HPLC and chemometrics for the quality consistency evaluation of Shuanghuanglian injection.
A high-performance liquid chromatography method with diode array detection was developed for simultaneous analysis of organic acids (chlorogenic acid, caffeic acid, 4,5-dicaffeoylquinic acid) and flavonoids (baicalin, baicalein, wogonin) in Shuang-huang-lian injection, a traditional Chinese medicine being prescribed widely for anti-bacterial, anti-viral and immunostimulant activity. All calibration curves showed good linear correlation (r(2) > 0.9997) within the test ranges. Validation proved that the repeatability of the method was good and recovery was satisfactory. The validated method was successfully applied to 24 batches of Shuang-huang-lian injection. The result showed that there was a great variation among different samples. Principal component analysis further proved considerable variations among the samples from eight manufacturers, and suggested that chlorogenic acid and baicalin might have the greatest variations among the 24 batches. In conclusion, these results demonstrated that the method proposed was very useful for the analysis and quality consistency evaluation of Shuang-huang-lian injection.


Solute-solvent contact by intermolecular cross-relaxation. 2. The water-micelle interface and the micellar interior.
The intermolecular dipole-dipole cross-relaxation is measured between 19F nuclei of sodium perfluorooctanoate in micelles and 1H nuclei of the water solvent. The cross-relaxation rates for fluorines in the different moieties along the surfactant vary strongly by the resonance frequency in the investigated range of 188-470 MHz. This frequency dependence indicates that the cross-relaxation between water and amphiphilic aggregates is not controlled solely by the fast local water dynamics but significantly contributed to by the long-range translational diffusion of water. The cross-relaxation rates, analyzed in the framework of a model (Nordstierna, L.; Yushmanov, P. V.; Furó, I. J. Chem. Phys. 2006, 125, 074704), provide information about the dynamic retardation of water molecules by the micellar headgroup region and the location of the various moieties along the hydrophobic tail with respect to the water-micelle interface. Both intermolecular cross-relaxation and aggregation-induced 19F chemical shift changes indicate no direct water contact to fluorines except for those closest to the head group.


Nocturnal eating is part of the clinical spectrum of restless legs syndrome and an underestimated risk factor for increased body mass index.
We aimed to investigate the prevalence of night eating syndrome (NES) in a large cohort of patients with restless legs syndrome (RLS). Our cross-sectional study included 120 patients examined at the University of Bologna Centre for Sleep Disorders, Bologna, Italy, and met all four International RLS criteria for the diagnosis of RLS. Each patient underwent a semistructured telephone interview investigating demographic data and general health status, RLS features and severity, presence of excessive daytime sleepiness, and presence of NES. The sample included 37 men and 83 women with a mean age of 63.8±11.5 years. There were 31% of patients who reported episodes of nocturnal eating (NE); among them, 17% fulfilled the new diagnostic criteria for NES. Comparing RLS patients with and without NE, there were no differences in RLS features. However, RLS patients with NE were older (67.2±11.6 vs. 62.4±11; P=.038), were in a higher body mass index (BMI) range (27.7±3.8 vs. 26.1±4.1 kg/m2; P=.023), were taking more drugs for concomitant diseases (89% vs. 72%; P=.031), were more likely to report insomnia (40% vs. 23%; P=.041), and were using more hypnotic agents (37.8% vs. 19.3%; P=.050) and dopaminergic drugs (65% vs. 46%; P=.041). When comparing those RLS patients with NES diagnostic criteria and those without NES, no differences emerged in demographic, clinical, and RLS features; however, NES patients were in a higher BMI range (28.3±4.1 vs. 26.2±3.9kg/m(2), P=.037), were more frequently smokers (43% vs 17%; P=.027), and were more frequently using hypnotic agents (30% vs. 24%; P=.025). Lastly, no differences were found when comparing patients with a NES diagnosis and those with NE not fitting the diagnostic criteria for NES, except for a higher use of benzodiazepine drugs (BDZ) in this latter subgroup (29% vs. zero; P=.014). A nocturnal compulsion to eat seems to be an intrinsic part of the clinical spectrum of RLS manifestations and an odd risk factor for increases in BMI in RLS patients. However, it is still not clear if NE in RLS would fit in one of the two known categorized syndromes of NE (i.e., sleep-related eating disorder [SRED] or NES) or if it represents a different strictly RLS-related eating behavior.


Metallothioneins 2 and 3 contribute to the metal-adapted phenotype but are not directly linked to Zn accumulation in the metal hyperaccumulator, Thlaspi caerulescens.
To study the role of metallothioneins (MTs) in Zn accumulation, the expression of TcMT2a, TcMT2b, and TcMT3 was analysed in three accessions and 15 F(3) families of two inter-accession crosses of the Cd/Zn hyperaccumulator Thlaspi caerulescens, with different degrees of Zn accumulation. The highest expression levels were found in the shoots of a superior metal-accumulating calamine accession from St Laurent le Minier, with >10-fold TcMT3 expression compared with another calamine accession and a non-metallicolous accession. Moreover, F(3) sibling lines from the inter-accession crosses that harboured the MT2a or MT3 allele from St Laurent le Minier had higher expression levels. However, there was no co-segregation of TcMT2a or TcMT3 expression and Zn accumulation. To examine the functions of TcMTs in plants, TcMT2a and TcMT3 were ectopically expressed in Arabidopsis. The transformant lines had reduced root length in control medium but not at high metal concentrations, suggesting that the ectopically expressed proteins interfered with the physiological availability of essential metals under limited supply. The Arabidopsis transformant lines did not show increased tolerance to Cd, Cu, or Zn, nor increased Cd or Zn accumulation. Immunohistochemical analysis indicated that in roots, MT2 protein is localized in the epidermis and root hairs of both T. caerulescens and Arabidopsis thaliana. The results suggest that TcMT2a, TcMT2b, and TcMT3 are not primarily involved in Zn accumulation as such. However, the elevated expression levels in the metallicolous accessions suggests that they do contribute to the metal-adapted phenotype, possibly through improving Cu homeostasis at high Zn and Cd body burdens. Alternatively, they might function as hypostatic enhancers of Zn or Cd tolerance.


[Safety and efficacy of total dose intravenous iron infusion in the treatment of iron-deficiency anemia in adult non-pregnant patients].
Iron deficiency anemia (IDA) has a prevalence of 20-24.5% in Mexico, which is similar to other developing countries. Although the treatment of choice is oral iron therapy, several factors limit its efficacy. Intravenous administration of iron-dextran is an effective method that has been evaluated in pregnant women, children and renal patients and there are some studies demonstrating its safety in these groups. We carried out a prospective, longitudinal, uncontrolled clinical trial to evaluate the safety and efficacy of total-dose intravenous iron infusion in the treatment of IDA in adult, non-pregnant patients. Forty-seven patients (8 male, 39 female) with anemia and iron deficiency were included in the study. Iron deficit was calculated and a total dose iron infusion was administered intravenously diluted in normal saline over 4 hours. CBC were obtained at 2-week intervals until week 8 post-infusion. The percentage of hematocrit correction was calculated at week 8 post-infusion. Baseline hemoglobin values were 78 +/- 17.2 for the whole group, 85 +/- 20.4 for men and 78 +/- 16.7 g/L for women. At week 8 values were 134 +/- 10.7, 138 +/- 9.8 and 134 +/- 10.8 g/L for the whole group, men and women, respectively. Baseline hematocrit values were 0.27 +/- 0.05 for the whole group, 0.29 +/- 0.06 for men and 0.27 +/- 0.05 for women. At week 8 values were 0.42 +/- 0.03, 0.43 +/- 0.03 and 0.42 +/- 0.03 for the whole group, men and women, respectively. The percentage of hematocrit correction was 51.5 +/- 28.6 at week 2 and 80.3 +/- 21.3 at week 8. Thirty-two percent of patients developed adverse reactions, all but one being mild. We confirmed that total-dose iron infusion is a safe and effective method to treat IDA that may be used in patients with intolerance to oral iron or in patients with failure to other iron schedules, as well as initial therapy in selected cases. Besides it provides a swift correction of hematocrit allowing, in some cases, to perform elective surgery without the need of blood transfusion.


Quality of Patient Education Materials on Safe Opioid Management in the Acute Perioperative Period: What Do Patients Find Online?
Guidelines on postoperative pain management recommend inclusion of patient and caregiver education on opioid safety. Patient education materials (PEMs) should be written at or below a sixth grade reading level. We designed this study to compare the readability of online PEMs related to postoperative opioid management produced by institutions with and without a regional anesthesiology and acute pain medicine (RAAPM) fellowship. With institutional review board exemption, we constructed our cohort of PEMs by searching RAAPM fellowship websites from North American academic medical centers and identified additional websites using structured Internet searches. Readability metrics were calculated from PEMs using the TextStat 0.4.1 textual analysis package for Python 2.7. The primary outcome was the Flesch-Kincaid Grade Level (FKGL), a score based on words per sentence and syllables per word. We also compared fellowship-based and nonfellowship PEMs on the presence or absence of specific content-related items. PEMs from 15 fellowship and 23 nonfellowship institutions were included. The mean (SD) FKGL for PEMs was grade 7.84 (1.98) compared with the recommended sixth grade level (P < 0.001) and was not different between groups. Less than half of online PEMs contained explicit discussion of opioid tapering or cessation. Disposal and overdose risk were addressed more often by nonfellowship PEMs. Available online PEMs related to opioid management are beyond the recommended reading level, but readability metrics for online PEMs do not differ between fellowship and nonfellowship groups. More than two-thirds of RAAPM fellowship programs in North America are lacking readable online PEMs on safe postoperative opioid management.


The spatial unmasking of speech: evidence for better-ear listening.
Speech reception thresholds (SRTs) were measured for target speech presented concurrently with interfering speech (spoken by a different speaker). In experiment 1, the target and interferer were divided spectrally into high- and low-frequency bands and presented over headphones in three conditions: monaural, dichotic (target and interferer to different ears), and swapped (the low-frequency target band and the high-frequency interferer band were presented to one ear, while the high-frequency target band and the low-frequency interferer band were presented to the other ear). SRTs were highest in the monaural condition and lowest in the dichotic condition; SRTs in the swapped condition were intermediate. In experiment 2, two new conditions were devised such that one target band was presented in isolation to one ear while the other band was presented at the other ear with the interferer. The pattern of SRTs observed in experiment 2 suggests that performance in the swapped condition reflects the intelligibility of the target frequency bands at just one ear; the auditory system appears unable to exploit advantageous target-to-interferer ratios at different ears when segregating target speech from a competing speech interferer.


Significance of Quantitative Interferon-gamma Levels in Non-small-cell Lung Cancer Patients' Response to Immune Checkpoint Inhibitors.
We aimed to study the association between the quantitative interferon-gamma (IFN-γ) levels and clinical outcomes in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Sample collection for IFN-γ release assay (IGRA) was performed within 14 days before treatment (T1), on day 22±7 (T3), and on day 43±7 (T4). The stored specimens over 10 IU/ml in IGRA were re-examined using the dilution method (with saline as the dilution medium). The patients were classified into Lower and Higher groups by 7.06 IU/ml as a cut-off of IFN-γ levels at T1. Median progression-free survival in the Higher group was significantly longer than that in the Lower group. IFN-γ levels in the non-progression disease group were significantly higher than those in the progression disease group. IFN-γ levels at T1 in patients with immune-related adverse events were significantly lower compared to those at T3. IFN-γ could be a biomarker for NSCLC patients receiving ICIs.


The chromosome glue gets a little stickier.
Since their discovery, the cohesin proteins have been intensely studied in multiple model systems to determine the mechanism of chromosome cohesion. Recent studies have demonstrated that cohesin is much more than a molecular glue that holds chromosomes together in mitosis. Indeed, cohesin performs critical roles in gene regulation, possibly through the formation of higher-order chromatin structure. Moreover, this newly appreciated role is necessary for proper development in metazoan species, with mutations in the cohesin pathway resulting in human developmental disorders.


Development of clinical sign based algorithms for community based assessment of omphalitis.
In developing countries, newborn omphalitis contributes significantly to morbidity and mortality. Community based identification and management of omphalitis will require standardised clinical sign based definitions. To identify optimal sign based algorithms to define omphalitis in the community and to evaluate the reliability and validity of cord assessments by non-specialist health workers for clinical signs of omphalitis. Within a trial of the impact of topical antiseptics on umbilical cord infection in rural Nepal, digital images of the umbilical cord were collected. Workers responsible for in-home examinations of the umbilical cord evaluated the images for signs of infection (pus, redness, swelling). Intraworker and interworker agreement was evaluated, and sensitivity and specificity compared with a physician generated gold standard ranking were estimated. Sensitivity and specificity of worker evaluations were high for pus (90% and 96% respectively) and moderate for redness (57% and 95% respectively). Swelling was the least reliably identified sign. Measures of observer agreement were similar to that previously recorded between experts evaluating subjective skin conditions. A composite definition for omphalitis that combined pus and redness without regard to swelling was the most sensitive and specific. Two sign based algorithms for defining omphalitis are recommended for use in the community. Focusing on redness extending to the skin around the base of the stump will identify cases of moderate and high severity. Requiring both the presence of pus and redness will result in a definition with very high specificity and moderate to high sensitivity.


[Sites of prolactin inhibition on gonadotropin-induced estrogen production in cultured rat granulosa cells].
We studied the sites of prolactin inhibition upon FSH-iniduced ovarian steroidogenesis and the ability of prolactin (Prl) to inhibit the synthesis of estradiol and cAMP accumulation under the stimulation of FSH or cAMP-dependent activators. The participation of other signal pathways such as PKC and Gi proteins on the inhibitory actions of Prl was also investigated using calfostine C and pertusis toxin as inhibitors. Results showed a dose-dependent prolactin decrease in FSH-induced estradiol and cAMP production prior and after the generation of the cyclic nucleotide by a mechanisn involving the catalytic subunit of adeniyl cyclase and/or through activation of PKC or by the interaction with pertusin toxin-sensitive G proteins. Our results suggest a mechanism by which G protein-coupled receptors are linked with those coupled with tyrosine kinase through the involvement of a Gi protein mediated mechanism.


Hand preference in the use and manufacture of tools by tufted capuchin (Cebus apella) and lion-tailed macaque (Macaca silenus) monkeys.
The purpose of this study was to examine hand preference in the use and manufacture of probing tools by tufted capuchin and lion-tailed macaque monkeys (Cebus apella and Macaca silenus). Hand preference for the tool-using sequence was noted in 4 of 5 capuchins (a left-hand preference was noted in 3 ss) and 3 of 4 macaques (a left-hand preference was noted in 2 ss). The monkeys frequently used bimanual action in the initial and final segments of the 3-component task and typically modified tools through coordinated action of the hands and teeth. These data provide evidence consistent with the hypotheses that (a) hemisphere specialization for manual control evolved in primates prior to intensive use of tools by early hominids and (b) monkeys prefer the left hand for precise, visually guided, manipulative actions.


The multicomponent meningococcal serogroup B vaccine (4CMenB): origin, composition, health impact and unknown aspects.
Neisseria meningitidis serogroup B is the main cause for meningococcal invasive disease in many parts of the world. Since 2013, a new multicomponent vaccine against meningococcal serogroup B (4CMenB) has been licensed in Europe, Australia, Canada, Chile, Uruguay, USA and Brazil with different immunization schedules. Clinical trials involving adults, adolescents, children and infants showed 4CMenB has a good immunogenicity and safety profile. Strain coverage estimates are similar to or better than other recently approved vaccines, ranging from 66% in Canada to 91% in Unites States. Some points still remain to be clarified such as the best immunization strategy, the effect of 4CMenB on carriage, the long-term persistence of protective bactericidal antibodies titers, long-term safety outcomes, the possible emergence of N. meningitidis escape mutants and the vaccine cost-effectiveness. In this review, we focus on the vaccine composition, clinical trials and suggested schedules, safety data, potential strain coverage and future challenges.


Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema.
Smoking is a common risk factor for both chronic obstructive pulmonary disease (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor for vertebral fracture; however, the effects of smoking or emphysema on bone health remain largely unknown. We report bone deterioration in a mouse model of emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short-term exposure for 4-weeks decreased bone turnover and increased bone volume in mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from suppression to promotion of bone resorption. This long-term CS exposure increased osteoclast number and impaired bone growth, while it increased bone volume. Strikingly, long-term CS exposure deteriorated bone quality of the lumbar vertebrae as illustrated by disorientation of collagen fibers and the biological apatite c-axis. This animal model may provide a better understanding of the mechanisms underlying the deterioration of bone quality in pulmonary emphysema caused by smoking.


The level of non-Western immigrants' use of acute psychiatric care compared with ethnic Norwegians over an 8-year period.
Immigrants are assumed by many to have more mental health problems than the population in the countries they have emigrated to, and clinicians have the impression that an increasing number of non-Western immigrants are referred to acute psychiatric care. Patients referred over an 8-year period to an acute care facility, responsible for a catchment area of close to 100,000 inhabitants in Oslo, Norway, were scrutinized to study the latter assumption. In total 792 men and 701 women (47.0%) were referred. There were 168 men and 59 women among the non-Western immigrants, i.e. 26.0% of the non-Western immigrants were women, whereas 50.2% or 611 out of 1217 ethnic Norwegians were women. Non-Western immigrants were referred twice as often in 2007, n=40, as in 2000, n=19. Non-Western immigrants as a percentage of the other referred patients increased from 15.2% to 16.0% in 2006, which was lower than the representation in the general population. Mean age was lower for non-Western immigrants, 34.6 (standard deviation, s=14.7) than for ethnic Norwegians 39.5 (s=11.6). Mean length of stay was lower for ethnic Norwegians. If the prevalence of mental disorders is the same or higher in immigrants than in the original population, this study indicates that they are under-represented among referred patients from the catchment area population. This seems to be the case especially for women.


Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene.
A cDNA clone for the histamine H1 receptor was isolated from a human lung cDNA library; it encoded a protein of 487 amino acids which showed characteristic features of G-protein-coupled receptors. The percentages of identity of the deduced amino acid sequence with bovine, rat and guinea pig H1 histamine receptors were 82.6%, 79.4% and 73.3%, respectively, whereas these percentages decreased to 74.6%, 66% and 56.7% for the amino acid sequence of the third intracellular loop. The human H1-receptor cDNA was transfected into Chinese hamster ovary cells (CHO) via an eukaryotic expression vector; the receptor protein present on cell membranes specifically bound [3H]mepyramine with a Kd of 3.7 nM. The binding was displaced by H1-histamine-receptor antagonists and histamine. Northern blot analysis indicated the presence of two histamine H1 receptor mRNAs of 3.5 kb and 4.1 kb in various human tissues and an additional mRNA of 4.8 kb restricted to the human brain. Finally, by means of somatic cell hybrids segregating either human or rat chromosomes, the gene for histamine H1 receptor was found to reside on human chromosome 3 and rat chromosome 4.


Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus.
Defining the mechanism for the vaccine-enhanced illness associated with respiratory syncytial virus (RSV) is critical for advancing RSV vaccine development. Previous studies in which infants were vaccinated with formalin-inactivated alum-precipitated whole virus did not protect from RSV infection, and those infected had a high incidence of severe illness. In contrast, previous clinical trials evaluating live attenuated RSV showed no associated vaccine-enhanced illness. We have used a mouse model to explore the immunopathogenesis of RSV infection. In this study cytokine mRNA expression was examined using 32P-labeled oligonucleotide probes in Northern blot analyses of polyA RNA extracted from lungs of mice primed with various vaccine preparations then challenged nasally with live RSV. We have shown that upon challenge, priming of mice with inactivated virus or subunit F glycoprotein induced a pattern of cytokine mRNA expression suggesting a dominant Th2-like lymphocyte response (relative increase in IL-4 mRNA expression). In contrast, challenge of mice primed with live RSV by parenteral or mucosal routes induced a Th1-like pattern of cytokine mRNA expression (relative decrease in IL-4 mRNA expression compared to IFN-gamma mRNA expression). Thus, the formulation and route of delivery of vaccine products can influence the pattern of cytokine expression in lung upon RSV challenge.


Swallowing function after occipitocervical arthrodesis for cervical deformity in patients with rheumatoid arthritis.
Some patients develop dysphagia after OC arthrodesis with RA. A previous report has indicated that establishing appropriate occipito-C2 is important for avoiding these side effects. However, a more recent report has demonstrated that the O-C2 angle did not have a significant effect on the incidence of postoperative dysphagia. To investigate the swallowing function of patients with rheumatoid arthritis (RA) before and after they underwent occipitocervical (OC) fusion. The study was performed in collaboration with the Departments of Orthopaedic, Otorhinolaryngology, and Rehabilitation. Seven consecutive patients (3 men and 4 women; mean age, 66.4 years) with RA-induced upper cervical deformity were enrolled from 2013 to 2014. The patients underwent deglutition analysis, which was performed by otorhinolaryngologists, before and after surgery, and comprised videofluoroscopy and fiberoptic endoscopy. We examined the relationship between imaging studies and swallowing function. Preoperatively, subjective dysphagia was reported by 2 patients. Videofluoroscopy identified dysmotility of the epiglottis and incomplete closure of the laryngeal inlet in 2 patients, with contrast medium entering the larynx, and endoscopy identified food residue in the larynx of 1 patient during swallowing evaluation. Postoperatively, 2 patients with preoperative impaired deglutition showed dysphagia. Imaging examinations of the 2 patients revealed a 10°-reduction in the O-C2 angle of 1 patient, but the angle was unchanged in the other patient. To the best of our knowledge, this is the first report to evaluate swallowing function before and after O-C3 arthrodesis. The preoperative O-C2 angle was unchanged after surgery. Impairment of deglutition may be closely associated with air leakage from the oropharynx due to impaired mobility of the soft palate. Because the precise mechanism of dysphagia has not been fully elucidated, further study using dynamic videofluoroscopy and videoendoscopy is needed to examine the swallowing mechanism.


[Effect of hospital policies on patient mobility: Siennese experience].
The Italian National Health Service (S.S.N.), adopted in 1978 (Law n 833) and based on Beveridge's model, emphasises the citizens freedom to choose and the equal opportunity in accessing health care structures. Local Health Authorities--L.H.A. (U.S.L.--Unità Sanitarie Locali) become owners of almost all the structures in their territories and directly responsible for the satisfaction of all residents health needs. The former hospitals' network, based on independent first, second and third level public hospitals, in potential competition, was dismantled. Hospitals' financing, the main economic role of the S.S.N., was based on the documented running expenses: therefore the hospital interest to attract patients diminished and expenses increased in a uncontrolled way. In 1992, the Italian Government, (re)introduced (Law n 502) the quasi-market administered competition between Italian hospitals, making the major ones independent (Aziende Ospedaliere--A.O.) from the L.H.A. Hospital income from then is based on DRGs; the L.H.A. (and hospitals) leadership is now entrusted to managers and not politicians. We describe now how these changes were experienced by our hospital (A.O. Senese), placed in Southern Tuscany, Italy. We elaborated hospitalisation data regarding residents in the province of Siena (252,000 inhabitants) and activity data regarding its main hospital (A.O. Senese, 1200 beds, 47,000 admissions/year). Using the Gandy's Nomogram, we show the variation of patients mobility from 1988 to 1999. Our survey demonstrates that the Italian hospital system answers well enough to the legislative regulations: following the Law 833/1978 our hospital diminished its ability to attract patients from other areas; at the same time migrations of hospitals patients from Siena increased. Following the Law 502/1992, the power of attraction of our hospital is increased. Nevertheless the flow of escape continued to increase. It appears that to discourage the attraction power means to promote the loss of perceived quality and that it is difficult to correct such effects.


The effect of aging on the epidemiology of blood transfusions in North Khorasan province, Iran.
Additional knowledge on the epidemiology and recipients of blood transfusions will help health-care managers to estimate the future needs. The study was performed to define the blood transfusion rate based on gender, sex, and clinical features of patients receiving blood products in all hospitals of the North Khorasan province of Iran. Data on blood transfusion implementation were extracted from blood bank documents. The data for all patients who received at least one blood product were collected from March 2018 to March 2019. Among blood transfused patients, the highest transfusion rate was for packed red blood cells (PRBC) (47.7%). The two other most frequently used products were fresh frizzed plasma (FFP) (27.2%) and platelets (PLT) (21.9%). The patients in the age group of 51-80 years received the majority of PRBCs and FFPs. Patients aged 21-40 and 61-70 yrs had the highest transfusion rates for PLT. Elderly female patients (57.4%) received more blood products than their male counterparts. The highest blood transfusion rates were among patients with neoplasms, anemia, gastrointestinal bleeding, and gastric diseases. The primary Iranian blood recipients were elderly patients. Population aging is associated with an increase in the number of blood recipients and simultaneously declines the blood donors pool. It highlights the need for optimizing the use of blood in hospitals and having better strategies for overcoming the shortage of blood.


Differentiation of fetal and adult bloodstains by pyrolysis-gas-liquid chromatography.
A pyrolysis-gas-liquid chromatographic method has been developed for the differentiation of adult and fetal bloodstains. In a blind-coded study, five adult and three fetal bloodstains were correctly identified on the basis of the pyrograms of stain extracts. The differentiation between adult and fetal bloodstains is based on the peak height ratio of two long-retention-time peaks appearing in their pyrograms. The first of these peaks has been tentatively identified as indole derived from the pyrolysis of tryptophan, while the second peak is an as-yet unidentified molecular fragment produced by the pyrolysis of some component of the hemoglobin molecule other than the amino acids tryptophan, tyrosine, and phenylalanine.


An evaluation of the pharmacokinetics and pharmacodynamics of the histrelin implant for the palliative treatment of prostate cancer.
Seventeen patients with advanced prostate cancer were studied to evaluate the pharmacokinetics and pharmacodynamics of a hydrogel implant designed to deliver histrelin at a constant rate (50 microg/d) for 1 year. Serum histrelin levels were collected during the 52-week implantation period and after a second implant. Testosterone suppression was the primary pharmacodynamic endpoint, with treatment success defined as serum testosterone less than 50 ng/dL. The histrelin subdermal implant delivered constant histrelin levels, with mean serum histrelin of approximately 0.265 ng/mL over 52 weeks. At the end of 52 weeks, mean histrelin concentrations were 0.128 +/- 0.0652 ng/mL. Patients achieved chemical castration (testosterone less than 50 ng/mL) by week 4. In patients who had the first implant removed and received a new implant at the end of the first 52 weeks, testosterone suppression was not interrupted. The hydrogel implant provided consistent delivery of histrelin over 1 year and effectively suppressed testosterone in men with prostate cancer.


Characteristics of emergency room visits in patients with facial injuries in mainland China during the 60-day level I emergency response to COVID-19.
Chinese mainland launched the 60-day first-level response to major public health emergencies during the COVID-19 outbreak. This study aimed to determine the incidence and describe the characteristics and predictors of patients who presented to the emergency department (ED) with facial trauma during this period. A retrospective review was conducted on the basis of data on facial trauma presented at the ED of XXX Hospital from 24 January 2020 to 23 March 2020 and the same period in the previous two years. Multivariate linear regression model was employed to explore potential determinants associated with daily number of facial trauma. Significant reduction was observed in the amount of facial trauma during the COVID-19 level I emergency response. The trauma volume evenly distributed over the week. The declined most significantly by age group, 20-29 years, and by time range of visit, 00:00-08:00. Multivariate regression analyses revealed positive relationship between daily minimum temperature and facial trauma volume. The number of facial injuries decreased significantly during the COVID-19 Level 1 emergency response, with the least reduction in total daytime facial trauma and in infant and child facial trauma. And a higher minimum temperature may lead to increased number of facial trauma presentations.


IgA Fc receptor I signals apoptosis through the FcRgamma ITAM and affects tumor growth.
The IgA Fc receptor (FcalphaRI) has dual proinflammatory and anti-inflammatory functions that are transmitted through the immunoreceptor tyrosine-based activation motifs (ITAMs) of the associated FcRgamma subunit. Whereas the involvement of FcalphaRI in inflammation is well documented, little is known of its anti-inflammatory mechanisms. Here we show that monomeric targeting of FcalphaRI by anti-FcalphaRI Fab or serum IgA triggers apoptosis in human monocytes, monocytic cell lines, and FcalphaRI+ transfectants. However, the physiologic ligand IgA induced apoptosis only when cells were cultured in low serum conditions, indicating differences with induction of anti-inflammatory signaling. Apoptosis signaling required the FcRgamma ITAM, as cells transfected with FcalphaRI or with a chimeric FcalphaRI-FcRgamma responded to death-activating signals, whereas cells expressing a mutated FcalphaRI(R209L) unable to associate with FcRgamma, or an ITAM-mutated chimeric FcalphaRI-FcRgamma, did not respond. FcalphaRI-mediated apoptosis signals were blocked by treatment with the pan-caspase inhibitor zVAD-fmk, involved proteolysis of procaspase-3, and correlated negatively with SHP-1 concentration. Anti-FcalphaRI Fab treatment of nude mice injected subcutaneously with FcalphaRI+ mast-cell transfectants prevented tumor development and halted the growth of established tumors. These findings demonstrate that, on monomeric targeting, FcalphaRI functions as an FcRgamma ITAM-dependent apoptotic module that may be fundamental for controlling inflammation and tumor growth.


Probes for narcotic receptor mediated phenomena. 7. Synthesis and pharmacological properties of irreversible ligands specific for mu or delta opiate receptors.
Syntheses of affinity reagents for opiate receptors based on the fentanyl, endo-ethenotetrahydrooripavine, and etonitazene carbon-nitrogen skeletons are described. The isothiocyanate, bromoacetamido, and methylfumaramido alkylating functions were employed in these compounds, some of which had previously been shown to be mu specific (12, BIT) and delta specific (8, FIT and 19, FAO) in vitro. Antinociceptive activity of the title compounds was determined in the mouse hot-plate test, which revealed that certain compounds in each class showed morphine-like activity. The binding EC50 values against [3H]Dalamid for opiate receptors in NG108-15 (delta receptors) and rat brain membranes (mu + delta receptors) are also reported. With this type of experiment, it was possible to independently measure the apparent affinity of the etonitazene congeners 12-14 for the mu and delta receptors.


Characteristics of DRESS Syndrome in the Elderly: A Comparative Study of 55 Patients.
Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug reaction characterized by a skin rash, eosinophilia, and organ involvement. Objective: Our purpose is to focus on the clinical and epidemiological characteristics of DRESS in the elderly and to identify the incriminated drugs. Methods: This is a retrospective study including patients, hospitalized for DRESS with a RegiSCAR ≥4. The population was divided into 2 groups according to age: 65 years or older (G1) and <65 years (G2). The statistical study was performed using the comparative and multivariate analysis. Results: We included 55 patients (30.9% G1 and 69.1% G2). Skin manifestations were comparable in both groups. Lymphadenopathy was less common in G1 with a statistically significant difference (P = 0.012). Renal impairment was more frequent in the elderly with a statistically significant result (P = 0.005). DRESS in the elderly group was significantly associated with the occurrence of sepsis (P = 0.008). Allopurinol was the most common culprit associated with DRESS in G1 (P = 0.001). Relapses and recurrences were comparable in both groups (P = 0.71). Conclusions: DRESS in the elderly is associated with a high risk of complications, mainly kidney involvement and sepsis. Allopurinol is the most incriminated drug.


Topological Analysis for Arteriovenous Malformations via Computed Tomography Angiography: Part 2: Practical Application.
In a previous study, the authors outlined a technique for calculating the number of abnormal vascular loop structures described in 3-dimensional computed tomography angiography. To be developed into a quantitative evaluation method for soft-tissue arteriovenous malformations (AVMs), the concept needs assessment of validity. Computed tomography angiography results of 19 soft-tissue AVMs and 18 control abdominal vessels are utilized. Enhanced vascular lumen regions over 120 HU were extracted by a region growing method and skeletonized into wire frame graph models. The number of vascular loop structures in graphs is calculated as 1 - [Number of nodes] + [Number of edges], and results are compared between AVM/control groups, pre-/postprogression, and pre-/posttreatment. Average vascular lumen capacity of AVMs was 57.5 ml/lesion, and average number of vascular loops was 548 loops/lesion. Loop density of AVMs (weighted average, 9.5 loops/ml) exhibited statistically significant (P < 0.001) greater value than normal abdominal blood vessels (weighted average, 1.3 loops/ml). In all 4 cases without treatment, number of loops and loop density both increased. Particularly, number of loops increased greatly by 2 times or more in 3 cases. In all 7 cases with treatment, number of loops and vascular lumen capacity significantly (P = 0.0156) decreased. Particularly, number of loops showed clearer decrease in cases with entire lesion treatment than partial treatment. Total number of described vascular loop structures and their density or volume well reflected the existence, progression, and remission of soft-tissue AVMs. Topological analysis can be expected to be developed into a quantitative evaluation for AVMs.


Impact of insulin like growth factor-1 in development of coronary artery ectasia.
Coronary artery ectasia (CAE) is characterized by inappropriate dilatation of the coronary vasculature. The mechanisms of CAE are not well known. Insulin-like growth factor-1 (IGF-1) may make endothelial cells and smooth muscle cells more sensitive to the effects of growth hormone. In the present study, we hypothesized that IGF-1 may have an impact on the formation of ectasia and aneurysm in arterial system, and aimed to investigate the associations between the presence of CAE and serum IGF-1 levels in patients undergoing coronary angiography. The study included 2.980 subjects undergoing elective diagnostic coronary angiography. We selected 40 patients diagnosed with CAE as CAE group and 44 subjects with absolutely normal coronary arteries were assigned as normal control group. IGF-1 levels were measured in both groups of patients. Groups were similar in terms of age, sex and coronary artery disease risk factors. The serum IGF-1 levels were significantly higher in CAE patients with 109.64 ± 54.64 ng/mL than in controls with 84.76 ± 34.01 ng/mL (p=0.016). HDL levels were lower in ectasia group with 41.5 ± 10.7 mg/dL than controls with 47.7 ± 10.4 mg/dL (p=0.018). By means of logistic regression analysis, high IGF-1 and low HDL levels were found to be independent risk factors for the presence of CAE (p<0.02, p<0.016, respectively). The study revealed that there was a positive correlation between serum IGF-1 levels and presence of CAE, and high IGF-1 levels and low HDL levels were independent risk factors for the presence of CAE. Future studies are needed to confirm these results.


Idiopathic gingival fibromatosis: a case report.
Idiopathic or hereditary gingival fibromatosis is a benign oral disorder characterized by enlargement of the oral gingival tissues. This article describes a case of a female child who exhibited a generalized gingival overgrowth in both arches at birth. Other causes of gingival overgrowth and the clinical, radiographic, and histopathologic characteristics are discussed. Treatment consisted of surgical removal of the hyperplastic fibrous tissue in a series of gingivectomies. Medical history, clinical examination, and histopathologic and genetic findings were essential to rule out other systemic abnormalities. This unusual case of nonsyndromic idiopathic gingival fibromatosis was followed for 5 years, and no recurrence was seen.


Evaluation of fosfomycin combined with vancomycin against vancomycin-resistant coagulase negative staphylococci.
The pathogenic potential of coagulase-negative staphylococci (CoNS) is increasingly recognized worldwide. The aim of the present study was to evaluate different combinations of fosfomycin (FOS) with vancomycin (VAN) or oxacillin (OXA) against vancomycin-resistant clinical isolates of CoNS. Characterization of VAN resistance in selected isolates was also sought. Antibiotic susceptibility of isolates was tested by disc diffusion method, MICs of antibiotics were determined by the agar dilution method, and fosfomycin combinations were evaluated by a time-kill assay according to the guidelines of the CLSI. Moreover, oxacillin and glycopeptides (vancomycin and teichoplanin) resistances were also characterized phenotypically and genotypically in this study. Out of 258 staphylococci, 52 were CoNS (20.2%). All isolates were multidrug resistant with 75% (n = 39) oxacillin-resistant, most of them with oxacillin MIC levels of >32 mg/L. Moreover, vancomycin non-susceptibility was observed in 46.2% (n = 24) of the tested isolates with MIC range of 4-32 mg/L. Identification of selected isolates revealed that S. epidermidis was the most abundant among tested CoNS, followed by S. hominis, S. saprophyticus, and interestingly S. caseolyticus. Furthermore, Synergistic and bactericidal effects of FOS + VAN combination were observed in 3 of 9 isolates after 6 h of treatment and in all studied isolates at 24 h. On the other hand, FOS + OXA combinations were ineffective. This study provides evidence that fosfomycin combination with vancomycin could be considered as a therapeutic alternative for CoNS infections. It also sheds some light on the possible emergence of the otherwise harmless bacterium S. caseolyticus as a human pathogen.


Computational prediction of candidate miRNAs and their targets from Medicago truncatula non-protein-coding transcripts.
Identification and analysis of miRNAs enhances our understanding of the important roles that small RNAs play in complex regulatory networks. It is often difficult to perform large-scale validation of miRNA expression that is predicted from genomic regions. Expressed transcripts provide an alternative resource to facilitate identification of miRNAs and their targets. We developed a computational pipeline to scan for miRNA genes from polyadenylated transcripts that were associated with limited protein coding potentials, corresponding to the intergenic regions of Medicago truncatula genomic sequences. Each predicted miRNA was required to have a near perfect match with target genes. We also searched for miRNA conservation in other plant species, clustered highly similar miRNAs, and provided a functional classification of target genes.


Sensitive biological detection with a soluble and stable polymeric paramagnetic nanocluster.
We describe the design, synthesis, and biological characterization of manganese oxocluster-based "single molecule magnets (SMMs)". We demonstrate that polymeric micellar nanoparticles can serve as a carrier and help to stabilize delicate SMM molecules from breaking down easily and thus prevent their property loss. Concentrating thousands of Mn-clusters per micelle provided a high ionic and per-particle relaxivity allowing sensitive MR imaging in vivo. This reports one of the earliest examples of in vivo imaging of a rationally designed polymeric micelle that features SMM.


Farnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.
The farnesoid X receptor (FXR) is a key metabolic and homeostatic regulator in the liver. In the present work, we identify a novel role of FXR in antagonizing c-Jun N-terminal kinase (JNK) signaling pathway in liver carcinogenesis by activating superoxide dismutase 3 (SOD3) transcription. Compared with wild-type mouse liver, FXR(-/-) mouse liver showed elevated JNK phosphorylation. JNK1 deletion suppressed the increase of diethylnitrosamine-induced tumor number in FXR(-/-) mice. These results suggest that JNK1 plays a key role in chemical-induced liver carcinogenesis in FXR(-/-) mice. We found that ligand-activated FXR was able to alleviate H₂O₂or tetradecanoylphorbol acetate-induced JNK phosphorylation in human hepatoblastoma (HepG2) cells or mouse primary hepatocytes. FXR ligand decreased H₂O₂-induced reactive oxygen species (ROS) levels in wild-type but not FXR(-/-) mouse hepatocytes. FXR knockdown abolished the inhibition of 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-Benzoic acid (GW4064) on JNK phosphorylation and ROS production induced by H₂O₂in HepG2 cells. The gene expression of SOD3, an antioxidant defense enzyme, was increased by FXR activation in vitro and in vivo. An FXR-responsive element, inverted repeat separated by 1 nucleotide in SOD3 promoter, was identified by a combination of transcriptional reporter assays, EMSAs, and chromatin immunoprecipitation assays, which indicated that SOD3 could be a direct FXR target gene. SOD3 knockdown abolished the inhibition of GW4064 on JNK phosphorylation induced by H₂O₂in HepG2 cells. In summary, FXR may regulate SOD3 expression to suppress ROS production, resulting in decreasing JNK activity. These results suggest that FXR, as a novel JNK suppressor, may be an attractive therapeutic target for liver cancer treatment.


Pyrostegia venusta (Ker Gawl.) Miers Crude Extract and Fractions: Prevention of Dental Biofilm Formation and Immunomodulatory Capacity.
Caries and periodontal diseases remain as important diseases in the Brazilian population. One important pathogen associated with this situation is Streptococcus mutans and other important factor is this pathogen's ability to adhere firmly to the tooth surface leading to dental biofilm formation and caries development. Determine the antibacterial and other biological activities of P. venusta related to its potential to be used in the treatment of caries and periodontal disease. The growth inhibition by P. venusta of Streptococcus mutans, S. mitis, S. oralis and Candida albicans was determined using the broth microdilution method. In addition, the effect of the samples in adherence and reducing production of acids by S. mutans, and germ-tube formation of C. albicans was analysed. The Nitric Oxide (NO) production and cytotoxicity of P. venusta to peripheral blood mononuclear cells (PBMC) and RAW 264.7 Cell Line Murine Macrophage from Blood were assessed. The crude extract (CE) and ethyl-acetate (AF) and n-butanol (BF) fractions showed antibacterial activity. The ethyl-acetate (AF) fraction showed the highest inhibition percentage against the adherence of S. mutans and C. albicans cells without budding, beyond NO production inhibition. There was not any cytotoxicity in the murine macrophages RAW 264.7 cells. Our results suggest that P. venusta presents potential to be used as a preliminary source of compounds that can provide helpful activity when used in prophylaxis or treatment of caries or periodontal disease. Biological activities of Pyrostegia venusta and its potential for use in formulations for the prevention of oral diseases. Abbreviations used: NO: Nitric oxide, PBMC: Peripheral blood mononuclear cells, CE: Crude extract, AF: Ethyl-acetate fraction, BF: n-butanol fraction, HF: Hexane fraction, WF: Water fraction, MIC: Minimum inhibitory concentration, MBC: Minimum bactericidal concentration, ATCC: American Type Culture Collection, CFU: Colony-forming units, BHI: Brain heart infusion, RPMI: Roswell Park Memorial Institute, MOPS: 3-(N-morpholino)propanesulfonic acid, DMEM: Dulbecco's modified Eagle's médium, LPS: Lipopolysacharide, MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide, OD: Optical density, AC: Acteoside.


Traumatic Elbow Arthrotomy Pediatric Case Report: The Saline Load Test is a Reliable Method of Detection.
Lacerations and open elbow injuries are common emergency department visits which necessitate an orthopedic surgery evaluation for a traumatic elbow arthrotomy (TEA). A delay in this diagnosis can lead to septic arthritis, requiring more invasive surgical procedures, prolonged antibiotics, and possible long-term sequelae. To date, there is scarce literature on TEA. The purpose of this case report is to better educate the orthopedic community on a reliable method of detection for a TEA, including pediatric patients. Case 1 - Twelve-year-old boy sustained a traumatic dog bite to the right elbow by a large stray dog. Evaluation in the emergency department revealed five 1 centimeter or smaller lacerations over the lateral elbow and another 1 cm laceration to the volar and proximal forearm. A saline load test (SLT) was performed from a posterior approach and was positive after 20cc of normal saline was injected into the joint. An arthroscopic irrigation and debridement were performed as definitive treatment. He was discharged with Augmentin BID for 7 days. Follow-up appointments at 1 and 4 weeks post-operatively revealed no signs of infection.Case 2 - Seven-year-old boy who was in a bicycle accident and sustained a large laceration over the posterior elbow. Evaluation in the emergency department revealed an approximately 15 by 4 cm laceration over the posterior elbow. A SLT was positive after 30cc's was injected from the anterolateral approach. He underwent arthroscopic irrigation and debridement as definitive treatment and was discharged home with Cephalexin BID for 7 days. Follow-up appointments at 1 and 4 weeks post-operatively showed no signs of infection. Performing a SLT is a reliable method of detection to evaluate for a TEA. Our case report demonstrated confirmation of TEA in two pediatric patients based on positive SLT. We were able to treat these injuries appropriately with early surgical intervention and prophylactic antibiotics. Our early diagnosis and time-sensitive management prevented septic arthritis based on the patient's short-term follow-up examinations.


Antithrombotic effects of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats.
We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.


Syncope in cardiac amyloidosis and chronic ischemic heart disease: A case report.
Primary systemic amyloidosis is a relatively uncommon disease characterized by the production and deposition of pathological insoluble fibrillar proteins in organs and tissues. It has been estimated that between one-third and one-half of all patients with primary amyloidosis experience clinically significant cardiac involvement. The present study reports a case involving a 77-year-old woman with ischemic heart disease who presented to the cardiology department because of syncope due to slow atrial fibrillation. Laboratory tests revealed a monoclonal spike in the gamma fraction and impairment of renal function, normocytic anemia, mild hypercalcemia, hypoalbuminemia and increased levels of beta-2 microglobulin. Suspicion of cardiac involvement was supported by the echocardiographic pattern and increased levels of troponin I and brain natriuretic peptide, along with clinical signs of heart failure and systemic amyloidosis diagnosis, confirmed by abdominal fat aspiration.


From Continuity to Contiguity: A Response to the Fraught Temporality of Gender.
This paper examines current psychoanalytic engagements with the use of hormone blockers in transsexual children and the underlying premises concerning our understanding of the child's process of coming into his or her gendered self. Rather than taking sides in the debate, I explore how the "hormones question" becomes entangled in a series of misreadings and displacements through which the child's request could potentially be missed. In examining psychoanalytic conceptualizations of the trans child's agency, autonomy, and future and the relation between the natal body and gender, I ask, how is psychoanalytic discourse implicated in the very dilemmas it attempts to elucidate? Specifically, the essay examines critically the psychoanalytic use of continuity, authenticity, and alignment as implicit ideals, interrogates the focus on mourning as therapeutic horizon, and proposes that we conceive of gender as a good-enough placeholder with the potential to carry us from the ideal of continuity to an ethos of contiguity.


The Importance of Random Slopes in Mixed Models for Bayesian Hypothesis Testing.
Mixed models are gaining popularity in psychology. For frequentist mixed models, previous research showed that excluding random slopes-differences between individuals in the direction and size of an effect-from a model when they are in the data can lead to a substantial increase in false-positive conclusions in null-hypothesis tests. Here, I demonstrated through five simulations that the same is true for Bayesian hypothesis testing with mixed models, which often yield Bayes factors reflecting very strong evidence for a mean effect on the population level even if there was no such effect. Including random slopes in the model largely eliminates the risk of strong false positives but reduces the chance of obtaining strong evidence for true effects. I recommend starting analysis by testing the support for random slopes in the data and removing them from the models only if there is clear evidence against them.


Application of MRI-Based Radiomics in Preoperative Prediction of NF2 Alteration in Intracranial Meningiomas.
This study aimed to investigate the feasibility of predicting NF2 mutation status based on the MR radiomic analysis in patients with intracranial meningioma. This retrospective study included 105 patients with meningiomas, including 60 NF2-mutant samples and 45 wild-type samples. Radiomic features were extracted from magnetic resonance imaging scans, including T1-weighted, T2-weighted, and contrast T1-weighted images. Student's t-test and LASSO regression were performed to select the radiomic features. All patients were randomly divided into training and validation cohorts in a 7:3 ratio. Five linear models (RF, SVM, LR, KNN, and xgboost) were trained to predict the NF2 mutational status. Receiver operating characteristic curve and precision-recall analyses were used to evaluate the model performance. Student's t-tests were then used to compare the posterior probabilities of NF2 mut/loss prediction for patients with different NF2 statuses. Nine features had nonzero coefficients in the LASSO regression model. No significant differences was observed in the clinical features. Nine features showed significant differences in patients with different NF2 statuses. Among all machine learning algorithms, SVM showed the best performance. The area under curve and accuracy of the predictive model were 0.85; the F1-score of the precision-recall curve was 0.80. The model risk was assessed by plotting calibration curves. The p-value for the H-L goodness of fit test was 0.411 (p> 0.05), which indicated that the difference between the obtained model and the perfect model was statistically insignificant. The AUC of our model in external validation was 0.83. A combination of radiomic analysis and machine learning showed potential clinical utility in the prediction of preoperative NF2 status. These findings could aid in developing customized neurosurgery plans and meningioma management strategies before postoperative pathology.


Long-term consumption of saponins derived from Platycodi radix (22 years old) enhances hepatic insulin sensitivity and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed a high-fat diet.
Crude saponins derived from Chinese Platycodi radix have been reported to prevent increases in body weight and liver TAG in mice fed a high-fat diet. We investigated the effects of an extract (PR) taken from Korean Platycodi radix, which is cultivated for 22 years in the ground (Jangsaeng doraji), and its saponins (PRS) on insulin resistance and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed high-fat diets. Four groups were orally supplemented with 2 g PR, 0.2 g PRS, 20 mg rosiglitazone (positive control) or 0.5 g cellulose (negative control) per kg body weight on a daily basis for 8 weeks. We found that PRS lowered body weight, visceral fat mass and serum leptin levels in pancreatectomized rats in comparison to the control. PR enhanced first- and second-phase insulin secretion while PRS stimulated only first-phase insulin secretion. Glucose infusion rates to maintain euglycaemia at hyperinsulinaemic states decreased in a descending order of rosiglitazone, PRS, PR and control, but they increased hepatic glucose output in the same order. This reduction was associated with the storage of decreased TAG and increased glycogen, which was a result of enhanced tyrosine phosphorylation of anti-insulin receptor substrate-2 and serine473 phosphporylation of protein kinase B (PKB, Akt). Improved hepatic insulin signalling led to decreased phosphoenolpyruvate carboxykinase expression and reduced hepatic glucose output accordingly. In conclusion, PRS principally improves glucose homeostasis by enhancing hepatic insulin sensitivity as a consequence of reducing fat storage and stimulating insulin signalling in diabetic rats. In addition, PR contains components that promote glucose-stimulated insulin secretion.


The simian virus 40 small-t intron, present in many common expression vectors, leads to aberrant splicing.
Polymerase chain reaction analysis was used to identify aberrant splicing of the simian virus 40 small-t intron present in pRSVcat. We examined factors governing the selection and relative use of aberrant 5' splice sites derived from the chloramphenicol acetyltransferase-coding region. Our results indicated that transcripts from virtually any cDNA positioned upstream of the small-t intron could contain alternative 5' splice sites and therefore be subject to deletions within the protein-coding region.


Clinical trials in uremia-time to reappraise.
The construct of any road map of the progress of medical knowledge reveals a long and tortuous road, full of errors, misapprehensions, blind alleys, and a perpetual shuffling between authority, heresy, and reason; but one of continuous growth and steady progress, albeit at variable pace and achievement at different periods of history. Numerous factors account for this cumulative progress, notable among which are the transmission, scientification, and mathematization of medical knowledge that ultimately account for the progressive evolution of medical care over time, from its primitive beginnings in antiquity to its present sophisticated state of accomplishment. It was the mathematical precision provided by quantification and statistical analysis that established certainty in medicine and ultimately changed the conjectural art of clinical practice to a disciplined science founded on clinical investigation, especially in therapeutics. Randomized clinical trials (RCTs) introduced in the 1950s have since been instrumental in establishing certainty in the practice of medicine. Regrettably, the proliferation of RCTs driven by biased hypotheses and pharmaceutical-industrial interests have created serious flaws in the results of the onslaught of new RCTs that need to be reappraised. Another unfortunate trade-off during this evolution has been neglect of the individual patient's inborn biological variation from the norm, mean, or median, an omission that has come to erode the personal in medical care.


Automatic autism spectrum disorder detection using artificial intelligence methods with MRI neuroimaging: A review.
Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the Supplementary Appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We suggest future approaches to detecting ASDs using AI techniques and MRI neuroimaging.


The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures.
The groggy rat (strain name; GRY) exhibits ataxia, an unstable gait, and paroxysmal severe extension of the entire body. Adults show a reduction in size of the cerebellum and presynaptic and axon terminal abnormalities of Purkinje cells. These neurological abnormalities are inherited in an autosomal recessive manner, and the causative mutation has been named groggy (gry). In this study, we mapped gry on rat chromosome 19 and found a nonconservative missense (M251K) mutation in the alpha(1A) subunit of the P/Q-type voltage-gated Ca(2+) channel gene (Cacna1a) within the gry-critical region. This mutation was located at a highly conserved site close to the ion-selective pore and led to the shortening of the inactivation phase of the Ca(2+) channel current without a change of peak current density or current-voltage relationship in whole cell patch recordings of the recombinant Ca(2+) channel expressed in HEK cells. It has been well established that mice with a mutation at Cacna1a such as tottering and leaner show absence seizures. The Cacna1a-mutant GRY rat also exhibited absence-like seizures from 6 to 8 weeks of age, which were characterized by bilateral and synchronous 7-8 Hz spike-and-wave discharges concomitant with sudden immobility and staring, on cortical and hippocampal EEGs. The pharmacological profile of the seizures was similar to that of human absence epilepsy: the seizures were inhibited by ethosuximide and valproic acid but not phenytoin. Thus, the GRY rat with P/Q-type Ca(2+) channel disorders is a useful model for studying absence epilepsy and Cacna1a-related diseases.


Regulation of the mouse alpha A-crystallin gene: isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes.
We have shown by site-directed mutagenesis that the sequence between positions -69 and -40 of the mouse alpha A-crystallin gene is crucial for tissue-specific gene expression in a transfected mouse lens epithelial cell line transformed with the early region of simian virus 40. Gel retardation experiments with synthetic oligodeoxynucleotides revealed a mouse lens nuclear protein which bound specifically to the palindromic sequence 5'-GGGAAATCCC-3' at positions -66 to -57 in the alpha A-crystallin promoter. By screening a bacteriophage lambda gt11 expression library of the transformed lens cells, we isolated a 2.5-kilobase-pair cDNA encoding a fusion protein which bound to this sequence and to the regulatory element of the major histocompatibility complex (MHC) class I gene. This cDNA hybridized to a 10-kilobase-pair polyadenylated RNA present in many different tissues, including lens. It encoded a protein, tentatively called alpha A-CRYBP1, containing at least two zinc fingers. alpha A-CRYBP1 is either homologous or very similar to the human nuclear proteins MBP-1 (Baldwin et al., Mol. Cell. Biol. 10:1406-1414, 1990), PRDII-BFI (Fan and Maniatis, Genes Dev. 4:29-42, 1990), and HIV-EP1 (Maekawa et al., J. Biol. Chem. 264:14591-14593, 1989), which bind to regulatory elements of the MHC class I, beta interferon, and human immunodeficiency virus genes, respectively. Our results suggest that the lens-specific alpha A-crystallin, MHC class I, beta interferon and other genes have a similar cis-acting DNA regulatory motif that shares alpha A-CRYBPI, MBP-1, PRDII-BF1, HIV-EP1, or other closely related proteins as trans-acting factors.


(Benzofuran-2-yl)(3-methyl-3-phenylcyclobutyl)methanone.
The structure of the title compound, C20H18O2, consists of a dimeric arrangement of benzofuran molecules around an inversion centre, linked via C-H...O hydrogen bonds. There are also C-H...pi ring interactions. All these interactions result in the formation of infinite chains parallel to the [100] axis. The cyclobutane ring is puckered, with a dihedral angle of 29.03 (13) degrees between the two three-atom planes.


Airborne pollen calendar of Lublin, Poland.
Pollen concentration in the atmosphere of Lublin (eastern Poland) was studied by means of volumetric method using Hirst sampler (VPPS 2000, Lanzoni) in 2001-2002. The pollen trap was mounted at the height of 15 m in the centre of Lublin. On the basis of analysis of mean daily values of pollen concentration, the pollen calendar was constructed for 16 taxa producing the allergenic pollen: Alnus, Corylus, Populus, Ulmus, Fraxinus, Betula, Carpinus, Quercus, Fagus, Pinaceae, Poaceae, Rumex, Plantago, Chenopodiaceae, Artemisia, Urticaceae. Great differences referring to the course of pollen seasons for most of the studied taxa of trees within the 2 years of study were found. They were associated with the beginning and end of the pollen season, the amount and the date of maximum pollen concentration occurrence, as well as annual sums of pollen grains. Much lower differentiation was observed in the case of herbaceous plants. This referred mainly to maximum concentration occurrence dates (Urtica, Poaceae) and the length of pollen season (Chenopodiaceae). The most similar course of pollen seasons during 2 years was recorded for Artemisia. Among trees, the highest pollen concentrations were recorded for Betula, Pinaceae and Alnus; the lowest for Ulmus, Fagus and Corylus. Very high concentration of herbaceous plant's pollen was observed for Poaceae and Urtica; Plantago and Chenopodiaceae showed the lowest level. Annual sums of pollen grains for Alnus, Populus, Quercus, Betula and Pinaceae were much higher in 2001, but in the case of Ulmus, Fraxinus, Carpinus, Fagus the annual sums of pollen grains in 2002 were almost twice as high as in 2001. For 5 among 7 herbaceous taxa, annual sums of pollen grains in both years were similar.


Clinical and serologic features of primary Sjögren's syndrome concomitant with autoimmune hemolytic anemia: a large-scale cross-sectional study.
Autoimmune hemolytic anemia (AIHA) is an uncommon but clinically significant disorder in primary Sjögren's syndrome (pSS). Among 565 pSS patients hospitalized in Peking University People's Hospital from January 2000 to March 2013, 16 patients were diagnosed with AIHA (2.8% prevalence). AIHA presented at the onset of pSS without overt sicca symptoms in 3 of the 16 patients. Primary biliary cirrhosis (PBC) was more prevalent in the patients with SS-AIHA than in those without (p = 0.007). Edema, fever, and liver involvement occurred significantly more frequently in pSS patients with AIHA than those without AIHA (p = 0.035, p = 0.029, p = 0.024, respectively). The pSS patients with AIHA were more vulnerable to leukopenia and thrombocytopenia than those without AIHA (p = 0.004 and p = 0.001, respectively). Additionally, the levels of complement component 3 (C3) and complement component 4 (C4) were significantly lower in the SS-AIHA group (p = 0.008 and p = 0.037, respectively). Taken together, our results indicate that pSS should be considered in the differential diagnosis of AIHA, even in the absence of sicca symptoms. Among pSS patients, the existence of PBC, cytopenia, or hypocomplementemia suggests a higher risk of suffering from AIHA.


Isolation and identification of a glutathione peroxidase homolog gene, gpxA, present in Neisseria meningitidis but absent in Neisseria gonorrhoeae.
Antioxidant enzymes are thought to be important for the survival of pathogenic Neisseria species. We isolated a glutathione peroxidase-related gene (gpxA) from Neisseria meningitidis FAM20. The N. meningitidis glutathione peroxidase homolog was 49 to 57% identical to seven other glutathione peroxidase family members over a 49-amino-acid region which is conserved among various species. The gpxA sequence was present in all 7 meningococcal strains tested but absent in 10 gonococcal strains and 6 nonpathogenic neisserial strains as determined by Southern hybridization. The homology of gpxA to mammalian glutathione peroxidases and the presence of this gene specifically in the meningococcus suggest that it is important in the cellular metabolism or defense processes particular to this pathogen.


Two-dimensional porous molecular networks of dehydrobenzo[12]annulene derivatives via alkyl chain interdigitation.
The self-assembly of a series of hexadehydrotribenzo[12]annulene (DBA) derivatives has been scrutinized by scanning tunneling microscopy (STM) at the liquid-solid interface. First, the influence of core symmetry on the network structure was investigated by comparing the two-dimensional (2D) ordering of rhombic bisDBA 1a and triangular DBA 2a (Figure 1). BisDBA 1a forms a Kagomé network upon physisorption from 1,2,4-trichlorobenzene (TCB) onto highly oriented pyrolytic graphite (HOPG). Under similar experimental conditions, DBA 2a shows the formation of a honeycomb network. The core symmetry and location of alkyl substituents determine the network structure. The most remarkable feature of the DBA networks is the interdigitation of the nonpolar alkyl chains: they connect the pi-conjugated cores and direct their orientation. As a result, 2D open networks with voids are formed. Second, the effect of alkyl chain length on the structure of DBA patterns was investigated. Upon increasing the length of the alkyl chains (DBAs 3c-e) a transition from honeycomb networks to linear networks was observed in TCB, an observation attributed to stronger molecule-substrate interactions. Third, the effect of solvent on the structure of the nonpolar DBA networks was investigated in four different solvents: TCB as a polar aromatic solvent, 1-phenyloctane as a solvent having both aromatic and aliphatic moieties, n-tetradecane as an aliphatic solvent, and octanoic acid as a polar alkylated solvent. The solvent dramatically changes the structure of the DBA networks. The solvent effects are discussed in terms of factors that influence the mobility of molecules at the liquid-solid interface such as solvation.


The zebrafish's swim to fame as an experimental model in biology.
The zebrafish has long been the favorite organism in many scientific disciplines. Although its attributes as a model were expounded for many years and thus were no secret, the zebrafish sat in the wings while other more popular vertebrates such as chick, amphibians, and mouse were examined at length. We cannot say there was a resurgence in popularity, but more an explosion of research utilizing the zebrafish beginning in the late 1970s when investigators at the University of Oregon began using it as their model in neuroscience. Prior to this reawakening, the zebrafish was one of the significant organisms in the study of teratology and toxicology, development, and, to some extent, behavior. Recently, however, the field of zebrafish genetics has gained immense popularity and success, in part owing to the fact that zebrafish are diploid and are amenable to genetic manipulations. Here we present an overview of the multidisciplinary research that has laid some of the foundation of our present understanding of the biochemical, cell biological, and molecular genetic events accompanying zebrafish development.


Pump-signal combiner with large-core signal fiber feed-through for fiber lasers and amplifiers.
A pump-signal combiner with a new processing method is reported in this paper. The core deformation of the signal fiber can be avoided by this method, and an 8+1 to 1 pump-signal combiner with 100 μm core-signal fiber feed-through is fabricated. The pump and signal coupling efficiencies are 96.8% and 98.0%, respectively. Furthermore, this pump-signal combiner is applied to a CW large mode area fiber laser with a counter pump configuration. The output power of the laser is 87 W.


The role of kurtosis and kurtosis-adjusted energy metric in occupational noise-induced hearing loss among metal manufacturing workers.
Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (β), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (β ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (β < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when β ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.


[Vitamin C].
Vitamin C or ascorbic acid is a hydrosoluble vitamin derived from glucose metabolism. It acts as a reductor agent required for synthesis of collagen fibers through hydroxylation of proline and lysine. It also protects the body against damage caused by the free radicals. Humans cannot synthesize ascorbic acid as they lack an enzyme called gulonolactone oxidase. Concentrations in plasma and leukocytes reflect the levels of the diet and body deposits respectively of this vitamin. Among foods with high vitamin C levels are tomatoes, potatoes, and citrus fruits such as limes, oranges and lemons. The current recommendation of daily intake of vitamin C is 90 mg/d for men and 75 mg/d for women. Patients with chronic diseases such as cancer or diabetes or those who smoke need higher doses in their usual diet. Ascorbic acid deficiency gives rise to the appearance of scurvy. This disease is rarely seen in developed countries. The symptoms develop with plasma levels below 0.15 mg/dL. Scurvy is characterized by the presence of weakness, joint pain or skin lesions in form of petechias, gum bleeding, ease of developing bruises or delay in wound healing. The most characteristic skin manifestations are purpuric perifollicular hyperkeratotic papules and the presence of kinky hair.


A BIOPHYSICAL ANALYSIS TO ASSESS X-RAY SENSITIVITY OF HEALTHY AND TUMOUR CELLS.
The mechanobiology is providing novel perspectives in the study of cancer and is contributing to evaluate the cancer responses, from a biophysical point of view, to classical therapeutic approaches- radiotherapy and chemotherapy. Here we have explored the effects of two doses (4 and 8 Gy) of 6 MeV photons on spreading, focal adhesions, migration and mechanical properties of BALB/c 3T3 and their SV40 transformed equivalent, SVT2. Cell biophysical responses to 4 and 8 Gy were analysed and compared with those reported in previous published work when lower doses (1 and 2 Gy) were administered Panzetta et al. (Effects of high energy X-rays on cell morphology and functions. Proc. Book 2017;16:116). We observed that the range of sensitivity to ionising radiations profoundly changes depending on the patho-physiological state of cells. In particular, we found that X-rays induce morphological and functional variations in both cell lines (decreased motility, increased adhesion and increased cytoskeleton stiffness). These changes were slightly dependent on doses in the case of SVT2 cells and may indicate a possible mechanical normalisation in their phenotype. Nevertheless, the responses of BALB/c 3T3 were negligible only for the low dose of 1 Gy and increased significantly in a dose-dependent manner with higher doses. We believe that the characterisation of X-rays effects on the cell mechanobiology could shed new light in the design and customisation of radiotherapy treatments.


Circadian Regulation of Light-Evoked Attraction and Avoidance Behaviors in Daytime- versus Nighttime-Biting Mosquitoes.
Mosquitoes pose widespread threats to humans and other animals as disease vectors [1]. Day- versus night-biting mosquitoes occupy distinct time-of-day niches [2, 3]. Here, we explore day- versus night-biting female and male mosquitoes' innate temporal attraction/avoidance behavioral responses to light and their regulation by circadian circuit and molecular mechanisms. Day-biting mosquitoes Aedes aegypti, particularly females, are attracted to light during the day regardless of spectra. In contrast, night-biting mosquitoes, Anopheles coluzzii, specifically avoid ultraviolet (UV) and blue light during the day. Behavioral attraction to/avoidance of light in both species change with time of day and show distinct sex and circadian neural circuit differences. Males of both diurnal and nocturnal mosquito species show reduced UV light avoidance in anticipation of evening onset relative to females. The circadian neural circuits of diurnal/day- and nocturnal/night-biting mosquitoes based on PERIOD (PER) and pigment-dispersing factor (PDF) expression show similar but distinct circuit organizations between species. The basis of diurnal versus nocturnal behaviors is driven by molecular clock timing, which cycles in anti-phase between day- versus night-biting mosquitoes. Observed differences at the neural circuit and protein levels provide insight into the fundamental basis underlying diurnality versus nocturnality. Molecular disruption of the circadian clock severely interferes with light-evoked attraction/avoidance behaviors in mosquitoes. In summary, attraction/avoidance behaviors show marked differences between day- versus night-biting mosquitoes, but both classes of mosquitoes are circadian and light regulated, which may be applied toward species-specific control of harmful mosquitoes.


Correlation between intra-operative high rate neural response telemetry measurements and behaviourally obtained threshold and comfort levels in patients using Nucleus 24 cochlear implants.
The correlation between high rate 250 Hz intra-operative threshold neural response telemetry (t-NRT) with behaviourally obtained psychophysical threshold (T) and comfort (C) levels of the most recent and stable maps of 90 consecutive cochlear implantees using Cochlear Implant 24 Mini (CI 24 M) (M: F - 26:19), aged between two and 60 years with a mean age of 9.61 +/-12.07, was studied. The intra-operative t-NRT levels were seen to fall between the T and C levels and a good correlation was found between t-NRT and T and C levels (r = 0.327 at p < 0.005 for the T level and r = 0.648 at p < 0.001 for C level vs intra-operative t-NRT). The present study supports the view that 250 Hz NRT is not only a valuable clinical tool in evaluating the integrity of the implant and status of peripheral auditory nerves but can be used in programming the speech processor for young and difficult recipients, as has been previously shown using low rate NRT.


Fire in the operating room: principles and prevention.
Fire is a rare but potentially disastrous operating room misadventure. In this article, the authors describe the elements of operating room fires and present an illustrative case. The risk of fire can be minimized when the operating room team understands the interactions among the three sides of the classic fire triangle: oxidizers, fuels, and ignition sources. Lists of fire prevention techniques and steps to take in the event of an operating room fire are provided.


Delaying the mitochondrial decay of aging.
Mitochondrial dysfunction may be a principal underlying event in aging, including the degenerative diseases of aging such as brain degeneration. Mitochondria provide energy for basic metabolic processes, and their decay with age impairs cellular metabolism and leads to cellular decline. Progress over the last decade in delaying the mitochondrial decay of aging is reviewed.


Biodistribution of radioactive epidermal growth factor in normal and tumor bearing mice.
The biodistribution of iodinated epidermal growth factor in normal and tumor bearing mice was analyzed. The uptake of epidermal growth factor was high in the liver, skin and submaxillary gland, which all have detected receptors for the growth factor. Organs, such as lung, heart, spleen, intestine, bone and central nervous system, which lack the receptor, did not retain the growth factor. In tumor bearing mice, the growth factor accumulated in receptor positive tumors, but to a lesser extent than in the liver. This finding will probably prevent the use of epidermal growth factor as a carrier for radionuclides for a therapeutic purpose.


Whole body insulin resistance in myotonic dystrophy.
To quantitate the degree of whole body insulin resistance in patients with myotonic dystrophy, three separate euglycemic insulin infusions were given to ambulatory patients and the results compared with findings in normal control subjects. Basal glucose and insulin values were similar for the two groups. There was no significant difference in insulin clearance rates between normal subjects and patients at the three insulin infusion rates used. A highly significant decrease in the whole body glucose disposal rate was seen during the 120-minute insulin infusion in the patients with myotonic dystrophy compared with normal subjects at all three insulin dosages (20 mU/m2/min: 2.18 +/- 0.29 [standard error] versus 5.49 +/- 1.72 mg/kg/min, p less than 0.0001; 80 mU/m2/min: 4.16 +/- 0.34 versus 8.49 +/- 0.45 mg/kg/min, p less than 0.0001; 200 mU/m2/min: 5.22 +/- 0.53 versus 10.06 +/- 0.50 mg/kg/min, p less than 0.0001). These marked decreases in glucose disposal rates for the patients were adjusted in accordance with their 24-hour urinary creatinine excretion rate to correct for the difference in muscle mass between patients and controls. This adjusted glucose disposal rate was 15 to 25% lower (p less than 0.02) in the patients with myotonic dystrophy at insulin infusion rates of 20 and 80 mU. During the 200 mU insulin infusions, the adjusted glucose disposal rate remained lower than that in normal subjects but was of borderline statistical significance. These studies suggest that moderately severe whole body insulin resistance is responsible for the postprandial hyperinsulinemia typically seen in patients with myotonic dystrophy.


How the configurational changes influence on molecular characteristics. The alkyl 3-azido-2,3-dideoxy-D-hexopyranosides - Theoretical approach.
In this paper we present two currents of our research. The first goal was the geometry optimization of the structures of derivatives of the alkyl 3-azido-2,3-dideoxy-D-hexopyranosides. Then, we examine the influence of the applied quantum methods on the values of molecular features describing these structures. We use two methods for geometry optimization: the semi-empirical PM7 method and DFT B3LYP/6-31++G* method. The results of comparison parameters of descriptors indicate that there are no statistical differences obtained from both methods. Thus, we recommend the PM7 method for geometry optimization of the derivatives of the alkyl 3-azido-2,3-dideoxy-D-hexopyranosides due to its time and computer resources requirements. Another part of the research was the examination, which groups of descriptors are the most suitable for identifying the similarities in the configuration, the substituents pattern and the molecular mass of 232 examined structures. To explore relation between configuration changes of the 3-azidosaccharides and influence of these changes on the molecular characteristic, we use hierarchical cluster analysis (HCA), where WHIM, 3D-MORSE, RDF and GETAWAY descriptors were selected. Depending on the group of descriptors, molecules are divided in various ways. In general, saccharide' structures are divided into groups based on the configuration of substituents (combination of epimers) or length of the O-glycoside chain. Never before, these saccharides derivatives, were investigated by chemometric analysis. The most problematic issue in experimental and theoretical research is the configuration of substituents in pyranoside ring. Due to vast number of configurations, it is possible to obtain massive amount of diverse structures. This problem concerns us and opens opportunity in investigation the effect of configuration on the parameter of molecules.


Collagen treatment of complex anorectal fistula: 3 years follow-up.
Fistula in ano is a common anorectal disease in adults. Currently, surgery remains the definitive therapeutic approach, but in some cases, it can lead to serious complications as faecal or gas incontinence. Therefore, sphincter sparing treatments should be considered for complex fistulas. One of the sphincteric preserving treatment is the filling with a dermal extract commonly called "collagen glue" as Salvecoll-E® gel. This is a multicentric, prospective, observational study on the use of Salvecoll-E® gel in treatment of complex anal fistulas. We treated 70 patients from May 2016 to May 2017. In the first phase, we debrided the fistula tract using a loose seton kept for 4-6 weeks. In the second phase, the seton was removed and the fistula tract was filled with Salvecoll-E® gel. In this article, we report results at 36 months of follow-up. Fifty patients (71.4%) had completely healed fistula within 36 months of follow-up. Twenty-eight patients (28.2%) had recurrences. Among these failures, 65% were within 6 months. All low transphincteric fistulas healed. Recurrences occurred only in median and high transphincteric fistulas. No patient had a worsening of continence status measured with Cleveland Clinic Florida Incontinence Severity score. Salvecoll-E® gel is a recent finding among sphincter-sparing treatments. In this study, we demonstrate that it is a safe option in the treatment of complex fistulas. Final results are satisfactory and in line with the best results published in literature among mini-invasive treatments.


Long-term follow-up of reduced-intensity allogeneic hematopoietic stem cell transplantation for refractory or relapsed follicular lymphoma.
Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative treatment for refractory or relapsed follicular lymphoma (FL), transplant-related mortality (TRM) greatly interferes with the success. A variety of reduced-intensity conditionings (RICs) have been used to reduce TRM, but an optimal conditioning for FL has not been fully established. We retrospectively evaluated the outcome of allogeneic HSCT for FL with RIC consisting of fludarabine and melphalan. Nineteen adult patients with relapsed or refractory FL were conditioned with fludarabine (125 mg/m2) and melphalan (140 mg/m2), and received grafts from an HLA-identical sibling (n = 6) or an unrelated donor (n = 13). For the prophylaxis of graft-versus-host disease (GVHD), cyclosporine A or tacrolimus with short-term methotrexate was given. There were no early deaths before engraftment, and all patients achieved engraftment. Three patients died of extensive-type chronic GVHD (n = 2) or bacterial infection (n = 1) without disease progression. With a median follow-up period of 75.2 months (range: 33.3–111.9 months), 16 patients were alive without disease progression. Both the 5-year overall and progression-free survival rates were 84.2% (95% CI: 67.7–100%). These results strongly suggest that allogeneic HSCT with RIC using fludarabine and melphalan could be a promising treatment choice for refractory or relapsed FL.


Concomitant multiple revascularizations in supra-aortic arteries: short-term results in 50 patients.
The outcome for simultaneous revascularization of more than 1 supra-aortic arterial stenosis has not been evaluated because of concerns regarding the increased risk of additional procedures. We evaluated the feasibility and safety of concomitant multiple supra-aortic arterial revascularizations (CMSAR). We retrospectively evaluated 50 consecutive patients who underwent CMSARs with angioplasty and stent placement. The study included a separate lesion group (LG) (n = 28), ipsilateral LG (n = 17) including adjacent (n = 6) and remote (n = 11) tandem lesions, and triple LG (n = 5). We assessed the procedural success (defined as residual stenosis <30%) and periprocedural event rate (ER) (minor or major stroke, and death). We compared the ERs in the lesion (ipsilateral vs separate) and symptom (unstable vs stable) pattern groups with the Fisher exact test. Procedural success was achieved in all patients (50/50). Periprocedural events within 30 days were noted in 5 (10%). ER within 2 days after the procedure was higher in the ipsilateral LG (4/17) than in the separate LG (0/28) (P = .016). Major events consisting of a major stroke and a death occurred in 2 patients in the unstable group (4%) and was more common in the unstable (2 of 7) than in the stable group (0/38) (P = .029). During the mean 11-month follow-up period, there was 1 symptomatic recurrence. CMSARs are feasible with a high procedural success rate resulting in a favorable short-term outcome. However, they must be carefully performed in ipsilateral LG, especially in patients in the unstable group.


A Negative Feedback Loop in Ultraviolet A-Induced Senescence in Human Dermal Fibroblasts Formed by SPCA1 and MAPK.
Secretory pathway calcium ATPase 1 (SPCA1) is a calcium pump localized specifically to the Golgi. Its effects on UVA-induced senescence have never been examined. In our study, expression of SPCA1 was increased in UVA-irradiated human dermal fibroblasts (HDFs) by activating mitogen-activated protein kinase (MAPK) and its downstream transcription factor, c-jun. Dual-luciferase reporter and chromatin immunoprecipitation assays revealed that c-jun regulated SPCA1 by binding to its promoter. Furthermore, downregulating SPCA1 with siRNA transfection aggravated UVA-induced senescence due to an elevation of intracellular calcium concentrations and a subsequent increase in reactive oxygen species (ROS) and MAPK activity. In contrast, overexpression of SPCA1 reduced calcium overload, consequently lowering the ROS level and suppressing MAPK activation. This alleviated the cellular senescence caused by UVA irradiation. These results indicated that SPCA1 might exert a protective effect on UVA-induced senescence in HDFs via forming a negative feedback loop. Specifically, activation of MAPK/c-jun triggered by UVA transcriptionally upregulated SPCA1. In turn, the increased SPCA1 lowered the intracellular Ca2+ level, probably through pumping Ca2+ into the Golgi, leading to a reduction of ROS, eventually decreasing MAPK activity and diminishing UVA-induced senescence.


An autopsy case of H.C.G. secreting intracranial teratoma.
An autopsy case of intracranial malignant teratoma, in an 8 years old female, is presented in this report. Clinically, pregnancy test was positive and human chorionic gonadotropins of high titer were found in the urine but precocious puberty was not seen. The tumor was composed of differentiated teratomatous components and embryonal carcinoma with small foci of chorio-carcinoma. Embryonal carcinoma seemed to undergo trophoblastic differentiation. These histological findings have been discussed from the viewpoint of its histogenesis and differentiation.


Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a.
The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that beta-catenin is expressed in DA precursor cells and that beta-catenin signaling takes place in these cells, as assessed in TOPGAL [Tcf optimal-promoter beta-galactosidase] reporter mice. We also found that Wnt-1, -3a, and -5a expression is differentially regulated during development and that partially purified Wnts distinctively regulate VM development. Wnt-3a promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 (Nurr1) but did not increase the number of tyrosine hydroxylase-positive neurons. Instead, Wnt-1 and -5a increased the number of rat midbrain DA neurons in rat embryonic day 14.5 precursor cultures by two distinct mechanisms. Wnt-1 predominantly increased the proliferation of Nurr1+ precursors, up-regulated cyclins D1 and D3, and down-regulated p27 and p57 mRNAs. In contrast, Wnt-5a primarily increased the proportion of Nurr1+ precursors that acquired a neuronal DA phenotype and up-regulated the expression of Ptx3 and c-ret mRNA. Moreover, the soluble cysteine-rich domain of Frizzled-8 (a Wnt inhibitor) blocked endogenous Wnts and the effects of Wnt-1 and -5a on proliferation and the acquisition of a DA phenotype in precursor cultures. These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles.


Human papillomavirus as a target for management, prevention and therapy.
The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinogenesis has made it a target for prophylactic and therapeutic vaccines, as well as a diagnostic tool in cervical screening. Whilst prophylactic vaccination has proven very effective in terms of preventing cervical cancer precursor lesions, therapeutic strategies have presented far greater challenges. HPV testing has shown itself to be extremely valuable in the triage of low grade cytological abnormalities, test of cure following treatment of cervical intraepithelial neoplasia (CIN), and will, over the next 10 years, gradually replace cytology as the mainstay of primary cervical screening. In this review, the latest evidence supporting HPV as both a biomarker of risk for cervical cancer and a target for prophylactic and therapeutic vaccination is presented.