Gut microbiome signatures distinguish type 2 diabetes mellitus from non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus (T2D), and these two metabolic diseases demonstrate bidirectional influences. The identification of microbiome profiles that are specific to liver injury or impaired glucose metabolism may assist understanding of the role of the gut microbiota in the relationship between NAFLD and T2D. Here, we studied a biopsy-proven Asian NAFLD cohort (n = 329; 187 participants with NAFLD, 101 with NAFLD and T2D, and 41 with neither) and identified Enterobacter, Romboutsia, and Clostridium sensu stricto as the principal taxa associated with the severity of NAFLD and T2D, whereas Ruminococcus and Megamonas were specific to NAFLD. In particular, the taxa that were associated with both severe liver pathology and T2D were also significantly associated with markers of diabetes, such as fasting blood glucose and Hb1Ac. Enterotype analysis demonstrated that participants with NAFLD had a significantly higher proportion of Bacteroides and a lower proportion of Ruminococcus than a Korean healthy twin cohort (n = 756). However, T2D could not be clearly distinguished from NAFLD. Analysis of an independent T2D cohort (n = 185) permitted us to validate the T2D-specific bacterial signature identified in the NAFLD cohort. Functional inference analysis revealed that endotoxin biosynthesis pathways were significantly enriched in participants with NAFLD and T2D, compared with those with NAFLD alone. These findings may assist with the development of effective therapeutic approaches for metabolic diseases that are associated with specific bacterial signatures.


Dispositional optimism: a psychological resource for Mexican-origin mothers experiencing economic stress.
Dispositional optimism is believed to be an important psychological resource that buffers families against the deleterious consequences of economic adversity. Using data from a longitudinal study of Mexican-origin families (N = 674), we tested a family stress model specifying that maternal dispositional optimism and economic pressure affect maternal internalizing symptoms, which, in turn, affects parenting behaviors and children's social adjustment. As predicted, maternal optimism and economic pressure had both independent and interactive effects on maternal internalizing symptoms, and the effects of these variables on changes over time in child social adjustment were mediated by nurturant and involved parenting. The findings replicate and extend previous research on single-parent African American families (Taylor, Larsen-Rife, Conger, Widaman, & Cutrona, 2010), and demonstrate the generalizability of the positive benefits of dispositional optimism in another ethnic group and type of family structure.


Successful treatment of uncomplicated gonococcal urethritis in HIV-infected patients with single-dose oral cefpodoxime.
Fluoroquinolones are no longer recommended for the treatment of gonococcal infections in the United States. Cephalosporins - ceftriaxone and cefixime - are the treatment of choice, as suggested by the Centers for Disease Control and Prevention (USA). There are limited data on the efficacy of cefpodoxime for the treatment of uncomplicated gonococcal infections. Two cases of HIV-infected homosexual men who were successfully treated with cefpodoxime for urethritis caused by Neisseria gonorrhoeae are described in the present study.


Developmental changes in hepatic activation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rabbit.
MeIQx, a potent bacterial mutagen formed when meat is cooked, requires metabolic activation to exert its genotoxicity, a reaction catalysed primarily by CYP1A2 in adult mammals. Little is known about mammalian developmental changes in the mutagneic activation of compounds such as MeIQx. In rabbits we have shown previously that expression of CYP1A2 increases with age and is inducible by 3-methylcholanthrene (MC) from as early as 4 days pre-parturition. We have therefore investigated the effect of age on rabbit liver activation of MeIQx (assessed in an Ames test using Salmonella typhimurium TA98) before and after treatment of the animals with MC. MeIQx activation could not be detected using hepatic microsomal fractions from rabbits of <17 days of age. Thereafter activation increased with age to peak in weanling animals. Following MC treatment MeIQx activation was increased, being detectable in samples from rabbits as young as 9-11 days. The inducibility of MeIQx activation increased with age, reaching a plateau between 17 and 35 days. These rates of activation were broadly parallel to the changes in CYP1A2 specific content. These results indicate that the ability of rabbit liver to activate MeIQx is dependent on CYP1A2 activity, the expression of which is developmentally regulated. Although it has been established that human activation of MeIQx is also CYP1A2 dependent, whether a similar situation exists in infant humans has yet to be determined, although there is evidence that CYP1A2-dependent activity reaches a peak in late childhood.


Protease-catalyzed hydrolysis of substrate mimetics (inverse substrates): A new approach reveals a new mechanism.
Contrary to common protease substrates, the hydrolysis of 4-guanidinophenyl esters of the Boc-Xaa-OGp type by trypsin and trypsin-like proteases performs easily and independently of the structure and chirality of the acyl moiety. The hydrolysis of this new class of substrate mimetics, previously called inverse substrates, is enabled by the highly specific leaving group. However, the mechanism cannot be explained on the basis of the conventional binding model which defines the interactions between the protease and its substrate. Hydrolysis and aminolysis kinetics, protein-ligand docking, and molecular dynamics studies have been carried out in order to get insight into the catalytic mechanism which holds for these substrate mimetics. The experimental and theoretical results obtained for the serine protease trypsin suggest a novel extended kinetic model. It explains the hydrolysis of these types of protease substrates and accounts for the structural consequences for their aminolysis.


Novel cyanobacterial biosensor for detection of herbicides.
The aim of this work was to generate a cyanobacterial biosensor that could be used to detect herbicides and other environmental pollutants. A representative freshwater cyanobacterium, Synechocystis sp. strain PCC6803, was chromosomally marked with the luciferase gene luc (from the firefly Photinus pyralis) to create a novel bioluminescent cyanobacterial strain. Successful expression of the luc gene during growth of Synechocystis sp. strain PCC6803 cultures was characterized by measuring optical density and bioluminescence. Bioluminescence was optimized with regard to uptake of the luciferase substrate, luciferin, and the physiology of the cyanobacterium. Bioassays demonstrated that a novel luminescent cyanobacterial biosensor has been developed which responded to a range of compounds including different herbicide types and other toxins. This biosensor is expected to provide new opportunities for the rapid screening of environmental samples or for the investigation of potential environmental damage.


Modeling Adipogenesis: Current and Future Perspective.
Adipose tissue is contemplated as a dynamic organ that plays key roles in the human body. Adipogenesis is the process by which adipocytes develop from adipose-derived stem cells to form the adipose tissue. Adipose-derived stem cells' differentiation serves well beyond the simple goal of producing new adipocytes. Indeed, with the current immense biotechnological advances, the most critical role of adipose-derived stem cells remains their tremendous potential in the field of regenerative medicine. This review focuses on examining the physiological importance of adipogenesis, the current approaches that are employed to model this tightly controlled phenomenon, and the crucial role of adipogenesis in elucidating the pathophysiology and potential treatment modalities of human diseases. The future of adipogenesis is centered around its crucial role in regenerative and personalized medicine.


A Comparison of the Surface Polysaccharides from Rhizobium leguminosarum 128C53 smrif with the Surface Polysaccharides from Its Exo Mutant.
The surface polysaccharides of Rhizobium leguminosarum 128C53 sm(r)rif(r) (parent) and its exo(-1) mutant were isolated and characterized. The parent carries out normal symbiosis with its host, pea, while the exo(-1) mutant does not nodulate the pea. The following observations were made. (a) The parent produces lipopolysaccharide (LPS), typical acidic extracellular polysaccharide (EPS), and three additional polysaccharides, PS1, PS2, and PS3. The PS1 and PS2 fractions are likely to be the capsular polysaccharide (CPS) and are identical in composition to the EPS. The PS3 fraction is a small-molecular-weight glucan. (b) The exo(-1) mutant produces LPS, EPS, and a PS3 fraction, but does not produce significant amounts of either PS1 or PS2. The LPS from the exo(-1) mutant appears to be identical to the parental LPS. Analysis of the EPS from exo(-1) shows that it consists of two polysaccharides. One polysaccharide is identical to the LPS and comprises 70% of the exo(-1) EPS. The second polysaccharide is identical to the exo(-1) PS3 and comprises 30% of the exo(-1) EPS. This result shows that the exo(-1) mutant does not produce any of the typical acidic parental EPS and that the major polysaccharide released into the media by the exo(-1) mutant is intact LPS. The exo(-1) mutant PS3 fraction was found to contain two polysaccharides, PS3-1 and PS3-2. The PS3-2 polysaccharide is identical to the parental PS3 described above. The PS3-1 polysaccharide has a composition similar to the polysaccharide portion of the LPS. This result suggests that the exo(-1) mutant produces LPS polysaccharide fragments. These LPS polysaccharide fragments are not produced by the parent strain.


Myogenic tone in mouse mesenteric arteries: evidence for P2Y receptor-mediated, Na(+), K (+), 2Cl (-) cotransport-dependent signaling.
This study examines the action of agonists and antagonists of P2 receptors on mouse mesenteric artery contractions and the possible involvement of these signaling pathways in myogenic tone (MT) evoked by elevated intraluminal pressure. Both ATP and its non-hydrolyzed analog alpha,beta-ATP triggered transient contractions that were sharply decreased in the presence of NF023, a potent antagonist of P2X(1) receptors. In contrast, UTP and UDP elicited sustained contractions which were suppressed by MRS2567, a selective antagonist of P2Y(6) receptors. Inhibition of Na(+), K(+), 2Cl(-) cotransport (NKCC) with bumetanide led to attenuation of contractions in UTP- but not ATP-treated arteries. Both UTP-induced contractions and MT were suppressed by MRS2567 and bumetanide but were insensitive to NF023. These data implicate a P2Y(6)-mediated, NKCC-dependent mechanism in MT of mesenteric arteries. The action of heightened intraluminal pressure on UTP release from mesenteric arteries and its role in the triggering of P2Y(6)-mediated signaling should be examined further.


Protein Supplementation Does Not Augment Adaptations to Endurance Exercise Training.
Recently, it has been speculated that protein supplementation may further augment the adaptations to chronic endurance exercise training. We assessed the effect of protein supplementation during chronic endurance exercise training on whole-body oxidative capacity (V˙O2max) and endurance exercise performance. In this double-blind, randomized, parallel placebo-controlled trial, 60 recreationally active males (age, 27 ± 6 yr; body mass index, 23.8 ± 2.6 kg·m; V˙O2max, 47 ± 6 mL·min·kg) were subjected to 12 wk of triweekly endurance exercise training. After each session and each night before sleep, participants ingested either a protein supplement (PRO; 28.7 g casein protein) or an isoenergetic carbohydrate placebo (PLA). Before and after the 12 wk of training, V˙O2max and endurance exercise performance (~10-km time trial) were assessed on a cycle ergometer. Muscular endurance (total workload achieved during 30 reciprocal isokinetic contractions) was assessed by isokinetic dynamometry and body composition by dual-energy x-ray absorptiometry. Mixed-model ANOVA was applied to assess whether training adaptations differed between groups. Endurance exercise training induced an 11% ± 6% increase in V˙O2max (time effect, P < 0.0001), with no differences between groups (PRO, 48 ± 6 to 53 ± 7 mL·min·kg; PLA, 46 ± 5 to 51 ± 6 mL·min·kg; time-treatment interaction, P = 0.50). Time to complete the time trial was reduced by 14% ± 7% (time effect, P < 0.0001), with no differences between groups (time-treatment interaction, P = 0.15). Muscular endurance increased by 6% ± 7% (time effect, P < 0.0001), with no differences between groups (time-treatment interaction, P = 0.84). Leg lean mass showed an increase after training (P < 0.0001), which tended to be greater in PRO compared with PLA (0.5 ± 0.7 vs 0.2 ± 0.6 kg, respectively; time-treatment interaction, P = 0.073). Protein supplementation after exercise and before sleep does not further augment the gains in whole-body oxidative capacity and endurance exercise performance after chronic endurance exercise training in recreationally active, healthy young males.


[Methodological problems and possibilities at the standardization of flavonoid containing extracts].
Flavonoid containing extracts may be divided into two groups regarding to the possibilities of their standardization. If known compound/s are responsible for the pharmacological effects, their selective determination is recommended. Extracts with unknown compositions are usually characterized by their flavonoid content. The latter may be carried out according to several methods official in pharmacopoeias. However the applicability of these methods for each plant material is in question. We have determined the flavonoid content of plant materials with various flavonoid composition following spectroscopic methods from pharmacopoeias official in Hungary. Comparing the measured results significant differences could be observed. Because these couldn't be explained even taking account of applying different evaluation methods, we have decided to study at large the possible parameters which may be responsible for the differences. The effect of the extraction, the hydrolisation, the cleaning steps, building up complexes and the flavonoid composition were proved in model experiments. Using the method of the VII. Hungarian Pharmacopoeia we experienced that this method wasn't applicable in case of the plant materials examined in our experiments.


Melanopsin, a Canonical Light Receptor, Mediates Thermal Activation of Clock Genes.
Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects of heat shock on the localization of melanopsin by immunocytochemistry. In both cell lines melanopsin was found in a region capping the nucleus and heat shock did not affect its location. The heat-induced increase of Per1 expression was inhibited when melanopsin was pharmacologically blocked by AA92593 as well as when its protein expression was suppressed by siRNA in both Melan-a and B16-F10 cells. These data strongly suggest that melanopsin is required for thermo-reception, acting as a thermo-opsin that ultimately feeds the local circadian clock in mouse melanocytes and melanoma cells.


Adenomyosis in a uterine horn of a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.
A 37-year-old woman with a previous diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome at 18 years of age was referred from a primary healthcare physician to a gynaecology appointment in our centre. She presented with a 2-year worsening pelvic pain and dyspareunia, symptoms that were previously absent and, at the time, with inadequate relief with oral analgesia. Physical examination showed absent uterine cervix and hypoplastic superior vagina. Transvaginal ultrasound and MRI suggested the presence of an hypoplasic uterus in left rotation. Laparoscopically, two asymmetric rudimentary horns were found, united by a fibrous central band, with an enlarged and congestive left horn. The three structures were removed as a whole. Histopathological examination reported the presence of multiple adenomyotic foci along the full thickness of the left rudimentary horn. The patient had an uneventful postoperative recovery and full remission of her symptoms.


Cleaning efficacy and soft tissue trauma after use of manual toothbrushes with different bristle stiffness.
The purpose of this study is to evaluate the efficacy of manual toothbrushes of the same type with different bristle stiffness concerning plaque removal, gingivitis development, and soft tissue trauma. In a randomized controlled trial, three groups with 40 subjects each used manual toothbrushes with either hard-, medium-, or soft-bristle stiffness. The at-home brushing time was set for 2 minutes, twice a day. Four and 8 weeks after the baseline examination, clinical parameters for plaque removal, gingivitis, and soft tissue damage were recorded again. Recruitment and examinations of the subjects were performed at the Department of Operative and Preventive Dentistry and Endodontics, Heinrich Heine University. A total of 120 volunteers (age range: 18 to 62 years) were recruited and stratified according to sex and age. Primary outcome measures were differences in the Quigley and Hein index (QHI) and papillary bleeding index (PBI) compared to baseline; secondary outcome measures were differences in the modified approximal plaque index (MAPI) and Danser gingival abrasion index. The QHI and MAPI showed lower index scores in subjects who used hard-bristled toothbrushes after 8 weeks (P <0.05 and P <0.001, respectively). In contrast, subjects who used toothbrushes with hard bristles demonstrated more gingival lesions (P <0.01) and higher PBI scores after 4 and 8 weeks (P <0.001) compared to subjects who used soft- or medium-bristled toothbrushes. Manual toothbrushes with hard bristles may better remove plaque, but may also cause more soft tissue trauma compared to brushes with softer bristles.


A solvent-free Diels-Alder reaction of graphite into functionalized graphene nanosheets.
A solvent-free Diels-Alder reaction was carried out by heating a mixture of graphite and a typical dienophile, maleic anhydride (MA) or maleimide (MI), in a sealed glass ampoule of argon. The functionalization of graphite with dienophiles was confirmed by various characterization techniques, suggesting the efficient functionalization and delamination of graphite into a few layers of graphitic nanosheets.


A semiflexible chain model of local denaturation in double-stranded DNA.
Double-stranded DNA (dsDNA) is known to form a locally denatured structure ("bubble") below its denaturation temperature (T(c)). We have investigated the physical behavior of the bubbles using a model of dsDNA as two wormlike chains containing interacting complementary base pairs. The model incorporates two biologically relevant features, i.e., semiflexibility of the strand and overdamping nature of aqueous background. Computer simulations using the Langevin equation are performed to examine the size distribution and dynamics of bubbles. The results show that the entropy associated with semiflexibility of DNA sensitively affects the size distribution and lifetime of bubble. In particular, the lifetime grows with bubble size m as m(2.7) at temperature close to T(c), which is consistent with our analysis based on a stochastic model of bubble size dynamics.


Combined primary aldosteronism and Cushing's syndrome due to a single adrenocortical adenoma complicated by Hashimoto's thyroiditis.
A 43-year-old Japanese woman presented hypertension, hypokalemia and typical Cushingoid signs. Autonomous secretion of both aldosterone and cortisol was shown. Abdominal computed tomography demonstrated a single tumor in the right adrenal gland, which established the diagnosis of combined primary aldosteronism and Cushing's syndrome. The resected tumor was a golden yellow-colored adenoma (diameter 4.3 cm) which expressed P450(aldo) and P450(11beta), causing oversecretion of both hormones from this adenoma. After tumor resection, overproduction of both hormones disappeared and she developed adrenal insufficiency, suggesting the strong suppression of normal adrenal function. This case was complicated by Hashimoto's thyroiditis.


Effect of glucagon-like peptide 1(7-36)amide in insulin-treated patients with diabetes mellitus secondary to chronic pancreatitis.
Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.


Teaching Pediatric Palliative Care Communication Skills to Fourth-Year Medical Students Through Role-Play.
Despite growing recognition of pediatric palliative care's importance, training in palliative care communication remains a gap in medical education. Graduating medical students frequently feel unprepared to initiate or facilitate goals of care conversations with their patients, particularly in pediatrics. We created a 3-hour session featuring an introductory lecture on pediatric palliative care, communication drills on responding to emotion, and small-group case-based discussions utilizing role-play, targeting fourth-year medical students as the primary learners. Senior residents were also given the opportunity to develop skills by role-playing the patient parent and cofacilitating case discussions alongside palliative care faculty. Students evaluated session utility and their own confidence through pre- and postsession surveys using a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree). Twenty-six students were included in the analysis over 3 years. All agreed that the session was useful (M = 4.9). Students showed significant improvement in confidence in explaining pediatric palliative care (presession M = 3.2, postsession M = 4.1, p < .001), understanding the family experience (presession M = 2.7, postsession M = 4.1, p < .001), and eliciting goals and values from families whose children face serious illnesses (presession M = 3.1, postsession M = 4.1, p < .001). Pediatric resident cofacilitators also felt the session benefited their own teaching and communication skills. This 3-hour interactive session on pediatric palliative care utilizing communication drills and role-play was effective in improving fourth-year medical students' confidence in communicating with families of children facing life-threatening illnesses.


Alcohol handrubbing and chlorhexidine handwashing are equally effective in removing methicillin-resistant Staphylococcus aureus from health care workers' hands: A randomized controlled trial.
We conducted a randomized controlled trial in a tertiary-care hospital in a real-time setting to evaluate the effectiveness of 3 hand hygiene protocols in reducing hand carriage of methicillin-resistant and methicillin-sensitive Staphylococcus aureus among health care workers. Our study shows that use of alcohol handrub, either covering all hand surfaces in no particular order or using the 7-step technique, and chlorhexidine handwashing were equally effective in removing hand carriage of these pathogens.


Nondestructive detection of hidden chemical compounds with laser Compton-scattering gamma rays.
A nondestructive assay method for measuring a shielded chemical compound has been proposed. The chemical compound is measured by using a nuclear resonance fluorescence (NRF) measurement technique with an energy tunable laser Compton-scattering (LCS) gamma-ray source. This method has an advantage that hidden materials can be detected through heavy shields such as iron plates of a thickness of several centimeters. A detection of a chemical compound of melamine, C(3)H(6)N(6), shielded by 15-mm-thick iron and 4-mm-thick lead plates is demonstrated. The NRF gamma-rays of (12)C and (14)N of the melamine are measured by using the LCS gamma-rays of the energies of up to 5.0 MeV. The observed ratio ((12)C/(14)N)(exp)=0.39+/-0.12 is consistent with (C/N)(melamine)=0.5.


[The transosseous osteosynthesis by intra- and periarticular fractures of the knee joint].
105 patients with intra- and periarticular fractures of the knee joint were operated on with the use of nail and spin-nail apparatus constructed by A.I. Gorodnichenko. The possibility of atraumatic closed bone fragments fixation allowed quick patients' activization, and, as follows, improved their life quality, decreased the hospital stay and minimized complication rate. Fracture consolidation was achieved in all cases, the only complication registered was skin inflammation around the nail in 5 patients.


[Oral jewelry: a review].
Oral jewelry is popular. One of the most widely spread types are so-called tooth diamonds made of composite materials which are applied to the teeth with an adhesive. Note that parents are required to sign a release form for under-aged patients in Switzerland. Tooth cap grills and gold teeth are considered status symbols within the Hip-Hop fashion scene. However, tooth ornaments favour the accumulation of plaque and can diminish the ability to articulate. With respect to jewelry in oral soft tissue especially tongue and lip piercings are of significance to dentists. Besides the systemic complications, which are mostly caused by a lack of hygiene or the failure of noting medical contraindications by the piercer, local complications occur frequently. After surgery, pain, swelling, infections as well as hemorrhages or hematomas can be observed. Long-term effects can be problematic: gingival recession can be discernes mainly in the case of lip piercings the loss of hard tooth substance in the case of tongue piercings. Because of that, conservation therapies can become indespensable. Patients wearing dental jewelry have to be aware of risks of tooth damage, and they regularly have to undergo dental check-ups. Information campaigns--for dentists as well as patients--are necessary.


Cross-species approaches to seed dormancy and germination: conservation and biodiversity of ABA-regulated mechanisms and the Brassicaceae DOG1 genes.
Seed dormancy is genetically determined with substantial environmental influence mediated, at least in part, by the plant hormone abscisic acid (ABA). The ABA-related transcription factor ABI3/VP1 (ABA INSENSITIVE3/VIVIPAROUS1) is widespread among green plants. Alternative splicing of its transcripts appears to be involved in regulating seed dormancy, but the role of ABI3/VP1 goes beyond seeds and dormancy. In contrast, DOG1 (DELAY OF GERMINATION 1), a major quantitative trait gene more specifically involved in seed dormancy, was so far only known from Arabidopsis thaliana (AtDOG1) and whether it also has roles during the germination of non-dormant seeds was not known. Seed germination of Lepidium sativum ('garden cress') is controlled by ABA and its antagonists gibberellins and ethylene and involves the production of apoplastic hydroxyl radicals. We found orthologs of AtDOG1 in the Brassicaceae relatives L. sativum (LesaDOG1) and Brassica rapa (BrDOG1) and compared their gene structure and the sequences of their transcripts expressed in seeds. Tissue-specific analysis of LesaDOG1 transcript levels in L. sativum seeds showed that they are degraded upon imbibition in the radicle and the micropylar endosperm. ABA inhibits germination in that it delays radicle protrusion and endosperm weakening and it increased LesaDOG1 transcript levels during early germination due to enhanced transcription and/or inhibited degradation. A reduced decrease in LesaDOG1 transcript levels upon ABA treatment is evident in the late germination phase in both tissues. This temporal and ABA-related transcript expression pattern suggests a role for LesaDOG1 in the control of germination timing of non-dormant L. sativum seeds. The possible involvement of the ABA-related transcription factors ABI3 and ABI5 in the regulation of DOG1 transcript expression is discussed. Other species of the monophyletic genus Lepidium showed coat or embryo dormancy and are therefore highly suited for comparative seed biology.


Changes in composition and levels of hemolymph proteins during metamorphosis of Manduca sexta.
The tobacco hornworm, Manduca sexta, is a lepidopteran model species widely used to study insect biochemical processes. Some of its larval hemolymph proteins are well studied, and a detailed proteomic analysis of larval plasma proteins became available in 2016, revealing features such as correlation with transcriptome data, formation of immune complexes, and constitution of an immune signaling system in hemolymph. It is unclear how the composition of these proteins may change in other developmental stages. In this paper, we report the proteomes of cell-free hemolymph from prepupae, pupae on day 4 and day 13, and young adults. Of the 1824 proteins identified, 907 have a signal peptide and 410 are related to immunity. Drastic changes in abundance of the storage proteins, lipophorins and vitellogenin, for instance, reflect physiological differences among prepupae, pupae, and adults. Considerably more proteins lacking signal peptide are present in the late pupae, suggesting that plasma contains relatively low concentrations of intracellular components released from remodeling tissues during metamorphosis. The defense proteins detected include 43 serine proteases and 11 serine protease homologs. Some of these proteins are members of the extracellular immune signaling network found in feeding larvae, and others may play additional roles and hence confer new features in the later life stages. In summary, the proteins and their levels revealed in this study, together with their transcriptome data, are expected to stimulate focused explorations of humoral immunity and other physiological systems in wandering larvae, pupae, and adults of M. sexta and shed light upon functional and comparative genomic research in other holometabolous insects.


Low-Level Laser Therapy Facilitates Superficial Wound Healing in Humans: A Triple-Blind, Sham-Controlled Study.
OBJECTIVE: Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief. However, according to the results of in vivo studies, the effectiveness of this modality varies. Our purpose was to assess the putative effects of LLLT on healing using an experimental wound model. DESIGN AND SETTING: We used a randomized, triple-blind, placebo-controlled design with 2 within-subjects factors (wound and time) and 1 between-subjects factor (group). Data were collected in the laboratory setting. SUBJECTS: Twenty-two healthy subjects (age = 21 +/- 1 years, height = 175.6 +/- 9.8 cm, mass = 76.2 +/- 14.2 kg). MEASUREMENTS: Two standardized 1.27-cm(2) abrasions were induced on the anterior forearm. After wound cleaning, standardized digital photos were recorded. Each subject then received LLLT (8 J/cm(2); treatment time = 2 minutes, 5 seconds; pulse rate = 700 Hz) to 1 of the 2 randomly chosen wounds from either a laser or a sham 46-diode cluster head. Subjects reported back to the laboratory on days 2 to 10 to be photographed and receive LLLT and on day 20 to be photographed. Data were analyzed for wound contraction (area), color changes (chromatic red), and luminance. RESULTS: A group x wound x time interaction was detected for area measurements. At days 6, 8, and 10, follow-up testing revealed that the laser group had smaller wounds than the sham group for both the treated and the untreated wounds (P < .05). No group x wound x time differences were detected for chromatic red or luminance. CONCLUSIONS: The LLLT resulted in enhanced healing as measured by wound contraction. The untreated wounds in subjects treated with LLLT contracted more than the wounds in the sham group, so LLLT may produce an indirect healing effect on surrounding tissues. These data indicate that LLLT is an effective modality to facilitate wound contraction of partial-thickness wounds.


Bead-selected antitumor genetic cell vaccines.
Cancer vaccines have always been in the scope of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. However, to become a clinical reality, tumor cells must suffer a long and risky process from the extraction from the patient to the reimplantation as a vaccine. In this work, we explain our group's approach to reduce the cell number required to achieve an immune response against a melanoma murine model, employing bead-selected B16 tumor cells expressing GM-CSF and B7.2.


Nanostructure Design and Catalytic Performance of Mo/ZnAl-LDH in Cationic Orchid X-BL Removal.
The nanostructure of ZnAl-layered double hydroxide (ZnAl-LDH) was designed to promote the catalytic performance of Mo-based ZnAl-LDH (Mo/ZnAl-LDH) catalysts, in a catalytic wet air oxidation (CWAO) process, under room temperature and pressure, in degradation of dye wastewater. Four most commonly used preparation methods, traditional precipitation (TP), hydrothermal synthesis (HS), sol-gel (SG), and urea co-precipitation (UC) were employed to prepare the ZnAl-LDH. The resulting Mo/ZnAl-LDH samples were contrasted through surface area, crystal structure, chemical state, and morphology. The degradation of cationic orchid X-BL, under room temperature and pressure, was developed to determine the catalytic activity of these Mo/ZnAl-LDH samples. The results showed that the nanostructure of ZnAl-LDH, prepared by HS, enhanced the adhesion of the catalytic active component, thus Mo/ZnAl-LDH had the highest catalytic activity of 84.2% color removal efficiency and 73.9% total organic carbon removal efficiency. Specific Mo species, such as Na₂Mo₂O₇, Mo dispersion, and O2- ions were proved to be related with catalytic performance. These findings preliminarily clarified that LDHs preparation methods make a difference in the performance of Mo/LDHs.


Efficacy of allergen-specific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials.
Allergen-specific immunotherapy (allergen-SIT) is the only treatment directed at the cause of IgE-mediated allergic diseases. However, there is controversy over the use of SIT for patients with atopic dermatitis. We performed a systematic review and meta-analysis to assess the efficacy of SIT for patients with atopic dermatitis. We performed manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane databases (through December 10, 2012) for randomized controlled trials that compared SIT with placebo for patients with atopic dermatitis. The outcome of interest was a dichotomous variable, in terms of treatment success; a meta-analysis was performed by using a random-effects analysis. Subgroup analyses were carried out to evaluate the effects of long-term treatment (more than 1 year), SIT for severe atopic dermatitis, SIT for children, and subcutaneous and sublingual administration of immunotherapy. We analyzed 8 randomized controlled trials that comprised a total of 385 subjects. We found that SIT has a significant positive effect on atopic dermatitis (odds ratio [OR], 5.35; 95% CI, 1.61-17.77; number needed to treat, 3; 95% CI, 2-9). SIT also showed significant efficacy in long-term treatment (OR, 6.42; 95% CI, 1.50-27.52) for patients with severe atopic dermatitis (OR, 3.13; 95% CI, 1.31-7.48), and when administered subcutaneously (OR, 4.27; 95% CI, 1.36-13.39). A meta-analysis provides moderate-level evidence for the efficacy of SIT against atopic dermatitis. However, these findings are based on an analysis of a small number of randomized controlled trials, with considerable heterogeneity among trials.


High Rate of Return to Running for Athletes After Hip Arthroscopy for the Treatment of Femoroacetabular Impingement and Capsular Plication.
Femoroacetabular impingement (FAI) is most commonly diagnosed in athletes who sustain repetitive flexion loading to their hips. No studies to date have focused solely on patients' return-to-running ability after hip arthroscopy. To evaluate patients' ability to return to running after hip arthroscopy for FAI and capsular plication. Case series; Level of evidence, 4. Clinical data were retrospectively retrieved for 51 consecutive patients with FAI (22 men, 29 women) who had undergone hip arthroscopy for the treatment of FAI and identified themselves as recreational or competitive runners on intake forms. Two-year outcome measures included the modified Harris Hip Score (mHHS) and the Hip Outcome Score Activities of Daily Living (HOS-ADL) and Sport-Specific (HOS-SS) subscales. A postoperative return-to-running survey was used to obtain running-specific information. Patient age and body mass index (BMI) were a mean (±SD) of 26.3 ± 7.8 years and 23.7 ± 3.3 kg/m2, respectively. Before surgery, patients had refrained from running because of pain for a mean of 8.1 ± 5.7 months. After surgery, 48 patients (94%) returned to running at a mean of 8.5 ± 4.2 months. Patients who had discontinued running for more than 8 months before surgery had a longer return-to-running time than did those who had stopped for less than 8 months (10.6 ± 4.2 vs 7.6 ± 4.1 months; P = .01). After 2 years, mean preoperative distance had decreased significantly ( P < .01) from 9.5 ± 6.5 miles per week when healthy to 6.4 ± 5.8 miles postoperatively. Despite decreased mileage, all 2-year outcomes scores improved significantly ( P < .001). Recreational and competitive runners with FAI returned to running 94% of the time at a mean of 8.5 months after hip arthroscopy. However, runners should be counseled before their surgery that they may run fewer miles than when they were pain free. Additionally, patients with a higher BMI and/or longer preoperative lull may have a longer recovery time.


Hepsin inhibits the cell growth of endometrial cancer.
Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3sigma expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.


Mrr instigates the SOS response after high pressure stress in Escherichia coli.
The bacterial SOS response is not only a vital reply to DNA damage but also constitutes an essential mechanism for the generation of genetic variability that in turn fuels adaptation and resistance development in bacterial populations. Despite the extensive depiction of the SOS regulon itself, its activation by stresses different from typical DNA damaging treatments remains poorly characterized. Recently, we reported the RecA- and LexA-dependent induction of the SOS response in Escherichia coli MG1655 after exposure to high hydrostatic pressure (HP, approximately 100 MPa), a physical stress of which the cellular effects are not well known. We now found this HP mediated SOS response to depend on RecB and not on RecF, which is a strong indication for the involvement of double strand breaks. As the pressures used in this work are thermodynamically unable to break covalent bonds in DNA, we hypothesized the involvement of a cellular function or pathway in the formation of this lesion. A specialized screening allowed us to identify the cryptic type IV restriction endonuclease Mrr as the final effector of this pathway. The HP SOS response and its corresponding phenotypes could be entirely attributed to the HP triggered activation of Mrr restriction activity. Several spontaneously occurring alleles of mrr, incapable of triggering the HP-induced SOS response, were isolated and characterized. These results provide evidence for a specific pathway that transmits the perception of HP stress to induction of the SOS response and support a role for Mrr in bacterial stress physiology.


Development of a new Er: YAG laser conception for laser sclerostomy ab externo: experimental and first clinical results.
The erbium:YAG laser is a preferable energy source for laser sclerostomy ab externo due to the high absorption of its radiation (2940-nm wavelength) in the aqueous parts of scleral tissue. It has thus far been a disadvantage that laser energy has to be transmitted from the laser source to the application site via very susceptible special optical fibers (ZrF). As a consequence of technical improvements, the laser source could be integrated into the application probe. Therefore, only a robust quartz fiber was necessary for contact application. A fiber diameter of 400 microns was chosen according to the experience gained in previous studies. A total of 24 eyes with chronical open-angle glaucoma were treated. A fistula end-point detection unit was developed for safe indication of a full-thickness perforation of the sclera. With a fiber diameter of 400 microns, a postoperative success rate of about 54% was achieved at 6 months follow-up. The automated full-thickness perforation detection prevented the application of additional, surplus laser pulses in the anterior chamber. The postoperative success rate could be improved over that achieved in previous studies. The new device/conception offers more technical reliability and is a further step toward minimally invasive fistulating laser surgery of open-angle glaucoma.


Nitrogen nucleation in a cryogenic supersonic nozzle.
We follow the vapor-liquid phase transition of N(2) in a cryogenic supersonic nozzle apparatus using static pressure measurements. Under our operating conditions, condensation always occurs well below the triple point. Mean field kinetic nucleation theory (MKNT) does a better job of predicting the conditions corresponding to the estimated maximum nucleation rates, J(max) = 10(17±1) cm(-3) s(-1), than two variants of classical nucleation theory. Combining the current results with the nucleation pulse chamber measurements of Iland et al. [J. Chem. Phys. 130, 114508-1 (2009)], we use nucleation theorems to estimate the critical cluster properties. Both the theories overestimate the size of the critical cluster, but MKNT does a good job of estimating the excess internal energy of the clusters.


Dysmorphogenesis elicited by microinjected acetaminophen analogs and metabolites in rat embryos cultured in vitro.
Direct additions of acetaminophen (APAP), 3,5-dimethylacetaminophen, 3-hydroxyacetaminophen or 3-methoxyacetaminophen to the medium of cultured embryos each produced an increased incidence of morphologically similar, abnormally open anterior neuropores. Approximate concentrations required to produce an equal incidence were 0.5 mM, 1.0 mM, 0.1 mM and 0.75 mM, respectively. In contrast, 2.6-dimethylacetaminophen and N-acetyl-p-benzoquinoneimine failed to produce elevated incidences of abnormal neurulation unaccompanied by marked growth retardation. However, with intra-amniotic microinjections, 3-hydroxyacetaminophen and N-acetyl-p-benzoquinoneimine were roughly equipotent for eliciting abnormal neurulation, whereas 3-methoxyacetaminophen required greater than 30-fold higher concentrations. This suggests that N-acetyl-p-benzoquinoneimine does not readily transit the visceral yolk sac and would likely not be a major factor in APAP-elicited neural tube abnormalities unless generated in target tissues. The differential effects produced by two dimethylated (2.6 and 3.5) APAP analogs further suggest that sulfhydryl oxidation is associated more closely than sulfhydryl conjugation with the neurulation defect. Intra-amniotic microinjections of large quantities (3500 ng) of 7-hydroxy-2-acetylaminofluorene (7-OH-AAF) or APAP failed to produce the specific neurulation defect. Microinjections of 7-OH-AAF into the exocoelomic cavity effected the characteristic abnormal neurulation. Conversion by conceptal homogenates of 7-OH-AAF was roughly 7- to 8-fold more rapid than conversion of APAP to respective catechol metabolites, and specific activities in yolk sac tissues were greater than those in the embryo. Rates of conceptal conversion to the quinoneimine were approximately 2- to 3-fold lower than catechol generation.(ABSTRACT TRUNCATED AT 250 WORDS)


The attenuating effect of intraglossal atropine on the oculocardiac reflex.
Bradycardia during strabismus surgery is reduced better by intravenous than by intramuscular (deltoid) anticholinergics, but recent studies suggest that injection into the tongue works faster than into the deltoid. We sought to study this using the suppression of the oculocardiac reflex during eye surgery as a parameter. 804 children and adults underwent calibrated extraocular muscle tensioning during controlled, inhalational general anesthesia. A systemic anticholinergic agent was distributed by different routes to patient-subject sub-groups: preoperative oral, or induction intravenous, intramuscular (deltoid) and intraglossal (submucosal at the base of the tongue). A large control group received no anticholinergic. The control group had an oculocardiac reflex averaging 17.2% heart rate reduction (bradycardia), 6% of whom had greater than a 50% heart rate reduction. This oculocardiac reflex bradycardia was reduced to only a 6.7% heart rate reduction by oral and intradeltoid routes and was essentially eliminated by both intravenous (-2.3%) and intraglossal (-0.9%) routes. Intraglossal atropine is an effective alternative for oculocardiac reflex prophylaxis when intravenous access is not readily available in strabismus surgery. The intraglossal route is in fact slightly more effective in this regard that the intravenous route per se.


[Dependency syndrome].
The most common causes of lower limb edema include cardiac insufficiency, venous insufficiency, insufficiency of lymph flow, and side effects of drugs. It can also be due to dependency syndrome, in which the edema and skin changes can only be explained by a passive calf muscle pump and the resulting venous hypertension. Underlying the drop foot is always immobilization for one reason or other. The patient must be given an explanation about the situation, activated to move if possible, and in any case guided to the use of support stockings and postural therapy.


Contrast echocardiography: a valid and sensitive imaging method in the investigation of transmyocardial laser-revascularization in an acute ischemia model.
In an acute porcine myocardial ischemia model we examined the effect of transmyocardial laser-revascularization (TMLR) on the regional micro perfusion and oxygen supply. In clinical practice, contrast echocardiography is a reliable tool for the measurement of changes in regional blood flow in the ischemic myocardium. We compared contrast echocardiography with the laser Doppler measurement of micro perfusion and with the quantification of regional tissue oxygen tension using a Clark electrode. 22 pigs were randomised in the interventional group and 12 in the control group. Measurements with all three methods were performed before and after occlusion of the first diagonal branch of the left anterior descending coronary artery and, in the interventional group, after TMLR. We investigated not only the effects in the dependent ischemic myocardium, but also in two other myocardial areas, not involved in the coronary occlusion. There was a significant effect of TMLR on regional micro perfusion and local oxygen tension in the dependent ischemic myocardial area. Contrast echocardiography is a successful experimental tool to measure changes in regional myocardial perfusion which cannot be perceived using clinical imaging methods.


Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression.
Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes. Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel-Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg's test. A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar. Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.


Exploration of the Polarization Curve for Proton-Exchange Membrane Fuel Cells.
The polarization curve is the most important profile to evaluate the performance of proton-exchange membrane fuel cells (PEMFCs). To explore the important thermodynamic parameters and their correlation with the composition, fabrication, and operational settings, a comprehensive data set consisting of 446 polarization curves from 191 perfluorosulfonate and 255 sulfonated hydrocarbon-based PEMs is collected. Then, a Markov chain Monte Carlo simulation within the Bayesian frame provides higher than 93% confidence to extract six important thermodynamic parameters including open-circuit potential, the transfer coefficient, the current loss, the reference exchange current density, the internal resistance, and the limiting current density. An extreme gradient boosting algorithm affords a mean determinative coefficient of 0.89 to predict the whole polarization curve and a confidence of 94% to predict the peak power density (PPD). Both approaches to explore the polarization curve for PEMFCs show good robustness in the blind test. Overall, the PPD is positively correlated with the ion-exchange capacity of the polymer, operational temperature, and humidity and is negatively affected by internal resistance, membrane thickness, and the loading of the catalyst. The flow rate of fuels can effectively enhance them, while the increase of catalyst loading or fuel concentration shows deleterious impacts.


Light yield sensitization by X-ray irradiation of the BaAl4O7:Eu(2+)ceramic scintillator obtained by full crystallization of glass.
We report the scintillation properties of BaAl4O7:Eu(2+), a transparent polycrystalline ceramic prepared by full and congruent crystallization of glass. We show that a small deviation from the stoichiometric composition as well as thermal treatment duration play a crucial role in the formation of charge carrier traps, leading to a strong influence on the scintillation yield. We demonstrate that when the traps are not entirely removed, X-ray irradiation allows them to be permanently filled in order to significantly enhance the scintillation output. Finally, the best sample obtained demonstrates performances able to compete with a commercially available scintillating material, CsI:Tl.


Association of Neighborhood Deprivation With Cognitive and Mood Outcomes in Adults With Pharmacoresistant Temporal Lobe Epilepsy.
Temporal lobe epilepsy (TLE) is the most common adult form of epilepsy and is associated with a high risk of cognitive deficits and depressed mood. However, little is known about the role of environmental factors on cognition and mood in TLE. This cross-sectional study examined the relationship between neighborhood deprivation and neuropsychological function in adults with TLE. Neuropsychological data were obtained from a clinical registry of patients with TLE and included measures of intelligence, attention, processing speed, language, executive function, visuospatial skills, verbal/visual memory, depression, and anxiety. Home addresses were used to calculate the Area Deprivation Index (ADI) for each individual, which were separated into quintiles (i.e., quintile 1 = least disadvantaged and quintile 5 = most disadvantaged). Kruskal-Wallis tests compared quintile groups on cognitive domain scores and mood and anxiety scores. Multivariable regression models, with and without ADI, were estimated for overall cognitive phenotype and for mood and anxiety scores. A total of 800 patients (median age 38 years; 58% female) met all inclusion criteria. Effects of disadvantage (increasing ADI) were observed across nearly all measured cognitive domains and with significant increases in symptoms of depression and anxiety. Furthermore, patients in more disadvantaged ADI quintiles had increased odds of a worse cognitive phenotype (p = 0.013). Patients who self-identified as members of minoritized groups were overrepresented in the most disadvantaged ADI quintiles and were 2.91 (95% CI 1.87-4.54) times more likely to be in a severe cognitive phenotype than non-Hispanic White individuals (p < 0.001). However, accounting for ADI attenuated this relationship, suggesting neighborhood deprivation may account for some of the relationship between race/ethnicity and cognitive phenotype (ADI-adjusted proportional odds ratio 1.82, 95% CI 1.37-2.42). These findings highlight the importance of environmental factors and regional characteristics in neuropsychological studies of epilepsy. There are many potential mechanisms by which neighborhood disadvantage can adversely affect cognition (e.g., fewer educational opportunities, limited access to health care, food insecurity/poor nutrition, and greater medical comorbidities). Future research will seek to investigate these potential mechanisms and determine whether structural and functional alterations in the brain moderate the relationship between ADI and cognition.


3D-printed Point-of-Care Platform for Genetic Testing of Infectious Diseases Directly in Human Samples Using Acoustic Sensors and a Smartphone.
The objective of this work is to develop a methodology and associated platform for nucleic acid detection at the point-of-care (POC) that is sensitive, user-friendly, affordable, rapid, and robust. The heart of this system is an acoustic wave sensor, based on a Surface Acoustic Wave (SAW) or Quartz Crystal Microbalance (QCM) device, which is employed for the label-free detection of isothermally amplified target DNA. Nucleic acids amplification and detection is demonstrated inside three crude human samples, i.e., whole blood, saliva, and nasal swab, spiked in with 10-100 Salmonella cells. To qualify for POC applications, a portable platform was developed based on 3D printing, integrating inside a single box: (i) simple fluidics based on plastic tubing and a mini peristaltic pump, (ii) a heating plate combined with disposable reaction tubes for isothermal amplification; (iii) a mini antenna analyzer operated through a tablet; and (iv) an acoustic wave device housing unit. The simplicity of the method combined with smartphone operation and detection, rapid sample-to-answer analysis time (30 min), and high performance (detection limit 4 × 103 CFU/ml) in three of the most important human samples in diagnostics suggest that the methodology could become a tool of choice for nucleic acid detection at the POC. In addition, the low cost of the platform and assay holds promise for its adoption in resource limited areas. The acoustic detection method is shown to give similar results with a standard colorimetric assay carried out in saliva and nasal swab but can also be used to detect nucleic acids inside whole blood, where a colorimetric assay failed to perform.


Effects of viewing distance on the responses of vestibular neurons to combined angular and linear vestibular stimulation.
Effects of viewing distance on the responses of vestibular neurons to combined angular and linear vestibular stimulation. The firing behavior of 59 horizontal canal-related secondary vestibular neurons was studied in alert squirrel monkeys during the combined angular and linear vestibuloocular reflex (CVOR). The CVOR was evoked by positioning the animal's head 20 cm in front of, or behind, the axis of rotation during whole body rotation (0.7, 1.9, and 4.0 Hz). The effect of viewing distance was studied by having the monkeys fixate small targets that were either near (10 cm) or far (1.3-1.7 m) from the eyes. Most units (50/59) were sensitive to eye movements and were monosynaptically activated after electrical stimulation of the vestibular nerve (51/56 tested). The responses of eye movement-related units were significantly affected by viewing distance. The viewing distance-related change in response gain of many eye-head-velocity and burst-position units was comparable with the change in eye movement gain. On the other hand, position-vestibular-pause units were approximately half as sensitive to changes in viewing distance as were eye movements. The sensitivity of units to the linear vestibuloocular reflex (LVOR) was estimated by subtraction of angular vestibuloocular reflex (AVOR)-related responses recorded with the head in the center of the axis of rotation from CVOR responses. During far target viewing, unit sensitivity to linear translation was small, but during near target viewing the firing rate of many units was strongly modulated. The LVOR responses and viewing distance-related LVOR responses of most units were nearly in phase with linear head velocity. The signals generated by secondary vestibular units during voluntary cancellation of the AVOR and CVOR were comparable. However, unit sensitivity to linear translation and angular rotation were not well correlated either during far or near target viewing. Unit LVOR responses were also not well correlated with their sensitivity to smooth pursuit eye movements or their sensitivity to viewing distance during the AVOR. On the other hand there was a significant correlation between static eye position sensitivity and sensitivity to viewing distance. We conclude that secondary horizontal canal-related vestibuloocular pathways are an important part of the premotor neural substrate that produces the LVOR. The otolith sensory signals that appear on these pathways have been spatially and temporally transformed to match the angular eye movement commands required to stabilize images at different distances. We suggest that this transformation may be performed by the circuits related to temporal integration of the LVOR.


[Plasma activity of diamine oxidase after heparin in patients with diabetic enteropathy].
Diamine oxidase (DAO) is an enzyme found almost exclusively in the enterocyte of the villous tips. In the basal state plasma DAO activity is low but increases significantly after i.v. injection of heparin. It is well recognised that postheparin plasma activity of DAO reflects clearly the integrity of the small bowel mucosa. The aim of this study was to investigate postheparin plasma DAO activity in diabetics with enteropathy. The study was carried out in a group of 72 individuals subdivided into five groups. Group I consisting of 16 patients with type 1 diabetes, group II--20 patients with type 2 diabetes, group III--8 patients with newly diagnosed type 1 diabetes, group IV--8 diabetics with enteropathy and group V--the control group. Blood samples were taken at the time 0' and at 60' and 120' intervals following i.v. injection of heparin. DAO activity was assessed by RIA methods. Basal values of DAO were nearly the same in all of the subjects (< 50 pmol/min/ml). After injection of heparin a very high DAO activity was observed in all groups (> 400 pmol/min/ml) except group IV (< 270 pmol/min/ml) (p < 0.001). There were no significant differences between the groups according to the type of diabetes, its duration and the methods of treatment. In conclusion, the postheparin plasma DAO activity in diabetics with enteropathy was very low, but of itself, diabetes and its treatments had no effect on the results under investigation.


Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years.
To evaluate the long-term effect of ixekizumab (IXE) on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), and to identify potential predictors of progression. This study evaluates patients from COAST-V (ClinicalTrials.gov: NCT02696785, biologic disease-modifying antirheumatic drug-naïve) and COAST-W (NCT02696798, tumor necrosis factor inhibitor-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with IXE (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Among patients with evaluable radiographs who were originally assigned to IXE (n = 230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of nonprogressors over 2 years was 89.6% if defined as mSASSS change from baseline < 2 and 75.7% if defined as mSASSS change from baseline ≤ 0. Predictors of structural progression at year 2 (mSASSS change > 0) were age ≥ 40, baseline syndesmophytes, HLA-B27 positivity, and male sex. Week 52 inflammation in Spondyloarthritis Research Consortium of Canada spine was also a predictor of radiographic progression at year 2 in patients with magnetic resonance imaging data in COAST-V (n = 109). The majority of patients with r-axSpA receiving IXE had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.


Anorexia nervosa--irony, misnomer and paradox.
Anorexia nervosa is a condition full of irony and paradox. Perhaps the most enigmatic of these is that professionals tend to hold the same morbid preoccupation with weight, BMI and targets as do our patients. In this article we outline why we believe that an over-emphasis on weight/BMI and targets is inappropriate, misleading and potentially harmful. Although this view is not always greeted with enormous enthusiasm by some, others are relieved that this particular 'holy cow' is at last being challenged. It is important that we should all have an open mind to the possibility that one of the main tenets of our practice may actually be unhelpful. Some ancient wisdom is drawn upon to support this view.


Adaptive spectral window sizes for extraction of diagnostic features from optical spectra.
We present an approach to adaptively adjust the spectral window sizes for optical spectra feature extraction. Previous studies extracted features from spectral windows of a fixed width. In our algorithm, piecewise linear regression is used to adaptively adjust the window sizes to find the maximum window size with reasonable linear fit with the spectrum. This adaptive windowing technique ensures the signal linearity in defined windows; hence, the adaptive windowing technique retains more diagnostic information while using fewer windows. This method was tested on a data set of diffuse reflectance spectra of oral mucosa lesions. Eight features were extracted from each window. We performed classifications using linear discriminant analysis with cross-validation. Using windowing techniques results in better classification performance than not using windowing. The area under the receiver-operating-characteristics curve for windowing techniques was greater than a nonwindowing technique for both normal versus mild dysplasia (MD) plus severe high-grade dysplasia or carcinama (SD) (MD+SD) and benign versus MD+SD. Although adaptive and fixed-size windowing perform similarly, adaptive windowing utilizes significantly fewer windows than fixed-size windows (number of windows per spectrum: 8 versus 16). Because adaptive windows retain most diagnostic information while reducing the number of windows needed for feature extraction, our results suggest that it isolates unique diagnostic features in optical spectra.


A novel developmental role for kisspeptin in the growth of gonadotrophin-releasing hormone neurites to the median eminence in the mouse.
The puberty- and fertility-regulating neuropeptide kisspeptin (KISS1) exerts dramatic effects on the physiology of adult gonadotrophin-releasing hormone (GnRH) neurones as a master regulator of mammalian reproduction. Given the action of KISS1 directly on adult GnRH neurones, and that KISS1 activates a signal transduction cascade involved in neurite growth in other neurones, we investigated whether KISS1 may play a role in the normal growth of GnRH neurites to the median eminence. A reverse transcription-polymerase chain reaction demonstrated the expression of Kiss1 mRNA in the embryonic mediobasal hypothalamus, the target region for GnRH neurite termination, as early as embryonic day 13.5 (E13.5), a time when the first GnRH neurites are arriving. Complementary expression of the mRNA encoding the KISS1 receptor, Kiss1r, in the preoptic area (POA) at E13.5 was also observed, suggesting that POA-resident GnRH neurones can respond to KISS1 from an early age. To examine the effects of KISS1 on GnRH neurite growth in isolation, E15.5 POA explants, containing GnRH neurones actively extending neurites, were grown in three-dimensional collagen gels. In the presence of KISS1 (1 μm), both the number and length of GnRH neurites were increased significantly compared to controls without KISS1. The effects of KISS1 on GnRH neurite growth could be inhibited by pretreatment with the phospholipase C inhibitor U73122 (50 μm), indicating that embryonic and adult GnRH neurones respond to KISS1 with the same intracellular signalling pathway. KISS1 provided in a concentration gradient from a fixed source had no effect on GnRH neurite growth, indicating that KISS1 does not function as a long-range chemoattractant. Taken together, these results identify KISS1 as a stimulator of GnRH neurite growth, and suggest that it influences GnRH neurites at close-range to innervate the median eminence. These data add a novel developmental role to the repertoire of the functions of KISS1 in mammalian reproduction.


Influence of the temperature on the opto-acoustophoretic effect.
Opto-acoustophoretic mobility has been demonstrated recently for fluorescent and colored particles acoustically levitated in a stationary ultrasonic field when illuminated with the appropriate optical wavelength [Dumy, Hoyos, and Aider, J. Acoust. Soc. Am. 146, 4557-4568 (2019); Zhou, Gao, Yang, Li, Shao, Zhang, Li, and Li, Adv. Sci. 5, 1800122 (2018)]. It is a repeatable phenomenon, needing both acoustic trapping and specific optic excitation to occur. However, the physical origin of the phenomenon is still debated. In this study, we provide more insights into the probable origin of this phenomenon by confronting numerical simulations with temperature controlled experiments. The phenomenon properties are well reproduced by our model, relying on a thermofluidic instability, hinting at the potential thermally induced fluid density gradient as a drag source for the observed ejection of particles. Thermostated experiments exhibit a surprising threshold above which the phenomenon is not observed anymore no matter how large the optic or acoustic energies used. This exciting observation differs from the initial interpretation of the phenomenon, altering its potential application without removing its interest because it suggests the possible contactless generation of customized flows by acoustically trapped particles.


Supportive Relationships in Autism Spectrum Disorder: Perspectives of Individuals with ASD and Supporters.
This study explored 17 dyads of academically successful people with Autism Spectrum Disorder (ASD) and individuals who they identified as supportive. Qualitative methods, including in-depth interviews, participant observations, and document analysis, were used to study these supportive relationships. The purpose of the study was to develop a substantive grounded theory regarding supportive relationships within the lives of individuals with ASD. A dynamic model of supportive relationships emerged, with trust, unity, and support as the three core categories of these relationships. The data suggest that the quality of the relationship between an individual with ASD and the support provider can be a critical factor within effective support. These findings suggest that there is much yet to be learned about the social world of individuals with ASD.


How single molecule detection measures the dynamic actions of life.
Biomolecules dynamically work in cells in which a variety of molecules assemble and interact in unique manner. The molecular mechanisms underlying several biological processes have been elucidated from the results obtained from the descriptions of cell function, from the snapshots of the structures of biomolecules involved in these processes, and from the biochemical properties of these reactions in vitro. Recently developed single molecule measurements have revealed the dynamic properties of the biomolecules that have been hidden in the data that have been averaged over large numbers of molecules in both ensemble measurement and in cells. Single molecule imaging and manipulation of single molecules have allowed the visualization of the dynamic operations of molecular motors, enzymatic reactions, structural dynamics of biomolecules, and cell signaling processes. The results have shown that the single molecule techniques are powerful tools to monitor the dynamic actions of biomolecules and their assemblies. This approach has been applied to a variety of fields within the life sciences. As new information emerges about the dynamic actions of biomolecules using methods of single molecule detection new views on how biological processes work will be revealed.


Alteration of predominant gastrointestinal flora and oxidative damage of large intestine under simulated hypobaric hypoxia.
Hypobaric hypoxia is an immediate and crucial starting mechanism of acute mountain sickness included with some non-specific gastrointestinal (GI) complications. To study the effect of hypoxia on GI microflora and its upshot to this system, male albino rats were exposed to 55 kPa (air pressure ~ 4872.9 m altitude) consecutively 30 days for 8 hours/day. The different indicator group of large intestinal microbial populations were enumerated and correlated with the levels of antioxidant indicators like catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of large intestinal epithelial cells. In addition, the histological study was performed by haematoxylin eosin (HE), periodic acid schiff staining (PAS) and scanning electron microscopy (SEM). It was observed that the density of total aerobes (104 folds) significantly (p < 0.05) decreased but the population of total anaerobes (209 folds) and Escherichia coli (125 folds) elevated after 30 days of hypoxic stress. The strict anaerobes like Bifidobacterium spp. (3 folds), Bacteroides spp. (134 folds), Lactobacillus spp. (7 folds) and other selected obligate anaerobes like Clostridium perfringens (40 folds), Peptostreptococcus spp. (21 folds) increased in respect to their control population. The growth direction index (GDI) of anaerobic populations was positive and correlated with gas formation aptitude. The activities of CAT and SOD in the large intestinal epithelia decreased significantly (p < 0.05) and GSH/GSSG pool turned into oxidized state with higher MDA (p < 0.05) formation. Histological study revealed the necrotized epithelial layer with higher lymphocytes infiltration in lamina propia accompanied by reduction of acidic mucins secreting goblet cells. From this experiment, it can be hypothesized that high altitude induced hypoxia manipulated the bacterial imprint and damaged the epithelial barrier of the large intestine which may cause systemic infection.


[Molecular mechanism of mutagenesis induced by aflatoxin B1 using a shuttle vector pSP189/mammalian cell system].
AFB1 is one of the most potent carcinogenic mycotoxins, naturally occurred in foods. We applied a new SV40-based shuttle vector pSP189 and African Green kidney cells (VeroE6 cell line), which constitute shuttle vector/mammalian cell system to detect mutagenesis induced by AFB1 and to study the effects of AFB1 on the mutation site, type and sequence specificity of DNA molecular level through sequence analysis of pSP189 target gene SupF TRNA. The results indicated that through various time treatment of AFB1 and rat liver microsome, the mutants were obtained by transformation of E. Coli MBM 7070 with progeny of pSP189 generated during replication in veroE6 cells, which increased gradually with the lapse of time, and this experiment showed a significant dose-response relationship. Most detected mutants were point mutations evidenced by agarose gel electrophoresis analysis. The results of direct sequencing SupF TRNA of 53 independent mutants showed that most mutations (about 84.9%) were single base substitutions, among which 95.2% of base substitutions happened on the site of G:C base pair, the predominant mutation was G:C-->T:A transversion, accounting for 53.3%, followed by G:C-->A:T transition, accounting for 35.6%. AFB1-induced mutations did not distributed randomly, and had mutation hot spots and sequence specificity, which contained 5 base pair sequence 5'-NNTTC-3'. The mutations on the SupF shuttle vector were consistent with the results from studies of oncogene tumor suppressor genes and DNA adduct.


Binding of Protein Factor CTCF within Chicken Genome Alpha-Globin Locus.
A systematic search for DNA fragments containing potential CTCF transcription factor binding sites in the chicken alpha-globin domain and its flanking regions was performed by means of the two-dimension electrophoretic mobility shift assay. For the alpha-globin domain fragments selected, the occupancy by the CTCF in erythroid and lymphoid chicken cells was tested by chromatin immunoprecipitation. Only one of 13 DNA fragments capable of CTCF binding in vitro was efficiently bound to this protein in vivo in erythroid cells, and somewhat less efficiently - in lymphoid cells. So, binding of CTCF to the DNA fragment in vitro in most cases does not mean that this fragment will be occupied by CTCF in the cell nucleus. Yet, CTCF binding in vivo, as a rule, is accompanied by the binding of the protein to this DNA region in vitro. During the erythroid differentiation, no significant changes in CTCF binding to the DNA fragments studied were detected.


The last forty-eight hours of life in a Portuguese palliative care unit: does it differ from elsewhere?
The last few days of life have received significant attention in the literature. Reports have shown similarities and differences between programs. As a palliative care service in a cultural context that has not been reported on, we thought that an audit of our own experience in the care of patients in the last 48 hours of life and a comparison with other programs would be important. A prospective audit was designed to record data for four general domains: general demographic information, symptom prevalence, patient performance status, and perceived level of comfort. The inclusion criteria of patients were: older than 15 years of age (an admission criterion for patients of the unit), diagnosis of cancer, no active cancer-direct treatments, and patients who were on the unit for longer than 48 hours. The audit was completed when the 300th eligible patient died in the unit. Twenty-nine of 300 patients (9.6%) required sedation and the most common cause was delirium. Morphine was the most widely prescribed medication (85% of patients). The subcutaneous route was utilized extensively. Only 12% of the patients received parenteral fluids, usually via hypodermoclisis. Death was considered by staff to have been peaceful in 86% of cases. Our practice appears to mirror that of other palliative care groups.


Early Adolescent and Peer Drinking Homogeneity: Similarities and Differences Among European and North American Countries.
This study examined associations between perceived peer and adolescent alcohol use in European and North American countries. Self-reported monthly alcohol use and adolescents' report of their peers' alcohol use were assessed in nationally representative samples of students aged 11.5 and 13.5 years (n = 11,277) in Greece, Scotland, Switzerland, and the United States who participated in the 2005/2006 Health Behavior in School-Aged Children survey. Cross-national associations between perceived peer and adolescent alcohol use were examined using logistic regressions and interactions by gender and country. Perceived peer and adolescent alcohol use were positively associated in all countries, but the association was notably weaker in Greece than in Scotland (boys), and in Greece compared to Switzerland (girls). Further examination of the underlying processes that explain stronger and weaker associations between perceived peer and adolescent alcohol use in some settings could guide the development of effective, culture-specific interventions.


Topological edge states of a long-range surface plasmon polariton at the telecommunication wavelength.
Confining light by plasmonic waveguides is promising for miniaturizing optical components, while topological photonics has been explored for robust light localization. Here we propose combining the two approaches into a simple periodically perforated plasmonic waveguide (PPW) design exhibiting robust localization of long-range surface plasmon polaritons. We predict the existence of a topological edge state originating from a quantized topological invariant, and numerically demonstrate the viability of its excitation at telecommunication wavelength using near-field and waveguide-based approaches. Strong modification of the radiative lifetime of dipole emitters by the edge state, and its robustness to disorder, are demonstrated.


Familial episodic pain syndrome: a case report and literature review.
The purpose of this case report and literature review is to show that familial episodic pain syndrome (FEPS) is a non-inflammatory genetically inherited pain syndrome. A 3-year-old boy presented at our hospital with pain in both his forearms and lower limbs below the knees for more than 3 years. There were no abnormalities in the blood tests, blood smears, liver and kidney function tests, trace elements tests, cellular immunity test, humoral immunity test, autoantibody tests, C-reactive protein (CRP) test, erythrocyte sedimentation rate (ESR) test, and tumor-related and bone marrow cytology examinations. Additionally, the imaging examination results showed no abnormalities. From the patient's medical history, we found that the mother of the child had a family history of a similar disease. To date, only 21 cases of FEPS3 caused by the sodium voltage-gated channel alpha subunit 11A (SCN11A) gene mutation have been reported. Although the age of onset is different, most of them are inherited in families. The results of the genetic examination revealed that the pain mainly came from the genetic inheritance of the maternal family line. The whole exon gene test revealed that the pain was caused by 2 heterozygous mutations of c.674G > T and c.671T > C in the SCN11A gene.


[Quantification and improvement of speech transmission performance using headphones in acoustic stimulated functional magnetic resonance imaging].
Functional magnetic resonance imaging (fMRI) has made a major contribution to the understanding of higher brain function, but fMRI with auditory stimulation, used in the planning of brain tumor surgery, is often inaccurate because there is a risk that the sounds used in the trial may not be correctly transmitted to the subjects due to acoustic noise. This prompted us to devise a method of digitizing sound transmission ability from the accuracy rate of 67 syllables, classified into three types. We evaluated this with and without acoustic noise during imaging. We also improved the structure of the headphones and compared their sound transmission ability with that of conventional headphones attached to an MRI device (a GE Signa HDxt 3.0 T). We calculated and compared the sound transmission ability of the conventional headphones with that of the improved model. The 95 percent upper confidence limit (UCL) was used as the threshold for accuracy rate of hearing for both headphone models. There was a statistically significant difference between the conventional model and the improved model during imaging (p < 0.01). The rate of accuracy of the improved model was 16 percent higher. 29 and 22 syllables were accurate at a 95% UCL in the improved model and the conventional model, respectively. This study revealed the evaluation system used in this study to be useful for correctly identifying syllables during fMRI.


Crystal structure of the cell cycle-regulatory protein suc1 reveals a beta-hinge conformational switch.
The Schizosaccharomyces pombe cell cycle-regulatory protein suc1, named as the suppressor of cdc2 temperature-sensitive mutations, is essential for cell cycle progression. To understand suc1 structure-function relationships and to help resolve conflicting interpretations of suc1 function based on genetic studies of suc1 and its functional homologs in both lower and higher eukaryotes, we have determined the crystal structure of the beta-interchanged suc1 dimer. Each domain consists of three alpha-helices and a four-stranded beta-sheet, completed by the interchange of terminal beta-strands between the two subunits. This beta-interchanged suc1 dimer, when compared with the beta-hairpin single-domain folds of suc1, reveals a beta-hinge motif formed by the conserved amino acid sequence HVPEPH. This beta-hinge mediates the subunit conformation and assembly of suc1: closing produces the intrasubunit beta-hairpin and single-domain fold, whereas opening leads to the intersubunit beta-strand interchange and interlocked dimer assembly reported here. This conformational switch markedly changes the surface accessibility of sequence-conserved residues available for recognition of cyclin-dependent kinase, suggesting a structural mechanism for beta-hinge-mediated regulation of suc1 biological function. Thus, suc1 belongs to the family of domain-swapping proteins, consisting of intertwined and dimeric protein structures in which the dual assembly modes regulate their function.


Structural characterization and antimicrobial activity of the Zn(II) complex with P113 (demegen), a derivative of histatin 5.
Zinc binding to P113 (or demegen), a 12 amino acid (AKRHHGYKRKFH-NH(2)) fragment of histatin 5, was investigated by means of NMR and CD techniques, yielding delineation of the metal binding site and the 3D structure of the complex in water and in DMSO as well. The three His imidazole and the N-terminus nitrogens were found to act as the zinc coordinating atoms. A comparison with the previously reported Cu(II)-P113 complex disclosed that the two structures were rather diverse, in spite of an identical donor set. The two complexes were also tested for their antimicrobial activity in vitro against seven bacteria and two yeast strains: a minor activity of both complexes vs that of free ligand was given evidence, suggesting both metal ions may possibly play a negative role in vivo.


Maturation affects the maximal pulmonary response to methacholine in rabbits.
Maximal bronchoconstriction in normal adults produces only small reductions in pulmonary function; however, in normal infants severe airway obstruction limits testing to low agonist concentrations. In this study, maximal pulmonary response to methacholine was evaluated in 5 immature (1 month old) and 5 mature (6 months old) rabbits. Animals were anesthetized, paralyzed, and mechanically ventilated via a tracheostomy tube. Changes in pulmonary function were assessed from maximal deflation flow volume curves following inhalation of doubling concentrations of methacholine between 0.6 and 320 mg/mL. Following 320 mg/mL methacholine, the immature rabbits had a greater percent decline in forced vital capacity (FVC) than the mature animals (55 +/- 15% vs. 36 +/- 10%; P < 0.05). At 50% FVC, isovolume flows were measurable in the 5 mature rabbits, and 4 of 5 had plateaus in their dose-response curves. At the higher methacholine doses, only 1 of 5 immature animals had measurable isovolume flows because of the decrease in FVC. There was no significant difference between immature and mature animals in the methacholine dose required to decrease baseline flows by 50%. We conclude that in rabbits maturation affects maximal pulmonary response but not the sensitivity to methacholine.


Interactions of a Rel protein with its inhibitor.
Cactus, a Drosophila homologue of I kappa B, binds to and inhibits Dorsal, a homologue of the p50 and p65 components of NF-kappa B. We describe experiments in yeast with various Dorsal and Cactus derivatives showing that Cactus blocks the DNA binding and nuclear localization functions of Dorsal. In contrast, Dorsal's transcriptional activating region is functional in the Dorsal-Cactus complex. We identify two Dorsal mutants, Dorsal C233R and Dorsal S234P, that escape Cactus inhibition in vivo, and we show that these mutants fail to interact with Cactus in vitro. From this and data of others, we identify the likely surface of Dorsal that binds Cactus. We also describe a modified PCR mutagenesis procedure, easier to use than conventional methods, that produces a library of high complexity.


Cross-sectional and longitudinal tests of the Personality and Role Identity Structural Model (PRISM).
A conceptual hierarchy termed the Personality and Role Identity Structural Model, or PRISM, is offered as a framework for incorporating situational information into trait models. PRISM assumes that personality is structured hierarchically with general dispositions subsuming context-specific dispositions (role identities), which, in turn, subsume role-based thoughts, feelings, and behaviors. At Wave 1 (N = 149), we found that general traits account for commonalities across traits measured within role identities and that role identities mediate the relationship between general traits and role criteria. In a longitudinal follow-up of a subsample of the original participants (Wave 2; N = 62), we found that general traits and role-identity traits were more stable than role experiences over time. Also, changes in role experiences were related to changes in role-identity traits, and, in turn, changes in role-identity traits were related to changes in general traits. The potential of PRISM for use in understanding the development of personality traits is discussed.


The breast cancer prevention trial: should women at risk take tamoxifen?
Tamoxifen is nonsteroidal antiestrogen originally developed in 1996 as a contraceptive. Recently, tamoxifen has been under study within the massive Breast Cancer Prevention Trial-but have we learned enough to recommend tamoxifen for breast cancer prevention? This article looks at the drug therapies, including tamoxifen, currently under development for fighting and preventing breast cancer.


Surgical treatment of necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is a serious problem in nurseries for premature infants and neonatal intensive care units, with a high incidence of morbidity and mortality. During the 5-year period 1973-77, 86 infants with NEC were treated at the University of Iowa Hospitals and Clinics; 43 of them underwent surgery and 43 were treated medically. The surgical candidates were more seriously ill, and their survival rate was 42% compared with 63% for those treated conventionally. Early diagnosis and aggressive surgical treatment of NEC may decrease or even prevent the severity of life-threatening complications.


Evidence for Ah receptor mediation of increased ACTH concentrations in primary cultures of rat anterior pituitary cells exposed to TCDD.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to increase plasma ACTH concentrations in male Sprague-Dawley rats and in male rat primary anterior pituitary cell cultures. The present study examined whether the anterior pituitary effects observed after TCDD exposure are mediated via the Ah receptor (AhR). Primary anterior pituitary cell cultures were prepared from normal 180- to 220-g male rats and the cultures treated with alpha-naphthoflavone (ANF), an antagonist; beta-naphthoflavone (BNF), an agonist; BNF + TCDD; 3,3',4,4',5-pentachlorobiphenyl (PCB), which is known to bind to the AhR; and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), which does not bind the AhR. Support for the TCDD-AhR-mediated increases in ACTH concentrations is provided by the following observations: (1) ANF inhibited both the 1.3- to 2-fold TCDD-induced increase in basal medium and intracellular ACTH concentrations and the 30% TCDD-induced decrease in medium ACTH levels and the 1.2-fold increase in intracellular ACTH levels in corticotropin-releasing hormone (CRH)-stimulated cells, (2) BNF increased basal medium (1.7-fold) and intracellular (1.3-fold) ACTH concentrations, (3) BNF + TCDD demonstrated additivity by increasing basal medium (2.4-fold) and intracellular (1.7-fold) ACTH concentrations, (4) PCB increased basal medium (1.8- to 2.1-fold) and intracellular (1.3- to 1.8-fold) ACTH concentrations and inhibited medium ACTH secretion in CRH stimulated cells by 24-43%, and (5) HCB did not effect basal or CRH stimulated medium and intracellular ACTH concentrations. From this study it appears that TCDD-induced changes in ACTH secretion and synthesis by cultured anterior pituitary cells is mediated through the Ah receptor.


Neutrophil: A New Player in Metastatic Cancers.
The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an "audience" in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, with a specific focus on their pro-metastatic functions. We also discuss the potential and challenges of neutrophils as therapeutic targets. A better understanding the role of neutrophils in cancer will discover new mechanisms of metastasis and develop new immunotherapies by targeting neutrophils.


[Antidepressant drugs and central monoaminergic receptors].
A characteristic feature of antidepressant therapy is the lag phase in onset of clinical efficacy. This applies to both typical tricyclics agents and atypical antidepressants, mianserin or maprotiline. Attempts to delineate the molecular mechanisms of action of antidepressants on the basis of acute studies are limited value, and increasing attention is being focused on resultant adaptive changes stemming from their chronic treatment. The drug-induced adaptive modification can occur both pre-and postsynaptically. Regarding presynaptic sites, adaptation in the synthesis and release of norepinephrine (NE) and presynaptic alpha2-receptors and dopamine autoreceptors occur. However, the changes cannot be regarded as being primarily responsible for the therapeutic action of antidepressants. Chronic antidepressant treatments affect also post-synaptic aminergic systems eliciting a reduction of beta-adrenoceptors and in the sensitivity of NE-stimulated adenylate cyclase (NE-AC), and a decrease of 5HT2-receptors. The postsynaptic changes are more pertinent to the mechanisms of action of the drug. However, these properties can not extend to all atypical antidepressants. Fluoxetine, trazodone, alprazolam or MIA fails to alter beta-receptor density or the NE-AC sensitivity, and electroconvulsive therapy produces an increases in 5HT2 sites. More recently, new experiments demonstrate 1) a biomolecular linkage between 5HT and NE neuronal systems at the level of beta-receptors; 2) an acceleration of beta-receptor reduction with combined administration of antidepressants and alpha 2-receptor antagonists; 3) an existence of imipramine-like substance (endocoid) in the brain and a reduction of [3H]imipramine binding sites after chronic treatment with imipramine. While the end result downstream may be the same clinical efficacy, the initial biochemical steps leading to this goal may not be identical for all forms of antidepressants. It is expected that the new approaches can lead to the finding a common mechanism of action to all form of antidepressants.


Hydroxide ion binding to methemerythrin. An investigation by resonance Raman and difference spectroscopy.
The pH dependence for the interconversion of the acid and base forms of methemerythrin from Themiste dyscritum was investigated by difference spectroscopy. A new technique was designed to be able to study mixtures without knowledge of extinction coefficients or exact protein concentrations. The resultant pKa value of 8.4 proved that T. dyscritum hemerythrin crystals used for previous X-ray crystallographic studies at pH less than or equal to 6.5 were in the acid form. Since this material contains a 5-coordinate iron atom with no evidence of a ligated water molecule, it is more appropriately referred to as methemerythrin than aquomethemerythrin. The presence of an iron-bound hydroxide in the base form of methemerythrin was verified by resonance Raman spectroscopy for both T. dyscritum and Phascolopsis gouldii. At pH greater than 9, the protein from either species exhibited a new feature at 490 cm-1 that shifted to 518 cm-1 in D2O and was assigned to a coupled Fe-OH stretching and O-H bending vibration. Thus, hydroxomethemerythrin is the correct designation for the base form of the protein. The other resonance-enhanced vibration, the Fe-O-Fe symmetric stretch, was observed at 506 cm-1 in hydroxomethemerythrin and at 511 cm-1 in methemerythrin and was unaffected by deuteration. Addition of perchlorate to methemerythrin had no effect on the Raman spectrum, despite its known role in stabilizing the met form relative to the hydroxomet form.