Chemistry and catalytic activity of molybdenum(VI)-pyrazolylpyridine complexes in olefin epoxidation. Crystal structures of monomeric dioxo, dioxo-μ-oxo, and oxodiperoxo derivatives.
The dioxomolybdenum(VI) complexes [MoO2Cl2(PzPy)] (1) and [MoO2(OSiPh3)2(PzPy)] (5) (PzPy = 2-[3(5)-pyrazolyl]pyridine) were synthesized and characterized by vibrational spectroscopy, with assignments being supported by DFT calculations. Complex 5 was additionally characterized by single crystal X-ray diffraction. Recrystallization of 1 under different conditions originated crystal structures containing either the mononuclear [MoO2Cl2(PzPy)] complex co-crystallized with 2-[3(5)-pyrazolyl]pyridinium chloride, binuclear [Mo2O4(μ2-O)Cl2(PzPy)2] complexes, or the oxodiperoxomolybdenum(VI) complex [MoO(O2)2Cl(PzPyH)], in which a 2-[3(5)-pyrazolyl]pyridinium cation weakly interacts with the Mo(VI) center via a pyrazolyl N-atom. The crystal packing in the different structures is mediated by a variety of supramolecular interactions: hydrogen bonding involving the pyridinium and/or pyrazolyl N-H groups, weak CH · · · O and CH · · · π contacts, and strong π-π stacking. Complexes 1 and 5 are moderately active catalysts for the epoxidation of cis-cyclooctene at 55 °C using tert-butylhydroperoxide as oxidant, giving 1,2-epoxycyclooctane as the only reaction product. Insoluble materials were recovered at the end of the first catalytic runs and characterized by IR spectroscopy, elemental analysis, scanning electron microscopy (SEM)-energy dispersive spectroscopy (EDS), and powder X-ray diffraction. For complex 5 the loss of the triphenylsiloxy ligands during the catalytic run resulted in the formation of a tetranuclear complex, [Mo4O8(μ2-O)4(PzPy)4]. The recovered solids could be used as efficient heterogeneous catalysts for the epoxidation of cyclooctene, showing no loss of catalytic performance between successive catalytic runs.


New Jersey's license plate decal requirement for graduated driver licenses: attitudes of parents and teenagers, observed decal use, and citations for teenage driving violations.
On May 1, 2010, New Jersey implemented a law requiring teenagers with learner's permits or probationary licenses to display reflective decals on the front and rear license plates when they drive. The current study examined attitudes of parents and teenagers toward this requirement, use of decals, and reported violations and police enforcement of the graduated driver license law. Statewide telephone surveys of representative samples of parents and teenagers were conducted in February to April 2010 and March to June 2011. Use of decals among probationary license holders was observed at 4 high schools in fall 2010 and in spring 2011 and hand-out surveys were distributed. Data on citations issued for violations of the graduated driver license law were obtained. When interviewed in spring 2011, a large majority of parents of probationary license holders, parents of learner's permit holders, and teenagers with probationary licenses disapproved of decals for probationary licenses. About two thirds of both sets of parents and about half of teenagers disapproved of decals for learner's permits. Support for decals for both license types declined significantly from 2010 to 2011. For parents and teenagers alike, opposition was mainly attributed to concern about identifying and/or targeting teenage drivers by other drivers, predators, or police. In 2011, 77 percent of parents of probationary license holders said that their teenagers had decals for the vehicles driven most often; 46 percent said their teenagers always used decals. Fifty-six percent of parents of learner's permit holders said that their teenagers had decals for the vehicles driven most often; 37 percent said that their teenagers always used decals. Teenagers' reported violations of license restrictions either increased or were similar in 2011 compared to 2010. Observed rates of decal use by probationary license holders at high schools in spring 2011 ranged from 24 to 64 percent. The number of statewide citations for teenage licensing law violations doubled in the year after the decal requirement took effect compared to the prior year. Excluding decal violations, citations increased by 52 percent. Early examination of New Jersey's decal requirement found widespread opposition, primarily due to concerns about identifying/targeting teenage drivers, though first-hand reports of such incidents were very rare. Many teenagers do not use the decals. Increased issuance of citations for violations of the teenage licensing law suggests that decals are facilitating police enforcement. However, based on teenagers' self-reports, the requirement does not appear to have achieved the ultimate goal of increased compliance.


Office Spirometry in Primary Care for the Diagnosis and Management of COPD: National Lung Health Education Program Update.
The use of office spirometry was recommended by the National Lung Health Education Program (NLHEP) consensus conference in 1999 for detection and management of COPD. Since that time, spirometry utilization has increased, but its role in the diagnosis of COPD is still evolving. This update reviews the role of spirometry for screening and case finding in COPD as well as for asthma. Spirometry has been used for disease management in patients with airway obstruction, with varying results. The diagnostic criteria for COPD using spirometry have also evolved in the past 17 years, with differences arising between the Global Initiative for Chronic Obstructive Lung Disease and NLHEP recommendations. More sophisticated spirometers as well as new reference equations are widely available. Standardization guidelines from the American Thoracic Society/European Respiratory Society published in 2005 provide a robust framework for performing and interpreting spirometry, but clinicians still need hands-on training and meaningful feedback to perform high-quality spirometry in the office setting.


Clinical-Grade-Expanded Regulatory T Cells Prevent Graft-versus-Host Disease While Allowing a Powerful T Cell-Dependent Graft-versus-Leukemia Effect in Murine Models.
We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong Mixed Lymphocytes Reaction inhibition. In vitro amplification did not induce any karyotypic modification. To evaluate the graft-versus-host disease (GVHD)/graft-versus-leukemia (GVL) bifunctional axis, expanded Tregs and conventional T cells (Tcons) were tested in NOD/SCID/IL2Rgnull mice injected with primary acute myeloid leukemia (AML) cells, AML cell line, acute lymphoid leukemia Philadelphia cell line, or Burkitt-like lymphoma cell line. All mice that received leukemia cells together with expanded Tregs and Tcons were rescued from leukemia and survived without GVHD, showing that Treg expansion procedure did not compromise GVHD control and the strong Tcon-mediated GVL activity. This report might represent the basis for treating high-risk leukemia and/or relapsed/refractory leukemia patients with high-dose Treg/Tcons.


Factors Associated With Nocturia-Related Quality of Life in Men With Lower Urinary Tract Symptoms and Treated With Tamsulosin Oral Controlled Absorption System in a Non-Interventional Study.
Nocturia impairs quality of life (QoL). We have performed a non-interventional study in which men with lower urinary tract symptoms (LUTS) were treated for at least 3 months with tamsulosin oral controlled absorption system (0.4 mg q.d.). Other than observing efficacy and tolerability of this drug formulation, the study was designed to explore the relative roles of number of nocturia episodes and of non-urological causes of nocturia on nocturia-related QoL at baseline and treatment-associated changes thereof. The study enrolled 5775 men seeking treatment of their LUTS. Tamsulosin improved LUTS, e.g. International Prostate Symptom Score from 19.5 ± 5.9 to 10.1 ± 4.9 (means ± SD). This was associated by clinically meaningful improvements in the Nocturia QoL score (from 45 ± 19 to 73 ± 17 points) and other QoL scores. Number of nocturnal voids was the key driver of all QoL scores at baseline; change of number of nocturia episodes that of improvement of all QoL scores upon treatment. In contrast, non-urological causes of nocturia such as heart failure, diabetes, sleep apnea, fluid or alcohol intake or use of diuretics or hypnotics had only small if any effects on baseline QoL or treatment-associated improvements thereof. The observed effects of non-urological causes on QoL apparently were largely driven by their effect on number of nocturnal voids. These data further support the idea that improvement of nocturia may be an important treatment goal in male LUTS.


Selective Gas-Phase Oxidation and Localization of Alkylated Cysteine Residues in Polypeptide Ions via Ion/Ion Chemistry.
The thiol group in cysteine residues is susceptible to several post-translational modifications (PTMs), including prenylation, nitrosylation, palmitoylation, and the formation of disulfide bonds. Additionally, cysteine residues involved in disulfide bonds are commonly reduced and alkylated prior to mass spectrometric analysis. Several of these cysteine modifications, specifically S-alkyl modifications, are susceptible to gas-phase oxidation via selective ion/ion reactions with periodate anions. Multiply protonated peptides containing modified cysteine residues undergo complex formation upon ion/ion reaction with periodate anions. Activation of the ion/ion complexes results in oxygen transfer from the reagent to the modified sulfur residue to create a sulfoxide functionality. Further activation of the sulfoxide derivative yields abundant losses of the modification with the oxidized sulfur as a sulfenic acid (namely, XSOH) to generate a dehydroalanine residue. This loss immediately indicates the presence of an S-alkyl cysteine residue, and the mass of the loss can be used to easily deduce the type of modification. An additional step of activation can be used to localize the modification to a specific residue within the peptide. Selective cleavage to create c- and z-ions N-terminal to the dehydroalanine residue is often noted. As these types of ions are not typically observed upon collision-induced dissociation (CID), they can be used to immediately indicate where in the peptide the PTM was originally located.


Chemical defense balanced by sequestration and de novo biosynthesis in a lepidopteran specialist.
The evolution of sequestration (uptake and accumulation) relative to de novo biosynthesis of chemical defense compounds is poorly understood, as is the interplay between these two strategies. The Burnet moth Zygaena filipendulae (Lepidoptera) and its food-plant Lotus corniculatus (Fabaceae) poses an exemplary case study of these questions, as Z. filipendulae belongs to the only insect family known to both de novo biosynthesize and sequester the same defense compounds directly from its food-plant. Z. filipendulae and L. corniculatus both contain the two cyanogenic glucosides linamarin and lotaustralin, which are defense compounds that can be hydrolyzed to liberate toxic hydrogen cyanide. The overall amounts and ratios of linamarin and lotaustralin in Z. filipendulae are tightly regulated, and only to a low extent reflect the ratio in the ingested food-plant. We demonstrate that Z. filipendulae adjusts the de novo biosynthesis of CNglcs by regulation at both the transcriptional and protein level depending on food plant composition. Ultimately this ensures that the larva saves energy and nitrogen while maintaining an effective defense system to fend off predators. By using in situ PCR and immunolocalization, the biosynthetic pathway was resolved to the larval fat body and integument, which infers rapid replenishment of defense compounds following an encounter with a predator. Our study supports the hypothesis that de novo biosynthesis of CNglcs in Z. filipendulae preceded the ability to sequester, and facilitated a food-plant switch to cyanogenic plants, after which sequestration could evolve. Preservation of de novo biosynthesis allows fine-tuning of the amount and composition of CNglcs in Z. filipendulae.


The Relationship Between rs3212986C>A Polymorphism and Tumor Stage in Lung Cancer Patients.
Background The nucleotide excision repair (NER) system is one of the most important deoxyribonucleic acid (DNA) repair mechanisms and is critical for chemotherapy resistance. We conducted the present study to investigate the association between two polymorphisms of excision of repair cross-complementing group 1 (ERCC1), the key component of the NER pathway, and the clinicopathological features of patients with non-small cell lung cancer (NSCLC). Methods A total of 38 patients with confirmed NSCLC were included in our study. DNA was extracted from peripheral blood. ERCC1 rs3212986 (8092) and rs11615 (118) were genotyped using molecular assays including polymerase chain reaction (PCR) with restriction fragment length polymorphism (by MboII and HpyCH4 enzymes) and sequencing. Results The PCR results indicated the correct performance of the genomics extraction and molecular protocols. The distribution of C/C, C/A and A/A genotypes at position 8092 was 42.10%, 47.36%, and 10.52% respectively (P=0.03). Multivariate regression analysis showed that there was a significant correlation between C8092A (rs3212986) polymorphism and metastasis, grade of the tumor, and response to treatment. Individuals carrying the rs3212986 CA genotype and A allele had a significantly worse response to the treatment. Also, the correlation between alteration at this genomics location and patients with NSCLC who used to smoke cigarettes was positive. However, no significant association was detected between rs11615 C118>T polymorphism and demographic characteristics of patients with NSCLC. Conclusion We concluded that in lung cancer patients there is a relationship between tumor stage and rs3212986C>A polymorphism.


Initial experience with a new on-line transthoracic three-dimensional technique: assessment of feasibility and of diagnostic potential.
Despite its wide diagnostic potential, three-dimensional (3D) echocardiography is a quite rarely employed technique. The ideal method to obtain transthoracic 3D imaging is on-line 3D echocardiography, but first-generation real-time instruments had technical limitations. A new on-line 3D technology which allows true real-time volume rendering of the cardiac anatomy has been recently introduced and its feasibility and diagnostic advantages have been evaluated in the clinical setting. The system utilizes a "matrix" transducer with a dedicated software. It allows instantaneous acquisition and rendering on-line 3D images and interactive manipulation of 3D data. Eighty-three adult patients with various cardiac pathologies underwent on-line 3D echocardiography. Long- and short-axis views of the aorta, mitral valve and left ventricle and surgical views of these structures were attempted. The duration of acquisition and reconstruction, and the quality and incremental clinical value of 3D images in comparison with two-dimensional imaging were annotated. The mean time of 3D examination was 10 +/- 5 min; the mean number of acquisitions was 10.8 per patient. The quality of the 3D images was optimal in 39%, good in 37%, sufficient in 19%, and insufficient in 5% of the patients. In all cases at least one optimal or good live 3D image was obtained from the parasternal and apical views. The reconstruction of surgical or en face views was easily and rapidly (1-2 min) achieved by two experts in 3D echocardiography. The additional clinical values of 3D vs two-dimensional imaging was demonstrated in 7 patients with mitral valve disease, 3 with aortic valve pathology, and 3 with congenital heart disease. Several on-line 3D images that have not correspondence with two-dimensional echocardiography were reconstructed, creating projections dedicated to the diagnostic goal. On-line 3D echocardiography can be easily performed in adult patients and allows for unique planes and projections. The instant rendering of 3D images facilitates the recognition of cardiac structures and increases the diagnostic potential of transthoracic echocardiography.


[Septic temperatures in questionable ascites].
The case history of a 40 year old male with septical temperatures and ascites is presented. Because of skin-pigmentation, hypotension, low rate of electrolytes, augmented renin-activity, and septical temperatures there was a suspicion of Addison's disease. A protein-rich ascites without tumor cells and erythrocytes, but with lymphocytes gives the diagnosis of peritonitis tuberculosa. Addison's disease and peritonitis tuberculosa are late manifestations of an organ tuberculosis, about 20 years after pulmonal tuberculosis.


GaCl(3)-catalyzed insertion of diazene derivatives into the cyclopropane ring.
GaCl3 has been found to efficiently catalyze the formal cycloadditions of diazene derivatives 6 onto 2-arylcyclopropane-1,1-dicarboxylates 5, giving rise to the pyrazolidine derivatives 7. The insertion into the cyclopropane ring proceeds with complete regioselectivity to furnish 5-arylpyrazolidine-1,2,3,3-tetracarboxylates exclusively; however, the cis-configured azo compound N-phenyltriazolinedione gave the two possible regioisomeric pyrazolidine derivatives in ratios varying from 1:1.5 to 1:3. Conceivable mechanisms of these transformations are being discussed.


[Therapy of chronic viral hepatitis type B in children after previous ineffective interferon-alpha treatment].
THE AIM of this study was to estimate the efficacy of nucleoside analogue (lamivudine) in the therapy of chronic viral hepatitis type B in children, after previous, ineffective treatment with interferon-alpha. we analyzed 53 children with chronic viral hepatitis type B, who had not responded to Interferon-alpha treatment conducted 1-7,5 years before this study (mean 4,0 +/- 7,5; median 4 years). Inclusive criteria to re-therapy with lamivudine were as follows: increased serum alanine aminotransferase activity, detected at least three times during 6 months before treatment, HBsAg and HBeAg present in the blood, viral HBV DNA detected for at least 6 months before the beginning of lamivudine therapy (above 200 genome copies per mL) and inflammation activity observed in liver biopsy specimen (biopsy performed within previous 24 months). Evaluation of side-effects of lamivudine therapy was based on anamnesis (subjective data) and laboratory tests performed regularly in the time of clinical visits during and after the end of the treatment. all the children concluded the treatment. Before lamivudine therapy, serum alanine aminotransferase activity ranged between 20-590 IU/L. In 28,4% of children it was less than 100 IU/L. In almost all the children moderate staging and grading were observed in liver biopsy specimens. HBV DNA in serum ranged between 200-200000 copies/mL: in 31 children (58,4%) HBV DNA exceeded 200000 copies/mL, in 5 (28,3%) was between 10000 and 200000 copies/mL, and in 7 (13,2% ) was below 10000 copies/mL. Applied treatment resulted in alanine aminotransferase activity normalization in 79,2% of children, mostly after 2-11 months (mean 3,9 +/- 2,7; median 3,8 months). HBeAg/HBeAb seroconversion was achieved in 28,3% of children, usually at the end of lamivudine therapy (approximately after 12 months). Sustained viral response was observed in 24,5% of treated children. There were no undesirable effects of therapy noted. Serum alanine aminotransferase activity increased slightly and temporarily in 4 children between 3rd and 12th month of therapy. In 2 of these children YMDD mutation was detected. lamivudine is effective, safe and well tolerated in treatment of chronic viral hepatitis type B, following unsuccessful interferon-alpha therapy. Serum alanine aminotransferase activity normalized in most of the patients. HBeAg/HBeAb seroconversion as well as positive viral response is mostly connected with low level of HBV DNA before therapy.


[Chemical constituents, biological activities and clinical applications of artemisia rupestris].
Artemisia rupestris is a traditional medicine in Uygur and Kazak in Xinjiang Province, mainly distributed in the territory of Xinjiang Altai area, Tianshan mountains and the Kunlun mountains, growing at an altitude of 1 500 to 4 000 meters of grassland and forest areas. As the broad research on chemical constituents, pharmacological activity, the effective components of A. rupestris have attracted the interest to make up new drugs. Based on the latest research from A. rupestris, identification and geographic distribution, chemical constituents, pharmacological effects, clinical applications were summarized in this article, in the view of Medicinal Ethnobotany. At the same time, some suggestions were proposed for future research.


Sepsis increases putrescine concentration and protein synthesis in mucosa of small intestine in rats.
Recent studies suggest that sepsis stimulates mucosal polyamine and protein synthesis. It is not known in which cell type polyamine biosynthesis is increased during sepsis and if polyamines regulate mucosal protein synthesis. We examined the effect of sepsis in rats on polyamine biosynthesis in isolated jejunal enterocytes and measured mucosal protein synthesis following inhibition of ornithine decarboxylase (ODC) activity with difluoromethylornithine. ODC and S-adenosylmethionine decarboxylase (SAMDC) activities and putrescine concentrations were increased in isolated jejunal enterocytes 16 h after induction of sepsis by cecal ligation and puncture. Enterocyte spermidine and spermine levels were not influenced by sepsis. Mucosal ODC and SAMDC activities and polyamine levels were increased following treatment of rats with interleukin-1 but not tumor necrosis factor. Treatment of rats with difluoromethylornithine prevented the sepsis-induced increase in mucosal ODC activity, putrescine concentration, and protein synthesis rate. The results suggest that sepsis increases ODC and SAMDC activities and putrescine concentrations in enterocytes of the small intestine. This metabolic response to sepsis may be regulated by interleukin-1 although other mechanisms may also be involved. Increased mucosal protein synthesis during sepsis may at least in part be regulated by increased putrescine levels.


An empirical evaluation of reasons for non-completion of treatment in a dangerous and severe personality disorder unit.
Individuals deemed to be of high risk to others, and diagnosed with severe personality disorders have become the focus for developing clinical services in England. Such services often require highly secure accommodation and labour-intensive therapeutic interventions. There is, however, uncertainty about the capacity to engage such patients effectively in therapies. Here, we examine service evaluation monitoring data to identify the level of completion of therapeutic programmes in a high secure severe personality disordered population, and analyse reasons for failure to complete. Guidelines for classifying reasons for non-completion were developed, based on the multifactorial offender readiness model (MORM). Electronic case notes were searched for references to non-completion, and recorded reasons for non-completion were classified. Non-completion was at a relatively modest level. The main reasons for non-completion were: (1) affective: general distress of the patient or specific emotional reactions to previous offending, e.g. shame; (2) volitional: pursuing goals other than treatment; and (3) cognitive: negative self-efficacy beliefs and negative evaluations (low trust) of staff and the programme. External factors included exclusion from treatment and transfer to another unit. This study identifies specific readiness areas that might need to be addressed in efforts to improve engagement and retention in treatment. A wider range of methodologies is required for future studies.


Transient peritumoral enhancement during dynamic MRI of the liver: cavernous hemangioma versus hepatocellular carcinoma.
The purpose of this work was to compare the incidence and pattern of transient peritumoral parenchymal enhancement for cavernous hemangioma and hepatocellular carcinoma during dynamic MRI of the liver. Two hundred seven hemangiomas and 155 hepatocellular carcinomas up to 4 cm in size were retrospectively assessed. The peritumoral enhancement was comparatively analyzed in terms of the shape, extent, signal intensity, and dependence on the size and degree of contrast enhancement of each tumor. For small lesions (<2 cm), hemangiomas (16/141; 11.3%) showed a higher incidence (p = 0.026) of peritumoral enhancement than hepatocellular carcinomas (3/87; 3.5%). For larger lesions (2-4 cm), there was no significant difference (p > 0.05) in the incidence of peritumoral enhancement of hemangiomas (15/66; 22.7%) and hepatocellular carcinomas (15/68; 22.1%). Nineteen (61.3%) of the 31 hemangiomas showed contrast agent filling the entire tumor volume at the phase of peritumoral enhancement. In spite of the limited specificity, for a <2 cm small focal lesion with homogeneous contrast enhancement on early phase dynamic MR images in the liver, peritumoral enhancement could suggest a higher possibility of hemangioma rather than hepatocellular carcinoma.


[Analysis of refractive status without cycloplegia in 2046 Pupils].
To observe the eyes' refractive status without cycloplegia in 2046 pupils. The cross-sectional study was conducted in 2046 pupils of 4092 eyes in Xi'an city primary schools. The objective ophthalmic examinations were done on all participants,which included non-cycloplegic objective refraction, visual acuity, ocular pressure, fundus evaluation by special trained ophthalmologists and nurses. The special designed inventory scale was filled in and input special computer program, then the data were statistically analyzed with SPSS10.0. In the primary school of 2046 pupils of 4092 eyes, the detective rate of emmetropia was 32.0% of 1309 eyes, hypermetropia was 4.2% of 170 eyes, myopia was 63.8% of 2613 eyes, low myopia was 51.4% of 2102 eye, moderate myopia was 11.3% of 464 eyes, and high myopia was 1.1% of 47 eyes in total. In both eyes, the detective rate was 61.2%of 1348 eyes in 2204 boys, 67% of 1265 in 1888 girls. Among 6 grades, the constituent ratio of moderate and high myopia groups were significantly increased with the age's growing, including emmetropia 45.5% of 343 eyes out of 754 in 1st grade and 19.2% of 122 eyes out of 634 in 6th grade.The average refractive error of spherical equivalent refraction was (-1.32+/-1.60)D.Among 6 grades,the 1st grade' was (0.82+/-1.42)D,and the 6th grade's was (-1.82+/-1.68)D, there were significant differencesamong 6 grades(p<0.01).There was a significant difference between girls and boys(p<0.01). The average myopizing rate was -0.2 D at per year, -1.0 D in the total of the progression in 6 years. Poor condition of myopizing was showed in Chinese pupils. It should be taking seriously and making early intervention.


Progesterone for outpatient treatment of Pickwickian syndrome.
Ten patients with the Pickwickian syndrome, characterized by obesity, hypoxemia, hypercapnia, polycythemia, and cor pulmonale, underwent long-term treatment as outpatients with medroxyprogesterone acetate. Although there was no significant weight change in the group, PaO2 rose 12.6 +/- 2.7 mm Hg (SEM) from 49 +/- 2.6 mm Hg to 62 +/- 2.3 mm Hg (P less than 0.001), while PaCO2 fell 13 +/- 2.6 mm Hg from 51 +/- 1.9 mm Hg to 38 +/- 1.2 mm Hg (P less than 0.001). Hematocrit fell from 56 +/- 2.5% to 50 +/- 1.2%, a mean fall of 6% (P less than 0.01), during medroxyprogesterone acetate therapy. In the 2 patients who had cardiac catheterization before and during medroxyprogesterone acetate therapy, mean pulmonary arterial pressure fell 13 and 19 mm Hg. There were no recurrences of cor pulmonale during treatment. These effects on arterial blood gas values and clinical state were sustained during therapy. On withdrawal of medroxyprogesterone acetate during 1-month period, arterial oxygen and carbon dioxide tensions deteriorated to their previous pretreatment values. Reinstitution of medroxyprogesterone acetate caused improvement in both the oxygen and carbon dioxide tensions. We conclude that sublingual medroxyprogesterone acetate therapy is useful in the management of the Pickwickian syndrome.


In vitro methods for screening transdermal formulations.
This article provides a review of the critical in vitro assays utilized in transdermal drug development. In vitro assays such as percutaneous absorption testing and dissolution (drug release) testing are powerful tools for screening potential transdermal compounds and drug quality control, respectively. Several 2D single-cell cultures and 3D human skin equivalents are available for screening compounds with low irritation and sensitization potential. The role of each assay and its limitations and challenges will be further discussed below.


Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.
C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides. NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.


[Rectocolonic cancers in young patients. A population study (Côte-d'Or: 1976-1983].
Between 1976 and 1983, 1,783 colorectal cancers were diagnosed among the Cote-d'Or residents; of these 44 (2.5 p. 100) were under age 45. Cancer developed more often on familial polyposis (11.4 p. 100), ulcerative colitis (2.3 p. 100) or in the Lynch cancer family syndrome (4.6 p. 100) before 45 than in older patients: 0.2 p. 100 (p less than 0.01), 0.2 p. 100 (NS) and 0 p. 100 (p less than 0.01) respectively. There was no significant difference between young and older patients concerning the site, the histologic type or the stage of diagnosis. Curative resection rates were similar before age 45 (68.2 p. 100) as after that age (61.8 p. 100). Operative mortality was lower in younger (3.3 p. 100) than in older patients (12.6 p. 100; NS). After surgery for cure (operative mortality excluded) the 5-year corrected survival rates were similar in the two age groups: 69.4 +/- 8.8 p. 100 and 64.0 +/- 1.8 p. 100 respectively (NS). These data suggest that with the exception of predisposing diseases there is no important difference between young and older patients with regard to the anatomoclinical and evolutive aspects of colorectal cancers.


Cyclic denaturation and renaturation of double-stranded DNA by redox-state switching of DNA intercalators.
Hybridization of complementary nucleic acid strands is fundamental to nearly all molecular bioanalytical methods ranging from polymerase chain reaction and DNA biosensors to next generation sequencing. For nucleic acid amplification methods, controlled DNA denaturation and renaturation is particularly essential and achieved by cycling elevated temperatures. Although this is by far the most used technique, the management of rapid temperature changes requires bulky instrumentation and intense power supply. These factors so far precluded the development of true point-of-care tests for molecular diagnostics. To overcome this limitation we explored the possibility of using electrochemical means to control reversible DNA hybridization by using the electroactive intercalator daunomycin (DM). We show that redox-state switching of DM altered its properties from DNA binding to nonbinding, under otherwise constant conditions, and thus altered the thermodynamic stability of duplex DNA. The operational principle was demonstrated using complementary synthetic 20mer and 40mer DNA oligonucleotides. Absorbance-based melting curve analysis revealed significantly higher melting temperatures for DNA in the presence of oxidized compared to chemically reduced DM. This difference was exploited to drive cyclic electrochemically controlled denaturation and renaturation. Analysis with in situ UV-vis and circular dichroism spectroelectrochemistry, as two independent techniques, indicated that up to 80% of the DNA was reversibly hybridized. This remarkable demonstration of electrochemical control of five cycles of DNA denaturation and renaturation, under otherwise constant conditions, could have wide-ranging implications for the future development of miniaturized analytical systems for molecular diagnostics and beyond.


Effect of acetylcholinesterase inhibitors on post-surgical complications and mortality following a hip fracture: a cohort study.
There is increasing evidence suggesting that the use of acetylcholinesterase inhibitors may have beneficial effects on bone. Data on the potential post-surgical effects of these medications on orthopedic interventions are very limited. This study was designed to determine whether the use of acetylcholinesterase inhibitors is associated with a decrease in post-surgical mortality and complications in hip fracture patients with Alzheimer's disease. To accomplish this objective, a retrospective cohort study was performed using data from the Clinical Practice Research Database, UK. The study included 532 Alzheimer's disease patients of age 65 years and older, who sustained a hip fracture between 1998 and 2012. During the follow-up period, 34% of the patients died (n=182), 22% sustained a second hip fracture (n=118) and 5% (n=29) required reintervention. The users of acetylcholinesterase inhibitors had a 56% reduction in all-cause mortality (HR= 0.44, 95% CI 0.30-0.63) and a 41% reduction in second hip fracture incidence during a year of post-surgical follow-up (HR= 0.59, 95% CI 0.38-0.94) after adjusting for potential confounders. Our results show that acetylcholinesterase inhibitors may have the potential to reduce all-cause mortality and the risk of suffering a second hip fracture during the first year after surgery.


Application of the REAL-score prognostic index in decision making in rectal cancer surgery.
Colorectal anastomosis leak (AL) is the most feared complication of rectal cancer surgery (1-19%) as it increases morbidity and mortality and worsens oncological outcomes in terms of local recurrence and survival. The publication of the REAL-score index makes it possible to predict the risk of AL and compare the expected results with those obtained. Observational, descriptive, longitudinal and retrospective study of patients operated on for rectal cancer at the Miguel Servet University Hospital, in Zaragoza, Spain, in 2019. Statistical analysis of morbidity and mortality outcome variables and the REAL-score index using ROC curves. Of 80 patients operated on for rectal cancer, colorectal anastomosis was performed in 52 and temporary ileostomy in 11 (21.2%). Morbidity was high (38.4%), but severe only in 7.7% (Clavien-Dindo IIIb), with no deaths. There were four dehiscences: one type B and three type C. A direct relationship between high risk of AL and the practice of temporary stoma is observed when the cut-off point of the REAL-score exceeds 14.74%. REAL-score can help in decision-making in rectal cancer surgery. Above a cut-off point, the risk of AL would imply a selective ileostomy.


Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER.
Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 μg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.


MicroRNA-143 Targets ATG2B to Inhibit Autophagy and Increase Inflammatory Responses in Crohn's Disease.
Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including Crohn's disease (CD). Genetic analyses have found that microRNA (miRNA) levels are altered in the intestinal tissues of CD patients. The Sequencing Alternative Poly-Adenylation Sites (SAPAS) method was used to compare the 3' end of the total mRNA sequence of 3 surgical specimens of CD patients (including inflamed tissues and corresponding noninflamed tissues in each case). The levels of autophagy-related 2B (ATG2B), LC3, and miR-143 were compared between inflamed tissues and noninflamed tissues using immunoblot and quantitative reverse transcription polymerase chain reaction. Luciferase assays were used to verify the interactions between miR-143 and ATG2B. Autophagy was measured by immunoblot analyses of LC3 and transmission electron microscopy. Inflammatory cytokines and IκBα were analyzed to evaluate the effect of miR-143 on inflammatory response. The tandem repeat 3'-UTR of ATG2B was longer in inflamed tissues than in corresponding noninflamed tissues and contained an miR-143 target site. miR-143 expression was elevated, whereas ATG2B and LC3-II were downregulated in inflamed tissues. The direct interaction between miR-143 and ATG2B was verified by a 3'-UTR dual-luciferase reporter assay. Constitutive expression of miR-143 or depletion of ATG2B in cultured intestinal epithelial cells inhibited autophagy, reduced IκBα levels, and increased inflammatory responses. miR-143 may induce bowel inflammation by regulating ATG2B and autophagy, suggesting that miR-143 might play a critical role in the development of CD. Therefore, miR-143 could be a promising novel target for gene therapy in CD patients.


The need for a control animal pathology database: an international survey.
1. The sensitivity of long-term toxicity tests is impaired due to the 'background noise' of spontaneous lesions which are unrelated to treatment. 2. The need for a comprehensive source of computerized information concerning the occurrence and incidence of spontaneous lesions in control animals has been highlighted by initiatives in Europe and the USA. It is, however, essential to identify the potential users, and the type of information required for such a database to be of value. 3. This information has been acquired following an international survey of the pharmaceutical industry in Europe, Japan and the USA, including responses from 48 toxicologists and toxicopathologists representing 38 company groups. 4. Thirty-eight respondents indicated that they would use a historical control database that was regularly updated with the majority of respondents suggesting that they currently use external sources (Breeder's data, the literature, other companies) occasionally to acquire information on control animal pathology data. 5. The majority (94%) of the respondents indicated that a control animal database should contain information on both neoplastic and non-neoplastic lesions for use in evaluating long-term studies, in particular carcinogenicity studies. 6. The survey confirms the need for a historical control animal pathology database wider then those currently available.


Bilateral osteochondrosis of the distal tibial epiphysis: a case report.
Osteochondrosis is a developmental disease characterized by an alteration of endochondral ossification. Genetic causes, repetitive mechanical stresses, vascular abnormalities, hormonal imbalances, and interruption of the blood supply to the epiphyseal cartilage are all described causes of osteochondrosis and the etiology is probably multifactorial. Osteochondrosis can occur in different apophysis and epiphysis in all immature skeletons. Distal tibial epiphysis is rarely involved and most of the time unilaterally. We report on an 11-year-old female with bilateral osteochondrosis on distal tibial epiphysis. Only one other similar case has been described in the literature to date.


Children with COVID-19 Who Manifest Febrile Seizure.
The COVID-19 pandemic is a challenge for all medical personnel in the world. Various studies have been conducted to gain more knowledge about SARS-CoV-2, but studies in the pediatric population are still very limited. We report a case of a boy aged two years and seven months who came to the hospital with an atypical generalized seizure for less than 5 minutes and immediately regained consciousness after the seizure. Other symptoms included fever, productive cough, rhinorrhea, and shortness of breath. The X-ray showed a well-defined homogeneous consolidation in the upper right lobe and a small spot in both lungs which consistently showed top right lobar pneumonia and bronchopneumonia. From the SARS-CoV-2 nucleic acid test, positive results were obtained on the third day of hospitalization. The patient received antiseizure therapy, antibiotics, and other supportive therapies by Indonesian Pediatrician Association (IDAI) guidelines. During treatment, the patient responded well to the treatment given, with no other seizure episodes. A negative result on the SARS-CoV-2 nucleic acid test was obtained after twelve days of hospitalization as well as improvements of the lungs as seen from the X-ray.


Mechanisms on the Impacts of Alkalinity, pH, and Chloride on Persulfate-Based Groundwater Remediation.
Persulfate (S2O82-)-based in situ chemical oxidation (ISCO) has gained more attention in recent years due to the generation of highly reactive and selective sulfate radical (SO4•-). This study examined the effects of important groundwater chemical parameters, i.e., alkalinity, pH, and chloride on benzene degradation via heterogeneous persulfate activation by three Fe(III)- and Mn(IV)-containing aquifer minerals: ferrihydrite, goethite, and pyrolusite. A comprehensive kinetic model was established to elucidate the mechanisms of radical generation and mineral surface complexation. Results showed that an increase of alkalinity up to 10 meq/L decreased the rates of persulfate decomposition and benzene degradation, which was associated with the formation of unreactive surface carbonato complexes. An increase in pH generally accelerated persulfate decomposition due to enhanced formation of reactive surface hydroxo complexation. A change in the chloride level up to 5 mM had a negligibly effect on the reaction kinetics. Kinetics modeling also suggested that SO4•- was transformed to hydroxyl radical (HO•) and carbonate radical (CO3•-) at higher pHs. Furthermore, the yields of two major products of benzene oxidation, i.e., phenol and aldehyde, were positively correlated with the branching ratio of SO4•- reacting with benzene, but inversely correlated with that of HO• or CO3•-, indicating that SO4•- preferentially oxidized benzene via pathways involving fewer hydroxylation steps compared to HO• or CO3•-.


Nutrition attitudes and knowledge of nursing students.
A demographic and attitudinal questionnaire and a knowledge test were administered to baccalaureate nursing students upon entry to their first nutrition course. Attitudes were assessed regarding the role of the dietitian in the hospital, the role of the nurse in nutrition education, nutrition education in nursing, and general nutrition. Attitudes were not greatly altered during the nutrition course, but changes that occurred were favorable. Scores on the knowledge test were significantly greater after nursing students completed the nutrition course.


Inflammatory effects of blood leukocytes: association with vascular function in neuropeptide Y proline 7-genotyped type 2 diabetes patients.
We investigated the associations of inflammatory blood cell activation with vascular parameters in patients with type 2 diabetes to elucidate the possible mechanisms of accelerated atherosclerosis observed in subjects with the Leucine 7 to Proline 7 polymorphism (Leu7Pro) in the neuropeptide Y (NPY). Our study included 31 Caucasian patients with type 2 diabetes; 12 of them had the Leu7Pro7 (heterozygous), and 19 had the Leu7Leu7 (wild type) genotype. Vascular parameters were determined by ultrasound methods. Leukocyte analyses were performed from blood samples using flow cytometry. NPY concentrations were determined in plasma. The amount of platelet-granulocyte complexes was positively correlated with NPY concentration (p=0.008) and carotid intima-media thickness (p=0.035) in the Leu7Pro7 group. Interferon gamma (IFN-γ) expression in monocytes correlated negatively with brachial artery flow-mediated dilatation also in the Leu7Pro7 group (p=0.037). The expression of tissue factor on monocytes correlated negatively with brachial artery diameter in the Leu7Pro7 patients as well (p=0.019). The results indicate significant associations between inflammatory cell activation in blood and vascular atherosclerosis in genetically prone subjects, and provide possible mechanistic information about the role of NPY and the Leu7Pro polymorphism in the development of atherosclerosis.


Nomograms predicting overall survival and cancer-specific survival in osteosarcoma patients (STROBE).
The aim of this study was to develop nomograms to predict long-term overall survival and cancer-specific survival of patients with osteosarcoma.We carried out univariate and multivariate analyses and set up nomograms predicting survival outcome using osteosarcoma patient data collected from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (2004-2011, n = 1426). The patients were divided into a training cohort (2004-2008, n = 863) and a validation cohort (2009-2011, n = 563), and the mean follow-up was 55 months.In the training cohort, 304 patients (35.2%) died from osteosarcoma and 91 (10.5%) died from other causes. In the validation cohort, 155 patients (27.5%) died from osteosarcoma and (12.3%) died from other causes. Nomograms predicting overall survival (OS) and cancer-specific survival (CSS) were developed according to 6 clinicopathologic factors (age, tumor site, historic grade, surgery, AJCC T/N, and M), with concordance indexes (C-index) of 0.725 (OS) and 0.718 (CSS), respectively. The validation C-indexes were 0.775 and 0.742 for OS and CSS, respectively.Our results suggest that we have successfully developed highly accurate nomograms for predicting 5-year OS and CSS for osteosarcoma patients. These nomograms will help surgeons customize treatment and monitoring strategies for osteosarcoma patients.


Mean-Field Scenario for the Athermal Creep Dynamics of Yield-Stress Fluids.
We develop a theoretical description based on an existent mean-field model for the transient dynamics prior to the steady flow of yielding materials. The mean-field model not only reproduces the experimentally observed nonlinear time dependence of the shear-rate response to an external stress, but also allows for the determination of the different physical processes involved in the onset of the reacceleration phase after the initial slowing down and a distinct fluidization phase. The fluidization time displays a power-law dependence on the distance of the applied stress to an age-dependent yield stress, which is not universal but strongly dependent on initial conditions.


Does surgery for Scheuermann kyphosis influence sagittal spinopelvic parameters?
To analyze changes in sagittal spinopelvic parameters (SSPs) after surgical treatment of Scheuermann's Kyphosis (SK). We analyzed 20 patients affected by SK and subjected to posterior correction of the kyphosis by facetectomy, Ponte osteotomy, fusion and multilevel instrumentation with pedicle screw system. Four spinal and three pelvic parameters were measured: sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS) and pelvic tilt (PT). Analysis of changes in postprocedural SSPs compared to preoperative values was performed. TK passed from 78.6° preoperatively to 45.8° (p = 0.003). LL passed from 74.5° preoperatively to 53.5° (p = 0.01). No significant changes occurred in SVA, SS, PT and PI compared to preoperative values. We confirm the positive effect of surgery by Ponte osteotomy and posterior spinal fusion on TK and LL in patients with SK. In our experience, pelvic parameters did not change after surgery.


Surgical outcome and clinical follow-up in patients with symptomatic myocardial bridging.
Myocardial bridging with systolic compression of the left anterior descending coronary artery (LAD) may be associated with myocardial ischaemia. The clinical outcome in patients with surgical treatment for symptomatic myocardial bridging remains undetermined. This study assessed the middle- and long-term results of surgical treatment for symptomatic myocardial bridging. From 1997 to 2006, 37,463 patients received selective coronary angiography in the Fuwai Cardiovascular Hospital, Beijing, China. Of these, 484 patients had angiographic diagnosis of myocardial bridging. Of the 484 patients, 35 underwent surgery for treatment of myocardial bridging with significant systolic arterial compression. Among the surgical treatment patients, 24 presented with other cardiac disorders, and the remaining 11 symptomatic patients with isolated myocardial bridging were included in the follow-up study. The angiographic prevalence of myocardial bridging was 1.3% in this study. The coronary angiographies of the 11 patients revealed myocardial bridging in the middle segment of LAD causing systolic compression > or = 75% (ranging from 75% to 90%). The mean age of patients was 48.4 years. Surgical myotomy was performed in 3 patients and coronary artery bypass grafting (CABG) in 8 patients. Eight patients were operated on with an off-pump approach and 3 with a cardiopulmonary bypass technique after median sternotomy. Conversion to on-pump CABG surgery was necessary in 1 patient because of perforation of the right ventricle. The left internal mammary artery was used in all patients with CABG. The acute clinical success rate was 100% with respect to the absence of myocardial infarction, death or other major in-hospital complications. All of the patients were followed up clinically. The median follow-up was 35.3 months (range: 6 to 120 months). Nine patients were free from symptoms and one of them continued taking beta blockers. The remaining 2 patients with myotomy had atypical chest pain. One received coronary angiography again and no stenosis was found two years after operation; while exercise testing was performed in the other patient and revealed no evidence of myocardial ischaemia. None of the patients sustained a myocardial infarction or other major adverse cardiac events (death or vessel revascularization) during follow-up. Myocardial bridging is a relatively common angiographic finding. Surgical myotomy or CABG should be limited to patients who are refractory to oral medication. Surgical relief of myocardial ischaemia due to systolic compression of intramyocardial coronary arteries can be accomplished with low operative risk and excellent middle- and long-term results.


Disc calibration for digital templating in hip replacement.
Digital radiography is becoming widespread. Accurate pre-operative templating of digital images of the hip traditionally involves positioning a calibration object at its centre. This can be difficult and cause embarrassment. We have devised a method whereby a planar disc placed on the radiographic cassette accounts for the expected magnification. Initial examination of 50 pelvic CT scans showed a mean hip centre distance of 117 mm (79 to 142) above the gluteal skin. Further calculations predicted that a disc of 37.17 mm diameter, placed on the cassette, would appear identical to a 30 mm sphere placed at the level of the centre of the hip as requested by our templating software. We assessed accuracy and reproducibility by 'reverse calibration' of 20 radiographs taken three months after hip replacement using simultaneous sphere and disc methods, and a further 20 with a precision disc of accurate size. Even when variations in patient size were ignored, the disc proved more accurate and reliable than the sphere. The technique is reliable, robust, cost effective and acceptable to patients and radiographers. It can easily be used in any radiography department after a few simple calculations and manufacture of appropriately-sized discs.


Dynamic SPECT with technetium-99m HM-PAO in meningiomas--a comparison with iodine-123 IMP.
Technetium-99m hexamethylpropyleneamine oxime ([99mTc]HM-PAO) has recently been introduced as an alternative to N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) for measurement of regional cerebral blood flow. This study compares dynamic SPECT studies using the two tracers in seven patients with meningiomas. Regions of interest were placed over the lesion and contralateral homologous presumed normal area. The counting-rate ratio for the lesion to the contralateral homologous area (L/N ratio) was then calculated in the first image. L/N ratios of [99mTc]HM-PAO single photon emission computed tomography (SPECT) were lower than those of [123I])IMP SPECT, particularly in hypervascular meningiomas. Furthermore, time-activity curves showed that the washout of [99mTc]HM-PAO in the tumors was very slow or incomplete, preventing an accurate assessment of vascularity of meningiomas with [99mTc]HM-PAO, as is generally possible with [123I]IMP.


Irisdichotins A-C, three new flavonoid glycosides from the rhizomes of Iris dichotoma Pall.
Three new compounds including one flavonol glycoside, irisdichotin A (1), and two flavanonol glycosides, irisdichotins B (2) and C (3), were isolated from the rhizomes of Iris dichotoma Pall. Their structures were elucidated on the basis of spectroscopic methods.


Propagation dynamics of generalized and symmetric Airy beams.
We present theoretically and experimentally generalized and symmetric Airy beams, where the two sidelobes are not mutually perpendicular, by introducing two rotary angle factors. The symmetric Airy beam is induced by a binary phase pattern. We demonstrate that the intensity distributions of generalized Airy beams are apparently different from those of normal Airy beams. Moreover, they can propagate along arbitrary trajectories. Numerical results show that the generalized and symmetric Airy beams still have the ability of self-healing and nondiffraction. The experimental results are in complete accord with numerical results. Some possible applications are also discussed, and these interesting properties will also likely have potential applications.


What Is the Color of Your Lymph Node?
We describe a case of tattoo ink in an axillary lymph node, which was observed during an axillary dissection and mastectomy surgery. It is important to be aware of this phenomenon and correctly identify it at the time of surgery, as a misdiagnosis can have serious consequences.


Evaluation of an acidic deproteinization for the measurement of ascorbate and dehydroascorbate in plasma samples.
The most popular pretreatment method of plasma samples for the measurement of ascorbate (AsA) and dehydroascorbate (DHA) has been an acidic deproteinization via metaphosphoric acid or trichloroacetic acid. In general, DHA is absent in plasma samples prepared from human blood in a conventional manner. However, when these plasma samples were subjected to acidic deproteinization, DHA was detected in the acidified sample solutions. In the present study, we demonstrate that the oxidation of AsA to DHA in the solutions was promoted by at least two mechanisms, one involving catalysis by ferric ion released from transferrin, and the other involving catalysis by plasma hemoglobin. In the acidified transferrin solution by trichloroacetic acid, an oxidation of AsA to DHA proceeded with standing time, whereas the oxidation was not observed in that by metaphosphoric acid. This oxidation appeared to be catalyzed by ferric ion released from transferrin. In contrast, plasma hemoglobin functioned as a catalyst for AsA oxidation in both metaphosphoric acid and trichloroacetic acid solutions. Therefore, DHA content in the trichloroacetic acid-treated plasma sample was markedly higher than that in the metaphosphoric acid-treated one. These results suggest that DHA detected in acidified plasma samples is an artifact resulting from AsA oxidation.


Inhibition of Autophagy Prolongs Recipient Survival Through Promoting CD8+ T Cell Apoptosis in a Rat Liver Transplantation Model.
In liver transplantation (LT), although various immunosuppressants have been used in clinical practice, acute rejection remains a common complication that significantly shortens recipient survival. In recent years, manipulating immune tolerance has been regarded as one of the promising solutions to rejection. Autophagy, an evolutionarily conserved protein degradation system, has been reported to be involved in immune rejection and may be a target to establish immune tolerance. However, the role of autophagy in acute rejection reaction after LT has not been elucidated. Here, we showed that the autophagy of CD8+ T cells was strongly enhanced in patients with graft rejection and that the autophagy level was positively correlated with the severity of rejection. Similar findings were observed in a rat acute hepatic rejection model. Furthermore, administration of the autophagy inhibitor 3-methyladenine (3-MA) largely decreased the viability and function of CD8+ T cells through inhibiting autophagy, which significantly prolonged graft survival in rats. In addition, inhibiting the autophagy of activated CD8+ T cells in vitro considerably suppressed mitochondria mediated survival and downregulated T cell function. Conclusions: We first showed that the inhibition of autophagy significantly prolongs liver allograft survival by promoting the apoptosis of CD8+ T cells, which may provide a novel strategy for immune tolerance induction.


DEFI 2005: a randomized controlled trial of the effect of automated external defibrillator cardiopulmonary resuscitation protocol on outcome from out-of-hospital cardiac arrest.
Using automated external defibrillators (AEDs) that implement the Guidelines 2000 resuscitation protocol constrains administration of cardiopulmonary resuscitation (CPR) to <50% of AED connection time. We tested a different AED protocol aimed at increasing the CPR administered to patients with out-of-hospital cardiac arrest. In a randomized controlled trial, patients with out-of-hospital cardiac arrest requiring defibrillation were treated with 1 of 2 AED protocols. In the control protocol, based on Guidelines 2000, sequences of up to 3 stacked countershocks were delivered, with rhythm analyses initially and after the first and second shocks. The study protocol featured 1 minute of CPR before the first shock, shorter CPR interruptions before and after each shock, and no stacked shocks. The primary end point was survival to hospital admission. Of 5107 out-of-hospital cardiac arrest patients connected to an AED, 1238 required defibrillation, and 845 were included in the final analysis. Study patients (n=421) had shorter preshock pauses (9 versus 19 seconds; P<0.001), had shorter postshock pauses (11 versus 33 seconds; P<0.001), and received more CPR (61% versus 48%; P<0.001) and fewer shocks (2.5 versus 2.9; P<0.001) than control patients (n=424). Similar proportions survived to hospital admission (43.2% versus 42.7%; P=0.87), survived to hospital discharge (13.3% versus 10.6%; P=0.19), achieved return of spontaneous circulation before physician arrival (47.0% versus 48.6%; P=0.65), and survived to 1 year (P=0.77). Following prompts from AEDs programmed with a protocol similar to Guidelines 2005, firefighters shortened pauses in CPR and improved overall hands-on time, but survival to hospital admission of patients with ventricular fibrillation out-of-hospital cardiac arrest did not improve. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00139542.


Phylogenetic distribution and prevalence of genes encoding class I Integrons and CTX-M-15 extended-spectrum β-lactamases in Escherichia coli isolates from healthy humans in Chandigarh, India.
Escherichia coli is generally considered as a commensal inhabitant of gastrointestinal tract of humans and animals. The aim of this study was to gain insight on the distribution of phylotypes and presence of genes encoding integrons, extended β-lactamases and resistance to other antimicrobials in the commensal E. coli isolates from healthy adults in Chandigarh, India. PCR and DNA sequencing were used for phylogenetic classification, detections of integrase genes, gene cassettes within the integron and extended β-lactamases. The genetic structure of E. coli revealed a non-uniform distribution of isolates among the seven phylogenetic groups with significant representation of group A. Integron-encoded integrases were detected in 25 isolates with class 1 integron-encoded intI1 integrase being in the majority (22 isolates). The gene cassettes identified were those for trimethoprim, streptomycin, spectinomycin and streptothricin. The dfrA12-orfF-aadA2 was the most commonly found gene cassette in intI1 positive isolates. Phenotypic assay for screening the potential ESBL producers suggested 16 isolates to be ESBL producers. PCR detection using gene-specific primers showed that 15 out of these 16 ESBL-producing E. coli harboured the blaCTX-M-15 gene. Furthermore, molecular studies helped in characterizing the genes responsible for tetracycline, chloramphenicol and sulphonamides resistance. Collectively, our study outlines the intra-species phylogenetic structure and highlights the prevalence of class 1 integron and blaCTX-M-15 in commensal E. coli isolates of healthy adults in Chandigarh, India. Our findings further reinforce the relevance of commensal E. coli strains on the growing burden of antimicrobial resistance.


Is single-view fluoroscopy sufficient in guiding cardiac ablation procedures?
The CARTO XP ablation system provides real-time data on 3D, color-coded maps of the electrical activity of the heart; however, it is expensive and can only use a dedicated costly magnetic catheter per patient intervention. The purpose of our study is to shorten the duration of the radiofrequency ablation procedure and increase its efficacy by developing an affordable prototype catheter navigation system that simulates the CARTO system. To obtain 3D geometrical data from catheter locations inside the heart chamber, we acquired only single-view images using an Integris Allura fluoroscope and estimated the depth of the mapping electrode using pattern recognition techniques. Validation was performed in ideal and clinical conditions. For phantom experiment, when using a 7-French catheter, the average recovered depth error was 2.05 +/- 1.46 mm using a single image. However, when using the 8-French catheter, the average recovered depth error was 1.54 +/- 1.29 mm. In clinical experimentation, the standard error of estimate for the estimated depth was about 13.1 mm and 10.1 mm, respectively, for the posterior and lateral views. In conclusion, this paper describes our achievements and shortfalls in developing an affordable fluoroscopic navigation system to guide RF catheter ablation of cardiac arrhythmias.


Understanding maternal postnatal blood pressure changes following hypertensive disorders in pregnancy: protocol for a prospective cohort study.
Hypertensive disorders occur in approximately 10% of women during pregnancy. There is robust population-based data to show that women who have hypertension in pregnancy are much more likely to develop cardiovascular disease (CVD) in the postpartum period. Women with a hypertensive disorder of pregnancy (HDP) are twice more at risk of heart disease and stroke, and four times more likely to develop hypertension after birth. Two out of three women who had HDP will die from CVD. Recent evidence suggests that young women with HDP develop signs of CVD in the immediate postpartum period, rather than several decades later as previously presumed. If confirmed, this concerning finding presents healthcare practitioners with an opportunity to influence women's cardiovascular health by advising on lifestyle choices and considering therapeutic interventions to prevent the development of CVD. This prospective cohort study design will ask approximately 300 participants to complete 3 days of home blood pressure monitoring every fortnight for 12 weeks postpartum and will culminate with a 24-hour episode of ambulatory blood pressure monitoring at 12 weeks postpartum. Women and healthcare professionals will complete questionnaires surrounding postpartum care for women who had HDP and knowledge of CVD risk. In addition, the relationship between hypertension and factors likely to influence outcomes such as severity of HDP, maternal age, body mass index and ethnicity will be analysed using logistic regression. Blood pressure and data from questionnaires will be analysed using descriptive statistics, with temporal stratification. Research ethics approval was obtained from London-West London & GTAC Research Ethics Committee. Research outputs will be published and disseminated through midwifery, obstetric or general practitioner targeted academic journals. The patient and public involvement group will disseminate findings to women who have experienced HDP among their peer groups. NCT05137808.


Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.
Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). We investigated the risk for SRD, RVO, and ION in patients using PDE5is. We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. HRs for SRD, RVO, and ION. In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.


The link between obesity and migraine in childhood: a systematic review.
Obesity and headache are two highly prevalent diseases both in adults and children and they are associated with a strong personal and social impact. Many studies suggest that obesity is comorbid with headache in general, and migraine in particular and obesity seems to be a risk factor for migraine progression and for migraine frequency both in adults and in children. Research shows that there are multiple areas of overlap between migraine pathophysiology and the central and peripheral pathways regulating feeding: inflammatory mediators such as the calcitonin gene-related protein (CGRP), neurotransmitters such as serotonin, peptides such as orexin and adipocytokines such as adiponectin (ADP) and leptin could explain the common pathogenesis. In this paper we discussed the association between obesity and migraine through the analysis of the most recent studies in children and we reviewed data from literature in order to assess the association between obesity and headache and to clarify the possible common pathogenic mechanisms.


The role of thiazolidinediones in hepatocellular carcinoma risk reduction: a population-based cohort study in Taiwan.
The aim of this study was to investigate the effect of thiazolidinediones (TZDs) on the risk of hepatocellular carcinoma (HCC) development among diabetes mellitus (DM) patients. We conducted a population-based case-control study in Taiwan based on data from the Taiwan National Health Insurance Research Database. A total of 76,349 newly diagnosed DM patients were identified from claims between 2000 and 2010. Among diabetics, 3,026 and 12,104 patients respectively, received or did not receive TZDs. Comparison frequency was matched with age, sex, and index date, excluding those with cancer at baseline. The incidence of HCC at the end of 2010 and the risks associated with the presence of hepatitis B and C infections were analyzed. The effect of TZDs use on the reduction of HCC risk was also assessed. The incidence of HCC was lower in the TZD cohort compared with the non-TZD cohort (418.3 vs. 484.6 per 100,000 person-years), with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval = 0.38-0.77) using multivariable Cox proportional hazard regression. In the stratified analysis, HCC risk reduction was greater for diabetics without the comorbidities of cirrhosis, hepatitis B, hepatitis C, nonalcoholic fatty liver disease, end-stage renal disease, and hyperlipidemia, in the TZD cohort than in the non-TZD cohort. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors predicting HCC (HRs of 1.43, 13.96, 2.31, and 2.15, respectively). This study suggests that the use of TZDs may reduce the risk of developing HCC among DM patients. Comorbidity with cirrhosis and/or hepatitis B/C infection appears to be associated with an extremely increased risk of developing HCC in this patient subset. These high-risk patients should be closely monitored.


A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.
Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.


Adaptation of Salmonella enterica Serovar Senftenberg to Linalool and Its Association with Antibiotic Resistance and Environmental Persistence.
A clinical isolate of Salmonella enterica serovar Senftenberg, isolated from an outbreak linked to the herb Ocimum basilicum L. (basil), has been shown to be resistant to basil oil and to the terpene alcohol linalool. To better understand how human pathogens might develop resistance to linalool and to investigate the association of this resistance with resistance to different antimicrobial agents, selective pressure was applied to the wild-type strain by sequential exposure to increasing concentrations of linalool. The results demonstrated that S Senftenberg adapted to linalool with a MIC increment of at least 8-fold, which also resulted in better resistance to basil oil and better survival on harvested basil leaves. Adaptation to linalool was shown to confer cross protection against the antibiotics trimethoprim, sulfamethoxazole, piperacillin, chloramphenicol, and tetracycline, increasing their MICs by 2- to 32-fold. The improved resistance was shown to correlate with multiple phenotypes that included changes in membrane fatty acid composition, induced efflux, reduced influx, controlled motility, and the ability to form larger aggregates in the presence of linalool. The adaptation to linalool obtained in vitro did not affect survival on the basil phyllosphere in planta and even diminished survival in soil, suggesting that development of extreme resistance to linalool may be accompanied by a loss of fitness. Altogether, this report notes the concern regarding the ability of human pathogens to develop resistance to commercial essential oils, a resistance that is also associated with cross-resistance to antibiotics and may endanger public health.IMPORTANCE Greater consumer awareness and concern regarding synthetic chemical additives have led producers to control microbial spoilage and hazards by the use of natural preservatives, such as plant essential oils with antimicrobial activity. This report establishes, however, that these compounds may provoke the emergence of resistant human pathogens. Herein, we demonstrate the acquisition of resistance to basil oil by Salmonella Senftenberg. Exposure to linalool, a component of basil oil, resulted in adaptation to the basil oil mixture, as well as cross protection against several antibiotics and better survival on harvested basil leaves. Collectively, this work highlights the hazard to public health while using plant essential oils without sufficient knowledge about their influence on pathogens at subinhibitory concentrations.


Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey.
Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive T-cell malignancy with a high mortality rate, resulting in a lack of information among ophthalmologists. Here, we investigated the state of ophthalmic medical care for ATL and ATL-related ocular manifestations by conducting the first large-scale nationwide survey in Japan. A total of 115 facilities were surveyed, including all university hospitals in Japan that were members of the Japanese Ophthalmological Society and regional core facilities that were members of the Japanese Ocular Inflammation Society. The collected nationwide data on the state of medical care for ATL-related ocular manifestations and ATL-associated ocular findings were categorized, tallied, and analyzed. Of the 115 facilities, 69 (60%) responded. Overall, 28 facilities (43.0%) had experience in providing ophthalmic care to ATL patients. ATL-related ocular manifestations were most commonly diagnosed "based on blood tests and characteristic ophthalmic findings." By analyzing the 48 reported cases of ATL-related ocular manifestations, common ATL-related ocular lesions were intraocular infiltration (22 cases, 45.8%) and opportunistic infections (19 cases, 39.6%). All cases of opportunistic infection were cytomegalovirus retinitis. Dry eye (3 cases, 6.3%), scleritis (2 cases, 4.2%), uveitis (1 case, 2.1%), and anemic retinopathy (1 case, 2.1%) were also seen. In conclusion, intraocular infiltration and cytomegalovirus retinitis are common among ATL patients, and ophthalmologists should keep these findings in mind in their practice.


Identification of a novel locus associated with skin colour in African-admixed populations.
Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals. We performed a genome-wide association study of melanin levels in 285 Hispanic/Latino individuals from Puerto Rico, analyzing 14 million genetic variants. A total of 82 variants with p-value ≤1 × 10-5 were followed up in 373 African Americans. Fourteen single nucleotide polymorphisms were replicated, of which nine were associated with skin colour at genome-wide significance in a meta-analysis across the two studies. These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 × 10-14, rs1426654) and SLC45A2 (minimum p = 9.71 × 10-10, rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 × 10-9, rs6602666). The most significant variant within this region is common among African-descent populations but not among Europeans or Native Americans. Our findings support the advantages of analyzing African-admixed populations to discover new genes influencing skin pigmentation.


Update on therapy for melanoma: opportunities for patient selection and overcoming tumor resistance.
The incidence of malignant melanoma is rising faster than any other malignancy. Although earlier stage patients can be cured with surgical resection with or without adjuvant therapy, a significant number of patients go on to develop disseminated disease. Currently, limited therapeutic options exist for patients with metastatic melanoma. Recent studies suggest that patient selection is feasible and may enable the restriction of treatment to those most likely to benefit. Additionally, several potential mechanisms of tumor resistance have been identified creating opportunities for circumventing them. This article will review current strategies for patient selection and overcoming therapeutic resistance. These strategies hold the promise of extending the clinical benefits of current therapies as well as facilitating the development of additional and more active treatments.


Telemedicine in ophthalmology.
Comprehensive telemedicine promises a world of medicine freed of geographic borders, time zones, and personnel shortages. It could open the door to more accessible medical delivery systems and economical widespread screening for disease. No region of the world would be too remote or too poor to receive high quality medical care. This article traces the development and current applications and initiatives in the field of telemedicine as applied to ophthalmology in the wider sense. Uses for clinical diagnosis and management, screening, research, education and peer interaction are discussed.


Dipropylcyclopentylxanthine triggers apoptosis in Jurkat T cells by a receptor-independent mechanism.
1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a xanthine analog used as selective antagonist of adenosine receptors, caused apoptosis in a human leukemia T cell line. Jurkat cells treated with DPCPX underwent apoptosis as demonstrated by flow cytometry, by DNA fragmentation and by accumulation of histones, H2A, H2B, H3 and H4, in the nucleoplasm of cells. Cell cycle and cell sorting analyses indicated an arrest of cells in G(2)/M followed by the appearance of apoptotic cells in G(1) and G(2)/M phases. The mechanism of programmed cell death does not seem to be mediated by signal transduction events at the plasma membrane since it did not involve activation of cell membrane receptors and modification of the intracellular levels of Ca(2+) or cAMP. Apoptosis by incorporation into DNA of a derivative of DPCPX is suggested in basis of the presence of radioactivity label in the DNA obtained from cells preincubated with [(3)H]DPCPX.


In vitro activity of AST-120 that suppresses indole signaling in Escherichia coli, which attenuates drug tolerance and virulence.
AST-120 (Kremezin) is used to treat progressive chronic kidney disease (CKD) by adsorbing uremic toxin precursors produced by gut microbiota, such as indole and phenols. In this study, we propose that AST-120 reduces indole level, consequently suppresses indole effects on induction of drug tolerance and virulence in Escherichia coli including enterohaemorrhagic strains. In experiments, AST-120 adsorbed both indole and tryptophan, a precursor of indole production, and led to decreased expression of acrD and mdtEF which encode drug efflux pumps, and elevated glpT, which encodes a transporter for fosfomycin uptake and increases susceptibility to aztreonam, rhodamine 6G, and fosfomycin. AST-120 also decreased the production of EspB, which contributes to pathogenicity of enterohaemorrhagic E. coli (EHEC). Aztreonam, ciprofloxacin, minocycline, trimethoprim, and sulfamethoxazole were also adsorbed by AST-120. However, fosfomycin, in addition to rifampicin, colistin and amikacin were not adsorbed, thus AST-120 can be used together with these drugs for therapy to treat infections. These results suggest another benefit of AST-120, i.e., that it assists antibacterial chemotherapy.


The cold Leidenfrost regime.
Superhydrophobicity (observed at room temperature) and Leidenfrost phenomenon (observed on very hot solids) are classical examples of nonwetting surfaces. It was found that combining the two effects by heating water-repellent materials leads to a marked yet unexplained decrease of the Leidenfrost temperature of water. We discuss here how heat enhances superhydrophobicity by favoring a "cold Leidenfrost regime" where water adhesion becomes nonmeasurable even at moderate substrate temperature. Heat is found to induce contradictory effects (sticking due to vapor condensation, and lift due to the spreading of vapor patches), which is eventually shown to be controllable by the solid surface texture. The transition to the levitating Leidenfrost regime is observed to be continuous as a function of temperature, contrasting with the transition on common solids.


Hidrotic ectodermal dysplasia in a Chinese pedigree: A case report.
We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia (HED) with a variation in GJB6 (c.31G>A). The patients in the family had a triad of clinical manifestations of varying degrees. Although the same variation locus have been reported, the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder, palmoplantar keratosis, and congenital hypotrichosis. This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED. The proband (IV4) was a male patient with normal sweat gland function and dental development, no skeletal dysplasia, no cognitive disability, and no hearing impairments. His parents were not consanguineously married. Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longitudinal ridges, in addition to mild bilateral palmoplantar hyperkeratosis. GJB6, GJB2, and GJA1 have been reported to be the causative genes of HED; therefore, we subjected the patient's samples to Sanger sequencing of these three genes. In this family, the variation locus was at GJB6 (c.31G>A, p.Gly11Arg). Overexpression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models, and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot, respectively. We report another HED phenotype associated with GJB6 variations, which can help clinicians to diagnose HED despite its varying presentations.


Hierarchy in inorganic membranes.
Thin films of a few μm thickness for particle filtration and gas separation cannot be applied as self-supporting layers since they are mechanically insufficiently strong. Therefore, these top layers for particle filtration and gas separation are usually deposited on porous mechanically strong supports with a hierarchical pore structure. To reduce the pressure drop of a gas stream over the membrane and to ensure high fluxes in filtration and gas separation, the cross section of the support is usually asymmetric or graded with a small thickness of the layer with the smallest pore size called the top layer. Since the pressure drop over a capillary with radius r is ∼r(4), the layer with the smallest pore size should be as thin as possible. The disk-like planar supports are usually prepared by sequential tape casting which is an expensive technology. Tubular supports with a hierarchical cross section can be prepared in one step by hollow fiber spinning, double mantle spinning or centrifugal casting.


Effects of position and orientation of the 72-base-pair-repeat transcriptional enhancer on replication from the simian virus 40 core origin.
A number of recent studies have reported that in papovaviruses such as simian virus 40 (SV40) and polyomavirus, the replication of the viral DNA in vivo is activated by the viral transcriptional enhancer or promoter sequences. Both viral and cellular transcriptional enhancers are well known for their ability to activate transcription in a position- and orientation-independent manner. In the present study, we investigated the effect of the position and orientation of the SV40 72-base-pair (bp) repeat enhancer on its replication activation function. We constructed plasmids containing one copy each of the SV40 core origin and enhancer placed in either order and orientation and at different distances from each other. We assayed the replication efficiencies of these plasmids in the presence of an internal control plasmid in COS-1 monkey kidney cells producing the SV40 T antigen required for replication. We found that the 72-bp repeat was capable of activating replication equally well in either orientation when placed 8 or 9 bp from the core origin. The activation of replication was totally abolished, and replication efficiencies in most instances were found to be lower than that obtained with the core origin alone, when the 72-bp repeat was separated from the core origin by distances of 99 bp or more. This was in direct contrast to the situation with polyomavirus, in which activation of replication by the homologous enhancer or by the SV40 72-bp repeat enhancer is known to be position independent. We also found that when the SV40 core origin and the 72-bp repeat enhancer were adjacent to each other, efficient activation of replication was obtained only if the end of the core origin containing the 17-bp A + T block was linked with the enhancer. In the other orientation of the core origin, activation of replication was either diminished or abolished. Hypotheses such as alteration of chromatin structure by the enhancer and interaction between trans-acting factors binding to the enhancer and the core origin mediating the activation effect are discussed.


Does footwear type impact the number of steps required to reach gait steady state?: an innovative look at the impact of foot orthoses on gait initiation.
Many studies have attempted to better elucidate the effect of foot orthoses on gait dynamics. To our knowledge, most previous studies exclude the first few steps of gait and begin analysis at steady state walking. These unanalyzed steps of gait may contain important information about the dynamic and complex processes required to achieve equilibrium for a given gait velocity. The purpose of this study was to quantify gait initiation and determine how many steps were required to reach steady state walking under three footwear conditions: barefoot, habitual shoes, and habitual shoes with a prefabricated foot orthoses. Fifteen healthy subjects walked 50m at habitual speed in each condition. Wearing habitual shoes with the prefabricated orthoses enabled subjects to reach steady state walking in fewer steps (3.5 steps+/-2.0) compared to the barefoot condition (5.2 steps+/-3.0; p=0.02) as well as compared to the habitual shoes condition (4.7 steps+/-1.6; p=0.05). Interestingly, the subjects' dynamic medial-lateral balance was significantly improved (22%, p<0.05) by using foot orthoses compared to other footwear conditions. These findings suggest that foot orthoses may help individuals reach steady state more quickly and with a better dynamic balance in the medial-lateral direction, independent of foot type. The findings of this pilot study may open new avenues for objectively assessing the impact of prescription footwear on dynamic balance and spatio-temporal parameters of gait. Further work to better assess the impact of foot orthoses on gait initiation in patients suffering from gait and instability pathologies may be warranted.


[Premature ovarian failure].
Premature ovarian failure (POF) is defined by at least four months of amenorrhea with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The different etiologies identified are 1) iatrogenic following chemotherapy and/or radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15, GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone replacement therapy in order to avoid an increase in cardiovascular risk and osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10% of the patients will have natural conception. When fertility is desired, women with POF should be oriented towards oocyte donation centers. Research is currently performed in order to identify new genes involved in POF.


Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi.
Trypanosoma cruzi chagasin belongs to a recently discovered family of cysteine protease inhibitors found in lower eukaryotes and prokaryotes but not in mammals. Chagasin binds tightly to cruzain, the major lysosomal T. cruzi cysteine protease, involved with infectivity and survival of the parasite in mammalian host cells. In the scope of a project to characterize proteins diferentially expressed during T. cruzi metacyclogenesis, we have determined the crystal structure of chagasin, which is now the first X-ray structure of a chagasin-like cysteine protease inhibitor to be reported. The structure was solved by the SIRAS method and refined at 1.7A resolution and a comparison with the two NMR structures available revealed some differences in the loops involved in binding to cysteine proteases. The highly flexible loop 4 could be entirely modeled and residues 29-33 from loop 2 form a 3(10)-helix structure that may be important to stabilize the loop conformation. Chagasin crystal structure was docked to the highest resolution structure available of cruzain and a model of chagasin-cruzain interaction was analyzed. The knowledge of the chagasin crystal structure may contribute to the elucidation of the molecular mechanism involved in the inhibition of cruzain and other T. cruzi cysteine proteases.


Nutrient dynamics and eutrophication in the Sea of Marmara: Data from recent oceanographic research.
This work was implemented to study the physicochemical and biological characteristics of the Sea of Marmara and the Turkish straits (TSS: Bosporus and Dardanelles straits) for the period 2010-2013 and to calculate winter and summer fluxes of nutrients (nitrates, phosphates) between the Aegean and Black Seas through the TSS. The brackish Black Sea waters reach the Dardanelles Strait with modified biochemical properties. The salinity and phosphates of the surface waters increased westwards. Biologically labile nutrients of Black Sea origin are utilized through biological processes in the Marmara Sea. On the other hand, increase of nutrients due to land based sources has led to eutrophication problems in the area. The sub surface water layer of Mediterranean origin is oxygen depleted (saturation<30%) and rich in nutrients. Higher oxygen values indicated water mixing of the Sea of Marmara during winter 2012. Ammonium was the predominant form of inorganic nitrogen. The study area has been classified from Moderate to Bad trophic status. İzmit Bay also faced serious eutrophication problems together with hypoxic conditions below the halocline. Nutrient fluxes through the TSS showed temporal variation in the upper and lower layers related to changes in both nutrient concentrations and the water mass volume fluxes. Surface nitrates and phosphates outflux from the Sea of Marmara to the Aegean Sea was higher than the influx from the Black Sea through Bosporus strait, indicating high enrichment of nutrients in the Sea of Marmara from anthropogenic sources.