Characterizing the developmental transcriptome of the oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae) through comparative genomic analysis with Drosophila melanogaster utilizing modENCODE datasets.
The oriental fruit fly, Bactrocera dorsalis, is an important pest of fruit and vegetable crops throughout Asia, and is considered a high risk pest for establishment in the mainland United States. It is a member of the family Tephritidae, which are the most agriculturally important family of flies, and can be considered an out-group to well-studied members of the family Drosophilidae. Despite their importance as pests and their relatedness to Drosophila, little information is present on B. dorsalis transcripts and proteins. The objective of this paper is to comprehensively characterize the transcripts present throughout the life history of B. dorsalis and functionally annotate and analyse these transcripts relative to the presence, expression, and function of orthologous sequences present in Drosophila melanogaster. We present a detailed transcriptome assembly of B. dorsalis from egg through adult stages containing 20,666 transcripts across 10,799 unigene components. Utilizing data available through Flybase and the modENCODE project, we compared expression patterns of these transcripts to putative orthologs in D. melanogaster in terms of timing, abundance, and function. In addition, temporal expression patterns in B. dorsalis were characterized between stages, to establish the constitutive or stage-specific expression patterns of particular transcripts. A fully annotated transcriptome assembly is made available through NCBI, in addition to corresponding expression data. Through characterizing the transcriptome of B. dorsalis through its life history and comparing the transcriptome of B. dorsalis to the model organism D. melanogaster, a database has been developed that can be used as the foundation to functional genomic research in Bactrocera flies and help identify orthologous genes between B. dorsalis and D. melanogaster. This data provides the foundation for future functional genomic research that will focus on improving our understanding of the physiology and biology of this species at the molecular level. This knowledge can also be applied towards developing improved methods for control, survey, and eradication of this important pest.


Association of heated tobacco product use with smoking cessation in Chinese cigarette smokers in Hong Kong: a prospective study.
Heated tobacco products (HTPs) are increasingly popular worldwide, but whether they aid or undermine cigarette abstinence remains uncertain. We examined the predictors of HTP initiation and the prospective association of HTP use with cigarette abstinence in community-based smokers in Hong Kong. Secondary analysis of a randomised clinical trial aimed to evaluate the effectiveness of brief advice and referral for smoking cessation. The interventions were not related to HTP use. 1213 carbon monoxide-verified daily cigarette smokers with intentions to quit or reduce smoking proactively recruited from community sites throughout Hong Kong MAIN EXPOSURE: Current (past 7 day) use of HTP at baseline. Self-reported 7-day point-prevalence cigarette abstinence at 6 months (exclusive use of HTP permitted). At baseline, 201 (16.6%) and 60 (4.9%) were ever and current HTP users, respectively. During the 6-month follow-up period, 110 of 1012 (10.9%) never users at baseline initiated HTPs. Younger age and higher education significantly predicted initiation. After adjusting for sociodemographic, smoking-related and quitting-related factors, current HTP use at baseline was not associated with cigarette abstinence at 6 months (adjusted prevalence ratio (aPR) 1.08, 95% CI 0.63 to 1.85). The results were similar in persistent users from baseline to 1-month/3-month follow-up (vs non-users; aPR 1.14, 95% CI 0.57 to 2.29). Use of smoking cessation service between baseline and 3-month follow-up significantly predicted cigarette abstinence (aPR 1.70, 95% CI 1.26 to 2.30). HTP use was not associated with cigarette abstinence at 6 months in a community-based cohort of smokers with intentions to quit or reduce smoking. Trial registration details ClinicalTrials.gov, NCT03565796.


The Effects of Crop Intensification on the Diversity of Native Pollinator Communities.
Increases in agricultural conversion are leading to declines in native grasslands and natural resources critical for beneficial insects. However, little is known regarding how these changes affect pollinator diversity. Land use types were categorized within 300 m and 3 km radii of pollinator sampling locations in Brookings County, SD. Pollinator abundance and species richness were regressed on the proportion of the landscape dedicated to row crops, grass and pasture, forage crops, small grains, and aquatic habitats using variance components modeling. Row crops had a negative effect on bee abundance at 300 m, after fixed effects modeling accounted for outliers skewing this relationship. At 3 km, corn positively affected bee abundance and richness, while soybean acreage decreased species richness. The landscape matrix of outlying sites consisted of large monocultured areas with few alternative habitat types available, leading to inflated populations of Melissodes and Halictidae. Syrphids had a positive parabolic relationship between diversity and row crops, indicating potential for competitive exclusion from intermediate landscapes. Unlike other studies, landscape diversity within 300 m was not found to significantly benefit pollinator diversity. Within especially agriculturally developed areas of the region, high abundances of pollinators suggest selection for a few dominant species. There was no effect of forage crops or aquatic habitats on pollinator diversity, indicating that less highly managed areas still represent degraded habitat within the landscape. Incorporating pollinator-friendly crops at the farm level throughout the region is likely to enhance pollinator diversity by lessening the negative effects of large monocultures.


Comparison of Two Naloxone Regimens in Opioid-dependent Methadoneoverdosed Patients: A Clinical Trial Study.
Methadone toxicity is one of the major causes of death in opioiddependent individuals. We aimed to compare two different protocols of naloxone administration in terms of reversal of overdose signs and symptoms and frequency of complications in opioid-dependent methadone-intoxicated patients. One-hundred opioid-dependent patients with signs/symptoms of methadone overdose were included. The patients were consecutively assigned into Tintinalli (group 1) or Goldfrank regimen protocol (group 2) of naloxone administration. Group 1 received naloxone with the dose 0.1 mg given every two to three minutes while group 2 received naloxone with the initial dose of 0.04 mg increasing to 0.4, 2, and 10 mg every two to three minutes to reverse respiratory depression. They were then compared regarding reversal of toxicity and risk of development of complications. The time to reversal of the overdose signs/symptoms was significantly less in Goldfrank regimen protocol (P<0.001). Frequency of withdrawal syndrome and recurrence of respiratory depression were not significantly different between the two groups. Aspiration pneumonia and intubation were more frequent in group 2, as well. It seems that gradual titration of naloxone by Tintinalli protocol can reduce major complications compared to the Goldfrank regimen. However, this protocol was not perfect in opioid-dependent methadone-overdosed patients, either, since it could induce complications, as well. We may need new protocols in overdosed opioid-dependent patients.


Phase transitions in wave turbulence.
We consider turbulence within the Gross-Pitaevsky model and look into the creation of a coherent condensate via an inverse cascade originating at small scales. The growth of the condensate leads to a spontaneous breakdown of statistical symmetries of overcondensate fluctuations: First, isotropy is broken, then a series of phase transitions marks the changing symmetry from twofold to threefold to fourfold. We describe respective anisotropic flux flows in the k space. At the highest level reached, we observe a short-range positional and long-range orientational order (as in a hexatic phase). In other words, the more one pumps the system, the more ordered the system becomes. The phase transitions happen when the system is pumped by an instability term and does not occur when pumped by a random force. We thus demonstrate nonuniversality of an inverse-cascade turbulence with respect to the nature of small-scale forcing.


Potential energy surface crossings and the mechanistic spectrum for intramolecular electron transfer in organic radical cations.
The structure of the potential energy surface for the intramolecular electron transfer (IET) of four different model radical cations has been determined by using reaction path mapping and conical intersection optimization at the ab initio CASSCF level of theory. We show that, remarkably, the calculated paths reside in regions of the ground-state energy surface whose structure can be understood in terms of the position and properties of a surface crossing between the ground and the first excited state of the reactant. Thus, in the norbornadiene radical cation and in an analogue compound formed by two cyclopentene units linked by a norbornyl bridge, IET proceeds along direct-overlap and super-exchange concerted paths, respectively, that are located far from a sloped conical intersection point and in a region where the excited-state and ground-state surfaces are well separated. A second potential energy surface structure has been documented for 1,2-diamino ethane radical cation and features two parallel concerted (direct) and stepwise (chemical) paths. In this case a peaked conical intersection is located between the two paths. Finally, a third type of energy surface is documented for the bismethyleneadamantane radical cation and occurs when there is, effectively, a seam of intersection points (not a conical intersection) which separates the reactant and product regions. Since the reaction path cannot avoid the intersection, IET can only occur nonadiabatically. These IET paths indicate that quite different IET mechanisms may operate in radical cations, revealing an unexpectedly enriched and flexible mechanistic spectrum. We show that the origin of each path can be analyzed and understood in terms of the one-dimensional Marcus-Hush model.


RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma.
Sarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized. RNA sequencing (RNA-seq) was performed on adjacent benign, clear cell, and sarcomatoid components from clinical specimens with sarcomatoid mRCC. M phase and cell-cycle pathways were enriched in sarcomatoid versus adjacent clear cell components, suggesting greater cell proliferation. The expression of aurora kinase A (AURKA) was increased as part of these pathways, and its increased expression was validated by quantitative PCR (qPCR). Immunohistochemical (IHC) analysis revealed that AURKA levels were increased in sarcomatoid tissue compared with their benign or clear cell parts. The increase in AURKA correlated with increased mTOR pathway activity, as evidenced by increased expression of phosphorylated mTOR (S2448) and ribosomal protein S6K (T389). When AURKA was stably expressed in a RCC cell line (Renca), it resulted in increased expression and activity of mTOR, suggesting that overexpression of AURKA can activate the mTOR pathway. These results warrant the analysis of a larger clinical cohort and suggest that targeting AURKA and/or mTOR in patients with sarcomatoid mRCC should be explored. Comparative RNA-seq of adjacent sarcomatoid and clear cell histology of RCC indicates a proliferative phenotype and increased AURKA-dependent activation of mTOR signaling in sarcomatoid RCC, which could be targeted by available agents.


ADP-ribosyltransferase activity of Legionella pneumophila is stimulated by the presence of macrophage lysates.
ADP-ribosyltransferases are among the most biologically active of bacterial products in eukaryotes, and act by transferring the ADP-ribosyl moiety of NAD to acceptor proteins. The detection of ADP-ribosylated Legionella proteins in ultrasonic lysates of Legionella pneumophila strain Philadelphia 1 is reported. The ADP-ribosylating reaction was not influenced by addition of guinea pig spleen-cell and lung-cell lysates, but was considerably increased in the presence of lysates of guinea pig peritoneal macrophages, which are known to be target cells for virulent Legionella. It is suggested that ADP-ribosylation may play an important role in the multiplication of this pathogenic bacterium in the tissues and cells of infected organisms.


The Rho-guanine nucleotide exchange factor Solo decelerates collective cell migration by modulating the Rho-ROCK pathway and keratin networks.
Collective cell migration plays crucial roles in tissue remodeling, wound healing, and cancer cell invasion. However, its underlying mechanism remains unknown. Previously, we showed that the RhoA-targeting guanine nucleotide exchange factor Solo (ARHGEF40) is required for tensile force-induced RhoA activation and proper organization of keratin-8/keratin-18 (K8/K18) networks. Here, we demonstrate that Solo knockdown significantly increases the rate at which Madin-Darby canine kidney cells collectively migrate on collagen gels. However, it has no apparent effect on the migratory speed of solitary cultured cells. Therefore, Solo decelerates collective cell migration. Moreover, Solo localized to the anteroposterior regions of cell-cell contact sites in collectively migrating cells and was required for the local accumulation of K8/K18 filaments in the forward areas of the cells. Partial Rho-associated protein kinase (ROCK) inhibition or K18 or plakoglobin knockdown also increased collective cell migration velocity. These results suggest that Solo acts as a brake for collective cell migration by generating pullback force at cell-cell contact sites via the RhoA-ROCK pathway. It may also promote the formation of desmosomal cell-cell junctions related to K8/K18 filaments and plakoglobin.


Relaxation Techniques in Low Back Pain Patients: A Randomized Controlled Trial.
Low back pain (LBP) is a common problem, affecting 11% of the population in Greece. Pain can last upwards of 6 wk and impact functional ability and quality of life. Treating LBP often includes the use of alternative methods, such as relaxation techniques. We tested whether relaxation techniques could reduce stress and pain and improve quality of life. Patients engaged in methods such as diaphragmatic breathing, progressive muscular relaxation, autogenic training, and guided imagery. The treatment group consisted of 31 randomized patients and the control group had 33. The treatment group followed an 8-wk relaxation program with weekly sessions and practiced techniques every day by listening to a compact disk at home (2×/d). The control group did not follow relaxation techniques. No statistically significant differences were present regarding the Perceived Stress Scale, body-mass index, and satisfaction with functional ability. However, statistically significant differences were found in the Brief Pain Inventory score and multidimensional locus of control. We also found decreases in all three cortisol measurements for the treatment group. Relaxation techniques provide positive results in pain reduction and cortisol decrease and must therefore be incorporated into rehabilitation protocols.


Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure.
Recent research has disclosed a tight connection between obesity, metabolic gut microbial activities and host health. Obtaining a complete understanding of this relationship remains a major goal. Here, we conducted a comparative metagenomic and metaproteomic investigation of gut microbial communities in faecal samples taken from an obese and a lean adolescent. By analysing the diversity of 16S rDNA amplicons (10% operational phylogenetic units being common), 22 Mbp of consensus metagenome sequences (~70% common) and the expression profiles of 613 distinct proteins (82% common), we found that in the obese gut, the total microbiota was more abundant on the phylum Firmicutes (94.6%) as compared with Bacteroidetes (3.2%), although the metabolically active microbiota clearly behaves in a more homogeneous manner with both contributing equally. The lean gut showed a remarkable shift towards Bacteroidetes (18.9% total 16S rDNA), which become the most active fraction (81% proteins). Although the two gut communities maintained largely similar gene repertoires and functional profiles, improved pili- and flagella-mediated host colonization and improved capacity for both complementary aerobic and anaerobic de novo B(12) synthesis, 1,2-propanediol catabolism (most likely participating in de novo B(12) synthesis) and butyrate production were observed in the obese gut, whereas bacteria from lean gut seem to be more engaged in vitamin B(6) synthesis. Furthermore, this study provides functional evidence that variable combinations of species from different phyla could 'presumptively' fulfil overlapping and/or complementary functional roles required by the host, a scenario where minor bacterial taxa seem to be significant active contributors.


Topology and geometry under the nonlinear electromagnetic spotlight.
For many materials, a precise knowledge of their dispersion spectra is insufficient to predict their ordered phases and physical responses. Instead, these materials are classified by the geometrical and topological properties of their wavefunctions. A key challenge is to identify and implement experiments that probe or control these quantum properties. In this Review, we describe recent progress in this direction, focusing on nonlinear electromagnetic responses that arise directly from quantum geometry and topology. We give an overview of the field by discussing theoretical ideas, experiments and the materials that drive them. We conclude by discussing how these techniques can be combined with device architectures to uncover, probe and ultimately control quantum phases with emergent topological and correlated properties.


Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis.
Extracellular adenosine is a potent immunosuppressor that accumulates during tumor growth. We performed proof-of-concept studies investigating the therapeutic potential and mechanism of action of monoclonal antibody (mAb)-based therapy against CD73, an ecto-enzyme overexpressed on breast-cancer cells that catalyzes the dephosphorylation of adenosine monophosphates into adenosine. We showed that anti-CD73 mAb therapy significantly delayed primary 4T1.2 and E0771 tumor growth in immune-competent mice and significantly inhibited the development of spontaneous 4T1.2 lung metastases. Notably, anti-CD73 mAb therapy was essentially dependent on the induction of adaptive anti-tumor immune responses. Knockdown of CD73 in 4T1.2 tumor cells confirmed the tumor-promoting effects of CD73. In addition to its immunosuppressive effect, CD73 enhanced tumor-cell chemotaxis, suggesting a role for CD73-derived adenosine in tumor metastasis. Accordingly, administration of adenosine-5'-N-ethylcarboxamide to tumor-bearing mice significantly enhanced spontaneous 4T1.2 lung metastasis. Using selective adenosine-receptor antagonists, we showed that activation of A2B adenosine receptors promoted 4T1.2 tumor-cell chemotaxis in vitro and metastasis in vivo. In conclusion, our study identified tumor-derived CD73 as a mechanism of tumor immune escape and tumor metastasis, and it also established the proof of concept that targeted therapy against CD73 can trigger adaptive anti-tumor immunity and inhibit metastasis of breast cancer.


The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon.
The heat and ethanol stress response of Bacillus licheniformis DSM13 was analyzed at the transcriptional and/or translational level. During heat shock, regulons known to be heat-induced in Bacillus subtilis 168 are upregulated in B. licheniformis, such as the HrcA, SigB, CtsR, and CssRS regulon. Upregulation of the SigY regulon and of genes controlled by other extracytoplasmic function (ECF) sigma factors indicates a cell-wall stress triggered by the heat shock. Furthermore, tryptophan synthesis enzymes were upregulated in heat stressed cells as well as regulons involved in usage of alternative carbon and nitrogen sources. Ethanol stress led to an induction of the SigB, HrcA, and CtsR regulons. As indicated by the upregulation of a SigM-dependent protein, ethanol also triggered a cell wall stress. To characterize the SigB regulon of B. licheniformis, we analyzed the heat stress response of a sigB mutant. It is shown that the B. licheniformis SigB regulon comprises additional genes, some of which do not exist in B. subtilis, such as BLi03885, encoding a hypothetical protein, the Na/solute symporter gene BLi02212, the arginase homolog-encoding gene BLi00198 and mcrA, encoding a protein with endonuclease activity.


In Vivo Characterization of a Red Light-Activated Vasodilation: A Photobiomodulation Study.
Nitric oxide dependent vasodilation is an effective mechanism for restoring blood flow to ischemic tissues. Previously, we established an ex vivo murine model whereby red light (670 nm) facilitates vasodilation via an endothelium derived vasoactive species which contains a functional group that can be reduced to nitric oxide. In the present study we investigated this vasodilator in vivo by measuring blood flow with Laser Doppler Perfusion imaging in mice. The vasodilatory nitric oxide precursor was analyzed in plasma and muscle with triiodide-dependent chemiluminescence. First, a 5-10 min irradiation of a 3 cm2 area in the hind limb at 670 nm (50 mW/cm2) produced optimal vasodilation. The nitric oxide precursor in the irradiated quadriceps tissue decreased significantly from 123 ± 18 pmol/g tissue by both intensity and duration of light treatment to an average of 90 ± 17 pmol/g tissue, while stayed steady (137 ± 21 pmol/g tissue) in unexposed control hindlimb. Second, the blood flow remained elevated 30 min after termination of the light exposure. The nitric oxide precursor content significantly increased by 50% by irradiation then depleted in plasma, while remained stable in the hindlimb muscle. Third, to mimic human peripheral artery disease, an ameroid constrictor was inserted on the proximal femoral artery of mice and caused a significant reduction of flow. Repeated light treatment for 14 days achieved steady and significant increase of perfusion in the constricted limb. Our results strongly support 670 nm light can regulate dilation of conduit vessel by releasing a vasoactive nitric oxide precursor species and may offer a simple home-based therapy in the future to individuals with impaired blood flow in the leg.


Conservation of immune responses to proteins isolated by preparative polyacrylamide gel electrophoresis from the outer membrane of nontypeable Haemophilus influenzae.
Outer membrane proteins P2, P4, and P6 and two with molecular masses of 26 and 28 kDa have been purified from a strain of nontypeable Haemophilus influenzae by a preparative form of polyacrylamide gel electrophoresis (PAGE). Outer membrane protein P6, with a molecular mass of 16 kDa (determined by sodium dodecyl sulfate [SDS]-PAGE) was purified by both native PAGE and SDS-PAGE from three strains of nontypeable H. influenzae and one strain of type b H. influenzae. The same conditions were required for purification from each strain. The suitability of proteins isolated by these methods was assessed by studying the immune response of rats immunized with P6 in incomplete Freund's adjuvant into the Peyer's patches. P6 purified by either native PAGE or SDS-PAGE did not differ significantly from P6 purified by gel filtration and anion-exchange chromatography in the ability to enhance pulmonary clearance of live bacteria. This study also investigated the effects of SDS on P2 immunological responses in vivo and the effects of the reagents Zwittergent and sodium lauryl sarcosinate on outer membrane protein lymphocyte-proliferative responses in vitro. It was found that the presence of SDS in the immunization emulsion enhanced the antigen-specific cell-mediated response but suppressed the antigen-specific antibody responses. The presence of residual traces of Zwittergent in an outer membrane protein preparation inhibited antigen-specific cell-mediated proliferation, whereas extraction of outer membrane proteins with sodium lauryl sarcosinate did not inhibit antigen-specific proliferation. These results demonstrate that preparative PAGE is a suitable method for the purification of proteins from the outer membrane of H. influenzae required for investigation of their immunological significance as vaccine candidates and that traces of reagents used during protein purification may play an important role in determining the success of in vivo and in vitro studies.


Two-photon excited fluorescence in the LYB:Eu monoclinic crystal: towards a new scheme of single-beam dual-voxel direct laser writing in crystals.
We report on two-photon excited fluorescence in the oriented Eu(3+)doped LYB monoclinic crystal under femtosecond laser tight focusing. Due to spatial walk-off, the two polarization modes of the incident femtosecond beam simultaneously provide the independent excitation of two distinct focuses, leading to a single-beam dual-voxel nonlinear excitation of fluorescence below material modification threshold. These observations emphasize on the anisotropy of both two-photon absorption as well as fluorescence emission. They demonstrate the localized control of the nonlinear energy deposit, thanks to the adjustment of both the input power and polarization, by properly balancing the injected energy in each voxel. Such approach should be considered for future direct laser writing of waveguides in propagation directions out of the dielectric axes, so as to optimally cope with the highly probable anisotropy of laser-induced material modification thresholds in these crystals. These results open new ways for further potential developments in direct laser writing as the simultaneous inscription of double-line structures for original waveguides processes.


Dorsal intercarpal ligament capsulodesis for chronic, static scapholunate dissociation: clinical results.
The purpose of this study was to review and report the results of using a new procedure, the dorsal intercarpal ligament capsulodesis (DILC), to treat a group of patients with chronic flexible scapholunate dissociation. This was a prospective study of 21 patients (22 wrists), ranging in age from 16 to 62 years followed up for 1 to 4 years. For this study all patients returned to complete a questionnaire and have a physical examination performed by physicians and therapists independent of the treating surgeons and to obtain standardized radiographs of the wrists. Patient demographics, mechanism of injury, range of motion, and grip strength were recorded. Patients completed the Mayo wrist, Short-Form (SF)-12, and Disabilities of Arm, Shoulder and Hand (DASH) questionnaires. Results showed there were significant improvements in scapholunate angle and scapholunate gap at final follow-up examination, with minor loss of range of motion and grip strength. Patients were satisfied with the outcomes, showing an average score of 17 on the DASH and 83 on the SF-12. The DILC procedure is a reasonable option for treating chronic scapholunate dissociation. The procedure has conceptual advantages to recommend it: it avoids a tether between radius and scaphoid and keeps the proximal carpal row linked as a functional unit. It reduces the scapholunate angle and gap. Overall the results to date are quite encouraging.


An electrochemical cell for in operando studies of lithium/sodium batteries using a conventional x-ray powder diffractometer.
An electrochemical cell has been designed for powder X-ray diffraction studies of lithium ion batteries (LIB) and sodium ion batteries (SIB) in operando with high time resolution using a conventional powder X-ray diffractometer. The cell allows for studies of both anode and cathode electrode materials in reflection mode. The cell design closely mimics that of standard battery testing coin cells and allows obtaining powder X-ray diffraction patterns under representative electrochemical conditions. In addition, the cell uses graphite as the X-ray window instead of beryllium, and it is easy to operate and maintain. Test examples on lithium insertion/extraction in two spinel-type LIB electrode materials (Li4Ti5O12 anode and LiMn2O4 cathode) are presented as well as first results on sodium extraction from a layered SIB cathode material (Na0.84Fe0.56Mn0.44O2).


Anti-idiotypic regulatory responses induced by vaccination with DNA encoding murine TCR Valpha5 and Vbeta2.
There is evidence suggesting that anti-idiotypic regulation against T cells plays a role in maintaining homeostasis in the immune system, although its mechanism is not fully understood. By using DNA constructs encoding the TCR Valpha5.2 and Vbeta2.1 chains derived from an ovalbumin (OVA)-specific T cell clone (OVA-T), we herein demonstrated that vaccination with TCR-DNA effectively induced anti-idiotypic cellular as well as humoral responses. Serum samples from the TCR-DNA-vaccinated BALB/c mice were able to stain T cells in an idiotype-specific manner. CD4+ T cells from the TCR-DNA-vaccinated mice proliferated in response to stimulation with irradiated syngeneic OVA-T cells and secreted interferon-gamma but very little IL-4. Splenocytes from the TCR-DNA-vaccinated mice showed strong idiotype-specific CTL activity against the OVA-T cells. Furthermore, adoptive transfer of the CD4+ or CD8+ T cells from the TCR-DNA-vaccinated mice resulted in hyporesponsiveness of syngeneic recipients. These results demonstrated that vaccination with DNA encoding TCR can effectively activate anti-idiotypic regulatory responses in vivo and thus providing a useful way for immunological intervention.


Selective detection of urease-producing bacteria on the genital skin surface in patients with incontinence-associated dermatitis.
We aimed to investigate the association between the presence of cutaneous urease-producing bacteria and the development of incontinence-associated dermatitis (IAD) using an original urea agar medium as a step toward developing advanced preventive measures. In previous clinical assessments, we developed an original urea agar medium to detect urease-producing bacteria via the medium's colour changes. In a cross-sectional study, specimens were collected via the swabbing technique at genital skin sites in 52 stroke patients hospitalised in a university hospital. The primary objective was to compare the presence of urease-producing bacteria between the IAD and no-IAD groups. Determining the bacterial count was the secondary objective. The prevalence of IAD was 48%. A significantly higher detection rate of urease-producing bacteria was observed in the IAD group than in the no-IAD group (P = .002) despite the total number of bacteria being equivalent between them. In conclusion, we discovered that there was a significant association between the presence of urease-producing bacteria and IAD development in hospitalised stroke patients.


Transient response in granular quasi-two-dimensional bounded heap flow.
We study the transition between steady flows of noncohesive granular materials in quasi-two-dimensional bounded heaps by suddenly changing the feed rate. In both experiments and simulations, the primary feature of the transition is a wedge of flowing particles that propagates downstream over the rising free surface with a wedge front velocity inversely proportional to the square root of time. An additional longer duration transient process continues after the wedge front reaches the downstream wall. The entire transition is well modeled as a moving boundary problem with a diffusionlike equation derived from local mass balance and a local relation between the flux and the surface slope.


A cDNA clone coding for a novel allergen, Cla h III, of Cladosporium herbarum identified as a ribosomal P2 protein.
Mold allergens represent a major cause of atopic disorders. Progress in the molecular characterization of allergens has been hampered by batch-to-batch variation and poor yields in mold extracts. In the present study, we established a cDNA library in lambda ZAP II by using mRNA isolated from a major allergen-producing mold, Cladosporium herbarum. From this library, a novel allergen has been cloned and sequenced. The clone encodes a full length protein of 111 amino acids with a molecular mass of 11.1 kDa and pI of 3.94. By using sequence homology analysis, the allergen was found to belong to the ribosomal P2 protein family. Approximately 60% peptide sequence homology was found between the cloned protein and other known fungal ribosomal P2 proteins. In addition to conserved C-terminal sequences and serine blocks for phosphorylation in all eukaryotic ribosomal P2 proteins, this protein also contains a potential N-glycosylation site at position 15-17. Northern blots demonstrated that mRNA molecules of this gene are present even at late stages of culture. The gene was expressed in Escherichia coli by using the pMAL-2c system, and murine antisera against the recombinant allergen (rCh2.1) were generated. The antisera revealed that the native allergen corresponding to rCh2.1 was present in extracts prepared by grinding mycelia under liquid nitrogen in the presence of protease inhibitors, but absent in extracts prepared by conventional methods. This result indicates the usefulness of recombinant allergens in characterization and standardization of mold allergenic extracts.


Oxidative stress, protein carbonylation and heat shock proteins in the black tiger shrimp, Penaeus monodon, following exposure to endosulfan and deltamethrin.
The impact of commonly used pesticides, endosulfan and deltamethrin, on the molecular stress level in black tiger shrimp Penaeus monodon, was assessed using classical oxidative stress biomarkers, protein carbonylation profiles, and levels of heat shock proteins. Results showed that 4 days exposure to 0.1 μg L(-1) deltamethrin significantly (p<0.05) increased lipid peroxidation (LPO) level in gills (64.3 ± 3.2 compared to 34.2 ± 5.3 nmol MDA equiv.g(-1) tissue at day 0). However, no pesticide treatment had significant effect on the activities of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). Carbonylated protein profiles were determined on gills following 2,4-dinitrophenylhydrazine derivatization and 2D-PAGE along with Western blotting. Immunoblotting with dinitrophenol-specific antibody revealed 17 protein spots carbonylated in response to 4 days exposure to 0.1 μg L(-1) deltamethrin while 24 protein spots specifically oxidized at day 0 were no longer detected after deltamethrin treatment. On the other hand, endosulfan exposure at 0.1 and 1 μg L(-1) induced up to 2.1-fold increase of HSP90 level in muscle. This approach is providing new insights into the molecular impacts of deltamethrin and endosulfan on an economically important crustacean. While deltamethrin has shown a pro-oxidant effect in gills, endosulfan exposure rather induced proteotoxic effects in muscles. This argues that LPO level, protein carbonylation specificities, and HSP90 levels may be potential discriminating biomarkers to assess the chemical stress level in farm shrimp.


Champagne wine polyphenols protect primary cortical neurons against peroxynitrite-induced injury.
White wines are generally low in polyphenol content as compared to red wines. However, Champagne wines have been shown to contain relatively high amounts of phenolic acids that may exert protective cellular actions in vivo. In this study, we have investigated the potential neuroprotective effects of Champagne wine extracts, and individual phenolics present in these extracts, against peroxynitrite-induced injury. Organic and aqueous Champagne wine extracts exhibited potent neuroprotective activity against peroxynitrite-induced injury at low concentrations (0.1 microg/mL). This protection appeared to be in part due to the cellular actions of individual components found in the organic extracts, notably tyrosol, caffeic acid, and gallic acid. These phenolics were observed to exert potent neuroprotection at concentrations between 0.1 and 10 microM. Together, these data suggest that polyphenols present in Champagne wine may induce a neuroprotective effect against oxidative neuronal injury.


Phase II Randomized, Clinical Trial Evaluating 2 Schedules of Low-Intensity Shockwave Therapy for the Treatment of Erectile Dysfunction.
To evaluate safety and clinical response of Low-intensity Shockwave Therapy (Li-SWT) for the treatment of erectile dysfunction. A single-institution, 2 arm, phase II randomized clinical trial was conducted between February 2017 and April 2019. Patients were randomized into 2 groups, with Li-SWT delivering a total of 3,600 shocks over 5 days (720 once a day, Group A) or over 2 weeks (600 once a day, 3 times a week, Group B). Patients were evaluated for the safety of therapy and completed the International Index of Erectile Function-Erectile Function domain and the Erectile Hardness Scale assessment at baseline, and at 1, 3, and 6 months visits. Among 87 evaluable patients, 45 and 42 were allocated to Groups A and B treatment schedules, respectively, and 80 patients (40 per group) completed the 6-month evaluation. No adverse events were reported during treatment or during follow-up. There were statistically significant (P < .05) improvements in International Index of Erectile Function-Erectile Function score (mean increase of 2.7 [95% CI = 1.2, 4.2] and 2.7 points [95% CI = 1.4, 4.1] for Groups A and B, respectively) and in Erectile Hardness Scale (mean increase of 0.6 points (95% CI = 0.3, 0.8) and 0.5 (95% CI = 0.2, 0.8) for Groups A and B, respectively) at 6 months, with no differences between groups. No difference in outcomes was found when Li-SWT 3,600 shocks were delivered over 1 or 2 weeks at 6 months follow-up and both schedules were safe with no adverse events during or after treatment. Further trials with longer follow-up and sham arm will provide valuable information regarding treatment efficacy and durability. Patel P, Katz J, Lokeshwar SD, et al. Phase II Randomized, Clinical Trial Evaluating 2 Schedules of Low-Intensity Shockwave Therapy for the Treatment of Erectile Dysfunction. Sex Med 2020;8:214-222.


Estrogens and bone health in men.
It has generally been held that estrogen and testosterone are the major sex steroids regulating bone metabolism in women and men, respectively. However, the description of several "experiments of nature" led to a reconsideration of this notion. Thus, a male carrying homozygous mutations in the ER-alpha gene and two males with homozygous mutations in the aromatase gene had osteopenia, unfused epiphyses, and elevated indices of bone turnover. Though these findings indicated that estrogen plays a role in regulating the male skeleton, they left unresolved the issue of whether estrogen acted on the male skeleton mainly to enhance bone mass acquisition during growth and maturation, or whether it also acted to retard bone loss in aging individuals. To address this issue, several cross-sectional observational studies have related bone mineral density (BMD) to sex steroids in elderly men, and found that estrogen correlated better than testosterone with BMD. In addition, recent longitudinal studies from our group indicate that bioavailable estrogen correlated better than testosterone both with the gain in BMD in young men and with loss of BMD in elderly men. These observational studies do not, however, prove causality, which requires direct interventional studies. Thus, we eliminated endogenous testosterone and estrogen production in 59 elderly men (mean age 68 years), studied them first under conditions of physiologic testosterone and estrogen replacement, and then assessed the impact on bone turnover of withdrawing both testosterone and estrogen, withdrawing only testosterone, only estrogen, or continuing both. We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining bone formation. Collectively then, these findings indicate that estrogen plays a dominant role in regulating the male skeleton.


Role of dipicolinic acid in resistance and stability of spores of Bacillus subtilis with or without DNA-protective alpha/beta-type small acid-soluble proteins.
Dipicolinic acid (DPA) comprises approximately 10% of the dry weight of spores of Bacillus species. Although DPA has long been implicated in spore resistance to wet heat and spore stability, definitive evidence on the role of this abundant molecule in spore properties has generally been lacking. Bacillus subtilis strain FB122 (sleB spoVF) produced very stable spores that lacked DPA, and sporulation of this strain with DPA yielded spores with nearly normal DPA levels. DPA-replete and DPA-less FB122 spores had similar levels of the DNA protective alpha/beta-type small acid-soluble spore proteins (SASP), but the DPA-less spores lacked SASP-gamma. The DPA-less FB122 spores exhibited similar UV resistance to the DPA-replete spores but had lower resistance to wet heat, dry heat, hydrogen peroxide, and desiccation. Neither wet heat nor hydrogen peroxide killed the DPA-less spores by DNA damage, but desiccation did. The inability to synthesize both DPA and most alpha/beta-type SASP in strain PS3664 (sspA sspB sleB spoVF) resulted in spores that lost viability during sporulation, at least in part due to DNA damage. DPA-less PS3664 spores were more sensitive to wet heat than either DPA-less FB122 spores or DPA-replete PS3664 spores, and the latter also retained viability during sporulation. These and previous results indicate that, in addition to alpha/beta-type SASP, DPA also is extremely important in spore resistance and stability and, further, that DPA has some specific role(s) in protecting spore DNA from damage. Specific roles for DPA in protecting spore DNA against damage may well have been a major driving force for the spore's accumulation of the high levels of this small molecule.


Synthesis, evaluation, and comparative molecular field analysis of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes as ligands for histamine H(1) receptors.
A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3-aminotetralins, PATs) previously was found to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain through interaction with a binding site labeled by [(3)H]-(-)-(1R,3S)-trans-H(2)-PAT. Recently, we have discovered that PATs also bind with high affinity to the [(3)H]mepyramine-labeled H(1) receptor in rat and guinea pig brain. Here, we report the synthesis and biological evaluation of additional PAT analogues in order to identify differences in binding at these two sites. Further molecular modifications involve the pendant phenyl ring as well as quaternary amine compounds. Comparison of about 38 PAT analogues, 10 structurally diverse H(1) ligands, and several other CNS-active compounds revealed no significant differences in affinity at [(3)H]-(-)-trans-H(2)-PAT sites versus [(3)H]mepyramine-labeled H(1) receptors. These results, together with previous autoradiographic brain receptor-mapping studies that indicate similar distribution of [(3)H]-(-)-trans-H(2)-PAT sites and [(3)H]mepyramine-labeled H(1) receptors, suggest that both radioligands label the same histamine H(1) receptors in rodent brain. We also report a revision of our previous comparative molecular field analysis (CoMFA) study of the PAT ligands that yields a highly predictive model for 66 compounds with a cross-validated R(2) (q(2)) value of 0.67. This model will be useful for the prediction of high-affinity ligands at radiolabeled H(1) receptors in mammalian brain.


Polarization method for imaging through the water surface.
The possibility of improving imaging of the bottom of a water body by suppressing an inhomogeneous light background that occurs as a result of skylight reflection from the water surface and being superimposed on the bottom image is theoretically studied. It is shown that the radiance of this background can be reduced by a polarization filter and the correct choice of the imaging direction. It has been determined how the optimal directions of the bottom imaging with a Polaroid and without it depend on the Sun's position. The possibility of expanding the bottom swath by about 2 times due to joint use of its imaging facilities in polarized and nonpolarized light is proved. Photographs that demonstrate the effect of improving the bottom imaging with a Polaroid are presented.


Species of Pythium Associated with Seedling Root and Hypocotyl Disease on Common Bean (Phaseolus vulgaris) in Western Australia.
The occurrence and distribution of Pythium spp. were determined by collecting isolates of Pythium from common bean (Phaseolus vulgaris) plants showing root or hypocotyl disease symptoms from different areas of Western Australia in 2012. Eight different Pythium species (Pythium conidiophorum, P. diclinum, P. intermedium, P. irregulare, P. lutarium, P. mamillatum, P. pachycaule, and P. perplexum) were isolated and identified according to molecular sequences. P. irregulare was the most widespread Pythium sp. All species, except P. perplexum, were pathogenic to the hypocotyl and root of common bean. We believe this is the first report of P. intermedium as a pathogen on common bean worldwide. This is also the first report of P. conidiophorum, P. intermedium, P. lutarium, P. mamillatum, P. pachycaule, and P. diclinum as pathogens on common bean in Australia and the first report of P. irregulare as a pathogen on common bean in Western Australia. P. intermedium was the most pathogenic species, causing the most severe disease on 'Gourmet Delight' (percent root disease index [%RDI] 75 ± 2.9 and percent hypocotyl disease index [%HDI] 59.2 ± 3.2) and 'Pioneer' (%RDI 75 ± 2.9 and %HDI 65.8 ± 3.2). That the relative susceptibility or resistance (the ability of a plant to reduce the extent of invasion by the pathogen) of a given bean variety to one Pythium sp. was, in general, similar across the other Pythium spp. was an important finding, because this opens up opportunities to utilize a single virulent isolate of one Pythium sp. to identify general resistance to a wider spectrum of Pythium spp.


An acceptability study of female-controlled methods of protection against HIV and STDs in south-western Uganda.
We aimed to assess the acceptability of a variety of formulations of female-controlled methods of protection against HIV and STDs among men and women in south-western Uganda. Pilot interviews were carried out with 50 men and 55 women and 25 focus group discussions (FGDs) were held with 138 women and 42 men. The female condom, foaming tablets, sponge, foam, gel and film were demonstrated to 146 women and 35 of their male partners, who then tried out 2 of the products. They were interviewed 7 times during the course of 5 months. At the end experiences were evaluated during a second series of FGDs. Sixty-five (45%) women completed the trial. The main reasons for non-completion were related to geographical mobility. Product preference after the initial demonstration was similar to that at the end of the trial. The most popular formulations were the sponge (25% of the women), foaming tablets (23%), and the female condom (19%). The foam was of medium popularity (16%). The gel (9%) and film (7%) were least popular. Ten per cent of the women and 14% of the men reported products interfering with sexual enjoyment; 24% of the women and 67% of the men said products increased enjoyment. 'Dry sex' is not popular in this area and increased lubrication was an important determinant of acceptability. Age, level of education and location did have some effect on preference. Although secrecy was a dominant theme in the FGDs, 87% of the women had informed their partners by the end of the trial. The products were generally well received. Female control was an important issue for both sexes. Male attitudes were ambivalent because female ownership of products increased women's control. Although they have clear preferences, women appear to accept the products generally and might use a single available product just as readily if choice was limited, as long as it conforms to general cultural preferences, such as those relating to wet/dry sex.


Coated vesicles from chicken liver bind ferritin.
The iron-storage protein ferritin was found to be associated with highly purified coated vesicles (CV) from chicken liver. Chicken liver ferritin was morphologically similar to ferritin from horse spleen and could be isolated using a specific anti-ferritin monoclonal antibody. This antibody recognized a 240 X 10(3) Mr form of chicken ferritin but not the 22 X 10(3) Mr ferritin subunit after protein transfer to nitrocellulose. CV purified by controlled-pore glass-bead chromatography also contained ferritin when assayed by monoclonal anti-ferritin antibody using a sensitive enzyme-linked assay. Ferritin remained associated with CV even after re-chromatography. Ferritin particles were observed to be associated with CV by electron microscopy. CV-associated ferritin could be quantitatively removed from CV by treatment of the CV with 0.5 M-Tris-HC1 + 2M-urea at pH 8.5, conditions that also lead to dissociation of the clathrin lattice. Triton X-100 detergent treatment did not affect the association of ferritin with CV. These results indicate that purified CV from chicken liver contain ferritin in association with the clathrin lattice. The possible functional significance of this association is discussed.


Phase I trial and pharmacokinetic study of ixabepilone administered daily for 5 days in children and adolescents with refractory solid tumors.
The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary response rate for ixabepilone, a microtubule-stabilizing agent, administered intravenously daily for 5 days in children and adolescents. Patients >or= 2 and <or= 18 years with relapsed or refractory solid tumors were enrolled onto sequential cohorts to the following five dose levels: 3.0 (n = 3), 4.5 (n = 4), 6.0 (n = 3), 8.0 (n = 6), and 10 (n = 3) mg/m(2)/d. Eligibility criteria, dose levels, definitions of DLT and MTD, and pharmacokinetic sampling times were designed to be as similar as possible to the adult phase I trial of ixabepilone on the same schedule. Nineteen children (median age, 10 years; range, 2 to 18 years) were enrolled, and 18 (12 with sarcomas) were assessable for toxicity. DLTs (grade 4 neutropenia for > 5 days and grade 3 fatigue) were observed in two of three patients receiving 10 mg/m(2)/d. The MTD of ixabepilone administered daily for 5 days every 21 days was 8 mg/m(2)/d. Myelosuppression, GI, and hepatic toxicities were common non-DLTs. Peripheral neuropathy was uncommon. Ixabepilone clearance was 475 +/- 247 mL/min/m(2), volume of distribution at steady-state was 12.2 +/- 5.4 L/kg, and half-life was 14 hours. The recommended dose of ixabepilone for phase II trials in solid tumors is 8 mg/m(2)/d daily for 5 days every 21 days. This dose is 33% higher than the MTD in adults receiving the same dosing schedule. Pharmacokinetic parameters in children and adolescents were highly variable but similar to adults.


Experimental endoscopic endovascular cannulation: a novel approach to thrombolysis in retinal vessel occlusion.
Recent studies suggest that the cannulation of retinal vessels may provide a potential access route for the administration of thrombolytic agents in retinal vessel occlusion. However, the major problem with available techniques is the limited visualization of retinal vessels with conventional surgical microscopes, making it difficult to effectively control the targeted injection of drugs. The authors developed a novel single-piece catheter system for the endoscopically guided puncture of microvessels. Experimental punctures of retinal vessels with injection of fluid were performed in porcine cadaver eyes using a standard high-resolution gradient index microendoscope introduced through the pars plana. Endoscopically guided punctures were successfully performed in porcine branch retinal veins at various distances from the optic disc. Injection of recombinant tissue plasminogen activator (rt-PA), hypertonic solution (hyper HES), or normal saline solution into the vessel lumen was accomplished under direct endoscopic view in a safe and reliable manner. Endoscopically guided puncture of retinal microvessels is feasible and can be performed through a pars plana entry without additional micromanipulation devices. This novel technique may be a safe and effective approach to catheter-directed endovascular thrombolysis in retinal vascular occlusive diseases.


Bipolar Sealer Devices Used in Posterior Spinal Fusion for Neuromuscular Scoliosis Reduce Blood Loss and Transfusion Requirements.
Reducing perioperative blood loss and the need for transfusions in patients undergoing spinal surgery is especially important for those with neuromuscular disorders. These patients require extensive spino-pelvic exposure and are often medically fragile. We have used Amicar to decrease blood loss since 2001. As an effort to further reduce blood loss and transfusions, we use a bipolar sealer device (Aquamantys) as an adjunct to electrocautery. We present the results of our first 64 neuromuscular patients to show the efficacy of the device. Using a prospectively maintained database we reviewed the operative time, estimated perioperative blood loss, cell saver use, and intraoperative and postoperative transfusion rate in patients who underwent posterior spinal fusion for neuromuscular scoliosis. Sixty-four patients were identified who fit these criteria since the use of the bipolar sealer device was instituted.We compared these patients with a control group of the preceding 65 patients in whom this device was not used for hemostasis. All patients, including those in the study group, received Amicar (infusion of 100 mg/kg over 15 to 20 min, then 10 mg/kg/h throughout the remainder of the procedure). The surgical technique did not differ between the 2 groups. Baseline characteristics between the 2 groups were similar except for the number of patients having an all-screw construct which was larger in the investigational group (25% vs. 8%, P=0.03). There were no significant differences in operative time or duration of hospital stay. Intraoperative blood loss was lower in the study group (741 mL) as compared with the control group (1052 mL, P=0.003). Total perioperative blood loss, however, showed no significant difference. Thirty-five (55%) patients in the study group and 50 (77%) patients in the control group required additional intraoperative or postoperative transfusions (P=0.01). The number of packed red cell units transfused per patient was 0.81 in the study group and 1.57 in the control group (P=0.001). Although the intraoperative cell saver transfusion was same, the total blood volume transfused, which includes cell saver and any other transfusions, was significantly lower in the study group, 425 mL versus 671 mL (P=0.002). Use of a bipolar sealer device in posterior spinal fusion for neuromuscular scoliosis significantly reduced intraoperative blood loss and transfusion rate when compared with a control group in this retrospective review. Level III-retrospective comparative study.


[Spatial distribution and scale effect of species diversity of secondary forests in montane region of eastern Liaoning Province, China.]
With secondary forest in the montane region of eastern Liaoning Province as research object, this paper analyzed the spatial distribution and scale effect of Gleason richness index, Simpson dominance index, Shannon diversity index and Pielou evenness index in a 4 hm2 plot. The results showed that spatial distributions of the four diversity indices showed higher spatial heterogeneity. Variance of the four diversity indices varied with increasing scale. Coefficients of variation of the four diversity indices decreased with increasing scale. The four diversity indices of the tree layer were higher than those of the shrub layer, and the variation tendency varied with increasing scale. The results indicated that sampling scale should be taken into account when studying species diversity in the montane region of eastern Liaoning Province.


Reliability of race assessment based on the race of the ascendants: a cross-sectional study.
Race is commonly described in epidemiological surveys based on phenotypic characteristics. Training of interviewers to identify race is time-consuming and self identification of race might be difficult to interpret. The aim of this study was to determine the agreement between race definition based on the number of ascendants with black skin colour, with the self-assessment and observer's assessment of the skin colour. In a cross-sectional study of 50 women aged 14 years or older, from an outpatient clinic of an University affiliated hospital, race was assessed through observation and the self-assignment of the colour of skin and by the number of black ascendants including parents and grandparents. Reliability was measured through Kappa coefficient. Agreement beyond chance between self-assigned and observed skin colour was excellent for white (0.75 95% CI 0.72-0.78) and black women (0.89 95% CI 0.71-0.79), but only good for participants with mixed colour (0.61 95% CI 0.58-0.64), resulting in a global kappa of 0.75 (95% CI 0.71-0.79). However, only a good agreement for mixed women was obtained. The presence of 3 or more black ascendants was highly associated with observed and self-assessed black skin colour. Most women self-assigned or observed as white had no black ascendants. The assessment of race based on the race of ascendants showed reasonable agreement with the ascertainment done by trained interviewers and with the self-report of race. This method may be considered for evaluation of race in epidemiological surveys, since it is less time-consuming than the evaluation by interviewers.


Sources of speciated atmospheric mercury at a residential neighborhood impacted by industrial sources.
Speciated measurements of atmospheric mercury plumes were obtained at an industrially impacted residential area of East St. Louis, IL. These plumes were found to result in extremely high mercury concentrations at ground level that were composed of a wide distribution of mercury species. Ground level concentrations as high as 235 ng m(-3) for elemental mercury (Hg0) and 38 300 pg m(-3) for reactive mercury species (reactive gaseous (RGM) plus particulate (PHg) mercury) were measured. The highest mercury concentrations observed during the study were associated with plumes that contained high concentrations of all mercury species (Hg0, RGM, and PHg) and originated from a source located southwest of the sampling site. Variations in proportions of Hg0/RGM/PHg among plumes, with Hg0 dominating some plumes and RGM and/or PHg dominating others, were attributed to differences in emissions from different sources. Correlations between mercury plumes and elevated NO(x) were not observed; however, a correlation between elevated SO2 and mercury plumes was observed during some but not all plume events. Despite the presence of six coal-fired power plants within 60 km of the study site, wind direction data along with Hg/SO2 and Hg/NO(x) ratios suggest that high-concentration mercury plumes impacting the St. Louis-Midwest Particle Matter Supersite are attributable to local point sources within 5 km of the site.


Influence of intracerebroventricular phenoxybenzamine on the renal action of intracerebroventricular morphine.
Renal function is under regulatory influence of the central nervous system, either through mediation of humoral agents or by way of renal nerves, with the sympathetic nerve playing the most important role. As it was recently shown that morphine and enkephalin, when administered intracerebroventricularly (icv), affect renal function in the rabbit, indicating that the opiate receptors are also involved in the central regulation of renal function, it was attempted to clarify whether the central adrenergic system participates in the center-mediated renal action of morphine, employing phenoxybenzamine (PBZ). Morphine, 10 micrograms/kg icv, produced profound and long-lasting antidiuresis and antinatriuresis. PBZ, 250 micrograms/kg icv, elicited marked diuresis with natriuresis and kaluresis, along with significant increases of osmolar clearance and free-water reabsorption, and these effects were not related to a transient increase in glomerular filtration. When PBZ was given 10 min after morphine, the morphine antidiuresis immediately disappeared and the renal action of PBZ unfolded itself undiminished. Also, when morphine was given after PBZ, the PBZ-diuresis developed fully, unaffected by morphine. These observations indicate that the central adrenergic system is involved in the regulation of renal function through central opiate receptors.


Influenza surveillance in Europe: establishing epidemic thresholds by the moving epidemic method.
Timely influenza surveillance is important to monitor influenza epidemics. (i) To calculate the epidemic threshold for influenza-like illness (ILI) and acute respiratory infections (ARI) in 19 countries, as well as the thresholds for different levels of intensity. (ii) To evaluate the performance of these thresholds. The moving epidemic method (MEM) has been developed to determine the baseline influenza activity and an epidemic threshold. False alerts, detection lags and timeliness of the detection of epidemics were calculated. The performance was evaluated using a cross-validation procedure. The overall sensitivity of the MEM threshold was 71·8% and the specificity was 95·5%. The median of the timeliness was 1 week (range: 0-4·5). The method produced a robust and specific signal to detect influenza epidemics. The good balance between the sensitivity and specificity of the epidemic threshold to detect seasonal epidemics and avoid false alerts has advantages for public health purposes. This method may serve as standard to define the start of the annual influenza epidemic in countries in Europe.


Chemical carcinogenesis: an overview.
A brief review is presented of some types of chemical carcinogens and their metabolic activation to DNA-binding intermediates, and of the influence of modifiers of carcinogenesis on the probability of tumor development. The relationship between human exposure to one group of carcinogens--the tobacco specific nitrosamines--and the development of tobacco-related cancers is discussed.


Engaging parents in preventive parenting groups: do ethnic, socioeconomic, and belief match between parents and group leaders matter?
The authors evaluate the relation of ethnic, socioeconomic status (SES), and belief match between parents and group leaders and engagement in a preventive intervention for parents of preschoolers. Engagement was assessed through attendance, retention, and quality of participation in sessions with 171 parents and 11 group leaders. SES match predicted attendance, retention, and quality of participation. Parents attended more sessions, remained longer in the program, and participated more actively when their group leader came from comparable SES backgrounds. Ethnic match predicted retention only, with parents attending longer when their ethnicity matched their group leader's. Engagement was unrelated to the extent of match across different characteristics, nor was the link between ethnic match and retention mediated by SES or belief match. Results suggest that social, cultural, and belief similarities between parents and group leaders may be less salient in preventive parenting interventions than is assumed. Implications for research and practice are discussed.


Interior Decoration of Stable Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) are a diverse class of hybrid organic/inorganic crystalline materials composed of metal-containing nodes held in place by organic linkers. Through a discerning selection of these components, many properties such as the internal surface area, cavity size and shape, catalytic properties, thermal properties, and mechanical properties may be manipulated. Because of this high level of tunability, MOFs have been heralded as ideal platforms for various applications including gas storage, separation, catalysis, and chemical sensing. (1-8) Regrettably, these theoretical possibilities are limited by the reality of constraining conditions for solvothermal synthesis, which typically include high temperatures (usually over 100 °C), the use of specific solvents, and necessary exposure to acidic or basic conditions. In order to incorporate more delicate functionalities, postsynthesis decoration methods were developed. This feature article focuses on developed interior decoration methods for stable MOFs and the dynamic relationship between such methods and MOF stability. In particular, methods to transform organic, inorganic, and organometallic MOF parts as well as combination techniques, the generation of defects, and the inclusion of enzymes are addressed.


Spatial and socioeconomic inequalities in the access to safe drinking water in Peruvian households.
Access to safe drinking water has increased in Peru over the last decades, from 47% (2008) to 52% (2018). Nevertheless, such access would differ according to socioeconomic and regional factors. Thus, this study aimed to assess the socioeconomic inequality in the access to safe drinking water and identify its spatial distribution. We conducted a cross-sectional study based on the secondary data analysis of the 2021 Peruvian Demographic and Health Survey. Access to safe drinking water was a dummy variable categorised as safe if the residual chlorine concentration was ≥0.5 mg/L. Nationwide, 29.22% of households had access to safe drinking water. A pro-rich inequality in access to safe drinking water was observed. The spatial distribution was clustered. Significant hotspots were found in the south and centre of the country; however, cold spots were found in most areas. SaTScan analysis identified 32 and 63 significant clusters at high and low risks of having access to safe drinking water, respectively. In conclusion, approximately one out of four Peruvian households has access to safe drinking water, which was mostly concentrated among the wealthier households. Intra- and interdepartmental inequalities in access to safe drinking water were found, with several high-risk clusters.


The cost-effectiveness of preoperative testing (basic office assessment vs. urodynamics) for stress urinary incontinence in women.
To compare the cost-effectiveness of preoperative testing strategies in women with stress incontinence symptoms, as although urodynamic testing is used to improve the diagnostic accuracy in women with incontinence, the clinical and economic consequences of different levels of testing have not been evaluated. Decision analysis was used to evaluate basic office assessment (BOA) and urodynamic testing for women with stress incontinence symptoms who were candidates for primary surgical treatment. Costs were calculated using the Federal Register. Parameter estimates for the effectiveness of treatment for different diagnoses of incontinence were based on published reports. Incremental cost-effectiveness was defined as the cost in dollars per additional patient cured of incontinence. Urodynamics did not improve the effectiveness of treatment; both strategies of a BOA and urodynamic testing resulted in a cure rate of 96% after initial and secondary treatments. The mean cost of care (including initial and secondary treatments and outcomes) was similar for the two strategies ($5042 for BOA, $5046 for urodynamic testing). With BOA reduced testing costs were balanced by increased costs for patients who failed the initial treatment. Under baseline assumptions, one additional cure of incontinence (incremental cost-effectiveness) using the urodynamic strategy cost $3847, compared with BOA. By sensitivity analyses, BOA was less costly than urodynamics when the prevalence of genuine stress incontinence was > or = 80%. These findings do not support the routine use of urodynamics before surgery in women likely to have genuine stress incontinence, and provide the justification for randomized trials of preoperative testing strategies.


Annual differences in daily variations in hepatic drug metabolizing enzyme activity and plasma hormone levels in the rat.
Daily variations in hepatic drug metabolism and in plasma corticosterone and insulin levels were examined at monthly intervals over the duration of 1 year. Annual differences were observed in the basal levels of all parameters. Consistent daily variations were observed only in plasma corticosterone levels, whereas daily variations in each of the other parameters occurred inconsistently over the year with significant variations being found in ethylmorphine metabolism and insulin levels only five times, and in aniline metabolism, six times. These data show that daily variations in the parameters examined do not occur in a regular manner.


Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer.
Pancreatic cysts are a group of lesions with heterogeneous malignant potential. Currently, there are no reliable biomarkers to aid in cyst diagnosis and classification. The objective of this study was to identify potential microRNA (miR) biomarkers in endoscopically acquired pancreatic cyst fluid that could be used to distinguish between benign, premalignant, and malignant cysts. A list of candidate miRs was developed using a whole-genome expression array analysis of pancreatic cancer (pancreatic ductal adenocarcinoma) and nonmalignant samples overlapped with existing literature and predicted gene targets. Endoscopically acquired pancreatic cyst fluid samples were obtained from a group of 38 patients who underwent cyst fluid aspiration and surgical resection. Selected miR expression levels in cyst fluid samples were assessed by quantitative real-time-PCR. Additionally, in situ hybridization (ISH) on corresponding cyst tissue samples was performed to identify the source and validate the expression level of fluid miRs. Of the six miRs that were profiled in the study, two showed differential expression in malignant cysts. miR-221 was expressed at significantly higher levels in malignant cysts compared with benign or premalignant cysts (P=0.05). miR-21 was also expressed at significantly higher levels in malignant cysts (P<0.01). Additionally, the expression of miR-21 was significantly higher in premalignant cysts than benign cysts (P=0.03). The differential expression of miR-21 among cyst categories was confirmed by ISH. In this small single-center study, miRs are potential pancreatic cyst fluid diagnostic biomarkers. In particular, miR-21 is identified as a candidate biomarker to distinguish between benign, premalignant, and malignant cysts. Additionally miR-221 may be of use in the identification of more advanced malignant disease.


A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family.
Microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a rare syndrome that was first described in 1992. Characteristic craniofacial features include severe microcephaly, upslanting palpebral fissures, prominent ears, a broad nose, and a long philtrum with a pointed chin. Recently, mutations in KIF11 have been demonstrated to cause dominantly inherited MLCRD syndrome. Herein, we present a patient with MLCRD syndrome whose parents were first cousins. The parents are unaffected, and thus a recessive mode of inheritance for the disorder was considered likely. However, the propositus carries a novel, de novo nonsense mutation in exon 2 of KIF11. The patient also had midline cleft tongue which has not previously been described in this syndrome.


Chemical and immunological characterization of the extracellular galactomannan of Aspergillus fumigatus.
The galactomannan (GM) produced extracellularly by Aspergillus fumigatus has been purified by a double sequential hydrazine-nitrous acid treatment of the ethanol precipitate of the culture filtrate. Nuclear magnetic resonance and gas-liquid chromatography-mass spectrometry analysis have been performed on intact GM, acid-hydrolyzed GM, and oligomers resulting from the acetolysis of the acid-hydrolyzed GM. Results show that A. fumigatus GM is composed of a linear mannan core with an alpha-(1-2)-linked mannotetraose repeating unit attached via alpha-(1-6) linkage. Side chains composed of an average of 4 to 5 beta-(1-5)-galactofuranose units are linked to C-6 and C-3 positions of alpha-(1-2)-linked mannose units of the mannan. The immunoreactivity of GM and HCl-hydrolyzed GM was studied by use of human sera from aspergillosis patients and an antigalactofuran monoclonal antibody. The alpha-(1-2) (1-6)-mannan core is not antigenic. The immunogenic galactofuran is found amongst several exocellular glycoproteins. According to a direct enzyme-linked immunosorbent assay with GM as the detector antigen, only 26% of the serum samples from aspergilloma patients (all positive by immunodiffusion assays) give optical density values superior to a cutoff estimated as the mean +/- 3 standard deviations of values obtained with control sera.


In vivo dynamics of the internal fibrous structure in smooth adhesive pads of insects.
Many insects with smooth adhesive pads can rapidly enlarge their contact area by centripetal pulls on the legs, allowing them to cope with sudden mechanical perturbations such as gusts of wind or raindrops. The short time scale of this reaction excludes any neuromuscular control; it is thus more likely to be caused by mechanical properties of the pad's specialized cuticle. This soft cuticle contains numerous branched fibrils oriented almost perpendicularly to the surface. Assuming a fixed volume of the water-filled cuticle, we hypothesized that pulls could decrease the fibril angle, thereby helping the contact area to expand laterally and longitudinally. Three-dimensional fluorescence microscopy on the cuticle of smooth stick insect pads confirmed that pulls significantly reduced the fibril angle. However, the fibril angle variation appeared insufficient to explain the observed increase in contact area. Direct strain measurements in the contact zone demonstrated that pulls not only expand the cuticle laterally, but also add new contact area at the pad's outer edge.


Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos.
The mitochondrial genome is believed to be maternally inherited in many eukaryotes. Sperm-derived paternal mitochondria enter the oocyte cytoplasm upon fertilization and then normally disappear during early embryogenesis. However, the mechanism responsible for this clearance has been unknown. Here, we show that autophagy, which delivers cytosolic components to lysosomes for degradation, is required for the elimination of paternal mitochondria in Caenorhabditis elegans. Immediately after fertilization, sperm-derived components trigger the localized induction of autophagy around sperm mitochondria. Autophagosomes engulf paternal mitochondria, resulting in their lysosomal degradation during early embryogenesis. In autophagy-defective zygotes, paternal mitochondria and their genome remain even in the first larval stage. Thus, fertilization-triggered autophagy is required for selective degradation of paternal mitochondria and thereby maternal inheritance of mitochondrial DNA.


Nonfimbrial Adhesin Mutants Reveal Divergent Escherichia coli O157:H7 Adherence Mechanisms on Human and Cattle Epithelial Cells.
Shiga toxin-producing, enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a major foodborne pathogen causing symptoms ranging from simple intestinal discomfort to bloody diarrhea and life-threatening hemolytic uremic syndrome in humans. Cattle can be asymptomatically colonized by O157:H7 predominantly at the rectoanal junction (RAJ). Colonization of the RAJ is highly associated with the shedding of O157:H7 in bovine feces. Supershedding (SS) is a phenomenon that has been reported in some cattle that shed more than 104 colony-forming units of O57:H7 per gram of feces, 100-1000 times more or greater than normal shedders. The unique bovine RAJ cell adherence model revealed that O157:H7 employs a LEE-independent mechanism of attachment to one of the RAJ cell types, the squamous epithelial (RSE) cells. Nine nonfimbrial adhesins were selected to determine their role in the characteristic hyperadherent phenotype of SS O157 on bovine RSE cells, in comparison with human HEp-2 cells. A number of single nucleotide polymorphisms (SNPs) were found amongst these nonfimbrial adhesins across a number of SS isolates. In human cells, deletion of yfaL reduced the adherence of both EDL933 and SS17. However, deletion of eae resulted in a significant loss of adherence in SS17 whereas deletion of wzzB and iha in EDL933 resulted in the same loss of adherence to HEp-2 cells. On RSE cells, none of these nonfimbrial deletion mutants were able to alter the adherence phenotype of SS17. In EDL933, deletion of cah resulted in mitigated adherence. Surprisingly, four nonfimbrial adhesin gene deletions were actually able to confer the hyperadherent phenotype on RSE cells. Overall, this study reveals that the contribution of nonfimbrial adhesins to the adherence mechanisms and functions of O157:H7 is both strain and host cell type dependent as well as indicates a possible role of these nonfimbrial adhesins in the SS phenotype exhibited on RSE cells.


The relation of cerebral vasospasm to the extent and location of subarachnoid blood visualized by CT scan: a prospective study.
In 41 cases of verified ruptured saccular aneurysm, we prospectively predicted the presence or absence of delayed symptomatic cerebral vasospasm. CT criteria quantifying the extent and location of subarachnoid blood (developed in our previous retrospective study) were used in this prospective series of patients. Twenty-two patients had recognizable subarachnoid clots larger than 3 X 5 mm or layers of blood more than 1 mm thick (measured on reproduced images). In 20 of the 22 patients with severe significant clot or thick layer, severe vasospasm was correctly predicted and localized (2 false positives). In 19 patients with no blood, or diffuse blood, or blood outside the subarachnoid space, the absence of severe vasospasm was correctly predicted in 14 (5 false negatives). All of the false-positive and false-negative cases could be explained by inadequate CT technique. The data indicate that the extent and location of blood in the subarachnoid space determine the severity and location of vasospasm and that patients in jeopardy of developing symptomatic cerebral vasospasm can now be identified. Early preventive measures may now be assessed more accurately.


Stopped flow ESR study of the action of carbohydrates on ascorbic acid oxidation in aqueous solution.
The influence of added carbohydrate on the decay kinetics of the ascorbic acid free radical generated in deaerated aqueous solutions by the action of potassium ferricyanide on ascorbic acid has been studied. Addition of carbohydrate (less than or equal to 0.5M) generally leads to a small decrease in radical decay rate. In our system this probably arises from reduced reactant diffusion in solutions of increased viscosity rather than the preferential chelation previously suggested to explain inhibition in the copper (II) catalyzed oxidation. The ascorbic acid free radical shows negligible tendency to react with glucose, sorbitol or maltose. The decrease in its decay rate observed on addition of carbohydrate is probably caused by the increase in solvent viscosity.


[Noise and machine failures: determining factors in the acceptance and behavior of O2 concentrator. The Asturias project].
Prospective study of compliance and performance with De Vilbiss concentrator (De Vo/44), in patients with COLD and domiciliary O2 therapy. 54/136 severe COLD patients who used de Vo/44 concentrator were followed-up for 1 year, with home interviews every 2 months. Physiological measurements: FVC, FEV1, PF, Hemoglobin, ECG, blood gas tension(breathing air), smoking habits, drug therapy, and De Vo/44 performance(machine failure, flow rate and oxygen concentration accuracy). During the 1 year study 9 patients (16.6%) died and 16 (29.6%) refused the concentrator. 18 devices needed to be changed due to machine failure. Flow rates measured at De Vo/44 were 58.15 +/- 12.9 l/hour vs a theorical of 56.60 +/- 15.4 l/hour, and the purity of O2 was 94.19 +/- 0.3%. The power consumption was 1.9 +/- 0.01/ampers/hour. Almost 1/3 of COLD patients refused O2 concentrators due to excessive noise, and 1/3 of the machines needed to be replaced due to malfunction. Thus level of noise and proper functioning of concentrator are two important factors, affecting compliance and performance of these machines.


Jejunal pouch reconstruction after total gastrectomy for cancer. A randomized controlled trial.
The authors determined the optimum reconstruction procedure after total gastrectomy in terms of the quality of life of the patients. Gastric replacement with various enteric reservoirs has been used to improve the postprandial symptoms and nutrition of patients after total gastrectomy. However, the effect of each is uncertain because no prospective randomized studies have been conducted. A randomized controlled trial was conducted to compare the usefulness of the three reconstruction procedures of simple Roux-en-Y (RY; N = 10), pouch and Roux-en-Y (PR; N = 10), and pouch and interposition (PI; N = 10). In each subject, the postprandial symptoms, food intake in a single meal, body weight, serum nutritional parameters, and emptying time of the gastric substitute were evaluated. The PR group showed significantly greater food intake in a single meal than the RY and PI groups, and greater weight recovery than the PI group. A gastric emptying test also revealed satisfactory retention capacity and emptying time of the gastric substitute in the PR group. Pouch and Roux-en-Y reconstruction is the most useful of the three procedures for improving the postoperative quality of life. In patients with pouch and interposition reconstruction, the clinical assessment was quite poor, even though it is a physiologic route.


Patient-Centered Precision Health In A Learning Health Care System: Geisinger's Genomic Medicine Experience.
Health care delivery is increasingly influenced by the emerging concepts of precision health and the learning health care system. Although not synonymous with precision health, genomics is a key enabler of individualized care. Delivering patient-centered, genomics-informed care based on individual-level data in the current national landscape of health care delivery is a daunting challenge. Problems to overcome include data generation, analysis, storage, and transfer; knowledge management and representation for patients and providers at the point of care; process management; and outcomes definition, collection, and analysis. Development, testing, and implementation of a genomics-informed program requires multidisciplinary collaboration and building the concepts of precision health into a multilevel implementation framework. Using the principles of a learning health care system provides a promising solution. This article describes the implementation of population-based genomic medicine in an integrated learning health care system-a working example of a precision health program.


Meristem size contributes to the robustness of phyllotaxis in Arabidopsis.
Using the plant model Arabidopsis, the relationship between day length, the size of the shoot apical meristem, and the robustness of phyllotactic patterns were analysed. First, it was found that reducing day length leads to an increased meristem size and an increased number of alterations in the final positions of organs along the stem. Most of the phyllotactic defects could be related to an altered tempo of organ emergence, while not affecting the spatial positions of organ initiations at the meristem. A correlation was also found between meristem size and the robustness of phyllotaxis in two accessions (Col-0 and WS-4) and a mutant (clasp-1), independent of growth conditions. A reduced meristem size in clasp-1 was even associated with an increased robustness of the phyllotactic pattern, beyond what is observed in the wild type. Interestingly it was also possible to modulate the robustness of phyllotaxis in these different genotypes by changing day length. To conclude, it is shown first that robustness of the phyllotactic pattern is not maximal in the wild type, suggesting that, beyond its apparent stereotypical order, the robustness of phyllotaxis is regulated. Secondly, a role for day length in the robustness of the phyllotaxis was also identified, thus providing a new example of a link between patterning and environment in plants. Thirdly, the experimental results validate previous model predictions suggesting a contribution of meristem size in the robustness of phyllotaxis via the coupling between the temporal sequence and spatial pattern of organ initiations.


Gene panel testing for inherited cancer risk.
Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process.


The burden and the challenge of treatment-resistant depression.
Treatment resistant depression (TRD) is a serious public health problem. It is estimated that around 20- 40% of patients with a major depressive episode (whether monopolar or bipolar) do not exhibit clinical response to the current treatment with antidepressants, that is at least 50% decline in the symptoms scale. Furthermore, about half of the patients with symptom amelioration present residual symptoms which continue to negatively affect their functioning and increase the chance of relapse. Therefore, only 20-40% of patients (36.8% in STAR*D)1 who receive therapy for a major depressive episode for the first time exhibit remission (i.e., at least 70% decrease in symptom severity or HAMD score ≤7/MADRS score ≤10)2 - which is the goal of current treatments. Even when remission is achieved, though, there is often a long way to recovery and to the patient's return to the prior state of occupational and social functioning. Moreover, long-term medical treatment is needed in order to achieve and maintain the above.3 TRD is characterized by high rates of comorbidity (hypertension, diabetes mellitus, heart failure), doubles the rates of hospitalizations and lengthens the time of hospitalization by 36%, while the percentage of suicidal incidents is seven times higher in TRD compared to cases of treatment-responsive depression.4 TRD exhibits higher rates of mortality than treatment-responsive depression, with all-cause mortality rate being higher5 by 29-35% and similar to that of older by 13 years, non-depressed individuals. Despite its common occurrence and the fact that TRD constitutes an important issue in the treatment of major depression disorder (MDD), experts still disagree on the exact meaning of the term. The most widely accepted and used term of TRD refers to treatment resistance as treatment with at least two different antidepressants (of the same or different classes), administered in the right doses and for an adequate amount of time, with verified patient compliance to treatment which, however, fails to produce significant clinical results.6 Other terms have also been used as an alternative, for example Difficult to Treat Depression in order to avoid nihilism - something often seen in these cases;7 Drug Resistant Depression so as to determine the exact kind of resistance and also to underline the need for combination therapy with intervention such as psychotherapy and ECT; Multiple Therapy Resistant MDD; Pernicious Depression8 etc. Treatment of TRD is a challenge for every clinician. After excluding the possibility of pseudo-resistance due to misdiagnosis, insufficient therapeutic regimen, comorbid disorders, such as anxiety disorders, eating disorders, personality disorders, substance abuse/addiction, PTSD, non-compliance to treatment, non-identified organicity and chronic stressors, the therapeutic methods used include: optimization, watchful waiting, past response, combination treatment, add-on treatments, ECT, TMS, vagus nerve stimulation, phototherapy, psychotherapy, neurosurgery. All the above are thoroughly discussed in this Supplement issue of Psychiatriki.9.


Stroke and Risk of Mental Disorders Compared With Matched General Population and Myocardial Infarction Comparators.
Accurate estimates of risks of poststroke outcomes from large population-based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage. During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year-matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity. Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0-7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3-1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7-0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4-0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but -0.2% (95% CI, -0.2 to -0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders. The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke.


Phylogenetic distribution of roseobacticides in the Roseobacter group and their effect on microalgae.
The Roseobacter-group species Phaeobacter inhibens produces the antibacterial tropodithietic acid (TDA) and the algaecidal roseobacticides with both compound classes sharing part of the same biosynthetic pathway. The purpose of this study was to investigate the production of roseobacticides more broadly in TDA-producing roseobacters and to compare the effect of producers and non-producers on microalgae. Of 33 roseobacters analyzed, roseobacticide production was a unique feature of TDA-producing P. inhibens, P. gallaeciensis and P. piscinae strains. One TDA-producing Phaeobacter, 27-4, did not produce roseobacticides, possibly due to a transposable element. TDA-producing Ruegeria and Pseudovibrio did not produce roseobacticides. Addition of roseobacticide-containing bacterial extracts affected the growth of the microalgae Rhodomonas salina, Thalassiosira pseudonana and Emiliania huxleyi, while growth of Tetraselmis suecica was unaffected. During co-cultivation, growth of E. huxleyi was initially stimulated by the roseobacticide producer DSM 17395, while the subsequent decline in algal cell numbers during senescence was enhanced. Strain 27-4 that does not produce roseobacticides had no effect on algal growth. Both bacterial strains, DSM 17395 and 27-4, grew during co-cultivation presumably utilizing algal exudates. Furthermore, TDA-producing roseobacters have potential as probiotics in marine larviculture and it is promising that the live feed Tetraselmis was unaffected by roseobacticides-containing extracts.


Hepatocyte nuclear factor 6: organization and chromosomal assignment of the rat gene and characterization of its promoter.
Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a family of tissue-specific transcription factors characterized by a bipartite DNA-binding domain consisting of a single cut domain and a novel type of homeodomain. We have previously cloned rat cDNA species coding for two isoforms, HNF-6alpha (465 residues) and beta (491 residues), which differ only by the length of the spacer between the two DNA-binding domains. We have now localized the rat Hnf6 gene to chromosome 8q24-q31 by Southern blotting of DNA from somatic cell hybrids and by fluorescence in situ hybridization. Cloning and sequencing of the rat gene showed that the two HNF-6 isoforms are generated by alternative splicing of three exons that are more than 10 kb apart from each other. Exon 1 codes for the N-terminal part and the cut domain, exon 2 codes for the 26 HNF-6beta-specific amino acids, and exon 3 codes for the homeodomain and the C-terminal amino acids. The transcription initiation site was mapped by ribonuclease protection and 5' rapid amplification of cDNA ends. Transfection experiments showed that promoter activity was contained within 0.75 kb upstream of the transcription initiation site. This activity was detected by the transfection of liver-derived HepG2 cells, but not of Rat-1 fibroblasts, suggesting that the promoter is sufficient to confer liver-specific expression.


Impact of race on predialysis discussions and kidney transplant preemptive wait-listing.
US registry data have consistently shown that blacks are less likely than whites to be wait-listed before beginning dialysis. The Comprehensive Dialysis Study (CDS) was a special study conducted by the US Renal Data System (USRDS) in which a national cohort of patients who began maintenance dialysis therapy in 2005-2007 were asked whether kidney transplantation (KT) had been discussed with them before they started dialysis. Using responses from black and white CDS participants and information from the USRDS, we investigated preemptive wait-listing as a function of patient-reported predialysis KT discussion. Among those reporting early KT discussion, 31.0% of patients preemptively wait-listed were black, compared to 27.5% of those not preemptively wait-listed. Two thirds of preemptively wait-listed patients had received nephrology care more than 12 months before starting dialysis and reported that KT was discussed with them 12 months or more before dialysis. Early KT discussion and higher serum albumin and hemoglobin levels remained significant predictors of preemptive wait-listing in an adjusted logistic regression analysis. Among those preemptively wait-listed, 33% of blacks and 60% of whites had received a transplant by September 30, 2009 (study end date). Early KT discussion appeared to reduce barriers to black patients' waiting list placement before the start of dialysis, which in turn may facilitate earlier access to a deceased donor organ transplant.


The multi-copper-ion oxidase CueO of Salmonella enterica serovar Typhimurium is required for systemic virulence.
Salmonella enterica serovar Typhimurium possesses a multi-copper-ion oxidase (multicopper oxidase), CueO (also known as CuiD), a periplasmic enzyme known to be required for resistance to copper ions. CueO from S. Typhimurium was expressed as a recombinant protein in Escherichia coli, and the purified protein exhibited a high cuprous oxidase activity. We have characterized an S. Typhimurium cueO mutant and confirmed that it is more sensitive to copper ions. Using a murine model of infection, it was observed that the cueO mutant was significantly attenuated, as indicated by reduced recovery of bacteria from liver and spleen, although there was no significant difference in recovery from Peyer's patches and mesenteric lymph nodes. However, the intracellular survival of the cueO mutant in unprimed or gamma-interferon-primed murine macrophages was not statistically different from that of wild-type Salmonella, suggesting that additional host factors are involved in clearance of the cueO mutant. Unlike a cueO mutant from E. coli, the S. Typhimurium cueO mutant did not show greater sensitivity to hydrogen peroxide and its sensitivity to copper ions was not affected by siderophores. Similarly, the S. Typhimurium cueO mutant was not rescued from copper ion toxicity by addition of the branched-chain amino acids and leucine.