Short outcome comparison of elderly patients versus nonelderly patients treated with transjugular intrahepatic portosystemic stent shunt: A propensity score matched cohort study.
A transjugular intrahepatic portosystemic stent shunt (TIPSS) has been widely used to treat portal hypertension and its complications. However, no established guidelines mentioned whether age was a risk factor for the treatment of TIPSS.The aim is to determine whether age is a risk factor for poor outcomes following TIPSS.The retrospective cohort study included 134 patients who received TIPSS treatment from 2003 to 2016. The adverse events after the TIPSS treatment were compared after propensity score matching to reduce the effect of selection bias. Multivariate logistic regression was conducted to confirm the potential confounders for rebleeding (RB) and ascites after TIPSS therapy.After excluding 10 patients, 124 patients were analyzed. Among them, 37 patients were included in the elderly group. In the propensity score matched cohort (32 pairs), there was no significant difference between the elderly group and the nonelderly group in terms of the event after TIPSS therapy (All P > .05). Multivariate logistic regression analysis revealed that hypertension (OR 13.246, 95% CI: [1.29, 136.073]; P = .03) was an independent risk factor for RB. In addition, smoking (OR 4.48, 95% CI: [1.43, 14.033]; P = .01) and preascites (OR 6.7, 95% CI: [2.04, 22.005]; P = .002) were independent risk factors for ascites after TIPSS treatment.Age is not an independent risk factor for poor outcomes following the treatment of TIPSS. Smoking and preascites are independent risk factors for patients' ascites, and hypertension is an independent risk factor for patients' RB after TIPSS therapy.


Recognition of (2S)-aminomalonyl-acyl carrier protein (ACP) and (2R)-hydroxymalonyl-ACP by acyltransferases in zwittermicin A biosynthesis.
Polyketide synthases elongate a polyketide backbone by condensing carboxylic acid precursors that are thioesterified to either coenzyme A or an acyl carrier protein (ACP). Two of the three known ACP-linked extender units, (2S)-aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP, are found in the biosynthesis of the agriculturally important antibiotic zwittermicin A. We previously reconstituted the formation of (2S)-aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP from the primary metabolites l-serine and 1,3-bisphospho-d-glycerate. In this report, we characterize the two acyltransferases involved in the specific transfer of the (2S)-aminomalonyl and (2R)-hydroxymalonyl moieties from the ACPs associated with extender unit formation to the ACPs integrated into the polyketide synthase. This work establishes which acyltransferase recognizes each extender unit and also provides insight into the substrate selectivity of these enzymes. These are important step toward harnessing these rare polyketide synthase extender units for combinatorial biosynthesis.


No-go theorem for passive single-rail linear optical quantum computing.
Photonic quantum systems are among the most promising architectures for quantum computers. It is well known that for dual-rail photons effective non-linearities and near-deterministic non-trivial two-qubit gates can be achieved via the measurement process and by introducing ancillary photons. While in principle this opens a legitimate path to scalable linear optical quantum computing, the technical requirements are still very challenging and thus other optical encodings are being actively investigated. One of the alternatives is to use single-rail encoded photons, where entangled states can be deterministically generated. Here we prove that even for such systems universal optical quantum computing using only passive optical elements such as beam splitters and phase shifters is not possible. This no-go theorem proves that photon bunching cannot be passively suppressed even when extra ancilla modes and arbitrary number of photons are used. Our result provides useful guidance for the design of optical quantum computers.


Treatment of bladder pain with transsacral nerve block.
Fifteen patients with bladder spasticity and pain of three different etiologies were referred to the pain clinic by urologic specialists. These patients were refractory to all prior methods of treatment, excluding major surgical procedures. In a prospective study started in 1976, these patients were treated with transsacral nerve blocks using 0.25% bupivacaine and, in most cases, subsequent 6% aqueous phenol at the right S-3 ventral foramen. If indicated, transsacral nerve blocks were performed at other levels, as described in the text. Of the patients studied 53% have had significant or complete relief of pain for an average of 26.5 months. The associated morbidity was negligible and there was no mortality. This is in contrast to the morbidity and mortality associated with some major surgical "curative" procedures. The technique is proposed as a successful and economical approach to treatment that can be managed on an outpatient basis.


[Effectiveness of gefitinib (Iressa) as first-line therapy for inoperable non-small-cell lung cancer with mutated EGFR gene (phase II study)].
Tumor regression was reported in 20-30% of patients with inoperable non-small-cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first-line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC.


Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.
Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01). Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.


Structure and sequence of a UDP glucose pyrophosphorylase gene of Dictyostelium discoideum.
Cell-cell contact and exogenous cAMP regulate the expression of uridine diphosphoglucose pyrophosphorylase (UDPGP) of Dictyostelium discoideum (B. Haribabu, A. Rajkovic and R. P. Dottin, 1986, Dev. Biol., Vol. 113, 436-442). cAMP appears to regulate gene expression in Dictyostelium by transmembrane signal transduction (B. Haribabu and R. Dottin, 1986, Mol. Cell. Biol. 6, 2402-2408). To further characterize the mechanism of action of cAMP on the expression of this gene and the nature of the defects in UDPGP mutants that abort development, we sequenced the cDNA and the genomic DNA, including intervening and flanking sequences. The deduced amino acid sequence predicts a polypeptide of 57,893 d. molecular weight. Three short (100-200 nucleotides) A+T rich introns occur within the coding sequences but only one of them contains a sequence TAACTAAC, similar to the yeast lariat acceptor site. The 5' flanking sequences are also A+T rich and contain an oligo A tract (-14 to -24), a TATA box (-25 to -32), and a short G+C rich region (-63 to -101) which may be a control region. From -196 to -209 is a sequence AAAGTAGTATTCAA which matches in 11 of its 14 nucleotides, a sequence found upstream from the hormonally regulated P-enolypyruvate carboxykinase gene of rat.


CT-guided transthoracic core needle biopsy for small pulmonary lesions: diagnostic performance and adequacy for molecular testing.
Computed tomography (CT)-guided transthoracic needle biopsy is a well-established, minimally invasive diagnostic tool for pulmonary lesions. Few large studies have been conducted on the diagnostic performance and adequacy for molecular testing of transthoracic core needle biopsy (TCNB) for small pulmonary lesions. This study included CT-guided TCNB with 18-gauge cutting needles in 560 consecutive patients with small (≤3 cm) pulmonary lesions from January 2012 to January 2015. There were 323 males and 237 females, aged 51.8±12.7 years. The size of the pulmonary lesions was 1.8±0.6 cm. The sensitivity, specificity, accuracy and complications of the biopsies were investigated. The risk factors of diagnostic failure were assessed using univariate and multivariate analyses. The sample's adequacy for molecular testing of non-small cell lung cancer (NSCLC) was analyzed. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy were 92.0% (311/338), 98.6% (219/222), and 94.6% (530/560), respectively. The incidence of bleeding complications was 22.9% (128/560), and the incidence of pneumothorax was 10.4% (58/560). Logistic multivariate regression analysis showed that the independent risk factors for diagnostic failure were a lesion size ≤1 cm [odds ratio (OR), 3.95; P=0.007], lower lobe lesions (OR, 2.83; P=0.001), and pneumothorax (OR, 1.98; P=0.004). Genetic analysis was successfully performed on 95.45% (168/176) of specimens diagnosed as NSCLC. At least 96.8% of samples with two or more passes from a lesion were sufficient for molecular testing. The diagnostic yield of small pulmonary lesions by CT-guided TCNB is high, and the procedure is relatively safe. A lesion size ≤1 cm, lower lobe lesions, and pneumothorax are independent risk factors for biopsy diagnostic failure. TCNB specimens could provide adequate tissues for molecular testing.


[Eprazinone exanthema with subcorneal pustulosis].
A drug eruption with subcorneal pustulation is presented, occurring in a patient during treatment with eprazinone . The biopsy of the initial lesions showed changes as in pustulosis subcornealis . The aetiopathogenetic relationship between administration of eprazinone and the pustular eruption was confirmed by patch test.


Comparison of curative effect of 131I and antithyroid drugs in Graves' disease: a meta-analysis.
Radioactive 131I is currently reported to be a potential effective intervention for Graves' disease treatment in China. Whether 131I treatment was associated with effective outcome or reduced risk of side effects, recurrence rate remained unknown. Eligible studies were selected from Chinese VIP, Wangfang, CNKI databases using the keywords "Iodine" and "Graves' disease". Finally, 13 clinical trials met the inclusion criterion and were included this meta-analysis. Our meta-analysis included 1355 patients diagnosed of Graves' disease with regular anti-thyroid drugs oral administration and 1320 patients with 131I therapy. The results showed that there was significant symptom improvement with radioactive iodine intervention (Odd Ratio [OR]=4.50, 95% CI: 3.55-5.71, P<0.01). Three studies mentioned side effects, 6 mentioned recurrence rate and another 6 mentioned hypothyroidism. The ORs and 95% CIs for these subgroups were 0.12 (0.06, 0.21), 0.08 (0.05, 0.13) and 2.27 (1.77, 2.92) respectively. It means a significant reduction of side effects and recurrence rate but increased hypothyroidism after 131I intervention in Graves' disease. Treatment with 131I was associated with better clinical outcome; it reduced side effects and reccurence rate but increased hypothyroidism in Graves' disease.


[DNA technology for diagnosis and characterization of agricultural animal pathogenic viruses].
Use of recombinant DNA for the development of diagnostic and therapeutic and preventive drugs became one of the priority trends in modern experimental veterinary. This paper discusses modern methods of virus analysis based on the DNA technologies: restriction mapping, nucleic acid hybridization, and polymerase chain reaction. Examples of utilization of these methods for clinical diagnosis and research of animal viruses are offered.


Serum albumin levels, an additional factor implicated in hyperparathyroidism outcome in peritoneal dialysis: a prospective study with paired bone biopsies.
Renal osteodystrophy encompasses several histologic subtypes, all of which can undergo change over time. In peritoneal dialysis (PD) patients, we studied bone histology and the factors influencing any changes over 1 year In 44 PD patients, we collected two paired bone biopsies (at baseline and after 12 months) and biochemical and treatment data (at baseline and every 3 months). Of the 44 original patients, 24 completed the study. Of these 24 patients, 19 were initially diagnosed with adynamic bone lesion (ABL). After 1 year, 12 still had ABL; the other 7 had changed to high turnover bone lesion (HTBL). Another 5 patients were initially diagnosed with HTBL. Among these, 4 still had HTBL at 1 year; 1 had changed to ABL. In patients who changed to HTBL from ABL, serum albumin had increased to 4.2 +/- 0.3 g/dL at month 12 from 3.7 +/- 0.4 g/dL at baseline (p < 0.05). In patients who still had ABL, serum albumin did not change. Additionally, the percentage increase in serum albumin over the study was higher in HTBL patients than in ABL patients (0.1408 +/- 0.139 g/dL vs. -0.0076 +/- 0.113 g/dL, p = 0.009). A lower likelihood of diabetes (p = 0.033) and a higher serum albumin [area under the curve: 0.822; 95% confidence interval (CI): 0.651 to 0.993] identified a HTBL diagnosis at 12 months. Older age increased the probability of changing to ABL (OR: 1.2935; 95% CI: 1.03 to 1.67; p= 0.02). Bone lesions can change over time, and this change is associated with age, diabetes, and serum albumin. A change to HTBL was associated with improvement in serum albumin. Protein status is possibly a factor influencing bone lesion outcome.


School performance and the risk of suicide attempts in young adults: a longitudinal population-based study.
Poor school performance is strongly associated with attempted suicide, but the mechanisms underlying this association are uncertain. We examined this relationship and the extent to which it is explained by (i) adult health behaviours and (ii) social conditions. Furthermore, we examined the potential modifying role of previous suicidal thoughts in the relationship. We conducted a longitudinal cohort study of 6146 individuals aged 18-33 years, recruited in 2002 and 2006 in Stockholm and resurveyed in 2007 and 2010 respectively. We estimated the risk of reported lifetime suicide attempts at follow-up among individuals without a history of suicide attempts at baseline and in relation to compulsory school-leaving grades, controlling for possible confounders and mediators. There were 91 cases of self-reported suicide attempts during the follow-up (5-year incidence of 1.5%). ORs ranged from 3.35 [95% confidence interval (CI) 1.88-5.96] for those in the lowest grade quartile to 2.60 (95% CI 1.48-4.57) and 1.76 (95% CI 0.99-3.13) for those in the second and third quartiles respectively. The relationship between school performance and risk of suicide attempts did not differ by sex. Adult health behaviours and social conditions marginally attenuated, but did not explain, the relationship. The gradient varied with baseline history of suicidal thoughts, and was found only among individuals without such a history. Poor school performance was found to predict suicide attempts among young adults without a history of suicidal thoughts. Adult health behaviours and social conditions did not explain this relationship. Instead, other factors linked with poor school performance, such as poor coping ability, may increase the risk of suicide attempts.


Photolysis of Caged-GABA Rapidly Terminates Seizures In Vivo: Concentration and Light Intensity Dependence.
The therapy of focal epilepsy remains unsatisfactory for as many as 25% of patients. The photolysis of caged-γ-aminobutyric acid (caged-GABA) represents a novel and alternative option for the treatment of intractable epilepsy. Our previous experimental results have demonstrated that the use of blue light produced by light-emitting diode to uncage ruthenium-bipyridine-triphenylphosphine-c-GABA (RuBi-GABA) can rapidly terminate paroxysmal seizure activity both in vitro and in vivo. However, the optimal concentration of RuBi-GABA, and the intensity of illumination to abort seizures, remains unknown. The aim of this study was to explore the optimal anti-seizure effects of RuBi-GABA by using implantable fibers to introduce blue light into the neocortex of a 4-aminopyridine-induced acute seizure model in rats. We then investigated the effects of different combinations of RuBi-GABA concentrations and light intensity upon seizure. Our results show that the anti-seizure effect of RuBi-GABA has obvious concentration and light intensity dependence. This is the first example of using an implantable device for the photolysis of RuBi-GABA in the therapy of neocortical seizure, and an optimal combination of RuBi-GABA concentration and light intensity was explored. These results provide important experimental data for future clinical translational studies.


Prevalence of Sexual Problems and Associated Distress in Aging Men Across 4 European Countries.
Among older men, comparable cross-cultural investigations of sexual problems and associated distress that also include a multitude of relevant explanatory variables of these sexual problem and related distress are rare in the research literature. To investigate prevalence rates of sexual problems and associated distress among older men across 4 European countries (Norway, Denmark, Belgium, and Portugal) and assess for associated mental and physical health-related factors. Multinational cross-sectional questionnaire study using self-report measures. Prevalence rates of sexual problems and associated distress levels. We found a high prevalence of sexual problems persisting for months or longer across countries, but noted that many affected men experienced minimal or no distress related to these problems. We also found marked cross-cultural differences in reported distress about sexual problems, with southern European men (ie Portugal) reporting significantly more distress related to the majority of sexual problems investigated compared with northern European men (ie Denmark and Norway). Finally, we identified several relational, physical, and mental health problems associated with the reported number of sexual problems and the distress related to these problems. We suggest that healthcare professionals also target distress when considering sexual problems among older men and contextualize these considerations within a multifactorial approach to general health in which (other) mental and physical health factors relevant to these patients' sexual health and function are also jointly considered. Strengths of this study include the large sample size, inclusion of participants from 4 European countries, assessment of distress associated with sexual problems, and similar research design and method of data collection across the 4 included countries. Limitations of the study include the cross-sectional design, which precludes causal conclusions; the low response rate in the Portuguese sample; the lack of homosexual participants; and the lack of comprehensive assessments of dyadic factors that may be of relevance to sexual problems and associated distress. This study identified a high prevalence of sexual problems persisting for 3 months or longer among older men across 4 European countries, but also found that many of the men with sexual problems experienced minimal or no distress related to these problems. G.M. Hald, C. Graham, A. Štulhofer, et al. Prevalence of Sexual Problems and Associated Distress in Aging Men Across 4 European Countries. J Sex Med 2019;16:1212-1225.


Parotid degeneration secretion of amylase in vitro in the rat following sympathectomy.
After extirpation of the superior cervical ganglion in the rat a degeneration secretion of amylase occurs in an in vitro preparation of the parotid gland. It can be detected about 14 h after the sympathectomy, reaches a maximum after about 17 h and then slowly subsides. It is abolished by atenolol, but not by dihydroergotamine or atropine, nor by tetrodotoxin. From this it is concluded that the phenomenon is due to an action mainly on beta 1-adrenoceptors exerted by noradrenaline, which is released from the degenerating sympathetic nerves at the neuro-glandular junctions, independently of propagated nerve impulses.


Analysis of Food Pairing in Regional Cuisines of India.
Any national cuisine is a sum total of its variety of regional cuisines, which are the cultural and historical identifiers of their respective regions. India is home to a number of regional cuisines that showcase its culinary diversity. Here, we study recipes from eight different regional cuisines of India spanning various geographies and climates. We investigate the phenomenon of food pairing which examines compatibility of two ingredients in a recipe in terms of their shared flavor compounds. Food pairing was enumerated at the level of cuisine, recipes as well as ingredient pairs by quantifying flavor sharing between pairs of ingredients. Our results indicate that each regional cuisine follows negative food pairing pattern; more the extent of flavor sharing between two ingredients, lesser their co-occurrence in that cuisine. We find that frequency of ingredient usage is central in rendering the characteristic food pairing in each of these cuisines. Spice and dairy emerged as the most significant ingredient classes responsible for the biased pattern of food pairing. Interestingly while individual spices contribute to negative food pairing, dairy products on the other hand tend to deviate food pairing towards positive side. Our data analytical study highlighting statistical properties of the regional cuisines, brings out their culinary fingerprints that could be used to design algorithms for generating novel recipes and recipe recommender systems. It forms a basis for exploring possible causal connection between diet and health as well as prospection of therapeutic molecules from food ingredients. Our study also provides insights as to how big data can change the way we look at food.


Serosurveillance for Japanese encephalitis, Akabane, and Aino viruses for Thoroughbred horses in Korea.
Recent global warming trends may have a significant impact on vector-borne viral diseases, possibly affecting vector population dynamics and disease transmission. This study measured levels of hemagglutination-inhibition (HI) antibodies against Japanese encephalitis virus (JEV) and neutralizing antibodies against Akabane virus (AKAV) and Aino virus (AINV) for Thoroughbred horses in Korea. Blood samples were collected from 989 racehorses in several provinces, between October 2005 and March 2007. Sera were tested using either an HI assay or a virus neutralization test. Approximately half (49.7%; 492/989) of the horses tested were antibody-positive for JEV. The HI titer against JEV was significantly correlated with racehorse age (p < 0.05). Horses with an HI antibody titer of 1 : 160 or higher accounted for 3.9% of the animals tested, indicating that vectors transmitting arthropod- borne viruses bit relatively few horses. In contrast, 3.8% (19/497) and 19.5% (97/497) of horse sera collected in March 2007 were positive against AKAV and AINV, respectively. The presence of antibodies against AKAV and AINV may indicate the multiplication of AKAV and AINV in these horses.


Nursing in an imperfect world: Storytelling as preparation for mental health nursing practice.
Storytelling is a valuable adjunctive method of preparing undergraduate mental health nursing students for practice. To explore the possibilities of this method of teaching, 100 stories were collected from experienced nurses working in mental health and analysed using a case study methodology. The aim was to explore the purpose of clinical anecdotes told by experienced nurses working in mental health settings to undergraduates and new recruits, with an ancillary purpose of looking at the implications of these anecdotes for the exploration of contemporary mental health practice and education. A framework for student discussion of stories is provided. The insights gained illuminate not only the history of mental health nursing and the daily activities of nurses working in mental health, but also some of the deep-level skills developed and used by these nurses as they work in the complexity and ambiguity of an imperfect world where the job requires managing the unexpected every shift, and where there might not always be a textbook-perfect solution to clinical situations.


Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model.
Visceral hypersensitivity in irritable bowel syndrome (IBS) is still poorly understood, despite that chronic abdominal pain is the most common symptoms in IBS patients. To study effects of BK channels on visceral hypersensitivity in IBS rats and the underlying mechanisms, IBS rats were established by colorectal distention (CRD) in postnatal rats. The expression of large-conductance calcium and voltage-dependent potassium ion channels (BK channels) of the thoracolumbar spinal cord was examined in IBS and control rats. The effects of BK channel blockade on visceral hypersensitivity were evaluated. The interaction of BK channels and N-methyl-D-aspartate acid (NMDA) receptors was explored, and synaptic transmission at superficial dorsal horn (SDH) neurons of the thoracolumbar spinal cord was recorded by whole-cell patch clamp in IBS rats. The expression of the BK channels of the thoracolumbar spinal cord in IBS rats was significantly reduced. The blockade of BK channels could reduce the visceral hypersensitivity in IBS rats. There was an interaction between BK channels and NMDA receptors in the spinal cord. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in SDH neurons is significantly reduced in IBS rats. The blockade of BK channels depolarizes the inhibitory interneuron membrane and increases their excitability in IBS rats. BK channels could interact with NMDA receptors in the thoracolumbar spinal cord of rats and regulate visceral hypersensitivity in IBS rats.


The Feasibility and Long-Term Outcomes of the Crossboss/Stingray for Treating Coronary Chronic Total Occlusions Lesions with Distal Diffuse Disease Landing Zone.
The feasibility and long-term outcomes of the CrossBoss/Stingray for treating coronary chronic total occlusions (CTO) with distal diffuse disease landing zone remain unclear. Consecutive CTO patients with distal diffuse lesions that underwent percutaneous coronary intervention by the CrossBoss/Stingray system at Xijing Hospital from April 2016 to October 2020, were included. Patients were analyzed by two groups according to the extent of stenosis in the distal landing zone: 50%-70% stenosis (moderate stenosis group) and >70% stenosis (severe stenosis group). The primary efficacy outcome was technical success, defined as the frequency of true lumen guidewire placement distal to the CTO. The composite endpoint of all-cause death, any stroke, or any revascularization was also explored. A total of 91 consecutive patients were included, with 32 patients in the moderate stenosis group and 59 patients in the severe stenosis group. The mean J-CTO score was 2.5 ± 1.1. The technical success rate was 79.1% (72/91) in the overall population and was similar between the 2 groups: 78.1% (25/32) and 79.7% (47/59) (p = 0.608). No coronary perforation occurred. With a median follow-up of 29 months (IQR: 53-92), the estimated rate of the composite endpoint of all-cause death, any stroke, or any revascularization was 50.4% (all-cause death: 16.6%, any stroke: 1.1%, any revascularization: 36.5%) in the overall population. No significant difference was observed in the rate of the composite endpoint between the moderate stenosis group and the severe stenosis group (45.1% vs. 54.3%, respectively, p = 0.797). In CTO lesions with distal diffuse disease landing zone, the technical success rates of CrossBoss/Stingray and the long-term clinical outcomes were not significantly different between the moderate stenosis group (50%-70%) and the severe stenosis group (>70%). However, the relatively high rate of long-term clinical outcomes, especially any revascularization, warrants further investigations on this indication in future studies.


A school-based suicide risk assessment strategy.
While school nurses are often uniquely positioned to conduct suicide risk assessments, many school nurses feel poorly equipped to undertake this venture. This article outlines a plan to put a suicide risk assessment strategy in place.


Acrylate-tethering drug carrier: covalently linking carrier to biological surface and application in the treatment of Helicobacter pylori infection.
The development of carriers to sustain drugs at stomach surface is an attractive strategy to increase drug bioavailability locally and systematically. So far, the only reported carrier that can form a covalent bond with mucus, the thiolated carrier, relies on a reversible disulfide exchange reaction between thiols on the carrier and disulfide bridges on the mucus. Here we show the design and fabrication of a cellulose carrier with tethering acrylate groups (denoted here as clickable carrier) that, under a nontoxic condition, can efficiently react with thiols on biomaterials in situ through the thermodynamically driven and kinetically probable Michael thiol-ene click reaction. Here we show the attachments of the clickable carriers to a mucin protein, a surface of human laryngeal carcinoma cells, and a surface of a fresh porcine stomach. We also show that the required thiol moieties can be generated in situ by reducing existing cystine disulfide bridges with either the edible vitamin C or the relatively nontoxic tris(2-carboxyethyl) phosphine. Comparing to a control carrier, the clickable carrier can increase some drug concentrations in an ex vivo stomach tissue, and improve the Helicobacter pylori treatment in infected C57BL/6 mice.


Unusual genitourinary tract activity.
A 23-year-old woman presented to the emergency department after manually inserting foreign bodies into the urinary bladder through her urethra. A plain abdominal film of the kidneys, ureters and bladder confirmed three radio-opaque densities in the urinary bladder. She was taken to the operating room where cystourethroscopy was performed. At cystoscopy 2 'corn-on-the-cob' skewers and 1 battery were identified but were too large to be retrieved safely with a grasper through the protective sheath. The objects were grasped with a 'sponge-holding forceps' (placed alongside the cystoscope) and extracted one at a time. A psychiatric consultation was sought and the patient was diagnosed and treated for borderline personality disorder. Unusual genitourinary activity (UGUA) has been described for several centuries and is characterised by the deposition of foreign objects in the genitalia. 1 The most common incentive for UGUA is sexual stimulation, but psychiatric disorders and intoxication are also associated. 2 Management involves retrieval of foreign bodies and evaluation of psychosocial factors.


Cell-type-specific type I interferon antagonism influences organ tropism of murine coronavirus.
Previous studies have demonstrated that mouse hepatitis virus (MHV) hepatotropism is determined largely by postentry events rather than by availability of the viral receptor. In addition, mutation of MHV nonstructural protein 2 (ns2) abrogates the ability of the virus to replicate in the liver and induce hepatitis but does not affect replication in the central nervous system (CNS). Here we show that replication of ns2 mutant viruses is attenuated in bone marrow-derived macrophages (BMM) generated from wild-type (wt) mice but not in L2 fibroblasts, primary astrocytes, or BMM generated from type I interferon receptor-deficient (IFNAR(-/-)) mice. In addition, ns2 mutants are more sensitive than wt virus to pretreatment of BMM, but not L2 fibroblasts or primary astrocytes, with alpha/beta interferon (IFN-α/β). The ns2 mutants induced similar levels of IFN-α/β in wt and IFNAR(-/-) BMM, indicating that ns2 expression has no effect on the induction of IFN but rather that it antagonizes a later step in IFN signaling. Consistent with these in vitro data, the virulence of ns2 mutants increased to near that of wt virus after depletion of macrophages in vivo. These data imply that the ability of MHV to replicate in macrophages is a prerequisite for replication in the liver and induction of hepatitis but not for replication or disease in the CNS, underscoring the importance of IFN signaling in macrophages in vivo for protection of the host from hepatitis. Our results further support the notion that viral tissue tropism is determined in part by postentry events, including the early type I interferon response.


[Distinction between benign and malignant pheochromocytomas].
To investigate the differences in morphology, immunohistochemistry, DNA ploidy status, LOH and MSI of 11q13 and 1p between benign and malignant pheochromocytomas, and to find the marker or markers useful in distinction between benign and malignant pheochromocytoma or for predicting the malignant potential of this tumor. Twenty-two cases of clinically documented benign and malignant pheochromocytomas from the files of Peking Union Medical College Hospital were analyzed. Aside from histological study, Ki-67, p53, CgA, S-100, PCNA and survivin immunohistochemistry studies were performed. DNA ploidy status was assessed by flow cytometry on cell suspensions prepared from formalin-fixed, paraffin-embedded sections. Twelve tumors (7 benign and 5 malignant) with paired normal tissues were microdissected. Tumor and normal tissue DNA were extracted. The obtained DNAs and 8 microsatellite markers related to 11q13 and 1q were subjected to PCR amplification for analysis of LOH and MSI. None of the tumors showed atypical mitosis, only 1 malignant tumor had a mitotic count > 1/10 HPF (2.3/10 HPF). Two malignant tumors exhibited confluent necrosis. Ki-67 index was low in benign tumors (average 0.73%), and high in malignant tumors (average 2.4%). The difference of Ki-67 index between benign and malignant tumors was statistically significant. DNA ploidy status did not correlate with malignancy. Although LOH and/or MSI of 11q13 and 1p were observed in several tumors, a statistically significant difference could not be reached due to the small number of tumors analyzed. Only Ki-67 index (> 3%) is an useful marker for distinguishing benign from malignant or for predicting the malignant potential of pheochromocytoma.


Chiral oxazolopiperidone lactams: versatile intermediates for the enantioselective synthesis of piperidine-containing natural products.
Phenylglycinol-derived oxazolopiperidone lactams are exceptionally versatile building blocks for the enantioselective construction of structurally diverse piperidine-containing natural products and bioactive compounds. These lactams are readily available in both enantiomeric series by cyclocondensation of the chiral amino alcohol with a delta-oxo acid derivative and allow the substituents to be introduced at the different ring positions in a regio- and stereocontrolled manner, providing access to enantiopure polysubstituted piperidines bearing virtually any type of substitution pattern, and also quinolizidines, indolizidines, perhydroquinolines, hydroisoquinolines, as well as complex indole alkaloids. Of particular interest are cyclocondensation reactions with racemic or prochiral delta-oxo (di)acid derivatives in processes involving dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups, as they directly lead to lactams that already incorporate the carbon substituents on the heterocyclic ring. The use of (S)-3,4-dimethoxyphenylalaninol or (S)-tryptophanol in the above cyclocondensation reactions expands the potential and the scope of the methodology, providing a straightforward route to enantiopure benzo[a]- and indolo[2,3-a]quinolizidines.


Althesin infusion for cardiac catheterisation.
A trial of a continuous intravenous infusion of Althesin is described for sedation during cardiac catheterisation, both for children and adults. The conditions produced for the procedure were very satisfactory. The advantages and problems of its use are discussed. The technique justifies further trials.


Chemical speciation of trace metals in the industrial sludge of Dhaka City, Bangladesh.
The objective of this study was to assess total concentration and chemical fractionation of trace metals in the industrial wastewater and sludge collected from seven different types of industries in Dhaka City, Bangladesh. The sludge from industries is either dumped on landfills or reused as secondary resources in order to preserve natural resources. Metals were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The ranges of Cr, Ni, Cu, As, Cd, and Pb in the sludges were 1.4-9,470, 4.8-994, 12.8-444, 2.2-224, 1.9-46.0 and 1.3-87.0 mg/kg, respectively. As a whole, the average concentrations of trace metals in samples were in the decreasing order of Cr > Ni > Cu > As > Pb > Cd. The results of the Community Bureau of Reference (BCR) sequential extraction showed that the studied metals were predominantly associated with the residual fraction followed by the oxidizable fraction. The study revealed that the mobile fractions of trace metals are poorly predictable from the total content, and bioavailability of all fractions of elements tends to decrease.


Conserved cell populations in doxorubicin-resistant human nasal natural killer/T cell lymphoma cell line: super multidrug resistant cells?
Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a distinct clinicopathological entity and EBV-associated disease that is highly aggressive. Many patients had failed to respond to conventional chemotherapy or relapsed after treatment. Multi-drug resistance is a major cause that leads to these desperate failures. However, the specific mechanism of drug resistance is still unclear. In the previous study, we firstly developed a doxorubicin-resistant ENKL cell line known as SNK-6/ADM, and then a small quantity of side population (SP) cells were derived from SNK-6/ADM and named SNK-6/ADM-SP. In order to explore the biological characteristics and mechanism of drug-resistance of these cells, SNK-6, SNK-6/ADM and SNK-6/ADM-SP cells were utilized to evaluate potentially differences of chemotherapy resistance index (RI), morphology, proliferation, cell cycles, expression of ATP-binding cassette (ABC) transporters (ABCG1, ABCG2 and ABCC4) and surface markers, cytokine sensitivity, and situation of EBV infection. We identified SNK-6/ADM-SP is a specific multidrug resistant cell population with a higher level of RI than SNK-6/ADM. Relevant evaluations showed that SNK-6/ADM-SP presented a series of conserved biological behaviors including relatively poor proliferation ability, high expression of ABCG2, weak sensitivity to IL-15 which could stimulate normal ENKL cells' proliferation and differentiation, and EBV inhibition with low level of EBV-DNA replication and EBV-antigen expression. This discovered cellular heterogeneity of ENKL could provide a new perspective to better understand the mechanisms of drug resistance and overcome elusive response to chemotherapy of ENKL.


Pathological Change and Whole Transcriptome Alternation Caused by ePTFE Implantation in Myocardium.
Expanded polytetrafluoroethylene (ePTFE) is commonly used in cardiovascular surgery, but usually causes postoperation complications. Although great efforts have been done to relieve these complications or to understand their mechanism, there are no applicable strategies available and no understanding mechanisms, especially in the myocardium. Here, ePTFE membranes are implanted into the right ventricular outflow tract of rabbits, and the implant-related myocardium is dissected and analyzed by histology and transcriptome sequencing. ePTFE implantation causes myocardium inflammation and fibrosis. There are 1867 differently expressed mRNAs (DEmRNAs, 1107 upregulated and 760 downregulated) and 246 differently expressed lncRNAs (DElncRNAs, 110 upregulated and 136 downregulated) identified. Bioinformatic analysis indicates that the upregulated DEmRNAs and DElncRNAs are mainly involved in inflammatory, immune responses, and extracellular matrix remodeling, while the downregulated DEmRNAs and DElncRNAs are predominantly functioned in the metabolism and cardiac remodeling. Analysis of coexpression and regulatory relationship of DEmRNAs and DElncRNAs reveals that most DElncRNAs are trans-regulated on the relevant DEmRNAs. In conclusion, ePTFE implantation causes severe myocardial tissue damages and alters the transcriptome profiles of the myocardium. Such novel data may provide a landscape of mechanisms underlying the adverse reactions caused by ePTFE implantation and uncover new therapeutic targets for inhibiting the ePTFE-related complications.


Aging of human bone and articular cartilage collagen: changes in the reducible cross-links and their precursors.
The age-dependent changes in reducible collagen cross-links, Schiff bases and their precursors were followed for human bone and articular cartilage throughout the whole life span from 3 to 89 years of age. With aging, the reduced Schiff bases dihydroxylysinonorleucine remarkable decreased, wheras hexitollysine peaks increased significantly in both collagens. Dihydroxynorleucine, the precursor of the cross-link, was found to increase slightly with age. But the changes in hydroxylysinonorleucine and lysinonorleucine were comparatively small. These changes were discussed in relation to the increased insolubility observed in both collagens at higher age.


Measuring Anomalous Heating in a Planar Ion Trap with Variable Ion-Surface Separation.
Cold ions trapped in the vicinity of conductive surfaces experience heating of their oscillatory motion. Typically, the rate of this heating is orders of magnitude larger than expected from electric field fluctuations due to thermal motion of electrons in the conductors. This effect, known as anomalous heating, is not fully understood. One of the open questions is the heating rate's dependence on the ion-electrode separation. We present a direct measurement of this dependence in an ion trap of simple planar geometry. The heating rates are determined by taking images of a single ^{172}Yb^{+} ion's resonance fluorescence after a variable heating time and deducing the trapped ion's temperature from measuring its average oscillation amplitude. Assuming a power law for the heating rate versus ion-surface separation dependence, an exponent of -3.79±0.12 is measured.


The paraganglia, a persisting endocrine system in man.
The paraganglia have been traced in surgical samples of para-aortic and pelvic retroperitoneal tissues using the formal-dehyde-induced fluorescence method for catecholamines. Clusters of catecholamine-storing cells were found in all (12) patients studied. Microspectrofluorometric recordings showed high amounts of catecholamine in the well-vascularized cell groups. A large proportion of the paraganglia, which are most prominent during the fetal period, also persist during postnatal life.


Psychostimulants induce low-frequency oscillations in the firing activity of dopamine neurons.
The reinforcing properties of psychostimulants depend critically on their effects on dopamine (DA) neurons in the ventral tegmental area (VTA). Using in vivo single unit recording in rats and spectral analysis, this study presents evidence for a new, non-DA-mediated effect of psychostimulants on VTA DA neurons. Thus, as previously observed with D-amphetamine, all psychostimulants tested, including cocaine, methamphetamine, and methylphenidate, had two opposing effects on firing rate of DA neurons: a DA-mediated inhibition and a non-DA-mediated excitation. The latter effect was normally masked by the DA-mediated inhibition and was revealed when the inhibition was blocked by a DA antagonist. Using spectral analysis, this study further showed that during psychostimulant-induced excitation, DA cells exhibited not only an increase in firing rate and bursting but also a low-frequency rhythmic oscillation (0.5-1.5 Hz) in their firing activity. The oscillatory response was unique to psychostimulants since it was not observed with the GABA(A) agonist muscimol, which also increased DA cell firing, and not mimicked by the nonpsychostimulant DA agonist L-dopa. Results further suggest that the effect requires activation of adrenergic alpha1 receptors and depends on intact forebrain inputs to DA neurons. Further understanding of this novel effect may provide important insights into both the mechanism of action of psychostimulants and the neuronal circuitry that controls the activity of DA neurons in the brain.


Facial Contour Features Measured on CT Reflects Upper Airway Morphology in Patients With OSA.
To determine facial contour features, measured on computed tomography (CT), related to upper airway morphology in patients with obstructive sleep apnea (OSA); certain phenotype of facial abnormalities implying restriction of craniofacial skeleton and adipose tissue nimiety has predicted the value of the severity of OSA. Sixty-four male patients with OSA [apnea-hypopnea index (AHI) ≥10/h] who had upper airway CT were randomly selected to quantitatively measure indicators of facial contour and upper airway structures. Pearson correlation analyses were performed. Partial correlation procedure was used to examine correlations while controlling body mass index (BMI). Upper airway anatomy can nearly all be reflected in the face, except retroglossal airway. Upper face width can be measured to assess the overall skeletal structures of the airway. Lower face width can be used to represent how much adipose tissue deposited. Hard palate, retropalatal, and hypopharyngeal airways have corresponding face indicators respectively. Midface width is a better predictor of AHI severity and minimum blood oxygen even than neck circumference because it contains the most anatomical information about the airway, including RP airway condition, soft palate length, tongue volume, etc. These correlations persisted even after correction for BMI. All anatomical features of the upper airway except retroglossal airway can be reflected in the face, and midface width is the best predictor of AHI severity and minimum blood oxygen, even better than neck circumference and BMI.


Interaction of vascular and bone disease in patients with normal renal function and patients undergoing dialysis.
The cardiovascular risk of patients undergoing dialysis is 20-30 times higher than that of individuals of the same age, without abnormal renal function, from the general population. Observational studies of patients with normal and abnormal renal function have shown that there is an association between bone disease, vascular calcification and cardiovascular outcome and that worsening of these conditions happens in parallel. Basic science studies are elucidating several mechanisms that could explain the interaction between bone disease, vascular calcification and cardiovascular outcome. For example, the expression of osteoprotegerin-a protein that regulates bone resorption by binding receptor activator of nuclear factor kappaB (RANK) ligand (RANKL), thus preventing interaction with the receptor RANK and the stimulation of osteoclast maturation-is regulated by several cytokines. Additionally, osteoprotegerin seems involved in the genesis of atherosclerosis. Imbalances of bone mineral metabolism, bone matrix secretion and vascular smooth-muscle-cell apoptosis seem involved in the ossification of the arterial wall in chronic kidney disease, and could explain some of the complex interactions between bone and vascular disease in renal failure. In this article we present a brief review of some of the basic mechanisms involved in vascular calcification and the clinical evidence of an association of vascular and bone disease.


The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific L-threonine aldolase that catalyzes cleavage of L-allo-threonine and L-threonine to glycine--expression of the gene in Escherichia coli and purification and characterization of the enzyme.
The GLY1 gene of Saccharomyces cerevisiae is required for the biosynthesis of glycine for cell growth [McNeil, J. B., McIntosh, E. V., Taylor, B. V., Zhang, F-R., Tang, S. & Bognar, A. L. (1994) J. Biol. Chem. 269, 9155-9165], but its gene product has not been identified. We have found that the GLY1 protein is similar in primary structure to L-allo-threonine aldolase of Aeromonas jandiae DK-39, which stereospecifically catalyzes the interconversion of L-allo-threonine and glycine. The GLY1 gene was amplified by PCR, with a designed ribosome-binding site, cloned into pUC118, and expressed in Escherichia coli cells. The enzyme was purified to homogeneity, as judged by polyacrylamide gel electrophoresis. The enzyme has a molecular mass of about 170 kDa and consists of four subunits identical in molecular mass. The enzyme contains 2 mol pyridoxal 5'-phosphate/4 mol of subunit as a cofactor, and its absorption spectrum exhibits maxima at 280 nm and 420 nm. The enzyme catalyzes the cleavage of not only L-allo-threonine to glycine but also L-threonine. We have termed the enzyme a low-specific L-threonine aldolase to distinguish it from L-allo-threonine aldolase.


Urethane-induced Mammary Carcinogenesis Susceptibility in Transgenic Mice Expressing a Dominant-negative TGF-β Type II Receptor.
Transforming growth factor-β (TGF-β) plays dual suppressive and oncogenic roles in mammary carcinogenesis. To analyze whether TGF-β exerts suppressive or oncogenic actions on mammary carcinogenesis, transgenic mice overexpressing a dominant-negative mutant type II TGF-β receptor (TβRII-DNR) driven by the mouse mammary tumor virus (MMTV) promoter were treated with a low dose of urethane, a carcinogen present in fermented food products and alcoholic beverages. Lobular proliferative lesions, showing high β-casein expression, developed in the mammary glands of TβRII-DNR+/+ mice aged >61 weeks. Compared with wild-type mice, TβRII-DNR+/+ mice administered with urethane showed significant increases in dysplastic hyperplasias and adenocarcinomas of the mammary glands. The functional decline of TGF-β signaling in mammary glands led to a high susceptibility to urethane-induced mammary carcinogenesis. TGF-β signaling may act as a tumor suppressor during mammary tumor development.


Tissue transglutaminase: from biological glue to cell survival cues.
Tissue transglutaminase (TG2, EC 188.8.131.52) is a ubiquitous enzyme that catalyzes Ca2+-dependent post-translational modification of proteins by inserting highly stable (epsilon-[gamma-glutamyl] lysine) isopeptide bonds or by conjugating polyamines at selected peptide-bound glutamine residues. The TG2-catalyzed cross-linked products (generally high molecular mass scaffold of proteins) are of great physiological significance; they are highly stable and resistant to mechanical, chemical and proteolytic degradation. The accumulation of isopeptide bonds can be observed in skin, hair and during blood clotting and wound healing. In addition to transamidation activity, TG2 also exhibits GTPase activity and in response to certain agonist hormones can serve as a signal transducing G protein. Although predominantly a cytosolic protein, TG2 can translocate to the nucleus with the help of importin alpha-3 protein or to the membranes in association with integrins. Moreover, TG2 can also be secreted outside the cell (by yet unknown mechanism) where it crosslinks proteins of the extracellular matrix (ECM) and promotes cell adhesion and spreading. Another important property of TG2 is that it has high binding-affinity for the ECM component protein, fibronectin and thus can promote interaction between cell surface integrin with fibronectin. In this review, we discuss the implications of increased TG2 expression in drug-resistant and metastatic cancer cells and that how TG2 expression can contribute in the development of these phenotypes.


Enhanced formation of aromatic amino acids increases fragrance without affecting flower longevity or pigmentation in Petunia × hybrida.
Purple Petunia × hybrida V26 plants accumulate fragrant benzenoid-phenylpropanoid molecules and anthocyanin pigments in their petals. These specialized metabolites are synthesized mainly from the aromatic amino acids phenylalanine. Here, we studied the profile of secondary metabolites of petunia plants, expressing a feedback-insensitive bacterial form of 3-deoxy-di-arabino-heptulosonate 7-phosphate synthase enzyme (AroG*) of the shikimate pathway, as a tool to stimulate the conversion of primary to secondary metabolism via the aromatic amino acids. We focused on specialized metabolites contributing to flower showy traits. The presence of AroG* protein led to increased aromatic amino acid levels in the leaves and high phenylalanine levels in the petals. In addition, the AroG* petals accumulated significantly higher levels of fragrant benzenoid-phenylpropanoid volatiles, without affecting the flowers' lifetime. In contrast, AroG* abundance had no effect on flavonoids and anthocyanins levels. The metabolic profile of all five AroG* lines was comparable, even though two lines produced the transgene in the leaves, but not in the petals. This implies that phenylalanine produced in leaves can be transported through the stem to the flowers and serve as a precursor for formation of fragrant metabolites. Dipping cut petunia stems in labelled phenylalanine solution resulted in production of labelled fragrant volatiles in the flowers. This study emphasizes further the potential of this metabolic engineering approach to stimulate the production of specialized metabolites and enhance the quality of various plant organs. Furthermore, transformation of vegetative tissues with AroG* is sufficient for induced production of specialized metabolites in organs such as the flowers.


Trough-to-peak ratio, smoothness index, and circadian blood pressure profile after treatment with once-daily fixed combination of losartan 100 and hydrochlorothiazide 25 in essential hypertension.
The once-daily fixed combination of losartan 100 mg/hydrochlorothiazide 25 mg was evaluated for safety and efficacy in a multicenter open study by using 24-h ambulatory blood pressure monitoring in untreated patients with moderate-to-severe essential hypertension or patients with uncontrolled hypertension despite treatment with monotherapy or low-dose combination. After a 2-week washout period, 41 patients (22 men, 19 women) aged 34-74 years, showing a mean daytime blood pressure > 135/85 mm Hg, were treated with losartan 100 mg/hydrochlorothiazide 25 for 8 weeks. Ambulatory blood pressure was monitored at the end of the washout period and during the last week of treatment. A significant reduction in the average values of clinic blood pressure (from 169.9 +/- 13.5 mm Hg to 139.5 +/- 15.6 mm Hg, p < 0.001 for systolic blood pressure [SBP]; and from 102.2 +/- 7.1 mm Hg to 85.1 +/- 9.5 mm Hg, p < 0.001 for diastolic blood pressure [DBP]) was observed after treatment in the whole group of 41 patients. Likewise, average values of both 24-h SBP and 24-h DBP were significantly reduced (from 145.7 +/- 13.1 mm Hg to 128.3 +/- 14.6 mm Hg, p < 0.001 for 24-h SBP; and from 90.3 +/- 7.3 mm Hg to 79.2 +/- 8.6 mm Hg, p < 0.001 for 24-h DBP). The average lowering at peak was 20.2 +/- 11.8 mm Hg for 24-h SBP and 12.1 +/- 7.4 mm Hg for 24-h DBP, whereas the lowering at trough was 17.8 +/- 12.0 mm Hg and 10.4 +/- 8.1 mm Hg, respectively. The trough-to-peak ratio (T/P) was 0.88 for SBP and 0.86 for DBP, and the smoothness index was 7.36 for SBP and 6.37 for DBP. The response rate was 87.8% (blood pressure lowering > 5 mm Hg of either 24-h SBP or 24-h DBP average values). Among responders, T/P ratio was 0.89 for SBP and 0.87 for DBP, and the smoothness index was 8.09 for SBP and 7.15 for DBP. No side effects or changes in metabolic parameters were observed. The fixed combination of losartan 100 mg/hydrochlorothiazide 25 was very effective and well tolerated.


Cytotoxic T-cell response to influenza A subunit vaccine in patients with type 1 diabetes mellitus.
The cytotoxic T-cell and humoral immune response to a commercially available influenza A-H1N1 subunit vaccine in 14 patients with type 1 diabetes mellitus was compared with the response in 13 healthy volunteers. Cytotoxic T-cell response to vaccination was poor in both patients and controls. At a calculated 50: 1 effector-target cell ratio, however, significantly more controls than patients showed an increase of over 5% cytotoxic T-cell mediated lysis after vaccination (P less than 0.05). In patients the cytotoxic T-cell response decreased with higher percentages of glycosylated haemoglobin (regression coefficient not equal to 0 with P less than 0.05). No significant difference was found between diabetic patients and control subjects with respect to antibody response after vaccination. Implications for vaccination strategy are discussed.


Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma.
Primary pulmonary mucinous adenocarcinoma (PPMA) is an uncommon subtype of lung adenocarcinoma. The present study attempted to clarify the diagnosis, clinicopathological characteristics, and pathologic significance of epithelial growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations and the prognosis of PPMA. A total of 29 patients with PPMA from among 1,469 surgically resected patients with lung adenocarcinoma were enrolled. All of the tumours expressed CK7 and 5 cases exhibited co-expression with CK20. A total of 8 cases expressed EGFR, 14 cases expressed P53 and 2 cases expressed CEA. The majority of mucinous adenocarcinomas expressed thyroid transcription factor 1, Napsin A, Villin and Cam5.2 proteins. KRAS mutations were observed in 62% of patients and were more prevalent in the lower lung lobe and in patients with invasive mucinous adenocarcinoma. A total of 2 cases exhibited an EGFR mutation, and the co-mutation of KRAS and EGFR was only detected in 1 case. The relapse-free and overall survival rates at 5 years were 70.4, and 81.5%, respectively. The results may assist to identify a molecular target and supply important information for a therapeutic strategy for patients with PPMA.


Statistical modeling of SARS-CoV-2 substitution processes: predicting the next variant.
We build statistical models to describe the substitution process in the SARS-CoV-2 as a function of explanatory factors describing the sequence, its function, and more. These models serve two different purposes: first, to gain knowledge about the evolutionary biology of the virus; and second, to predict future mutations in the virus, in particular, non-synonymous amino acid substitutions creating new variants. We use tens of thousands of publicly available SARS-CoV-2 sequences and consider tens of thousands of candidate models. Through a careful validation process, we confirm that our chosen models are indeed able to predict new amino acid substitutions: candidates ranked high by our model are eight times more likely to occur than random amino acid changes. We also show that named variants were highly ranked by our models before their appearance, emphasizing the value of our models for identifying likely variants and potentially utilizing this knowledge in vaccine design and other aspects of the ongoing battle against COVID-19.


Prostacyclin and analogues for acute ischaemic stroke.
Prostacyclin is an agent with a number of effects on platelets, blood vessels and nerve cells which might improve outcome after acute ischaemic stroke. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available, e.g. on completion of an appropriate study. The objective of this review was to assess the effect of prostacyclin or analogues on survival in people with acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999), Science Citation Index (1981 to 1999) and the Ottawa Stroke Trials Registry. We also contacted the manufacturers of prostacyclin and the principal investigators of the identified trials. Randomised trials comparing prostacyclin or analogues with placebo or control. Trials where people were entered within one week of stroke onset were included. Information on the methods of randomisation, blinding, analysis, the number of patients randomised, dose and timing of prostacyclin or analogue, patient withdrawals, the number of deaths occurring in each trial, and trial quality, were collected and assessed. Five trials involving 191 people were included. Six early deaths (within four weeks) occurred with prostacyclin, and nine with placebo (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.22 to 1.85). One trial of 32 patients reported late deaths (by 10 to 18 months) in 50% of patients in each group. Too few patients have been studied in randomised trials to allow conclusions to be drawn about the effect of prostacyclin treatment on survival of people with acute stroke.


[Polish Paediatric Leukaemia/Lymphoma Study Group - 25 years of activity].
In 1974, Professor Jerzy Armata initiated the organization of a multicentre cooperative group, which later became known as the Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG). At first the Group included three centres headed by Professor J. Armata (Cracow), Professor U. Radwanska (Poznan) and Professor J. Boguslawska-Jaworska (Wroclaw), but gradually it extended to nine university departments of paediatric hematologic oncology. Within the past 25 years, the introduction and employment of standardized, common treatment regimens based on our experience, as well as on the results of other oncological groups in Europe and the United States, resulted in a significant improvement of therapeutic results in childhood cancer, especially of the lymphatic and haematopoetic systems. The improvement in the recovery rates was as follows: in acute lymphoblastic leukaemia: from 25% to 84%, in non-Hodgkin's lymphoma recovery: from 28% to 82%, in Hodgkin's disease: from 80% to 90%. In acute non-lymphoblastic leukaemia the improvement in treatment results (from 15% to 40%) was also significant but still unsatisfactory.


Variants in DOK7 results in fetal akinesia deformation sequence: A case report and review of literature.
We report the third case of FADS due to biallelic DOK7 variants, which further strengthens the association of DOK7 with this lethal phenotype and lack of genotype phenotype correlation.


[Expert consensus on the clinical application of antibody drug conjugates in the treatment of malignant tumors (2023 edition)].
Antibody-drug conjugates (ADCs) are a class of targeted biological agents that link cytotoxic drugs to monoclonal antibodies through linkers. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. September 30, 2022, 14 anti-tumor ADC drugs have been approved for marketing in the world, and four ADCs have been approved in China. With the improvement of the clinical accessibility of ADC drugs, clinicians urgently need to understand the molecular characteristics and mechanisms of ADCs, and clarify the indications for rational use of drugs. Patients' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. In view of this, on the basis of the "Expert Consensus on the Clinical Application of Antibody-drug Conjugates for the Treatment of Malignant Tumors (2020 edition)" , Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti-Cancer Association fully combines the existing clinical research evidence and the feasibility of current ADC drugs in China to update the consensus content. This consensus aims to provide a systematic overview of ADC drugs, so as to provide practical and effective suggestions and references for clinicians to apply and manage ADC drugs more accurately.


Advancing taxonomy and bioinventories with DNA barcodes.
We use three examples-field and ecology-based inventories in Costa Rica and Papua New Guinea and a museum and taxonomic-based inventory of the moth family Geometridae-to demonstrate the use of DNA barcoding (a short sequence of the mitochondrial COI gene) in biodiversity inventories, from facilitating workflows of identification of freshly collected specimens from the field, to describing the overall diversity of megadiverse taxa from museum collections, and most importantly linking the fresh specimens, the general museum collections and historic type specimens. The process also flushes out unexpected sibling species hiding under long-applied scientific names, thereby clarifying and parsing previously mixed collateral data. The Barcode of Life Database has matured to an essential interactive platform for the multi-authored and multi-process collaboration. The BIN system of creating and tracking DNA sequence-based clusters as proxies for species has become a powerful way around some parts of the 'taxonomic impediment', especially in entomology, by providing fast but testable and tractable species hypotheses, tools for visualizing the distribution of those in time and space and an interim naming system for communication.This article is part of the themed issue 'From DNA barcodes to biomes'.


A statistical test for host-parasite coevolution.
A new method, ParaFit, has been developed to test the significance of a global hypothesis of coevolution between parasites and their hosts. Individual host-parasite association links can also be tested. The test statistics are functions of the host and parasite phylogenetic trees and of the set of host-parasite association links. Numerical simulations are used to show that the method has correct rate of type I error and good power except under extreme error conditions. An application to real data (pocket gophers and chewing lice) is presented.


RNA aptamers that reversibly bind photoresponsive azobenzene-containing peptides.
Modulation of biological networks assembled by diverse interactions among biologically active molecules has provided a platform for innovative biotechnologies. Here, we report RNA aptamers that bind to a photoresponsive peptide (KRAzR; Lys-Arg-azobenzene-Arg) containing azobenzene chromophore, which can change its structure by photoirradiation. Aptamers were identified after 10 cycles of an in vitro selection procedure starting with a DNA library containing a 70 nt random region. Surface plasmon resonance (SPR) analysis demonstrated that interactions between aptamers and KRAzR were fully controlled by appropriate photoirradiation to the SPR sensor chip. Upon irradiation of 360 nm on the KRAzR-immobilized surface, the binding of each aptamer to the surface was significantly decreased. Subsequent photoirradiation of the same surface with 430 nm restored the aptamer binding to the surface. We also observed that direct photoirradiation of the aptamer-peptide complex on a gold surface actively promoted dissociation of the complex. Furthermore, a doped reselection method was applied to acquire structural and sequence information of aptamer 66. From a data analysis of the conserved region and the mutation frequency, we were able to select a plausible secondary structure among three candidates predicted by computational folding simulation.


[Effect of oral appliance treatment on age-related changes of sleep respiratory function in patients with obstructive sleep apnea hypopnea syndrome].
Objective: The severity of obstructive sleep apnea hypopnea syndrome (OSAHS) has a tendency to increase with age. The purpose of this study was to explore whether oral appliance (OA) treatment can block this age-related change. Methods: This study was a retrospective study. Fifteen patients (12 males,3 females) of OSAHS treated with OA were selected as treatment group,with an average age of (47.44±10.00) years and initial body mass index (BMI) of (26.31±3.33) kg/m(2). The follow-up length was 54 [22, 100] months. Nineteen patients (13 males,6 females) with untreated OSAHS served as controls, with an average age of (45.00±9.26) years and initial BMI of (25.53±2.58) kg/m(2),and the follow-up length was 35 [26,63] months. There were no significant differences in terms of gender,age,initial BMI, apnea hypopnea index(AHI), and follow-up length between the two groups. Polysomnography(PSG) data for the two groups were compared to observe the sleep respiratory function changes as aging by Wilcoxon test. Results: There was no significant difference in BMI of the treatment group and the control group at the time of follow-up, with BMI of treatment group from (26.31±3.33) kg/m(2) to (25.67±3.65) kg/m(2),Z=-1.223,P=0.221; and BMI of control group from (25.53±2.58) kg/m(2) to (25.12±2.72) kg/m(2),Z=-1.193,P=0.233. There was no significant difference in the change of AHI within the treatment group, from 26.20 [11.50, 52.98]/h to 23.10 [16.00, 45.00]/h, Z=-0.284, P=0.776; AHI in the control group was higher than that at the first visit, and the AHI increased from 15.00 [10.72, 28.90]/h to 31.10 [13.00, 41.80]/h, Z=-3.481, P<0.001. The longest apnea duration was not statistically different in the treatment group, from 60.00 [56.40, 74.00] s to 63.00 [52.00, 77.00] s, Z=-0.345, P=0.730; the longest apnea duration in the control group increased from 42.00 [34.00, 56.70] s to 46.00 [37.00,62.00] s,Z=-2.274,P=0.023. There was no significant difference in the lowest blood oxygen saturation of the treatment group and the control group, with the treatment group from 72.47%±12.69% to 72.73%±17.59%, Z=-0.597, P=0.550; and the control group from 78.21%±9.30% to 76.42%±12.17%, Z=-0.153, P=0.879. Conclusion: Symptoms of sleep apnea in OSAHS patients tend to increase with age,and oral appliance treatment may have the effect of slowing down this age-related worsening effect.


Preliminary observations on the metabolic responses to exercise in humans, using 31-phosphorus nuclear magnetic resonance.
The new non-invasive method of 31P nuclear magnetic resonance (NMR) has been applied for the first time to human muscle. The metabolic response to exercise--a fall in intracellular pH, a fall in phosphocreatine content, and an increase in inorganic phosphate (Pi) content--occurs without any change in ATP content of the exercised muscle. Abnormal spectra occur in two myopathies examined to date: in McArdle's syndrome, pH rises during exercise, in contrast to the normal fall; and, in an unusual mitochondrial myopathy, Pi content is high, relative to phosphocreatine content, and in keeping with an excessive oxygen consumption in this patient. Intracellular pH reflected, in addition, the systemic pH of the subject; the anticipated abnormalities in muscle pH have been observed in association with lactic acidosis, renal failure and hyperventilation.


Classifying unknowns: the idiopathic problem.
The term, idiopathic, emerged as a key concept in the classification of disease in the 18th century and has become ingrained in our terminology in defining diseases and their aetiologies throughout all fields of medicine. Despite, or perhaps because of this, little has been written about the meaning or meanings of the word itself. Although most medical professionals will be able to offer a definition of idiopathic, different definitions of the word are in use and are often confused or used without an appreciation of the range of meanings. This article aims to clarify these different meanings with reference to historic and current uses. The change from the earlier nosological definition of 'primary' to the most widely accepted current definition, 'of unknown cause', occurred in the late 19th century, reflecting changing perspectives of disease causation. Far from being an innocent translation of 'unknown', idiopathic creates problems for future terminology and adds little to medical understanding. In masking the unknown, the term idiopathic maintains a paternalistic patient-practitioner relationship, and so should be avoided in modern medical terminology.


Corrosion Behavior and Mechanism of Basalt Fibers in Sodium Hydroxide Solution.
In this paper, the corrosion mechanism and tensile properties of basalt fibers in sodium hydroxide (NaOH) solution with various concentrations and temperatures were studied. The hydroxyl ions disrupt the ⁻Si⁻O⁻Si⁻ and ⁻Si⁻O⁻Al⁻ bonds leading to the formation of insoluble hydroxides. With the continuation of the hydration reaction, a hydration layer (corrosion shell) with high content of calcium, iron, manganese and titanium ions was formed on the fiber surface. The corrosion shell enabled an increase in the strength and elongation at break of basalt fibers, significantly. Results showed that the tensile strength of fibers was strongly dependent on temperature and concentration. After the basalt fibers were immersed in 1 mol/L NaOH solution at 50 °C for 1 h, 3 h, 6 h, 1 day and 3 days, their retention ratios of strength were 67.6%, 57.8%, 52.5%, 49.0%, 58.2%, respectively. Higher temperature accelerated the corrosion rate of basalt fibers, shortened the formation time of the corrosion shell and increased mass loss. From 25 to 70 °C, the mass loss of fibers increased from 2.4% to 33.8% for fibers immersed in 1 mol/L NaOH for 3 days. The experimental results from quantitative x-ray fluorescence (XRF) showed that the mass loss of basalt fibers was mainly due to the leaching of silicon, aluminum and potassium ions.


A primer on exocrine pancreatic insufficiency, fat malabsorption, and fatty acid abnormalities.
Exocrine pancreatic insufficiency (EPI) is characterized by a deficiency of exocrine pancreatic enzymes, resulting in deficits in digestion of all macronutrients, with deficiencies in digestion of fats being the most clinically relevant. The leading cause of EPI is chronic pancreatitis. However, many other causes and conditions may be implicated, including cystic fibrosis, pancreatic duct obstruction, gastric and pancreatic surgery, diabetes mellitus and other conditions. Physical and biochemical causes of EPI include decreased production and secretion of lipase, increased lipase destruction, pancreatic duct obstruction, decreased lipase stimulation and degradation, as well as gastrointestinal motility disorders. EPI is largely diagnosed clinically, and is often identified by symptoms such as steatorrhea, weight loss, abdominal discomfort, and abdominal bloating. Lifestyle modifications (eg, smoking cessation, limiting or avoiding alcoholic drinks, and reducing dietary fat intake) and exogenous pancreatic enzyme supplements are commonly used to help restore normal digestion and absorption of dietary nutrients in patients with EPI.


[The common issues of health policy in Russia concerning private system].
The article considers main principles of national policy specified in the constitution of the Russian Federation and other legislative acts concerning health care of population and development of private health care of Russia. The public policy intends wholeness and unity of national health care system and also state control of its functioning. All official documents and normative legislative acts relate to all sectors of national health care that substantiates unity of public policy. The important emphasis in actual policy is made on development of involvement of private sector in activities related to mandatory health insurance programs and implementation of various forms ofpublic-private partnership in health care. It is pointed out that omnipresent is delay of federal legislation from legislative base of regions, including its vagueness and incompleteness. The principle of self-regulation is described that is more and more implemented in private health care.


Commentary on "Applying CHW method to 2-in-1 design: gain or lose".
While 2-in-1 designs give a flexibility to make a clinical trial either an information generation Phase 2 trial or a full scale confirmatory Phase 3 trial, flexible sample size designs can naturally fit into the 2-in-1 design framework. This study is to show that the CHW design can be blended into a 2-in-1 design to improve the adaptive performance of the design. Commenting on the usual 2-in-1 design, we demonstrated that the CHW design can achieve the goal of a 2-in-1 design with satisfactory statistical power and efficient average sample size for a targeted range of the treatment effect.


In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive, and undifferentiated arthritis.
It has been reported that the mRNA of the type 1 cytokine, interferon-gamma (IFN-gamma)--but not the type 2 cytokine interleukin-4 (IL-4)--is detected in synovial tissues of rheumatoid arthritis (RA) patients, whereas both IFN-gamma and IL-4 mRNA are detected in reactive arthritis (ReA). To evaluate such data more extensively, we obtained 208 synovial specimens in a prospective study of 52 early synovitis patients (13 RA, 11 ReA, 28 undifferentiated oligoarthropathy) and analyzed type 1 and type 2 cytokine mRNA expression in specimens containing sufficient mRNA. Using a nested reverse transcriptase polymerase chain reaction technique, we measured the relative mRNA levels of 10 cytokines and CD3 delta chain. We detected IL-10, IL-15, and CD3 delta chain mRNA in all RA and ReA patients and frequently detected tumor necrosis factor-alpha, IL-1 beta, and IFN-gamma mRNA. IL-6 and IL-12 p40 mRNA were detected in approximately one-half of the patients. We also detected greater amounts of IL-2 and IFN-gamma mRNA in ReA than were detected in RA. However, we rarely detected IL-4 or IL-13 mRNA. Similar cytokine profiles were observed in undifferentiated oligoarthropathy. The amounts of cytokine mRNAs, except for IL-10, in specimens from the patients taking prednisone or second-line antirheumatic drugs tended to be less than in specimens from the patients taking neither prednisone nor second-line antirheumatic drugs. These results suggest that cytokine mRNA profiles in patients with RA, ReA, and undifferentiated arthritis in their early stages are skewed toward proinflammatory macrophage-derived and type 1 cytokines. IL-10--not IL-4 or IL-13--mRNA appears to be the major antiinflammatory cytokine mRNA. Drug therapy is associated with depressed proinflammatory and type 1 cytokine mRNA production. The differences in the expression of IL-2 and IFN-gamma mRNA between RA and ReA may reflect unique etiological or host factors associated with the early stages of these diseases.


Functionalization of 3D-printed titanium alloy orthopedic implants: a literature review.
Titanium alloy orthopedic implants produced by 3D printing combine the dual advantages of having a complex structure that cannot be manufactured by traditional techniques and the excellent physical and chemical properties of titanium and its alloys; they have been widely used in the field of orthopedics in recent years. The inherent porous structure of 3D-printed implants and the original modification processes for titanium alloys provide conditions for the functionalization of implants. To meet the needs of orthopedic surgeons and patients, functionalized implants with long-term stability and anti-infection or anti-tumor properties have been developed. The various methods of functionalization deserve to be summarized, compared and analyzed. Therefore, in this review, we will collect and discuss existing knowledge on the functionalization of 3D-printed titanium alloy orthopedic implants.


Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats.
Different effects of scopolamine on learning, memory, and nitric oxide (NO) metabolites in hippocampal tissues of ovariectomized (OVX) and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco) and OVX-Scopolamine (OVX-Sco) Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001). Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001), while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.


Degeneration of zonular fibrils in a case of exfoliation glaucoma.
We examined ultrastructurally zonules of the lens obtained from a patient with exfoliation glaucoma and lens dislocation. There was a great accumulation of exfoliation materials adjacent to and within degenerated zonules, and a gradual transition between zonular fibrils and exfoliation materials was observed. The initial change in the zonular fibrils was a loss of their regularity, next we could see fine granules deposited on degenerated zonular fibrils. A sparse and irregular deposition was found on the surface of the fibrils. Subsequently, the deposition became increased, and densely stained exfoliation materials, which were composed of a single degenerated zonular fibril and fine granules, were formed. Several fibrils accompanied by fine granules clustered together and became exfoliation materials of larger diameter. These observations suggest that degenerated zonular fibrils may develop into exfoliation materials.


Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.
Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics.


[Characteristics of non-tuberculous Mycobacterium -- pathogens of diseases in man].
The paper characterizes nontuberculosis mycobacteria (NTMB) by their species, shows the structure of mycobacteriasis pathogens, drug sensibility in NTMB and the degree of their virulence for laboratory animals. The specific proportion of NTMB is Mycobacterium avium (50.8%). A total of 136 cases of mycobacterium infection were examined. As high as 20.7% of isolates from mycobacteriasis patients have been found to have a high natural resistance to most antibacterial drugs. A combination of kanamycin, ethionamide, and ethambutol is the most effective in the treatment, additionally aminoglucosides--amikacin, gentamicin, sulfamides, such as biseptol, sulfadimethoxin, as well as the quinolones ciptobay and tarivid.


Recidivism and drug use among school-age children.
This paper is the result of an investigation of recidivism rates among teenaged children who completed a program designed to improve communication between the children and their parents. A sample of 62 children from 13 to 18 years old was utilized. All had been referred to a mental health program by juvenile courts for therapeutic intervention because of drug offenses. The intervention program stressed family communication and communication techniques and required both the child and parents to attend. Three types of rates of recidivism were then obtained from juvenile court records for each sample member including all referrals, adjusted referrals, (excluding such referrals for truancy, fighting, traffic offenses, etc.), and those referrals for drug offenses only. These were analyzed for both pre- and post- intervention length of time. Analysis of data revealed significant (p v .001) decrease for all three categories of referral. Notable was that the recidivism rate for drug offenses declined significantly. While this data is encouraging some considerations are necessary. First, the degree of experimental control was limited. The use of a control group would perhaps have been beneficial. Secondly, one must consider the effect of the "arrest experience" and its relationship to learning how to avoid getting caught for the same offense twice. This could be examined further if the pre- and post-intervention periods could be lengthened. A final consideration would be the effect of other intervention programs on recidivism. since many of the children were receiving more than one type of therapy. The question of which intervention program most effected the decline of recidivism would have to be answered before one could accept the conclusion that the communication program was indeed responsible for the significant decrease in recidivism.


Competency-Based Framework and Continuing Education for Preparing a Skilled School Health Workforce for Asthma Care: The Colorado Experience.
School health teams commonly address the needs of students with asthma, which requires specific knowledge and skills. To develop a skilled school health team, a competency-based framework for managing asthma in schools was developed. A modified Delphi with 31 panelists was completed. Consensus (≥80% agreement) was reached for all 148 items regarding the appropriateness as a minimum competency for asthma care in schools. The resultant Colorado Competency Framework for Asthma Care in Schools guided the development and pilot testing of a continuing education curriculum for school nurses. Pre- and postassessments demonstrated significant improvements in knowledge and self-confidence related to asthma care in schools and inhaler technique skills. This work is the first to use a consensus process to identify a framework of minimum competencies for providing asthma care in schools. This framework informed a continuing education curriculum that resulted in improved knowledge, confidence, and skills for school nurses.


Narrative Production in Arabic-speaking Adolescents with and without Hearing Loss.
The present study investigated oral personal narratives elicited from Arabic speaking adolescents with and without hearing loss. Analyses focused on macrostructure, microstructure, and Modern Standard Arabic (MSA). For macrostructure, narratives were examined for structural components (abstract, orientation, complication, evaluation, resolution, and coda) and narrative patterns: classic (a high point followed by a resolution), high point ending, chronological, and leap frogging (jumps from one event to another). Microstructure included morpho-syntactic errors and complex sentences. MSA features were lexis and syntax. The narratives of adolescents with hearing loss tended to lack an evaluation component (expressing the narrator's perspective), contained more morpho-syntactic errors, fewer complex sentences, and fewer expressions of MSA than narratives of their hearing peers. Findings are discussed in terms of dissociation between macrostructure and microstructure in an attempt to shed light on those features of narrative which might benefit clinicians and educators working with Arabic speaking adolescents with hearing loss.


Asymmetric Synthesis of a Bacteriochlorophyll Model Compound Containing trans-Dialkyl Substituents in Ring D.
Challenges to the de novo synthesis of bacteriochlorophyll a (BChl a), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans-dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle (BC-1), which contains a trans-dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2S,3S)-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans-dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E-enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans-dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 132-carbomethoxy substituent. The strategy wherein trans-dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.


Rigorous Bounds on Transport from Causality.
We use causality to derive a number of simple and universal constraints on dispersion relations, which describe the location of singularities of retarded two-point functions in relativistic quantum field theories. We prove that all causal dissipative dispersion relations have a finite radius of convergence in cases where stochastic fluctuations are negligible. We then give two-sided bounds on all transport coefficients in units of this radius, including an upper bound on diffusivity.


Exercise and the Microbiome: Mechanistic Perspectives of the Impact of Exercise on the Gut-Vascular Axis.
Given the participation of the microbiome in human health and disease, understanding the context of host-microbe interactions involved in vascular pathophysiology is now evolving through identifying microbial communities, specific taxa, and metabolic profiling which can be coupled to human health outcomes. Exercise has been used to define mechanisms related to improved vascular health, which may involve the microbiome. Motivated by the clinical significance that both exercise and the gut microbiome have; the objective of our work is to assist in defining the gut-vascular axis while identifying biomarkers of gut microbial health linked to vascular function. In this commentary, we will provide context to the mechanistic perspectives of exercise-induced improvements in gut microbial characteristics coupled to vascular health outcomes and offer insight on necessary future prospective investigations.


[The value of resection in pancreatic cancer: the analysis of an experience of 180 patients in 10 years].
Pancreatic cancer (PC) represents one of the most severe malignant diseases, with an extremely high mortality rate (80% in the first year following diagnosis). The only potentially curative treatment is resection. This report evaluates the last 10-year experience in surgical resection for pancreatic cancer in the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest--Romania), between 01.01.1995-01.05.2004. From a total of 832 patients with pancreatic cancer who were surgically treated, 180 underwent various resections (a resecability rate of 21.6%). There were 120 resections for cancer of the pancreatic head: 61 Whipple procedures, 10 pilorus preserving pancreaticoduodenectomies, 10 pancreaticoduodenectomies associated with complex resection, 17 pancreaticoduodenectomies with resection of the portal vein, 15 pancreaticoduodenectomies with extensive lymphodissection, 2 subtotal pancreatectomies and 5 total pancreatectomies; 60 standard splenopancreatectomies were performed for cancer of the pancreatic tail. The overall morbidity was 34%--61 patients (38 with cancer of the pancreatic head and 23 with pancreatic cancer of the tail), with the prevalent complication represented by pancreatic fistula. The mortality rate was 6.6%--12 patients (9 with cancer of the pancreatic head and 3 with cancer of the tail); there was a continuous decreasing trend from 9.1% between 1994-1999 to 1.6% between 2002-2004. In our Center an increasing preoccupation for pancreatic surgery, along with an improved surgical experience, resulted in a constant raise in the number of patients resected for pancreatic cancer, with a low morbidity and mortality rate.


Anti-gliadin and anti-endomysium antibodies in children with celiac disease consuming a gluten free diet.
A group of 26 children (13 boys and 13 girls; average age 12.2 years) with CD who had been on a gluten free diet for 5-15 years was examined in order to find out how effectively they could manage their diet. The diagnosis of CD was established on the basis of ESPGAN criteria (1969). 5-15 years ago. Antigliadin antibodies, IgG-, and IgA-AGA (by fluorescence enzyme immunoassay), Gliastick by ELISA technique, and Anti-endomysium antibodies (by indirect immunofluorescence on sections of monkey esophagus) were examined in the serum. Only 5 patients had no antigliadin or anti-endomysium antibodies. In 21 cases the IgG-AGA showed positive results; the IgA-AGA was positive in 6, the Gliastick in 19, and the anti-endomysium antibodies in 8 cases. The main cause of the mismanagement of the diet was inadequate food labeling; so it seems to be important to also establish a Food Intolerance Data Bank in Hungary. The 5 sero-negative children volunteered for a gluten challenge; 3 of them became positive in a few weeks or months. Two patients remained negative even after 1 year. Their gluten sensitivity may not prove to be permanent.


Involvement of RhoA/ROCK1 signaling pathway in hyperglycemia-induced microvascular endothelial dysfunction in diabetic retinopathy.
Diabetic retinopathy (DR) is a well-known serious complication of diabetes mellitus (DM), and can eventually advance to end-stage blindness. In the early stage of DR, endothelial cell barrier disorganized primarily and tight junction (TJ) protein composition transformed subsequently. The small GTPase RhoA and its downstream effector Rho-associated coiled-coil containing protein kinase 1 (ROCK1) regulate a mass of cellular processes, including cell adherence, proliferation, permeability and apoptosis. Although RhoA inhibitors have provided substantial clinical benefit as hypertonicity therapeutics, their use is limited by complex microenvironment as DR. While ample evidence indicates that TJ can be influenced by the RhoA/ROCK1 signaling, the underlying mechanisms remain incompletely understood. Here, we have uncovered a significant signaling network involved in diabetic retinal microvascular endothelial dysfunction (RMVED). Our results indicated that the activation of RhoA/ROCK1 pathway due to high glucose played a key role in microvascular endothelial cell dysfunction (MVED) by way of directly inducing TJ proteins over-expression during DR. We demonstrated that inhibition of RhoA/ROCK1 may attenuate the hypertonicity of endothelial cell caused by high glucose microenvironment meanwhile. Besides, chemical and pharmacological inhibitors of RhoA/ROCK1 pathway may partly block inflammation due to DR. Simultaneously, the apoptosis aroused by high glucose was also prevented considerably by fasudil, a kind of pharmacological inhibitor of RhoA/ROCK1 pathway. These findings indicate that RhoA/ROCK1 signaling directly modulates MVED, suggesting a novel therapeutic target for DR.