binding. The low-energy barrier between conformations allows submillisecond dynamics, which were time-averaged in previous NMR and FRET studies. Moreover, the small contact interfaces were likely overridden by lattice contacts as crystal structures were rarely sampled in simulations. Our hybrid approach can identify transient interdomain interactions, which are abundant in multidomain proteins yet often obscured by dynamic averaging.


Discrimination analysis of discontinuous breath sounds using higher-order crossings.
The paper evaluates the performance of an automatic discrimination analysis (DA) method used to discriminate efficiently the types of discontinuous breath sound (DBS), i.e. fine crackles (FCs), coarse crackles (CCs) and squawks (SQs); this may lead to more accurate characterisation of the pulmonary acoustical changes due to the related pathology. Based on higher-order crossings (HOCs), the proposed method, HOC-DA, captured the differences in the oscillatory patterns of FCs, CCs and SQs, which are only exposed when higher (> 1) crossings are employed. Prior to HOC-DA, wavelet-based de-noising of DBSs was employed to eliminate the effects of the vesicular sound (background noise) from their oscillatory pattern. The HOC-DA was applied to 157 discontinuous breath sounds corresponding to 16 cases included in three lung sound databases. Results showed that the HOC-DA efficiently separated FCs from CCs, SQs from CCs (both with an accuracy of 100%), and SQs from FCs (accuracy of 80%), with the optimum order ranging from 9 to 11. When compared with other classification tools, the HOC-DA resulted in high discrimination accuracy without involving high computational complexity. Owing to its simplicity, it could be implemented in a real-time context and be used in clinical medicine as a module of an integrated intelligent patient evaluation system.


Cue-induced resumption of heroin and cocaine seeking in rats using a conflict model of abstinence and relapse.
Most animal research on drug relapse involves the reinstatement model where abstinence is a result of drug removal (extinction). However, abstinence in humans often results from the aversive consequences that accompany drug seeking (conflict situation). This study was aimed at using a conflict-based animal model of abstinence/relapse in rats self-administering heroin or cocaine. Rats were trained to self-administer heroin (0.05 mg kg(-1) injection(-1)) or cocaine (0.5 mg kg(-1) injection(-1)) with each injection paired with a light cue. After stable responding was demonstrated, the floor near the levers was electrified, creating a barrier, in order to model the negative consequences of continued drug seeking. Shock intensities were increased over sessions until no responses occurred for three consecutive sessions. During a relapse test, where shock was maintained,the capacity of noncontingent drug cue presentations to induce active lever pressing was assessed. Ten of ten heroin animals and three of eight cocaine animals exposed to noncontingent cue presentations resumed responding. During the relapse test, for both drug groups, active lever pressing was significantly higher than during abstinence but only in the heroin group was it significantly higher than inactive lever pressing. The implementation of negative consequences for drug seeking can result in its cessation just as they might in human addicts. Similarly, exposure to drug cues can lead to resumption of drug seeking. This model may be useful for studying the mechanisms underlying abstinence and relapse and for developing strategies to prevent relapse.


17beta-estradiol stimulates MAPK signaling pathway in human lens epithelial cell cultures preventing collapse of mitochondrial membrane potential during acute oxidative stress.
17beta-estradiol (17beta-E2) protects against H2O2-mediated depletion of intracellular ATP and lessens the degree of depolarization of mitochondrial membrane potential (DeltaPsi(m)) in cultured lens epithelial cells consequential to oxidative insult. We now report that 17beta-E2 acts as a positive regulator of the survival signal transduction pathway, MAPK which, in turn, acts to stabilize DeltaPsi(m) in effect, attenuating the extent of depolarization of mitochondrial membrane potential in the face of acute oxidative stress. The SV-40 viral transformed human cell line, HLE-B3 was treated with 17beta-E2 over a time course of 60 min and phosphorylation of ERK1/2 was analyzed by Western blot. ERK1/2 was phosphorylated within 5-15 min in the presence of 17beta-E2. Cell cultures were exposed to the MEK1/2 inhibitor, UO126, subsequent to H2O2+/-17beta-E2 treatment and the DeltaPsi(m) examined using JC-1, a potentiometric dye which serves as an indicator for the state of mitochondrial membrane potential. UO126 treatment attenuated ERK1/2 phosphorylation irrespective of whether estradiol was administered. Mitochondrial membrane depolarization resulting from H2O2 stress was substantially greater in the presence of UO126. The greater the extent of depolarization, the less effective 17beta-E2 treatment was in checking mitochondrial membrane depolarization, indicating that the relative degree of ERK phosphorylation influences mitochondrial stability with oxidative insult. The data support a positive correlation between 17beta-E2 stimulation of ERK1/2 phosphorylation and mitochondrial stabilization that would otherwise cause a complete collapse of DeltaPsi(m).


Menin and bone metabolism.
Menin, a product of the MEN1 gene, is related to the ontogeny of several cancers such as MEN1 and sporadic endocrine tumors, although it is considered to be a tumor suppressor. Many proteins interact with menin, and it is involved in various biological functions in several tissues. Menin plays some physiological and pathological roles related to transforming growth factor-beta (TGF-β) signaling pathway in the parathyroid, and it is implicated in the tumorigenesis of parathyroid tumors. In bone, the bone phenotype was observed in some menin-deleted mice. Menin is considered to support BMP-2- and Runx2-induced differentiation of mesenchymal cells into osteoblasts by interacting with Smad1/5, Runx2, β-catenin and LEF-1, although it has different effects on osteoblasts at later differentiation stages through TGF-β-Smad3 and AP-1 pathways. Further research is expected to shed more light on the role of menin in bone.


Early detection and simplified management of obstructed Hickman and Broviac catheters.
Thrombotic occlusion of Hickman and Broviac central venous catheters is a serious obstacle to their long-term use. Because resistance to flow (R) through a catheter of lumen radius, r, is proportional to 1/r4, we hypothesized that measurement of R would provide an objective and sensitive monitor for partial occlusions. Our measurements showed that median R at a flow of 17 mL/min was 0.7 cmH2O/mL/min in normally functioning Hickman catheters, and 4.1 cmH2O/mL/min in Broviac catheters. In obstructed catheters, which by subjective standards resisted flushing or blood withdrawal, median R was 3.0 cmH2O/mL/min for Hickman and 5.6 cmH2O/mL/min for Broviac catheters, representing significant increases. In a series of obstructed lines in which urokinase was administered, R decreased from 7.7 to 4.5 in Hickman catheters and from 5.6 to 4.2 in obstructed Broviac catheters. The elevated resistance in Hickman catheters after urokinase suggested that residual catheter obstruction was present even though catheter function returned to normal. Elevated R was seen with abnormal venograms in seven of 13 patients. Four patients had normal R values and abnormal venograms, and two patients had elevated R values with normal venograms. Measurement of resistance in Hickman and Broviac catheters provides a simple technique that can supplement or replace venography in the serial assessment and treatment of partial obstruction.


Fluid distribution measurement between body compartments in primates in disclosing fluid retention during prolonged hypokinesia.
Body fluid homeostasis undergoes significant changes during hypokinesia (diminished movement). Understanding of fluid transfer between body fluid compartments and its regulating mechanisms was the aim of this study for disclosing impaired fluid retention during hypokinesia (HK). Studies were done on 12 male Macaca mulatta (rhesus monkeys) aged three to five years (5.15 to 6.56 kg) during 90 days period of pre-HK and 90 days period of HK. All primates were divided equally into two groups: vivarium control primates (VCP) and hypokinetic primates (HKP). Hypokinetic primates were kept for 90 days in small individual cages that restricted their movements in all directions without hindering food and fluid intakes. Control primates were housed in individual cages without their movements being restricted. Total body fluid (TBF), intracellular fluid volume (IFV) and circulating plasma volume (CPV) decreased significantly (p < 0.05), while extracellular fluid volume (EFV) and interstitial fluid volume (IsFV) decreased significantly (p < 0.05) at the initial seven days of the HK period and after the 7th day increase progressively in HKP compared with their pre-HK values and their respective control values in VCP. Fluid excretion, urinary and plasma sodium (Na) and potassium (K) levels increased significantly (p < 0.05), while fluid intake and fluid retention decreased significantly (p < 0.05) in HKP compared with their pre-HK values and their respective controls in VCP. The measured parameters did not change in VCP compared with their pre-HK values. It was concluded that decreased IFV and CPV may demonstrate fluid depletion, while marked increase of fluid loss despite of fluid depletion may demonstrate impair fluid retention during HK. Dissociation between fluid loss and fluid depletion may demonstrate the presence of reduced fluid retention as the mechanism of development of fluid depletion during HK.


Conditions required for citrate utilization during growth of Lactobacillus casei ATCC334 in chemically defined medium and cheddar cheese extract.
Conditions required for citrate utilization by Lactobacillus casei ATCC334 were identified. Citrate was utilized by this microorganism in modified Chemically Defined Media (mCDM) as an energy source, solely in the presence of limiting concentrations of galactose. The presence of glucose inhibited citrate utilization by this microorganism even when added in limiting concentrations. Utilization of citrate occurred at pH 6.0 +/- 0.2 and 5.1 +/- 0.2. Together these observations suggest that citrate is an energy source for L. casei in ripening cheese only when the residual levels of carbohydrate post-fermentation are limiting (<2.5 mM), and lactose or glucose are absent. However, citrate utilization by this organism was observed in Cheddar cheese extract (CCE), which naturally contains both lactose and galactose, at the beginning of late-logarithmic phase and regardless of the galactose concentration present in the media.


Randomization to a Provided Higher-Complex-Carbohydrate Versus Conventional Diet in Gestational Diabetes Mellitus Results in Similar Newborn Adiposity.
Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet. After diagnosis (at ∼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days). There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation. A ∼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM.


Immunoglobulin concentrations in Scottish Blackface lambs on a hill farm.
The serum immunoglobulin concentration in one- to 11-day-old Scottish Blackface lambs born outdoors on a hill farm were very similar to those in Scottish Blackface lambs born indoors on an experimental lowland farm. The concentrations were significantly higher in single lambs than in twins, and in lambs which survived for six months than in lambs which died, and showed significant annual variations which could not be related to the weather. They were significantly correlated with the ages of the dams, the lambs' gains in weight to weaning, but not with the weights or ratios of weights of the lambs and ewes after lambing, nor with the birth-coat types of sexes of the lambs. There were wide variations in the capacities of the abomasums at birth.


Under-detection of acute kidney injury in hospitalised patients: a retrospective, multi-site, longitudinal study.
Acute kidney injury (AKI) is a rapid deterioration of renal function, often caused by a variety of co-existing morbidities complicating its recognition and treatment, leading to short- and long-term adverse clinical outcomes. There are limited data on the incidence of AKI in Australia using the Kidney Disease Improving Global Outcomes creatinine-based consensus definition. To determine the incidence and estimate the extent of under-reporting of AKI in four hospitals in the South-Eastern Sydney/Illawarra regions of New South Wales, Australia. A laboratory algorithm based on the Kidney Disease Improving Global Outcomes creatinine-based definition for AKI was applied retrospectively to laboratory data for adult patients admitted to the study hospitals between 2009 and 2013 to identify those with AKI. The results were compared with the incidence of AKI based on diagnostic codes for AKI reported for the same period. AKI was detected in 12.4% of all hospitalisations (46 101/370 969) and 16.4% of patients (31 448/192 133) across the 5-year study period using the laboratory algorithm. Of these, 72.1% were AKI Stage 1 (33 246/46101). AKI was coded in only 15.9% of hospitalisations with AKI Stage 1 (5294/33 246), 38.5% of hospitalisations with Stage 2 (2381/6185), and 46.8% with Stage 3 (3120/6670). Yearly incidence of laboratory-identified AKI trended downward between 2009 and 2013, while annual incidence determined by coding trended upward. Although coding trends suggested a continuous increase in clinician awareness of AKI across the study period, AKI in hospitalised patients remained significantly under-reported.


Pharmacokinetic optimisation of antibacterial treatment in patients with cystic fibrosis. Current practice and suggestions for future directions.
Antibacterials play a central role in the medical management of patients with cystic fibrosis (CF). Administration of adequate dosages of antibacterials results in pronounced beneficial effects on the morbidity and mortality of this patient group. The dosage of the antibacterial that is needed for optimal treatment depends on the individual patient's pharmacokinetics and the pharmacokinetic-pharmacodynamic effect on the micro-organism of relevance in the host. In general, the disposition of antibacterial drugs in patients with CF is not as 'atypical' as once thought. Recent research with adequately matched controls demonstrated that, for a few beta-lactam antibacterials only, a CF-specific increase of the total body clearance seems to exist and that the large volumes of distribution observed are the result of malnutrition and the relative lack of adipose tissue. Pharmacokinetic-pharmacodynamic relationships in patients with CF are less well studied. Apart from the pharmacokinetics, there is a need for optimisation of antibacterial therapy. For the aminoglycosides, pharmacokinetic optimisation based on measured serum drug concentrations is common practice. The Sawchuk-Zaske method based on peak and trough drug concentrations is widely used. A more sophisticated approach is the 'goal-oriented model-based Bayesian adaptive control' method, where integration of mathematically determined optimally (D-optimally) sampled serum drug concentrations and a population model results in the most likely set of individual pharmacokinetic parameter values suitable for further pharmacokinetic optimisation of the therapy. A future development is the integration of changing serum drug concentrations and killing rates of the target micro-organism to a pharmacokinetic-pharmacodynamic surrogate relationship to optimise drug therapy. The latter approach may be extremely useful in deciding on the frequency of aminoglycoside administration as well as the optimal use of the beta-lactam antibacterials and fluoroquinolones.


Decreased sensitivity to insulin in white adipose tissue from adrenalectomised rats.
The ability of insulin to increase both [14C]-glucose incorporation into fatty acids and pyruvate dehydrogenase activity in incubated rat epididymal adipose tissues was considerably lessened after adrenalectomy. Insulin antagonism of adrenaline-stimulated lipolysis in isolated fat cells was abolished after adrenalectomy. Percentage stimulation of lipolysis above basal by adrenaline was not appreciably altered by adrenalectomy.


Ultrasound-guided anatomical liver resection using a compression technique combined with indocyanine green fluorescence imaging.
Anatomical resection (AR) is a recommended surgical treatment for hepatocellular carcinoma (HCC). However, the conventional procedure (dye injection) for AR is difficult to reproduce. As an alternative, the tumour-feeding portal pedicle compression technique (finger-compression technique) has been proposed as an easy and reversible procedure. Here, we propose a new method combining indocyanine green (ICG) imaging with the finger-compression technique. Eligible patients were prospectively enrolled to undergo ICG compression (ICG-C) anatomical hepatectomy for HCC. Fifteen patients underwent AR using the ICG-C technique. Overall, the surgical procedures included six segmentectomies, seven subsegmentectomies, and two right posterior sectionectomies. The median tumour size was 5.8 cm (range 2-7 cm). All procedures had an R0 margin. There were no major complications among patients, and minor morbidity occurred in three patients. ICG-C is a safe, feasible and effective technique for patients eligible for AR.


Six patient-reported outcome measurement information system short form measures have negligible age- or diagnosis-related differential item functioning in individuals with disabilities.
To evaluate the measurement invariance of 6 self-report measures selected for an ongoing longitudinal study of individuals with spinal cord injury, muscular dystrophy, postpolio syndrome, and multiple sclerosis. Participants completed and returned by mail surveys that included the targeted self-report measures. Ordinal logistic regressions methods were applied to evaluate items for differential item functioning (DIF) by diagnosis and age range. Community. Participants (N=2479) who had 1 of the 4 target diagnoses. None. Six short-form measures from the Patient-Reported Outcome Measurement Information System (PROMIS) were administered to participants to measure fatigue, pain interference, satisfaction with social roles, sleep disturbance, sleep-related impairment, and depression. One item of 1 measure (fatigue) exhibited DIF by diagnosis based on a published standard for meaningful DIF. However, scores corrected for this DIF were highly correlated with uncorrected scores (r>.999). No DIF by age range was found for any of the measures. Study findings support the use of the selected PROMIS short forms for comparing symptoms and quality of life indicators across different diagnoses and age ranges.


Fallopian tube microvasculature in the rabbit.
The microvascular architecture of rabbit Fallopian tube isthmic, ampullary and fimbrial regions was examined by the corrosion vascular cast-scanning electron microscope method. The aorta and inferior vena cava of virgin adult female rabbits (2.5-3.5 kg) were cannulated; after blood wash out, methacrylate casting medium was infused via the aorta. After plastic hardening, Fallopian tubes were excised, tissues corroded and casts prepared for scanning electron microscopy. The isthmic myosalpinx is encircled subserosally by an interlocking venous plexus. We suggest that a rise in pelvic venous pressure could lead to a decrease in isthmic luminal diameter and thus act as a sphincter contributing to the known delay in ovum transport at the ampullary isthmic junction. Stereo pairs of photomicrographs showed that isthmic plicae are supplied by arterioles which change little in diameter passing through the tubal wall. Near the apex of a fold, these arterioles terminate in a subepithelial capillary plexus which drains to deep mucosal and plical core venules. In contrast, the ampulla is supplied by smaller and less frequent arterioles. Frequent large venules extending high into the plicae drain the subepithelial capillary plexus. Based on this microvascular architecture, we suggest that the subepithelial capillary plexus of the apical region of the plicae probably contains high pressure blood in the isthmus and lower pressure blood in the ampulla. Therefore, plicae in these regions may be specialised for net luminal fluid secretion and absorption respectively, implying a role for the microvasculature in tubal transport by initiation or modification of fluid flow along the lumen.