Intraflagellar Transport 80 Is Required for Cilia Construction and Maintenance in Paramecium tetraurelia.
Intraflagellar transport (IFT) represents a bidirectional dynamic process that carries cargo essential for cilia building and the maintenance of ciliary function, which is important for the locomotion of single cells, intracellular and intercellular signalling transduction. Accumulated evidence has revealed that defects in IFT cause several clinical disorders. Here, we determined the role of IFT80, an IFT-B protein that is mutated in Jeune asphyxiating thoracic dystrophy. Using the RNAi method in the ciliate Paramecium as model, we found that loss of IFT80 prevents cilia biogenesis and causes strong cell lethality. A specific antibody against IFT80 was also prepared in our study, which labelled IFT80 in cilia of Paramecium. GFP fusion experiments were performed to illustrate the dynamic movement of IFT-A and IFT-B proteins in cilia of Paramecium; then, we found that the depletion of IFT80 in cells prevents IFT-A and IFT-B proteins from entering the cilia. Our results showed the distribution change of other IFT proteins in cells that were depleted of IFT80, and we discuss the possible roles of IFT80 in Paramecium.


Highly aggressive behavior and poor prognosis of small-cell carcinoma in the alimentary tract: flow-cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen.
The purpose of this study was to determine the clinical course, and effects of the histopathologic characteristics of specific tumors, including DNA contents and immunohistochemical aspects, in patients with small-cell carcinoma of the alimentary tract. Medical records of 14 patients who presented with small-cell carcinoma of the alimentary tract were retrospectively reviewed. Primary tumors were studied by immunohistochemical and flow cytometric analyses. Of these 14 small-cell carcinomas, 4 were esophageal, 8 gastric, and 2 colonic tumors. DNA aneuploidy was observed in 8 tumors. Staining for the p53 product was positive in 57.1% of all the tumors. The average proliferating cell nuclear antigen (PCNA) labeling rate (LR) was 72.4 +/- 11.6%. The average PCNA LR was significantly higher for the p53-positive group (p < 0.05). The estimated median survival was 253 days for all patients. Noncurative resection was associated with a significantly less favorable prognosis (p < 0.01). Distant metastases were observed in 13 of 14 patients. A higher PCNA LR of small-cell carcinoma may be an unfavorable characteristic of biological behavior. The patients with disseminated disease should undergo a symptomatically palliative operation combined with chemotherapy.


Mobile phone use among female entertainment workers in Cambodia: an observation study.
Text or voice messages containing health behavior change content may be an inexpensive, discreet, sustainable and scalable way to reach populations at high risk for HIV. In Cambodia, one of the important high-risk populations is female entertainment workers (FEWs). This ethnographic study aims to explore typical phone use, examining patterns and behaviors that may influence the design of future mHealth interventions. The study consisted of one 8-hour non-participant observation session for 15 randomly sampled FEWs. Observations focused on capturing normal daily use of mobile devices. Observation checklists were populated by observers during the observations and a post-observation survey was conducted. Findings were discussed with Cambodian HIV outreach workers and HIV research fellows and their interpretations are summarized below. In this ethnographic study, all 15 participants made calls, checked the time and received research-related texts. More than half (n=8) of the participants engaged in texting to a non-research recipient. About half (n=7) went on Facebook (FB) and some (n=5) listened to music and looked at their FB newsfeed. Fewer played a mobile game, posted a photo to FB, went on YouTube, used FB chat/messenger, watched a video on FB, played a game on FB, used FB call/voice chat, looked at their phone's background or used the LINE app. Fewer still shared their phones, left them unattended, added airtime or changed their SIM cards. When participants received a research text message, most did not share the text message with anyone, did not ask for help deciphering the message and did not receive help composing a response. Notable themes from observer notes, HIV outreach workers and researchers include reasons why phone calls were the most frequent mode of communication, examples of how cell phone company text messages are used as a form of behavior change, literacy as a persistent barrier for some FEWs, and FEWs' high interest in receiving health-related messages and less concern about privacy and phone-sharing issues than expected. This study suggests texting is a part of normal phone use although not as frequently used as voice calls or Facebook. Despite the less frequent use, FEWs were able to send and receive messages, were interested in health messages and were not overly concerned about privacy issues. Texting and voice messaging may be useful tools for health behavior change within the FEW population in Cambodia.


[Analysis of reliability and validity of the Chinese version of voice handicap index (VHI)].
To investigate the reliability and validity of the Chinese version of voice handicap index (VHI). The cross-cultural adaptation of health-related quality of life (HRQOL) measures was used to evaluate the Chinese version of VHI. Five hundred forty six dysphonic patients and 80 control subjects were included, 30 of patients and 20 of control subjects also had Hong Kong version VHI test simultaneously. The internal consistency reliability of overall VHI scores and three subscale scores of the Chinese version of VHI were 0.8657-0.9517. The reliability coefficients (test to retest, 2-week interval) was 0.992 (P < 0.001). The correlation coefficient of overall VHI scores and three subscale scores and internal subscale scores were 0.643-0.904 (P < 0.01). There were no significant difference between the Chinese version and Hong Kong Chinese version (Z = 0.397, P = 0.691 ) with high dependability (r = 0.995, P < 0.001). The factor analysis of construct validity shows that the eigenvalue of 6 factors is above 1. The cumulative proportion was 77.24%. The loading was higher than 0.4 among every item. VHI total scores were significantly higher in dysphonic patients than in control subjects (Z = 17.69, P = 0.000). This is also true for all VHI subscores in the functional (Z = 14.14, P = 0.000), physical (Z = 17.68, P = 0.000) and emotional domains (Z = 15.50, P = 0.000). The Chinese version of VHI had a good reliability and validity. It can be used to evaluate dysphonic patients.


Tailoring diffusion in analog spacetimes.
Diffusive transport is characterized by the scaling law (length)^{2}∝(time). In this paper we show that this relationship is significantly altered in curved analog spacetimes. This circumstance provides an opportunity to tailor diffusion: by a suitable design of the analog metric, it is possible to create materials where diffusion is either faster or slower than in normal media, as desired. This prediction can, in principle, be tested experimentally with optical analogs, curved graphene sheets, and so on (indeed with any analog spacetime).


Practical Synthesis of Terminal Vinyl Fluorides.
The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.


Basic statistical concepts in nutrition research.
Statistical principles are used in nutrition research to plan and conduct research studies and to answer research questions. This article describes general statistical concepts and provides some guidelines to assist in the interpretation of research literature. Prospective and retrospective study designs used in nutrition research are presented as well as the advantages and disadvantages of each of the study designs. Descriptive statistics used to summarize data and graphical tools used to display the shape of the distribution of a set of data guide nutrition support professionals to select appropriate statistical tests. Fundamental topics of statistics, including power analysis and sample size, confidence intervals and hypothesis testing, and analysis of variance and regression, are also reviewed. The article emphasizes the importance of effective collaboration with statisticians at an early stage of the research study to avoid potential pitfalls associated with improper utilization of statistical methods.


Hospital employee job resourcefulness: an empirical study and implications for health care marketing.
In today's competitive hospital marketing environment, it is imperative that administrators ensure that their hospitals are operating as efficiently and as effectively as possible. "Doing more with less" has become a mandate for hospital administrators and employees. The current research replicates and extends previous work devoted to this topic by examining the job resourcefulness construct in a hospital setting. Job resourcefulness, an individual difference variable, assesses the degree to which employees are able to overcome resource constraints in the pursuit of job-related goals. The work builds upon previous work and contributes to the hospital marketing literature by examining the relationships between resourcefulness, personality influencers, role stressors, and job tenure. Research implications and suggestions for future work in the area are presented.


Association analysis of bone mineral density and single nucleotide polymorphisms in two candidate genes on chromosome 1p36.
Two candidate genes for bone mineral density (BMD), tumor necrosis factor alpha receptor 2 (TNFRSF1B) and lysyl hydroxylase (PLOD1), have been scanned for single nucleotide polymorphisms (SNPs) within their coding and promoter regions. These two genes, separated by about 200 kb, are located within the chromosomal interval 1p36.2-1p36.3 that has been linked to femoral neck BMD. In a patient population (n = 104) of European descent, there were four SNPs within TNFRSF1B and six SNPs within PLOD1 that occurred with greater than 5% frequency. There was significant linkage disequilibrium within both genes. Single marker analysis revealed significant association for one SNP located in intron 6 of PLOD1 and lumbar spine BMD (P = 0.01). Allelic haplotypes that encompassed the four SNPs in TNFRSF1B or the six SNPs in PLOD1 were assigned using a Bayesian algorithm as implemented in the program Haplotyper. Association of TNFRSF1B haplotypes with femoral neck BMD was statistically significant (P = 0.01). Similarly, PLOD1 haplotypes demonstrated a statistically significant association with spinal BMD (P = 0.04). These findings strengthen the potential importance of chromosome 1p36.2-1p36.3 in contributing to BMD variation, and are consistent with genetic variation in either PLOD1, TNFRSF1B or nearby genes playing a role in the phenotype.


Cancer information by telephone: a two-year evaluation.
A two year evaluation of a cancer information system accessible to the general public by telephone found a reported positive impact on behavior directly related to physical health for about 40 percent of a systematic sample of callers interviewed several weeks after their initial contact with the system. Another 20 percent of the same sample reported taking some positive action not directly related to health, or reported some other positive impact such as relief of anxiety as a result of hearing one of the system's 36 pre-recorded cancer lectures. Callers showed greater cancer knowledge, when interviewed, than a sample of non-callers, but no clear conclusion could be drawn because pre-call knowledge levels of callers were not ascertained. Data also were collected from callers at the time of their initial contact; caller characteristics patterns of calling, topics selected, and source of information about the system are reported. Results of experiments to increase public response are summarized.


Induced in-source fragmentation for the selective detection of organic bound iodine by liquid chromatography/electrospray mass spectrometry.
The detection of unknown organic compounds, e.g., transformation products of known trace pollutants in environmental samples, is a difficult task which can be simplified if the compounds of interest are characterized by a functional group or a heteroatom which can selectively be detected. For the detection of iodinated benzene derivatives, used as X-ray contrast media, we have studied whether such compounds can be selectively detected by negative ion (NI) electrospray ionization via iodide as a product ion of in-source fragmentation, generated by applying a high cone voltage. It was found that selective detection of iodinated benzene derivatives is possible by liquid chromatography/negative ion electrospray ionization (LC/NI-ESI) if the compounds are destroyed before entering the mass spectrometer. To our knowledge this is the first report of the use of NI in-source fragmentation MS for analyses traditionally performed with inductively coupled plasma (ICP)-MS. The novel application of NI in-source fragmentation MS is a tool for those who do not possess the facilities to perform ICP-MS. Furthermore, NI-ESI at varying cone voltages provides both structural information and elemental detection, whereas ICP-MS can only provide elemental detection.


Special safety considerations in preparation of technetium Tc-99m DTPA for cerebrospinal fluid-related imaging procedures.
To review special safety considerations in the preparation of technetium 99m (Tc-99m) diethylenetriaminepentaacetic acid (DTPA; generic name, pentetate) for cerebrospinal fluid (CSF)-related imaging procedures. Review of practices and results at one institution supplemented with findings and recommendations from the literature. Literature searches were conducted via Medline/PubMed using the following terms: Tc-99m DTPA/pentetate, CSF, cisternography, intrathecal, and adverse reactions. The author's own files were also searched for articles (e.g., in newsletters) not indexed by Medline/PubMed. Articles considered appropriate for review included all human research studies, reviews, case reports, abstracts, and letters published in English on Tc-99m DTPA use in CSF-related imaging procedures, especially with regard to safety or adverse reactions. All information related to safety precautions and adverse reactions associated with Tc-99m DTPA injected intrathecally or otherwise used for CSF-related imaging procedures were considered. 18 years' experience in one institution was reviewed with the added perspective of literature findings and recommendations. With proper attention to safety considerations, Tc-99m DTPA can be safely used in CSF-related imaging procedures.


Genetically modified Lactococcus lactis producing a green fluorescent protein-bovine lactoferrin fusion protein suppresses proinflammatory cytokine expression in lipopolysaccharide-stimulated RAW 264.7 cells.
Lactoferrin (LF), an iron-binding glycoprotein distributed widely in the biological fluids of mammals, is believed to play an important role in host defenses against infection. Previous studies in animal models and humans demonstrated that combined administration of LF and probiotic lactic acid bacteria (LAB) can prevent sepsis. In this study, we genetically engineered a probiotic LAB strain, Lactococcus lactis, to produce recombinant bovine LF based on the green fluorescent protein (GFP)-fused expression system. Western blotting confirmed that the genetically modified L. lactis strain (designated NZ-GFP-bLF) produced a protein corresponding to a fusion of GFP and bLF in the presence of nisin, an inducer of target gene expression. The protein synthesized by NZ-GFP-bLF was fluorescent and thus we monitored the time-dependent change in the production level of the recombinant protein using fluorometric analysis. The utility of NZ-GFP-bLF in preventing sepsis was determined by investigating its anti-inflammatory property in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells. Pretreatment of RAW 264.7 cells with NZ-GFP-bLF significantly attenuated the LPS-induced mRNA expression and protein production of 3 proinflammatory cytokines (IL-1α, IL-6, and tumor necrosis factor-α) compared with pretreatment with a vector control strain of L. lactis. Our results suggest that NZ-GFP-bLF holds promise for the development of a new prophylaxis for sepsis.


Cross-Domain Assessment of Distress Intolerance: Associations With Borderline Personality Disorder Features.
Distress tolerance (DT) is central to major etiological theories of, and popular treatments for, borderline personality disorder (PD), but empirical evidence for the connection between DT and borderline PD is inconclusive. Such inconsistency is partly due to limited concordance across DT indices from different measurement domains (e.g., behavioral, physiological). In a student sample (N = 267), we assessed subjective perceptions of DT capabilities, task performance on a distressing laboratory challenge, and borderline pathology. Subjective and behavioral indices of DT were largely unrelated. Further, borderline PD features were moderately associated with self-perceived DT (r = -.53); in contrast, they were weakly related to performance on the DT task (r = -.09). We conclude that there is mixed evidence for an association between borderline pathology and DT. Further, we propose a systematic approach to examining the construct validity of DT in multimethod, multimeasure research that might resolve the equivocal results from prior work.


Nitrogen washout/washin, helium dilution and computed tomography in the assessment of end expiratory lung volume.
End expiratory lung volume (EELV) measurement in the clinical setting is routinely performed using the helium dilution technique. A ventilator that implements a simplified version of the nitrogen washout/washin technique is now available. We compared the EELV measured by spiral computed tomography (CT) taken as gold standard with the lung volume measured with the modified nitrogen washout/washin and with the helium dilution technique. Patients admitted to the general intensive care unit of Ospedale Maggiore Policlinico Mangiagalli Regina Elena requiring ventilatory support and, for clinical reasons, thoracic CT scanning were enrolled in this study. We performed two EELV measurements with the modified nitrogen washout/washin technique (increasing and decreasing inspired oxygen fraction (FiO2) by 10%), one EELV measurement with the helium dilution technique and a CT scan. All measurements were taken at 5 cmH2O airway pressure. Each CT scan slice was manually delineated and gas volume was computed with custom-made software. Thirty patients were enrolled (age = 66 +/- 10 years, body mass index = 26 +/- 18 Kg/m2, male/female ratio = 21/9, partial arterial pressure of carbon dioxide (PaO2)/FiO2 = 190 +/- 71). The EELV measured with the modified nitrogen washout/washin technique showed a very good correlation (r2 = 0.89) with the data computed from the CT with a bias of 94 +/- 143 ml (15 +/- 18%, p = 0.001), within the limits of accuracy declared by the manufacturer (20%). The bias was shown to be highly reproducible, either decreasing or increasing the FiO2 being 117+/-170 and 70+/-160 ml (p = 0.27), respectively. The EELV measured with the helium dilution method showed a good correlation with the CT scan data (r2 = 0.91) with a negative bias of 136 +/- 133 ml, and appeared to be more correct at low lung volumes. The EELV measurement with the helium dilution technique (at low volumes) and modified nitrogen washout/washin technique (at all lung volumes) correlates well with CT scanning and may be easily used in clinical practice. Current Controlled Trials NCT00405002.


Vascular endothelial growth factor rescues 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibition of coronary vasculogenesis.
We previously demonstrated that the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces coronary vascular development in chick embryos in vivo. In the current study, we assessed whether TCDD inhibits early events in coronary endothelial tube formation and outgrowth, and whether this inhibition occurs through a vascular endothelial growth factor (VEGF)-dependent mechanism. Fertile chicken eggs were treated with control (corn oil) or TCDD (0.3 pmol TCDD/g) on incubation day 0. On embryonic day 6, cardiac ventricle explants were cultured on a three-dimensional collagen gel, when coronary angioblasts are present, but prior to their assembly into endothelial tubes. Endothelial cells migrating out from explants were identified by immunohistochemistry, and endothelial tube number and length were quantitated. In addition, on incubation days 6 and 8, cardiac VEGF mRNA and protein were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Endothelial tube length and number were significantly reduced (40% +/- 1.7% and 36% +/- 3%, respectively) in TCDD explants, compared to controls. Recombinant exogenous VEGF, as well as hypoxic stimulation with CoCl2 or 10% O2, significantly increased the length and number of outgrowing tubes in TCDD cultures, and this stimulation was prevented by a VEGF neutralizing antibody. In contrast, VEGF neutralizing antibody reduced the length and number of tubes only in control cultures, and had no inhibitory effect on tube outgrowth from TCDD explants. Finally, hearts from TCDD-treated embryos exhibited a significant reduction in both VEGF mRNA and protein, compared to controls. These data suggest that TCDD inhibits early coronary vascular outgrowth via a VEGF-dependent mechanism.


Cross-reactions between Staphylococcus epidermidis and 23 other bacterial species.
By quantitative immunoelectrophoretic methods, 43 antigens were found in a mixture of sonicated preparations of four Staphylococcus epidermidis strains, using corresponding rabbit antiserum. Two of the antigens were identified as cell wall teichoic acid and a peptidoglycan antigen, respectively. Using this antigen/antibody reference system, cross-reactions between S. epidermidis antigens and antigens from other bacterial species were investigated. Fourteen of the S. epidermidis antigens cross-reacted with antigens from all S. aureus strains investigated. Only few cross-reactions were found between S. epidermidis and bacteria not belonging to the Micrococcaceae. The antigenic relatedness, expressed as a matching coefficient, seems promising for taxonomic work.


After Kennedy...
Edward Kennedy's book Partial Denture Construction was published in 1928. A number of the principles that he advocated are still taught, albeit in a modified manner, although the background reasoning supporting those principles has changed somewhat. This paper highlights some of those principles and makes the point that several of them do not appear to have achieved wide acceptance over 70 years later.


Assessment of two doses of intranasal midazolam for sedation of young pediatric dental patients.
The purpose of this study was to assess the effectiveness of two doses of intranasal midazolam on sedation of young children for dental treatment. Thirty uncooperative children, mean age of 32 months, who needed at least two restorative visits, participated in this study. The patients were assigned randomly to receive either 0.2 mg/kg or 0.3 mg/kg of midazolam intranasally, with the alternate regimen administered at the second appointment. All the children received 50% nitrous oxide, and were restrained in a Papoose Board (Olympic Medical Group, Seattle, WA) with a head holder. Degree of alertness, crying, and movement were evaluated at baseline and at 5-min intervals throughout the procedure. Evaluation of overall behavior at each session was performed by one investigator, blind to the dose, using a separate rating scale. The reliability of ratings was assessed by two investigators from videotapes of the procedures. Statistical analysis showed no differences (P > 0.05) in the behavior of the children receiving the two doses. Successful sedation, as assessed by lack of or minimal crying and/or movement that interrupted treatment, was observed in all the treatment visits with both doses (mean score 4.66 +/- 1.09 for 0.3 mg and 4.40 +/- 1.04 for 0.2 mg). No adverse effects were observed, and all the treatments were completed successfully.


Procedural justice in public health care resource allocation.
The legal studies literature on procedural justice identifies six key characteristics of procedural justice: accuracy, consistency, impartiality, reversibility, transparency and voice. However, the relative importance of these in the context of public health care resource allocation is unclear, as is whether they are valuable instrumentally (because it contributes to better outcomes) or inherently (for its own sake). A survey of 80-odd members of the UK public determined the following: the ranking of all the six characteristics; the pairwise comparisons of the characteristics; and whether each characteristic was important for instrumental reasons, for intrinsic reasons or for both. Respondents ranked the procedures in the order of accuracy, consistency, impartiality, reversibility and transparency. Procedural justice was valued for both instrumental and inherent reasons. A robust ranking of five of the six procedural characteristics was found. The ranking for voice was sensitive to the question format, which has methodological implications. Around a quarter to a third of respondents regarded a procedural characteristic to have entirely intrinsic value.


[Triptolide induces autophagy of ovarian granulosa cells via PI3K/AKT/m TOR pathway].
The aim of this paper was to observe the concentration,time and mechanism of autophagy induced by triptolide( TP) in ovarian granulosa cells( OGCs). CCK-8 method was used to compare the inhibitory effects of TP at different concentrations on primary cultured rat OGCs and IC50 was calculated. The effects of TP at different concentrations and time points on the expression of OGCs autophagy factor protein and the cascade of PI3 K/AKT/m TOR pathway were detected by Western blot. The effects of TP,autophagy inducer( brefeldin A) and PI3 K/m TOR inhibitor( NVP-BEZ235) on the expression of PI3 K/AKT/m TOR cascade and autophagy related factor protein were detected by Western blot. The results show that the IC50 of different concentrations of TP on OGCs of rat ovary was14. 65 μmol·L-1,and the minimum inhibitory concentration of TP was 0. 1 μmol·L-1( 100 nmol·L-1). Compared with the control group,the expression levels of beclin1 and LC3Ⅱ in each group were significantly higher than those in the control group( P<0. 05 or P<0. 01). After 12 hours of treatment with TP,brefeldin A and NVP-BEZ235,respectively,compared with the control group,TP could significantly promote the expression level of downstream autophagy effect or molecule beclin1,LC3Ⅱ and inhibit the expression level of LC3Ⅰ,p62 protein( P<0. 05 or P< 0. 01). Moreover,the expression of beclin1 and LC3Ⅱ/LC3Ⅰ in TP group was higher than that in brefeldin A group( P<0. 05 or P<0. 01),and the expression of p62 in TP group was lower than that in brefeldin A group( P<0. 05 or P<0. 01). At the same time,TP could significantly inhibit the expression of p-PI3 K,p-AKT,p-mTOR protein,and the inhibitory effect of TP was better than that of NVP-BEZ235 group. This study suggests that 100 nmol·L-1 TP could induce OGCs autophagy successfully in cultured rat ovary for 12 h; TP may induce OGCs autophagy by inhibiting PI3 k/Akt/m TOR signaling pathway.


The diurnal rhythm in vasopressin V1a receptor expression in the suprachiasmatic nucleus is not dependent on vasopressin.
The mammalian suprachiasmatic nucleus is the site of the circadian rhythm generator. The degrees of expression there of several neuropeptides, including vasopressin and vasoactive intestinal polypeptide, follow a diurnal rhythm. The vasopressin V1a receptor, whose activation results in phosphoinositol hydrolysis and mobilization of intracellular calcium, is expressed in this nucleus. This study used double simultaneous hybridization histochemistry to show that V1a receptor transcripts are present in both vasopressin and vasoactive intestinal polypeptide neurons and that their levels follow a diurnal rhythm. Furthermore, the expression of the V1a receptor is 12 h out of phase from that of vasopressin. However, the receptor's diurnal rhythm is still maintained in the vasopressin-deficient Brattleboro rat, indicating that the V1a receptor's rhythm is independent of any vasopressin feedback.


A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection.
Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.


Mesonia hitae sp. nov., isolated from the seawater of the South Atlantic Ocean.
A Gram-negative, non-motile, non-spore-forming, aerobic and short rod-shaped bacterial strain R32T, was isolated from seawater of the South Atlantic Ocean. Strain R32T grew at 10-40 °C (optimum 28 °C), at pH 6.0-8.0 (optimum 7.0), and in the presence of 3-8 % NaCl (w/v) (optimum 5 %). Cells were oxidase- and catalase-positive. The 16S rRNA gene sequence of strain R32T shared the highest similarities with Mesonia oceanica (98.3 %), followed by Salegentibacter salarius (93.0 %), Salegentibacter mishustinae (92.8 %), Salegentibacter salegens (92.5 %) and Mesonia maritima (92.4 %). The dominant fatty acids were iso-C15 : 0 (32.7 %) and iso-C17 : 0 3-OH (21.1 %). Menaquinone-6 (MK-6) was detected as the sole respiratory quinone. The polar lipids found were phosphatidylethanolamine, three aminolipids and three unidentified lipids. The DNA G+C content was 35.0 mol%. The ANI value and dDDH value between strain R32T and the Salegentibacter and Mesonia species were 70.5-85.8 % and 18.7-30.5 %, respectively. Based on the results of the polyphasic characterization, strain R32T is considered to represent a novel species of the genus Mesonia, for which the name Mesonia hitae sp. nov. is proposed. The type strain is R32T (=MCCC 1A09780T=KCTC 72004T).


A hybrid technique using bipolar energy in transurethral prostate surgery: a prospective, randomized comparison.
We assessed the efficacy and safety of transurethral resection and vaporization with bipolar PlasmaKinetic energy. During a 2-year period 101 men with benign prostatic hyperplasia were randomly assigned to PlasmaKinetic surgery or standard transurethral prostate resection (TURP). Patient demographics, indications for surgery, preoperative and postoperative International Prostate Symptom Score, uroflowmetry scores, operative time, catheterization duration, hospital stay and complication rates were compared. Complete data on 96 patients with a mean age +/- SD of 69.1 +/- 6.1 years was available at a mean followup of 18.3 +/- 6.7 months (range 12 to 23). In the PlasmaKinetic and TURP groups mean operative time was 40.3 +/- 11.4 (range 30 to 60) and 57.8 +/- 13.4 minutes (range 45 to 75), respectively (p <0.01). The mean volume of saline irrigation during the PlasmaKinetic procedure was significantly lower than that of hyperosmolar solution irrigation during TURP (p <0.05). Patients in the PlasmaKinetic and TURP groups were catheterized a mean of 2.3 +/- 0.7 (range 2 to 4) and 3.8 +/- 0.7 days (range 3 to 5), respectively (p <0.05). The mean improvement rate from baseline at month 12 in International Prostate Symptom Score and the maximal urinary flow rate was similar in the 2 groups. Severe irritative symptoms were the most common complaints after PlasmaKinetic surgery, as observed in 6 cases (12.2%). Recatheterization was necessary in 3 cases (6.1%) cases in the PlasmaKinetic group and in 1 (2.1%) in the TURP group. During followup urethral stricture formation was observed in 3 patients (6.1%) cases in the former group and in 1 (2.1%) in the latter group (p = 0.002). Reoperation was required in 2 (4.1%) and 1 (2.1%) cases in the PlasmaKinetic and TURP groups, respectively. : Transurethral surgery with PlasmaKinetic bipolar energy seems to be a promising alternative to prostatic tissue removal with shorter operative, catheterization and hospitalization times, although increased rates of postoperative irritative symptoms and urethral stricture formation must be further evaluated.


Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.
Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.


Casey's conundrum, a review of the genus Semanotus Mulsant (Coleoptera: Cerambycidae: Cerambycinae: Callidiini) in North America.
The North American species of Semanotus Mulsant, 1839 are reviewed. Semanotus ligneus (Fabricius, 1787), Semanotus amplus amplus (Casey, 1912) new status, S. amplus basalis (Casey, 1924) new status, Semanotus amplus sequoiae Van Dyke, 1923 new status, Semanotus conformis Casey, 1924 new status, Semanotus terminatus Casey, 1912 new status, Semanotus amethystinus (LeConte, 1853), Semanotus juniperi (Fisher, 1915), and Semanotus litigiosus (Casey, 1891) are recognized as valid. A key to the North American fauna, as well as to Semanotus japonicus Lacordaire, 1869 and Semanotus australis Giesbert, 1993 is included. A morphometric study was conducted using 37 measured characters from adults of S. litigiosus. Data were examined using stepwise discriminant analysis to determine which characters aid in the diagnosis of taxa, and their amounts of resolving power using canonical variates analysis. Morphometrics revealed significant sexual dimorphism among taxa and suggested that three taxa were present, however, only two taxa could be reasonably separated using observable characters. Phylogenetic analysis using a hypothetical ancestor as out-group returned a single most parsimonious tree for North American Semanotus.


Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity.
Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.


Surveillance and diagnosis of zoonotic foodborne parasites.
Foodborne parasites are a source of human parasitic infection. Zoonotic infections of humans arise from a variety of domestic and wild animals, including sheep, goats, cattle, camels, horses, pigs, boars, bears, felines, canids, amphibians, reptiles, poultry, and aquatic animals such as fishes and shrimp. Therefore, the implementation of efficient, accessible, and controllable inspection policies for livestock, fisheries, slaughterhouses, and meat processing and packaging companies is highly recommended. In addition, more attention should be paid to the education of auditors from the quality control (QC) and assurance sectors, livestock breeders, the fishery sector, and meat inspection veterinarians in developing countries with high incidence of zoonotic parasitic infections. Furthermore, both the diagnosis of zoonotic parasitic infections by inexpensive, accessible, and reliable identification methods and the organization of effective control systems with sufficient supervision of product quality are other areas to which more attention should be paid. In this review, we present some examples of successful inspection policies and recent updates on present conventional, serologic, and molecular diagnostic methods for zoonotic foodborne parasites from both human infection and animal-derived foods.


Women report more symptoms and impaired quality of life: a survey of Finnish COVID-19 survivors.
The long-term sequelae after COVID-19 are not yet fully known. Our aim was to evaluate subjective symptoms and quality of life in Finnish hospitalized COVID-19 patients at six months follow-up. Hospitalised adult patients with laboratory-confirmed SARS-CoV-2 infection from March to June 2020 were recruited. We conducted a survey on demographics and comorbidities, ten specific symptoms, and a RAND-36 quality of life questionnaire six months after hospital discharge. We collected clinical data manually from medical records. 101 patients (54 male) out of 246 invited completed the survey. Their median age was 60 years, and the mean hospital length of stay was 15 d. Most patients (90%) experienced symptoms, the most common of which were tiredness (88%), fatigue (79%), sleeping problems (76%), and dyspnoea (70%). In regard to gender, women showed a shorter time of hospitalization (p = .048) and lower peak flow of supplementary oxygen (p = .043). Women reported more frequently dyspnoea, fatigue, tiredness, sleeping problems, and mood problems (p = .008-.033), and a lower quality of life in seven of eight dimensions (p < .001-.015). Five explanatory variables for the reduced quality of life were identified in multivariate analysis: age, female sex, BMI, sleep apnoea, and duration of mechanical ventilation. Of the patients who worked full-time before COVID-19, 11% had not returned to work. Most patients experienced symptoms six months after hospital discharge. Women reported more symptoms and a lower quality of life than men. These findings highlight the differences in recovery between men and women and call for active rehabilitation of COVID-19 patients.


Decreased production of nitric oxide by peripheral blood mononuclear cells of patients with peripheral vascular disease.
Although prior studies have implicated nitric oxide (NO), a molecular messenger, in the development and progression of atherosclerosis, most of these studies have centered on atherosclerotic plaques. The current investigation determines whether a correlation exists between the presence of altered levels of NO production by peripheral blood mononuclear cells (PBMCs) and atherosclerotic disease. Venous blood was collected from 8 surgical patients having severe peripheral vascular disease and 8 healthy controls. PBMCs were separated by gradient centrifugation, diluted to 10(5) cells per mL, and cultured. Lipopolysaccharide (LPS), at doses of 10, 25, and 50 ng/mL, was used to stimulate NO production. Total nitric oxide assay was performed to determine the levels of NO produced by PBMCs at 24 and 48 hours. When stimulated by LPS there was an increase in NO production in the PBMCs cultured from control as well as patient samples, as compared to basal NO levels. However, the data demonstrate a significant decrease in the nitric oxide production in the patients with atherosclerosis as compared to that in the control group (p < 0.05). The differential production of nitric oxide by PBMCs of patients with atherosclerotic disease and healthy controls not only suggests that it has a role in the pathogenesis of this disease but also underlines its systemic nature. Blood cells circulating in the body with altered levels of NO production could have profound effects in the microvascular environment mediating molecular pathways and signaling cascades that activate and augment atherosclerosis.


An investigation into the effects of hemodynamic changes on the patient's clinical condition during the treatment of patients undergoing aneurysmal subarachnoid hemorrhage.
In this study, we investigated the hemodynamic changes in patients with aneurysmal subarachnoid hemorrhage (aSAH) during the intensive care unit and the effects of PiCCO on the hemodynamic clinical course during hydration and hypertension treatment. In our study, 15 adult aSAH patients, whose aneurysm had been treated by surgery or coiling, were examined for the signs of vasospasm in between the dates 03/01/2015 and 01/03/2016. The PICCO measurement was made at least twice in a day. Positive daily fluid balance was attempted to be at least 1000 mL and the value of the Global end-diastolic index (GEDI) was targeted to 680 to 800 mL/m2 for each patient. The values of mean arterial pressure (MAP), systolic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP), and cardiac index (CI), GEDI, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI) measured by PiCCO, and daily neurological outcome of patients and GCS values were recorded. It had been observed that CVP value was randomly changing during the volume therapy, but the GEDI value determined by thermodilution was consistent. A positive correlation was detected between the period of reaching the hospital and the first measured value of SVRI. Low GEDI value was detected as a risk factor in the perspective of vasospasm, but an ideal GEDI value could not be determined. GEDI values were correlated with daily fluid balance. While low GEDI value was found as a risk factor, we could not determine an ideal GEDI value.


13C-NMR and mass spectral data of steroids with a 17,17-dialkyl-18-nor-13(14)-ene substructure.
We present carbon-13 nuclear magnetic resonance (13C-NMR) and mass spectral data for several androstanes and estranes having a 17,17-dialkyl-18-nor-13(14)-ene substructure. These compounds are formed by a Wagner-Meerwein rearrangement of steroids bearing a tertiary 17-hydroxy group during the derivatization reaction with heptafluorobutyric anhydride. The 13C-NMR assignments are compared with those of natural products having a similar substructure. The mass spectra show characteristic fragment ions for which a fragmentation mechanism is proposed.


Spot urine samples compared with 24-h urine samples for estimating changes in urinary sodium and potassium excretion in the China Salt Substitute and Stroke Study.
The capacity of spot urine samples for detecting changes in population sodium and potassium excretion is unclear. Changes in urinary sodium and potassium excretion, over a 6-month to 2-year interval, were measured from 24-h urine samples and estimated from spot urine samples using several published methods in 3270 Chinese. Additional estimates were made by multiplying individual spot sodium and potassium concentrations by a single estimated 24-h urine volume derived from external data. The measured difference in 24-h urinary excretion between intervention and control groups was -0.35 g (95% CI: -0.68 to -0.02; P = 0.039) for sodium and 0.66 g (95% CI: 0.52 to 0.80; P < 0.001) for potassium, based upon 24-h urine samples. The corresponding estimates of sodium differences for the Tanaka (-0.06 g), Kawasaki (-0.09 g), Intersalt without potassium (-0.09 g) and Intersalt with potassium (-0.14 g) equations were all smaller and identified no reduction in sodium excretion (all P > 0.10). The estimates were -0.65 g for sodium and 1.11 g for potassium using individual spot urine concentrations and an externally derived standard urine volume (both P < 0.01). The published equations were unable to detect the differences in sodium excretion measured by 24-h urine samples. A method based upon spot urine electrolyte concentrations and a standard urine volume may offer an alternative approach to measuring differences in sodium and potassium excretion between population groups without requiring 24-h urine, but will need further investigation.


Correlation of serum anti-Müllerian hormone levels with positive in vitro fertilization outcome using a short agonist protocol.
We examined the predictive ability of anti-Müllerian hormone (AMH) for clinical pregnancy in women who underwent in vitro fertilization (IVF) cycles in a short agonist protocol. This is a retrospective cohort study of 222 women undergoing their first IVF attempt between June 2010 and March 2016. Multivariate logistic regression analysis was performed to evaluate the independent associations between clinical pregnancy and its possible predictors. 14.9% of cycles were cancelled, >3 oocytes were retrieved in 55.4% of cycles and embryo transfer was performed in 70.7% of cases. Live birth was the final outcome in 19.8% of subjects, miscarriage occurred in 4.1%, whereas no pregnancy occurred in the remaining 76.1% of the study sample. The number of oocytes, number of embryos, embryo transfer rate and pregnancy rates were positively associated with serum AMH concentrations (p <0.001, for each association). When analyzed by age quartiles, the overall association between AMH and clinical pregnancy rates was evident across all age strata. Serum AMH levels are a strong predictive marker of clinical pregnancy in women undergoing a short agonist IVF protocol. There is also a strong association with cancellation rate, number of oocytes retrieved, poor response (≤3 oocytes), number of embryos, embryo transfer rate and live birth rates.


[Case report of miliary TB, with mediastinal TB involving the aorta, trachea and esophagus with death due to hemorrhage from perforation of aorta into the esophagus during treatment].
A 32-year-old male was diagnosed as having miliary tuberculosis in May 1990. In spite of antituberculosis chemotherapy, he developed tuberculous meningitis and intracranial tuberculoma in September 1990. Miliary shadows on chest X-ray disappeared in December 1990. However, he developed left atelectasis, and bronchofiberscopy revealed soft tumor in the left main bronchus in January 1991. He suddenly vomited large amounts of blood and expired in February 1991. At autopsy, tuberculous lymphadenitis and cavitation were noted in the mediastinum, through which the left main bronchus, esophagus and descending aorta communicated. The patient died of massive bleeding which resulted from the rupture of tuberculous aortitis into the esophagus. This is a very rare case of tuberculous aortic aneurysm rupturing into both the bronchus and esophagus.


Cloning and sequence analysis of the estA gene encoding enzyme for producing (R)-beta-acetylmercaptoisobutyric acid from Pseudomonas aeruginosa 1001.
The estA gene encoding the enzyme that catalyzes the production of (R)-beta-acetylmercaptoisobutyric acid from (R,S)-ester from Pseudomonas aeruginosa 1001, was cloned in Escherichia coli and its nucleotide sequence was determined, revealing the presumed open reading frame encoding a polypeptide of 316 amino acid residues (948 nucleotides). The overall A + T and C + G compositions were 32.59% and 67.41%, respectively. The amino acid sequence of the estA gene product showed a significant similarity with that of the triacylglycerol lipase from Psychrobacter immobilis (38% identity), triacylglycerol lipase from Moraxella sp. (36% identity), and two forms of carboxyl esterases from Acinetobacter calcoaceticus (17% and 17% identities). The deduced amino acid sequences have a pentapeptide consensus sequence, G-X-S-X-G, having an active serine residue, and another active site, dipeptides H-G, located at 70-100 amino acids upstream of the G-X-S-X-G consensus sequence.


Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival.
Erythropoietin was traditionally considered an erythroid-restricted cytokine, but recent evidence indicates a broader role for it in nonhematopoietic tissues, specifically in neural development. Pediatric solid tumors are mostly developmental in origin, and more than 50% of the solid tumors are neural in origin. We found erythropoietin receptor and erythropoietin expression in common pediatric tumor cells: neuroblastomas, Ewing's sarcoma family of tumors, pediatric brain tumors (medulloblastoma, astrocytoma, and ependymoma), Wilms tumors, rhabdomyosarcomas, and hepatoblastomas (n = 24), and in cell lines derived from some of these tumors (n = 25). Expression of erythropoietin in tumor cell lines was hypoxia-inducible. Addition of exogenous erythropoietin to tumor cell lines expressing erythropoietin receptor increased nuclear DNA binding activity of nuclear factor kappa B and increased the expression of the antiapoptotic genes bcl-1, bcl-xL, and mcl-1. Additionally, exogenous erythropoietin increased production and secretion of angiogenic growth factors, vascular endothelial growth factor, or placenta growth factor from the tumor cell lines, which promoted endothelial cell proliferation and chemotaxis. Erythropoietin receptor expression that promotes tumor cell survival and releases angiogenic growth factors in pediatric tumors has not been previously described. Therefore, a careful evaluation of the impact of erythropoietin is warranted in vivo, in xenograft models of pediatric tumors, followed by evaluation in pediatric patients with cancer.


Ambient temperature shapes reproductive output during pregnancy and lactation in the common vole (Microtus arvalis): a test of the heat dissipation limit theory.
The heat dissipation limit theory suggests that heat generated during metabolism limits energy intake and, thus, reproductive output. Experiments in laboratory strains of mice and rats, and also domestic livestock generally support this theory. Selection for many generations in the laboratory and in livestock has increased litter size or productivity in these animals. To test the wider validity of the heat dissipation limit theory, we studied common voles (Microtus arvalis), which have small litter sizes by comparison with mice and rats, and regular addition of wild-caught individuals of this species to our laboratory colony ensures a natural genetic background. A crossover design of ambient temperatures (21 and 30°C) during pregnancy and lactation was used. High ambient temperature during lactation decreased milk production, slowing pup growth. The effect on pup growth was amplified when ambient temperature was also high during pregnancy. Shaving fur off dams at 30°C resulted in faster growth of pups; however, no significant increase in food intake and or milk production was detected. With increasing litter size (natural and enlarged), asymptotic food intake during lactation levelled off in the largest litters at both 21 and 30°C. Interestingly, the effects of lactation temperature on pup growth where also observed at smaller litter sizes. This suggests that vole dams trade-off costs associated with hyperthermia during lactation with the yield from investment in pup growth. Moreover, pup survival was higher at 30°C, despite lower growth, probably owing to thermoregulatory benefits. It remains to be seen how the balance is established between the negative effect of high ambient temperature on maternal milk production and pup growth (and/or future reproduction of the dam) and the positive effect of high temperatures on pup survival. This balance ultimately determines the effect of different ambient temperatures on reproductive success.


Effects of dilation and translation on a perceptron-type learning rule for higher order Hopfield neural networks.
In this paper, we will take a further look at a generalized perceptron-like learning rule which uses dilation and translation parameters in order to enhance the recall performance of higher order Hopfield neural networks without significantly increasing their complexity. We will practically study the influence of these parameters on the perceptron learning and recall process, using a generalized version of the Hebbian learning rule for initialization. Our analysis will be based on a pattern recognition problem with random patterns. We will see that in case of a highly correlated set of patterns, there can be gained some improvements concerning the learning and recall performance. On the other hand, we will show that the dilation and translation parameters have to be chosen carefully for a positive result.


Transduction efficacy of Tat-Cu,Zn-superoxide dismutase is enhanced by copper ion recovery of the fusion protein.
We previously reported that Tat-Cu,Zn-superoxide dismutase (Tat-SOD) can be directly transduced into mammalian cells across the lipid membrane barrier. To enhance the therapeutic potential of Tat-SOD for the treatment of various disorders that are related to this antioxidant enzyme, the transduction efficacy of Tat-SOD should be heightened. Therefore, we investigated whether copper ion recovery of the fusion protein could enhance the transduction potential of Tat-SOD in cultured HeLa cells. The results showed that the transduction potential of Tat-SOD was markedly enhanced by copper ions, and moderately increased by zinc ions. Compared with Tat-SOD, the Tat-SOD that recovered the copper ion (CR-Tat-SOD) achieved a significant increase in intracellular concentration and enzymatic activity. Therefore, CR-Tat-SOD was transduced into HeLa cells in a rapid saturation manner, but Tat-SOD was shown in a time-dependent manner. With the higher transduction efficacy of CR-Tat-SOD than that of Tat-SOD, the transduced CR-Tat-SOD significantly increased the viability of HeLa cells that were pretreated with paraquat, an intracellular superoxide anion generator. Although the mechanism of the enhanced transduction of Tat-SOD by copper ions is still unanswered, these results indicate that copper ions facilitate the transduction of SOD. These then significantly increase the biological effectiveness of this antioxidant enzyme.


Impaired cardiac autonomic function in women with prior gestational diabetes mellitus.
Cardiac autonomic neuropathy is a common dysfunction in manifest diabetes mellitus and is associated with duration of diabetes and/or an inadequate glycaemic control. Heart rate variability (HRV) reflects autonomic heart function. The aim of the present study was to investigate whether in women with prior gestational diabetes (GD; pre-type 2 diabetes) alterations of cardiac autonomic function can be observed after delivery in relation to insulin sensitivity and glycaemic control. Forty-eight healthy women with prior GD were consecutively admitted to the study. HRV was analysed by both time, as well as frequency, domain methods using 24-h Holter monitoring. In addition, 20 women with normal glucose tolerance during and after pregnancy were investigated as control subjects. All women underwent a frequently sampled intravenous glucose tolerance test (FSIGT) for measurement of insulin sensitivity. Time domain analysis (standard deviation of normal RR intervals; SDNN) showed a reduced HRV in 25 out of the 48 (52%) women with prior GD. Frequency domain analysis revealed that in these 25 subjects both low and high frequency components of power spectral density (reflecting mainly sympathetic respectively parasympathetic activity) were reduced, indicating that sympathetic as well as parasympathetic functional impairment may be assumed. However, a relative predominance of the sympathetic over parasympathetic cardiac function was observed. The impairment of cardiac autonomic function (reduced SDNN) was correlated with HbA1c values and the 2-h blood glucose concentration (oral glucose tolerance test) but not with insulin sensitivity. The present results demonstrate that in 52% of the women examined who had prior GD, an impairment of cardiac sympathetic as well as parasympathetic function was present, which related to glycaemic control, but not to insulin sensitivity. This infers that functional autonomic changes could be an early prognostic indicator in pre-type 2 diabetes.


Investigation of multimorbidity and prevalent disease combinations in older Irish adults using network analysis and association rules.
Multimorbidity (the presence of multiple medical conditions) is well known to increase with age. People with multimorbidities often have higher physical and functional decline as well as increased mortality. Despite growing evidence that integrated and collaborative care improves many undesirable outcomes of multimorbidity, the majority of health systems are based around treating individual diseases. A pattern analysis of comorbidities using network graphs and a novel use of association rules was conducted to investigate disease associations on 6101 Irish adults aged 50+. The complex network of morbidities and differences in the prevalence and interactions of these morbidities by sex was also assessed. Gender specific differences in disease prevalence was found for 22/31 medical conditions included in this study. Females had a more complex network of disease associations than males with strong associations found between arthritis, osteoporosis and thyroid issues among others. To assess the strength of these associations we provide probabilities of being diagnosed with a comorbid condition given the presence of an index morbidity for 639 pairwise combinations. This information can be used to guide clinicians in deciding which comorbidities should be incorporated into comprehensive assessments in addition to anticipating likely future morbidities and thus developing prevention strategies.


MET-Activating Ubiquitin Multimers.
Receptor tyrosine kinases (RTKs) are generally activated through their dimerization and/or oligomerization induced by their cognate ligands, and one such RTK hepatocyte growth factor (HGF) receptor, known as MET, plays an important role in tissue regeneration. Here we show the development of ubiquitin (Ub)-based protein ligand multimers, referred to as U-bodies, which act as surrogate agonists for MET and are derived from MET-binding macrocyclic peptides. Monomeric Ub constructs (U-body) were first generated by genetic implantation of a macrocyclic peptide pharmacophore into a structural loop of Ub (lasso-grafting) and subsequent optimization of its flanking spacer sequences via mRNA display. Such U-body constructs exhibit potent binding affinity to MET, thermal stability, and proteolytic stability. The U-body constructs also partially/fully inhibited or enhanced HGF-induced MET-phosphorylation. Their multimerization to dimeric, tetrameric, and octameric U-bodies linked by an appropriate peptide linker yielded potent MET activation activity and downstream cell proliferation-promoting activity. This work suggests that lasso-grafting of macrocycles to Ub is an effective approach to devising protein-based artificial RTK agonists and it can be useful in the development of a new class of biologics for various therapeutic applications.


Paramagnetic States in Oxygen-Doped Boron Nitride Extend Light Harvesting and Photochemistry to the Deep Visible Region.
A family of boron nitride (BN)-based photocatalysts for solar fuel syntheses have recently emerged. Studies have shown that oxygen doping, leading to boron oxynitride (BNO), can extend light absorption to the visible range. However, the fundamental question surrounding the origin of enhanced light harvesting and the role of specific chemical states of oxygen in BNO photochemistry remains unanswered. Here, using an integrated experimental and first-principles-based computational approach, we demonstrate that paramagnetic isolated OB3 states are paramount to inducing prominent red-shifted light absorption. Conversely, we highlight the diamagnetic nature of O-B-O states, which are shown to cause undesired larger band gaps and impaired photochemistry. This study elucidates the importance of paramagnetism in BNO semiconductors and provides fundamental insight into its photophysics. The work herein paves the way for tailoring of its optoelectronic and photochemical properties for solar fuel synthesis.


Is Shoulder Imbalance a Useful Parameter in the Screening of Idiopathic Scoliosis? A Preliminary Study.
Objective The present study aims to analyze the use of shoulder imbalance as a parameter for scoliosis screening as well as its relationship with other parameters of physical examination. Methods This study assesses a smartphone application that analyzes several parameters of the physical examination in adolescent idiopathic scoliosis. Medical and non-medical examiners applied the screening tool in students in a public school and in a private sports club. After data collection, interobserver correlation was done to verify shoulder imbalance and to compare shoulder imbalance with Adam's bending test and with trunk rotation. Results Eighty-nine participants were examined, 18 of whom were women and 71 of whom were men. Two subjects were excluded from the analysis. The mean age of subjects from the public school was 11.30 years and, for those from the sports club, it was 11.92 years. The examiners had poor-to-slight interobserver concordance on shoulder asymmetry in the anterior and posterior view. No significant statistical correlation was found between shoulder asymmetry and positive Adam's forward bending test. Conclusion Our preliminary study shows that the shoulder asymmetry has a poor correlation with the Adam's forward bending test and measuring trunk rotation using a scoliometer. Therefore, the use of shoulder imbalance might not be useful for idiopathic scoliosis screening. Level of Evidence III; Diagnostic Study.


Toxicology screening in acute spinal cord injury.
The validity of self-reported intoxication at time of spinal cord injury (SCI) was examined for 88 cases at admission to an acute SCI center by comparing self-reports with serum and urine analyses. Serum ethanol greater than 50 mg/dl was the most frequently found substance (observed in 40% of the cases) followed by urine analysis evidence of cocaine (14%), cannabinoids (8%), benzodiazipines (5%), and opiates (4%). Evidence of substances with abuse potential was found in urine for 35% of the sample. While 62% of the sample had either serum ethanol greater than 50 mg/dl or a positive urine analysis, only 42% of the sample reported being under the influence of some substance at the time of SCI. Although the relationship between these two measures was statistically significant, self-report and toxicology analyses were discordant in 34% of the cases. These results suggest that routine drug testing at admission to an SCI center will produce both false-negative and false-positive results if substance presence alone is interpreted as evidence of intoxication.


Methane Inhibition Alters the Microbial Community, Hydrogen Flow, and Fermentation Response in the Rumen of Cattle.
Management of metabolic hydrogen ([H]) in the rumen has been identified as an important consideration when reducing ruminant CH4 emissions. However, little is known about hydrogen flux and microbial rumen population responses to CH4 inhibition when animals are fed with slowly degradable diets. The effects of the anti-methanogenic compound, chloroform, on rumen fermentation, microbial ecology, and H2/CH4 production were investigated in vivo. Eight rumen fistulated Brahman steers were fed a roughage hay diet (Rhode grass hay) or roughage hay:concentrate diet (60:40) with increasing levels (low, mid, and high) of chloroform in a cyclodextrin matrix. The increasing levels of chloroform resulted in an increase in H2 expelled as CH4 production decreased with no effect on dry matter intakes. The amount of expelled H2 per mole of decreased methane, was lower for the hay diet suggesting a more efficient redirection of hydrogen into other microbial products compared with hay:concentrate diet. A shift in rumen fermentation toward propionate and branched-chain fatty acids was observed for both diets. Animals fed with the hay:concentrate diet had both higher formate concentration and H2 expelled than those fed only roughage hay. Metabolomic analyses revealed an increase in the concentration of amino acids, organic, and nucleic acids in the fluid phase for both diets when methanogenesis was inhibited. These changes in the rumen metabolism were accompanied by a shift in the microbiota with an increase in Bacteroidetes:Firmicutes ratio and a decrease in Archaea and Synergistetes for both diets. Within the Bacteroidetes family, some OTUs assigned to Prevotella were promoted under chloroform treatment. These bacteria may be partly responsible for the increase in amino acids and propionate in the rumen. No significant changes were observed for abundance of fibrolytic bacteria, protozoa, and fungi, which suggests that fiber degradation was not impaired. The observed 30% decrease in methanogenesis did not adversely affect rumen metabolism and the rumen microbiota was able to adapt and redirect [H] into other microbial end-products for both diets. However, it is also required dietary supplements or microbial treatments to capture the additional H2 expelled by the animal to further improve rumen digestive efficiency.


Usefulness of 24-hour recordings of electrocardiogram for the diagnosis and treatment of arrhythmias with special reference to the determination of indication of artificial cardiac pacing.
Twenty-four-hour recordings of electrocardiogram (ECG) were obtained from 1528 subjects. Sick sinus syndrome (SSS) was observed in 34 and advanced or complete AV block (CAVB) in 13 subjects. During the period studied 21 patients had died, who showed complicated ventricular premature contractions in 9 (multiform 6, short run 2, repetitive 2). Seventy-three patients with artificial cardiac pacing who were admitted at three different institutions were analyzed. The discrepancy of degree of block was observed between His bundle electrocardiographic findings and 24-hour ECG recordings. In 15 patients there was no correlation between sinus node recovery time following overdrive suppression and pauses following the termination of tachycardia (r = 0.0896, N. S.). In 49 normal subjects 24-hour heart rate ranged from a high of 170 to a low of 36 beats/min. Longest R-R interval ranged from 2.08 to 0.86 sec (mean 1.25 +/- 0.22 sec). The critical level of longest R-R interval to differentiate between normal group and groups with SSS or CAVB was about 1.6 sec. Above results suggest that Holter monitoring permits a precise diagnosis of arrhythmias and that both HBE and Holter monitoring should be used for the determination of pacemaker implantation especially in those with syncope or dizziness but without evidence of marked bradycardia.


Obesity, body weight regulation and the brain: insights from fMRI.
Obesity constitutes a major global health threat. Despite the success of bariatric surgery in delivering sustainable weight loss and improvement in obesity-related morbidity, effective non-surgical treatments are urgently needed, necessitating an increased understanding of body weight regulation. Neuroimaging studies undertaken in people with healthy weight, overweight, obesity and following bariatric surgery have contributed to identifying the neurophysiological changes seen in obesity and help increase our understanding of the mechanisms driving the favourable eating behaviour changes and sustained weight loss engendered by bariatric surgery. These studies have revealed a key interplay between peripheral metabolic signals, homeostatic and hedonic brain regions and genetics. Findings from brain functional magnetic resonance imaging (fMRI) studies have consistently associated obesity with an increased motivational drive to eat, increased reward responses to food cues and impaired food-related self-control processes. Interestingly, new data link these obesity-associated changes with structural and connectivity changes within the central nervous system. Moreover, emerging data suggest that bariatric surgery leads to neuroplastic recovery. A greater understanding of the interactions between peripheral signals of energy balance, the neural substrates that regulate eating behaviour, the environment and genetics will be key for the development of novel therapeutic strategies for obesity. This review provides an overview of our current understanding of the pathoaetiology of obesity with a focus upon the role that fMRI studies have played in enhancing our understanding of the central regulation of eating behaviour and energy homeostasis.


In vitro cytotoxic effects of gold nanoparticles coated with functional acyl homoserine lactone lactonase protein from Bacillus licheniformis and their antibiofilm activity against Proteus species.
N-acylated homoserine lactonases are known to inhibit the signaling molecules of the biofilm-forming pathogens. In this study, gold nanoparticles were coated with N-acylated homoserine lactonase proteins (AiiA AuNPs) purified from Bacillus licheniformis. The AiiA AuNPs were characterized by UV-visible spectra, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The synthesized AiiA AuNPs were found to be spherical in shape and 10 to 30 nm in size. Treatment with AiiA protein-coated AuNPs showed maximum reduction in exopolysaccharide production, metabolic activities, and cell surface hydrophobicity and potent antibiofilm activity against multidrug-resistant Proteus species compared to treatment with AiiA protein alone. AiiA AuNPs exhibited potent antibiofilm activity at 2 to 8 μM concentrations without being harmful to the macrophages. We conclude that at a specific dose, AuNPs coated with AiiA can kill bacteria without harming the host cells, thus representing a potential template for the design of novel antibiofilm and antibacterial protein drugs to decrease bacterial colonization and to overcome the problem of drug resistance. In summary, our data suggest that the combined effect of the lactonase and the gold nanoparticles of the AiiA AuNPs has promising antibiofilm activity against biofilm-forming and multidrug-resistant Proteus species.


High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.
High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm2) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score (p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm2) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.


Prospective randomized trial of interventions for vincristine-related neuropathic pain.
To evaluate the efficacy of gabapentin at 20 mg/kg per day in the treatment of vincristine-related neuropathic pain. Children aged 1-18 years who developed vincristine-induced neuropathy on a St Jude frontline acute lymphoblastic leukemia trial were prospectively enrolled on a randomized, double-blind, placebo-controlled, phase II trial with two treatment arms: gabapentin plus opioid versus placebo plus opioid. Daily evaluations of morphine dose (mg/kg per day) and pain scores were conducted for up to 21 days; the values of the two arms were compared to assess analgesic efficacy. Of 51 study participants, 49 were eligible for analyses. Twenty-five participants were treated with gabapentin, with a mean (SD) dose of 17.97 (2.76) mg/kg per day (median 18.26, range 6.82-21.37). The mean (SD) opioid doses taken, expressed as morphine equivalent daily (mg/kg per day), were 0.26 (0.43) in the gabapentin group (25 patients, 432 days) and 0.15 (0.22) in the placebo group (24 patients, 411 days; P = .15). Only the risk classification of acute lymphoblastic leukemia was significantly associated with the daily morphine dosage (P = .0178): patients in the lower risk arm received higher daily morphine dosages. Multivariate analyses revealed a significant difference between the groups' average daily scores for the previous 24 h and "right now." In this population of children with vincristine-related neuropathic pain, opioid consumption and pain scores were higher in the gabapentin group than in the placebo group. Future randomized, double-blind, placebo-controlled studies should test gabapentin given longer or at a higher dose.


Variations in risk-adjusted outcomes in a managed acute/long-term care program for frail elderly individuals.
To develop and investigate the properties of three performance measures based on risk-adjusted health outcomes for a frail, elderly, community-dwelling population enrolled in a managed, acute, and long-term care program. Retrospective analyses of an administrative dataset containing individual level records with information about socioeconomics, health, functional and cognitive status, diagnoses, and treatments. We estimated risk-adjustment models predicting mortality, decline in functional status, and decline in self-assessed health. Each model includes individual risk factors and indicator variables for the program site in which the individual enrolled. Sites were ranked based on their performance in each risk-adjusted outcome, and the properties of these performance measures were investigated. Twenty-eight sites of the Program of All-Inclusive Care for the Elderly (PACE) that provide primary, acute, and long-term care services under capitated Medicare and Medicaid payment to a nursing home certifiable, and functionally and cognitively frail community-dwelling elderly population. Three thousand one hundred and thirty-eight individuals who were newly enrolled between 1 January 1998 and 31 December 1999. The average age of these enrollees was 78 years, 27% were male, 50% were diagnosed with dementia, and they had approximately 4 Activities of Daily Living limitations and 7.4 Instrumental Activities of Daily Living limitations. Risk-adjustment models, performance ranking for each site, and correlations between performance rankings. We present risk-adjustment models for mortality, change in functional status, and self-assessed health status. We found substantial variation across sites in performance, but no correlation between performance with respect to different outcomes. The variations in outcomes suggest that sites can improve their performance by learning from the practices of those with the best outcomes. Further research is required to identify processes of care that lead to best outcomes.


[Pharmacokinetics of hylotelephin in Beagle dogs].
To investigate the pharmacokinetics of hylotelephin in Beagle dogs and obtain the main pharmacokinetic parameters. An HPLC method with UV detection was developed to study the pharmacokinetics of hylotelephin in dogs by joining an internal standard (anthracene). Benzoyl chloride was used to the pre-column derivatization of hylotelephin and methanol-water (64:36) was used as the mobile phase. According to the 3P97 pharmacokinetic program, the main parameters were calculated. The hylotelephin pharmacokinetics conforms to a two-compartment open model after a single iv dose of hylotelephin 10.6 or 21.3 mg x kg(-1) in Beagle dogs. The parameters of two groups were as follows: T(1/2) alpha were 2.3 and 2.1 min, T(1/2) beta were 1.9 and 2.0 h, K12 were 0. 12 and 0.11 min, K21 were 0.17 and 0.21 min, K10 were 0.011 and 0.0094 min, Vc were 0.54 and 0.54 L x kg(-1), AUC were 1.8 and 4.1 g x min x L(-1), CL were 0.0048 and 0.0056 L x kg(-1) x min(-1), MRT were 2.10 and 2.4 h, respectively. The pharmacokinetics of hylotelephin after iv administration showed a rapid distribution and elimination process in Beagle dogs and was of first order kinetics.


Magnetic resonance imaging overestimates patellar height compared with radiographs.
To evaluate the inter-observer and inter-method reliability for patellar height measurements between conventional radiographs (CR) and magnetic resonance imaging (MRI) using one or two slices. This was a reliability study, with 60 patients divided in two groups: 30 patients with patellar instability (patella group) and 30 patients with anterior cruciate ligament or meniscus injury (control group). CR and MRI were evaluated by two independent observers. Insall-Salvati index (IS) and Caton-Deschamps index (CD) were measured using three different methods: CR, one-slice MRI or two-slice MRI. Intra-class correlation coefficients (ICC) were calculated for inter-observer reliability and inter-method reliability. Bland-Altman agreement was also calculated. The inter-observer reliability was very good for the IS with ICCs of 0.93, 0.84 and 0.82, for the CR, one-slice MRI and two-slice MRI, respectively. Similarly, for the CD the ICCs were good, 0.76, 0.80 and 0.75 for the CR, one-slice MRI and two-slice MRI, respectively. No differences were found between the patella and the control group. The inter-method analysis results were: ICCs for IS (0.83, 0.86, 0.93) and CD (0.72, 0.82, 0.83), for the comparisons of CR/one-slice MR, CR/two-slice MRI and one-slice MRI/two-slice MRI, respectively. The Bland-Altman mean differences showed an 8% and a 7% increase on IS values with one-slice MRI and two-slice MRI compared to CR results, while the increase was of 9% and 1% in CD for the respective comparisons with CR. MRI can overestimate patellar height compared to CR, as much as an 8% increase in Insall-Salvati values when using one- or two-slice MRI measurements, and up to a 9% increase in Caton-Deschamps value when using the one-slice MRI method. It is recommended to use the CR as the preferred method when measuring patellar height. III.


Nasal Tip Schwannoma Coexisting With Vestibular Schwannoma.
Although a schwannoma can originate from any central or peripheral nerves, schwannomas originating from the nasal tip are extremely rare and only 4 cases have been reported so far in English literature. These 4 cases appeared solely without any other accompanying schwannomas. However, the authors recently treated a patient with a nasal tip schwannoma coexisting with vestibular schwannoma. The nasal tip schwannoma was successfully removed without cosmetic deformity by using an open rhinoplasty approach.


Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability.
Abnormally synchronized synaptic transmission in the brain leads to epilepsy. Neuroligin-1 (NL1) is a synaptic cell adhesion molecule localized at excitatory synapses. NL1 modulates synaptic transmission and determines the properties of neuronal networks in the mammalian central nervous system. We showed that the expression of NL1 and its binding partner neurexin-1β was increased in temporal lobe epileptic foci in patients and lithium-pilocarpine-treated epileptic rats. We investigated electrophysiological and behavioral changes in epileptic rats after lentivirally mediated NL1 knockdown in the hippocampus to determine whether NL1 suppression prevented seizures and, if so, to explore the probable underlying mechanisms. Our behavioral studies revealed that NL1 knockdown in epileptic rats reduced seizure severity and increased seizure latency. Whole-cell patch-clamp recordings of CA1 pyramidal neurons in hippocampal slices from NL1 knockdown epileptic rats revealed a decrease in spontaneous action potential frequency and a decrease in miniature excitatory postsynaptic current (mEPSC) frequency but not amplitude. The amplitude of N-methyl-D-aspartate receptor (NMDAR)-dependent EPSCs was also selectively decreased. Notably, NL1 knockdown reduced total NMDAR1 expression and the surface/total ratio in the hippocampus of epileptic rats. Taken together, these data indicate that NL1 knockdown in epileptic rats may reduce the frequency and severity of seizures and suppress neuronal hyperexcitability via changes in postsynaptic NMDARs.


Lateralization of interictal EEG findings.
Several reports indicate that interictal epileptiform discharges (IED) may be more likely to occur over the left cerebral hemisphere than over the right. The objective of our study was to determine the frequency and type of IED on routine and multihour EEGs in a tertiary epilepsy center to estimate the frequency of left-sided versus right-sided IED and to determine interictal spike distribution pattern differences between adult and pediatric epilepsy patients. The current study retrospectively reviewed 31,207 EEGs (25,793 routine EEGs and 5414 multihour EEGs) recorded on 24,003 patients during the period from 1993 to 2003. All EEGs were read according to a systematic EEG classification system. Every patient was considered only once by including the first abnormal EEG. Regional unilateral or bilateral IEDs were recorded in 1707 patients (7%). Regional unilateral or bilateral slow was recorded in 2297 patients (9.6%). Left-sided regional IED were seen in 828 patients and accounted for 58% of all unilateral IED. Left-sided slow was seen in 1389 patients and accounted for 65% of all unilateral slow. Lateralization of slow was due to intermittent slow, whereas continuous slow involved both hemispheres equally. There was no lateralization difference in benign focal epileptiform discharges of childhood. Lateralization shows a tendency toward greater left-sided lateralization of interictal findings with aging. Benign focal epileptiform discharges were only seen under the age of 20 years old. Regional IEDs were seen in approximately 7% of patients and slowing occurs in 10% of patients. Both abnormalities were seen more frequently in the left hemisphere. Age adjusted analysis of the data revealed that this left-sided predominance was mildly increased in adults as compared with pediatric patients.


An alternative approach to risk rank chemicals on the threat they pose to the aquatic environment.
This work presents a new and unbiased method of risk ranking chemicals based on the threat they pose to the aquatic environment. The study ranked 12 metals, 23 pesticides, 11 other persistent organic pollutants (POPs), 13 pharmaceuticals, 10 surfactants and similar compounds and 2 nanoparticles (total of 71) of concern against one another by comparing their median UK river water and median ecotoxicity effect concentrations. To complement this, by giving an assessment on potential wildlife impacts, risk ranking was also carried out by comparing the lowest 10th percentile of the effects data with the highest 90th percentile of the exposure data. In other words, risk was pared down to just toxicity versus exposure. Further modifications included incorporating bioconcentration factors, using only recent water measurements and excluding either lethal or sub-lethal effects. The top ten chemicals, based on the medians, which emerged as having the highest risk to organisms in UK surface waters using all the ecotoxicity data were copper, aluminium, zinc, ethinylestradiol (EE2), linear alkylbenzene sulfonate (LAS), triclosan, manganese, iron, methomyl and chlorpyrifos. By way of contrast, using current UK environmental quality standards as the comparator to median UK river water concentrations would have selected 6 different chemicals in the top ten. This approach revealed big differences in relative risk; for example, zinc presented a million times greater risk then metoprolol and LAS 550 times greater risk than nanosilver. With the exception of EE2, most pharmaceuticals were ranked as having a relatively low risk.


Simplified Graded Baseline Symptom Assessment in Patients With Lung Cancer Undergoing First-Line Chemotherapy: Correlations and Prognostic Role in a Resource-Constrained Setting.
There are limited data from developing countries on graded baseline symptom (BS) assessment in lung cancer. This prospective study aimed to assess the prognostic role of BS and correlation of BS with comorbidity, demographic, and investigation profiles in a cohort of 238 patients with lung cancer undergoing first-line chemotherapy over a 15-month period. The Medical Research Council (MRC) scale was used to assess dyspnea, whereas the visual analog scale (VAS; score of 1 to 10) was used to assess anorexia, fatigue, chest pain, and cough. Weight loss (WL) was noted as percentage of pre-illness baseline. All patients received histology-guided platinum doublet chemotherapy. Outcomes assessed were overall survival (OS) and radiologic responses by RECIST. Significant correlations (Spearman ρ) were noted for fatigue and anorexia with all other BSs. Dyspnea differed significantly among groups on the basis of either the simplified comorbidity score or Charlson comorbidity index. Median OS was 287 days (95% CI, 232 to 342 days). OS was significantly higher for anorexia VAS score less than 4 (388 v 229 days for VAS score ≥ 4), fatigue VAS score less than 3 (388 v 213 days for VAS score ≥ 3), WL less than 5% (410 v 259 days for WL ≥ 5%), and MRC dyspnea grade less than 3 (377 v 187 days for MRC grade ≥ 3). On univariable Cox proportional hazards analysis, worse OS was noted for all BSs, stage, and performance status, but on multivariable analysis, only fatigue (hazard ratio [HR], 1.21), Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 1.57), and stage IV disease (HR, 1.61) were significant. Nonresponders (stable disease and progressive disease [PD]) had a higher percentage of WL and higher mean VAS scores for cough, chest pain, anorexia, and fatigue. On multivariable logistic regression analysis, PD was associated with fatigue and percentage of WL. BSs are prognostic for patients with lung cancer on first-line chemotherapy. Fatigue is prognostic for worse OS and PD. Comorbidity and investigation profiles do not correlate with either OS or response rates.


Recommendations for the treatment of established fungal infections.
Evidence-based guidelines for the treatment of established fungal infections in the adult haematology/oncology setting were developed by a national consensus working group representing clinicians, pharmacists and microbiologists. These updated guidelines replace the previous guidelines published in the Internal Medicine Journal by Slavin et al. in 2004. The guidelines are pathogen-specific and cover the treatment of the most common fungal infections including candidiasis, aspergillosis, cryptococcosis, zygomycosis, fusariosis, scedosporiosis, and dermatophytosis. Recommendations are provided for management of refractory disease or salvage therapies, and special sites of infections such as the cerebral nervous system and the eye. Because of the widespread use newer broad-spectrum triazoles in prophylaxis and empiric therapy, these guidelines should be implemented in concert with the updated prophylaxis and empiric therapy guidelines published by this group.


Dual-System Families: Cash Assistance Sequences of Households Involved with Child Welfare.
Dual-system families, those involved with the child welfare system and receiving public cash assistance, may be more vulnerable than families only connected to either of the two systems. This study advances our understanding of the heterogeneous and dynamic cash assistance histories of dual-system families in the post-welfare reform era. With merged administrative data from [state name removed] over the period 1998 to 2009, we use cluster analysis to group month-to-month sequences of cash assistance use among households over the 37-month period surrounding child removal. Close to two thirds of families who received any assistance either had a short spell of Temporary Assistance for Needy Families (TANF) or lost TANF. Smaller percentages had steady support. Families who lose assistance are less likely than average to reunify while those who connect to benefits are more likely, suggesting coordination between systems may serve dual-system families well.


Socioeconomic risks of food insecurity during the Covid-19 pandemic in the UK: findings from the Understanding Society Covid Survey.
We estimated socioeconomic factors associated with food insecurity during the first year of the Covid pandemic in the UK and explored potential mechanisms explaining these associations. Data were from the April, July, and September 2020 waves of the UK Understanding Society Covid Survey. Food insecurity was measured as 'not having access to healthy and nutritious food' and 'reporting being hungry but not eating'. Logistic regression estimated the relationship between socioeconomic factors and food insecurity. A decomposition approach explored if financial vulnerability and having Covid-19 explained associations between socioeconomics factors and food insecurity. Single parents and young people aged 16-30 years had a higher odds of reporting both measures of food insecurity. Financial insecurity explained 5% to 25% of the likelihood of reporting being food insecure for young people and single parents depending on the food insecurity measure used. Experiencing Covid-19 symptoms explained less than 5% of the likelihood of being food insecure for single parents but approximately 30% of not having access to healthy and nutritious food for young people. Policies providing additional financial support may help to reduce the impact of Covid-19 on food insecurity in the UK.


SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes.
TCF and SOX proteins belong to the high mobility group box transcription factor family. Whereas TCFs, the transcriptional effectors of the Wnt pathway, have been widely implicated in the development, homeostasis and disease of the intestine epithelium, little is known about the function of the SOX proteins in this tissue. Here, we identified SOX9 in a SOX expression screening in the mouse fetal intestine. We report that the SOX9 protein is expressed in the intestinal epithelium in a pattern characteristic of Wnt targets. We provide in vitro and in vivo evidence that a bipartite beta-catenin/TCF4 transcription factor, the effector of the Wnt signaling pathway, is required for SOX9 expression in epithelial cells. Finally, in colon epithelium-derived cells, SOX9 transcriptionally represses the CDX2 and MUC2 genes, normally expressed in the mature villus cells of the intestinal epithelium, and may therefore contribute to the Wnt-dependent maintenance of a progenitor cell phenotype.


Basic proline-rich proteins from human parotid saliva: complete covalent structure of protein IB-9 and partial structure of protein IB-6, members of a polymorphic pair.
The complete amino acid sequence of a basic proline-rich protein, IB-9, from human parotid saliva was determined by automated Edman degradation of peptides obtained by enzymatic cleavage of the intact protein with clostripain. The protein was digested with papain and elastase to obtain overlapping peptides. Automated Edman degradation of the intact protein was also performed. The protein consists of 61 amino acids, of which 26 are proline residues. The partial sequence of another human parotid basic proline-rich protein, IB-6, was also obtained. With one exception the first 54 residues of the two proteins are identical. An exceptional degree of internal reiteration occurs in both molecules, including several repeated sequences of 12-14 amino acids. The proteins show a high degree of homology with the C-terminal portion of the salivary acidic proline-rich protein C.


High-Pressure Bulk Synthesis of InN by Solid-State Reaction of Binary Oxide in a Multi-Anvil Apparatus.
We present a new method to synthesize bulk indium nitride by means of a simple solid-state chemical reaction carried out under hydrostatic high-pressure/high-temperature conditions in a multi-anvil apparatus, not involving gases or solvents during the process. The reaction occurs between the binary oxide In2O3 and the highly reactive Li3N as the nitrogen source, in the powder form. The formation of the hexagonal phase of InN, occurring at 350 °C and P ≥ 3 GPa, was successfully confirmed by powder X-ray diffraction, with the presence of Li2O as a unique byproduct. A simple washing process in weak acidic solution followed by centrifugation allowed us to obtain pure InN polycrystalline powders as a precipitate. With an analogous procedure, it was possible to obtain pure bulk GaN, from Ga2O3 and Li3N at T ≥ 600 °C and P ≥ 2.5 GPa. These results point out, particularly for InN, a clean, and innovative way to produce significant quantities of one of the most promising nitrides in the field of electronics and energy technologies.


Gumma of the testis and penis.
The case is described of a patient suffering from gummata of the testes and of the penis, and asymptomatic neurosyphilis. The diagnosis was made on the clinical findings and the strongly positive serological tests for syphilis. It was further supported by the response to penicillin.