[Anxiety disorders in an attention-deficit/hyperactivity disorder clinical sample].
To evaluate the prevalence of anxiety disorders in a clinical referred sample of children and adolescents with attention deficit/hyperactivity disorder (ADHD). 78 children and adolescents with ADHD according to DSM-IV criteria were investigated with a semi-structured interview (P-CHIPS), complemented by clinical interviews with the children or adolescents and their parents. Their IQ was calculated with neuropsychological testing. A high prevalence of anxiety disorders (23.05%) was found in the sample. Generalized anxiety disorder was the most prevalent disorder (12,8%), followed by social phobia (3,84%) and separation anxiety disorder (3,8%). Two children showed more than one anxiety disorder. Children and adolescents with ADHD seem to be more prone to have comorbid anxiety disorders, at least in clinical samples referred to specialized units.


Bone mineral deposition in mice selected for body conformation.
Bone mineral content was investigated in 2 lines of mice (CBi/C and CBi/L) that carry different biomasses per unit of skeletal weight. These lines also differ in their femoral histomorphometry and bone biomechanics. The logarithmic form of the allometric equation describing the relationship between ash weight and body weight was used to compare the mineral content in both sexes of these genotypes. No statistical difference was observed in the slopes of the curves describing the changes in bone mineral content as a function of age. Both lines had greater values than the line for control animals. The selected lines did differ significantly in the intercepts of the curves on the y-axis. An independent determination of both allometric parameters by genetic factors is proposed. Genes or groups of genes could affect mineral deposition in two ways: one could produce positional changes of the allometric curves in the embryo but leave their postnatal slopes unchanged; another could modify the postnatal slope of the curve. The combined expression of these different genes should be important in preserving homeostatic functioning of the organism.


Intra-oral salivary gland tumours in the West Midlands.
Intra-oral salivary gland tumours reported from the West Midlands over the years 1975-88 were examined as to a number of epidemiological variables; the question as to their increasing incidence was also addressed. The findings were largely in agreement with those of most previous authors in that most of the tumours occurred in the palate, but whereas most of these were benign, a large proportion of those in other sites were malignant. However, firm conclusions are difficult to draw since there is much disagreement over reporting criteria. An international workshop and comprehensive tumour registries are required in order to determine more accurate data and conclusions. Similar cooperation is necessary in order to substantiate or refute the suggestion that the incidence of salivary gland tumours is increasing.


Motivation or demotivation of health workers providing maternal health services in rural areas in Vietnam: findings from a mixed-methods study.
Motivation is an important driver for health professionals to maintain their professional competencies, continue in the workforce and make a positive contribution to their workplace. While there is some research about the motivation of health workers in low- to middle-income countries, maternal morbidity and mortality remains high and this can be lowered by improving the quality of maternal health services and the training and maintenance of the skills of maternal health workers. This study examines the impact of motivation on maintenance of professional competence among maternal health workers in Vietnam using mixed methods. The study consisted of a survey using a self-administered questionnaire of 240 health workers in five districts across two Vietnamese provinces and in-depth interviews with 43 health workers and health managers at the commune, district and provincial level to explore external factors that influenced motivation. The questionnaire includes a 23-item motivation instrument based on the Kenyan health context, modified for Vietnamese language and culture. The 240 responses represented an estimated 95% of the target sample. Multivariate analysis showed that three factors contributed to the motivation of health workers: access to training (β = -0.14, P = 0.03), ability to perform key tasks (β = 0.22, P = 0.001) and shift schedule (β = -0.13, P = 0.05). Motivation was higher in health workers self-identifying as competent or who were enabled to provide more maternal care services. Motivation was lower in those who worked more frequent night shifts and those who had received training in the last 12 months. The interviews identified that the latter was because they felt the training was irrelevant to them, and in some cases, they do not have the opportunity to practice their learnt skills. The qualitative data also showed other factors relating to service context and organisational management practices contributed to motivation. The study demonstrates the importance of understanding the motivations of health workers and the factors that contribute to this and may contribute to more effective management of the health workforce in low- and middle-income countries.


The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC(50) values of 34.8 nM and 26.7 microM. Several compounds also showed moderate anti-proliferation at 10 microM against colon and liver cancer cell lines.


Empathy and its correlates in Iranian physicians: A preliminary psychometric study of the Jefferson Scale of Physician Empathy.
Empathy is one of the fundamental factors in patient care that is beneficial to both patient and physician. To assess the psychometric properties of the Persian version of the Jefferson Scale of Physician Empathy (JSPE) in a sample of Iranian physicians and examine its correlates. Two hundred and seven general physicians completed the JSPE. The associations of empathy scores with demographic characteristics and practice-related variables were examined. The scale showed an acceptable internal consistency (α = 0.78). Three of six extracted factors were considered as prominent based on the scree test, which were similar to those obtained in the US samples. Women scored higher than men. Empathy improved with increasing practice experiences. Other practice-related variables did not show a significant association with empathy. Results support the construct and criterion-related validities and reliability of the Persian version of the JSPE. Score difference between Iranian and American samples may not reflect a genuine difference in empathy trait and can be explained by cultural factors.


Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve.
The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38 years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls. Sixty-one patients were found to have ovarian endometriomas and 42 patients non-endometriotic cysts. A small amount of normal ovarian tissue was obtained during ovarian cystectomy. The follicles in normal ovarian tissue and resected cyst walls were histologically evaluated. The density of follicles in ovarian tissues correlated with the age of the patients in both groups. In women aged <35 years, the relative density of follicles in healthy ovarian tissues was consistently lower in the endometriotic cyst group compared to the non-endometriotic cyst group, with the relative ratio at age 20, 30 and 35 years calculated to be 35.4%, 46.8% and 62.7%, respectively. There was no significant difference between the groups in patients over the age of 35. The resection rate of normal ovarian tissue in cystectomy specimen of the endometriosis group was significantly higher than in the non-endometriotic cyst group (P < 0.001). Our data suggest that ovarian endometriomas have a detrimental impact on follicle reserve in younger patients. Further, laparoscopic cystectomy for endometriomas may accelerate the rate of oocyte loss associated with aging.


Multivariate statistical analysis of radioactive variables in two phosphate ores from Sudan.
Multivariate statistical techniques are efficient ways to display complex relationships among many objects. An attempt was made to study the radioactive data in two types of Sudanese phosphate deposits; Kurun and Uro phosphate, using several multivariate statistical methods. Pearson correlation coefficient revealed that a U-238 distribution in Kurun phosphate is controlled by the variation of K-40 concentration, whereas in Uro phosphate it is controlled by the variation of U-235 and U-234 concentration. Histograms and normal Q-Q plots clearly show that the radioactive variables did not follow a normal distribution. This non-normality feature observed may be attributed to complicating influence of geological factors. The principal components analysis (PCA) gives a model of five components for representing the acquired data from Kurun phosphate, where 89.5% of the total variance is explained. A model of four components was sufficient to represent the acquired data from Uro phosphate, where 87.5% of the total data variance is explained. The hierarchical cluster analysis (HCA) indicates that U-238 behaves in the same manner in the two types of phosphates; it associated with a group of four radionuclides; U-234, Po-210, Ra-226, Th-230, which the most abundant radionuclides, and all belong to the uranium-238 decay series. Two parameters have been adapted for the direct differentiate between the two phosphates. Firstly, U-238 in Uro phosphate have shown higher degree of mobility (CV% = 82.6) than that in Kurun phosphate (CV% = 64.7), and secondly, the activity ratio of Th-230/Th-232 in Uro phosphate is nine times than that in Kurun phosphate.


Effects of microwaving human milk: changes in IgA content and bacterial count.
On the basis of this study, IgA was best preserved in frozen human milk by thawing either overnight in the refrigerator or under warm running water. If either of those procedures are to be used, it is suggested that bacterial monitoring should be performed. Because current technology does not allow for accurate low internal temperature monitoring of liquids, it is concluded that use of the microwave oven for the treatment of human milk is inappropriate. However, because microwaving is as effective as holder pasteurization in killing bacteria, and because it would be less expensive and is faster, this process should be further investigated.


ECCO position statement: the use of biosimilar medicines in the treatment of inflammatory bowel disease (IBD).
Biologics have become key agents for the management of Crohn's disease and ulcerative colitis. Biosimilars are biological medicines similar to previously authorized biologics and are already available in some countries. This ECCO Position Statement defines the collective view of European specialist in inflammatory bowel disease (IBD) concerning biosimilars. Biosimilars are not comparable to generic small molecules, since both efficacy and toxicity are difficult to predict due to subtle molecular changes that can have profound effects on clinical efficacy and immunogenicity. Direct evidence of safety and benefit from clinical trials in IBD, post-marketing pharmacoviligance, and unequivocal identification of the product as a biosimilar should be requirements before approval. Switching from an established biologic to a biosimilar to save costs is likely to be as inappropriate and inefecctive as switching between current biologics that act on the same target, except when there is loss of response.


Which interventions improve HPV vaccination uptake and intention in children, adolescents and young adults? An umbrella review.
Human papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are. We conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail. From 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents. The evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.


Immunoperoxidase localization of keratin proteins, carcinoembryonic antigen, and factor VIII in adenomatoid tumors: evidence for a mesothelial derivation.
The histogenesis of adenomatoid tumors has been a source of controversy. Although most investigators favor a mesothelial derivation, recent ultrastructural evidence suggests that some adenomatoid tumors may be vascular neoplasms. This study reports the pattern of staining of seven adenomatoid tumors with antisera to keratin, factor VIII, and carcinoembryonic antigen (CEA), using an immunoperoxidase technique. All the tumors revealed strong cytoplasmic staining for keratin with no staining for factor VIII (an endothelial cell marker) or CEA. An identical staining pattern was evident in normal and reactive mesothelial cells. These findings support a mesothelial rather than an endothelial derivation for the tumors studied.


Prognostic role of heart rate variability in patients with a recent acute myocardial infarction.
A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).


Histotypic angiogenesis in vitro: light microscopic, ultrastructural, and radioautographic studies.
A model for the study of angiogenesis in vitro is described. Rat aortas, cultured in a tridimensional matrix of clotted chick plasma, gave rise to luxuriant outgrowth of vascular channels. We studied this process with light microscopic, radioautographic, and ultrastructural techniques. On the 2nd d of culture, endothelial cells sprouted from the intima of the aorta and its collateral branches into the surrounding clot, forming solid cellular cords. A complex vascular network was established within the 1st wk by spindly, poorly differentiated endothelial cells. At this stage cells were migrating, branching, and proliferating in a longitudinal fashion (labeling index: 67.4% +/- 7.7). Lumens, when present, appeared as slitlike spaces enclosed with junctional complexes. By the end of the 2nd wk the migratory activity decreased and proliferation occurred mostly in a cross-sectional plane, with formation of large patent lumens (labeling index: 48% +/- 3.1). Vascular channels were lined by prominent endothelial cells rich in rough endoplasmic reticulum, polysomes, mitochondria. Golgi apparatuses, and coated vesicles. Cells were enveloped with a ruthenium red positive layer, particularly abundant on the luminal surface and in the interendothelial space. A discontinuous basal lamina was present along the abluminal side. At 28 d the labeling index was reduced to 2.25% +/- 0.9. The still viable endothelium exhibited numerous microfilaments and microtubules, decreased cytoplasmic organelles, and increased pinocytotic activity. This experimental model, histophysiologic gradient culture, provides us with a new tool for the study of vascular morphogenesis, angiogenesis dependent growth of tumors, and neoplastic intravasation.


Use of glucose consumption rate (GCR) as a tool to monitor and control animal cell production processes in packed-bed bioreactors.
For animal cell cultures growing in packed-bed bioreactors where cell number cannot be determined directly, there is a clear need to use indirect methods that are not based on cell counts in order to monitor and control the process. One option is to use the glucose consumption rate (GCR) of the culture as an indirect measure to monitor the process in bioreactors. This study was done on a packed-bed bioreactor process using recombinant CHO cells cultured on Fibra-Cel disk carriers in perfusion mode at high cell densities. A key step in the process is the switch of the process from the cell growth phase to the production phase triggered by a reduction of the temperature. In this system, we have used a GCR value of 300 g of glucose per kilogram of disks per day as a criterion for the switch. This paper will present results obtained in routine operations for the monitoring and control of an industrial process at pilot-scale. The process operated with this GCR-based strategy yielded consistent, reproducible process performance across numerous bioreactor runs performed on multiple production sites.


Effects of diabetes on calcium uptake by rat brush border membrane vesicles.
1. We investigated the mechanism of decreased transmucosal calcium transport in the gut of the diabetic rat by comparing calcium uptake by brush border membrane vesicles from control and streptozotocin diabetic rats at 5 days. Brush border calcium uptake consists of saturable and non-saturable components. Saturable uptake is mediated by a specific mobile carrier mechanism and is defined by Vmax (saturable uptake of calcium at infinite medium calcium concentration) and KT (calcium concentration at Vmax/2). Non-saturable uptake is defined by kD (rate constant for non-saturable uptake per unit calcium concentration), and comprises both diffusive and surface binding components of calcium uptake. 2. We found both saturable and non-saturable calcium uptake to be decreased (P < 0.05) in diabetes. Comparing control and diabetic, Vmax was 247 compared to 152 (data are pmol/mg protein per 3 s); kD was 285 compared to 172 (data are pmol/mg protein per 3 s at 1 mmol/L calcium); and KT (mmol/L) did not differ between groups, 0.070 compared to 0.057. 3. The decreased Vmax in the setting of unchanged KT in vesicles from diabetics is consistent with decreased calcium transporter specific activity, rather than with altered transporter function. 4. Since (i) Vmax is decreased by vitamin D deficiency in the normal rat, and (ii) circulating 1 alpha, 25-dihydroxycholecalciferol is decreased in the diabetic rat, decreased Vmax in the diabetic may be related to the low 1 alpha,25-dihydroxycholecalciferol.(ABSTRACT TRUNCATED AT 250 WORDS)


Microneedle-based drug delivery: studies on delivery parameters and biocompatibility.
There is a significant interest in the application of microneedles in intradermal drug delivery systems. Previous studies have demonstrated that skin permeation of drugs can be increased by orders of magnitude with microneedle insertion. In this study, emphasis is placed on the development of low cost, painless intradermal microneedle systems that can enhance the percutaneous drug permeation. Microneedles of octagonal pyramidal shape with the length of 150 mum were employed, and the capabilities of skin permeation enhancement under different delivery conditions were examined. The delivery parameters taken into account included the insertion time and the area of insertion. It was found that when solid microneedle arrays of 150 mum in length were pierced into human dermatomed skin for 5 to 60 s, microconduits with the depth of 50 to 80 mum were created to facilitate the percutaneous permeation of drugs. In percutaneous tests, it was demonstrated that the permeability coefficient of calcein (MW = 622.55) was significantly increased by 10(4) to 10(5) times compared to that on intact skin. In terms of biocompatibility, biological evaluation indicated a broad spectrum of safety for the microneedle system. These results suggest that the octagonal pyramidal microneedles can be an effective tool in developing novel intradermal drug delivery system.


Left ventricular aneurysm, aortic stenosis, and arcade mitral valve: coexistence of three rare congenital heart defects.
This report presents two fetuses with three rare congenital heart defects: congenital ventricular aneurysm, arcade mitral valve, and unicommissural aortic valve. Because interaction between the endocardium and the myocardium is essential for development of the myocardium and heart valves, the authors hypothesized that these three defects could be related to abnormal signaling between the endocardium and the myocardium during critical phases of cardiac development. This combination of defects might be incompatible with fetal survival to term.


Sex-related differences after contemporary primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.
Whether outcomes differ for women and men after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains controversial. To compare 1-year outcomes after primary PCI in women and men with STEMI, matched for age and diabetes. Consecutive women with STEMI of<24 hours' duration referred (August 2007 to January 2011) for primary PCI were compared with men matched for age and diabetes. Rates of all-cause mortality, target vessel revascularization (TVR) and major cardiovascular and cerebrovascular events (MACCE) (death/myocardial infarction/stroke) were assessed at 1 year. Among 775 consecutive patients, 182 (23.5%) women were compared with 182 matched men. Mean age was 69±15 years, 18% had diabetes. Patient characteristics were similar, except for lower creatinine clearance (73±41 vs 82±38 μmol/L; P=0.041), more cardiogenic shock (14.8% vs 6.6%; P=0.017) and less radial PCI (81.3% vs 90.1%; P=0.024) in women. Rates of 1-year death (22.7% vs 18.1%), TVR (8.3% vs 6.0%) and MACCE (24.3% vs 20.9%) were not statistically different in women (P>0.05 for all). After exclusion of patients with shock (10.7%) and out-of-hospital cardiac arrest (6.6%), death rates were even more similar (11.3% vs 11.8%; P=0.10). Female sex was not independently associated with death (odds ratio 1.01, 95% confidence interval 0.55-1.87; P=0.97). In our consecutive unselected patient population, women had similar 1-year outcomes to men matched for age and diabetes, after contemporary primary PCI for STEMI, despite having a higher risk profile at baseline.


C-reactive protein and other predictors of poor outcome in patients hospitalized with exacerbations of chronic obstructive pulmonary disease.
CRP is elevated in patients with acute exacerbations of COPD (AECOPD), but there is little information on whether this biomarker can help to identify adverse short-term clinical outcomes. A 6-month prospective study of all patients with AECOPD requiring hospital admission. Clinical, laboratory (including plasma CRP levels at admission) and functional data were recorded. The outcome variable (the adverse outcome) consisted of: (i) death in hospital or within 15 days of discharge, (ii) transfer to the intensive care unit, or (iii) development of acute heart failure during hospitalization. Data from 147 patients with a total of 160 admissions were recorded. During follow up, 38 (23.7%) adverse outcomes were observed, including 13 (8.8%) and 8 (5.4%) patients who died during hospitalization or within 15 days of discharge, respectively. CRP at a level of 50 mg/L was related to an adverse outcome (OR 4.9, 95% CI: 1.92-12.6, P < 0.01), although by itself it was neither sensitive nor specific (area under the receiver operating characteristic curve (AUC) 0.69, 95% CI: 0.60-0.77). However, a risk score derived from the combination of CRP with other variables, such as 'current smoker', 'at least two comorbidities' and 'confusion,' at admission showed good predictive ability to identify an adverse outcome (AUC of 0.80, 95% CI: 0.72-0.88). Plasma CRP in combination with other variables obtained at admission may assist identification of high-risk patients with AECOPD.


Current recommendations for prevention and therapy of extravasation reactions in dermato-oncology.
Despite the introduction of many targeted therapies, a wide variety of cytostatic agents are still frequently used in dermato-oncology. In order to avoid further morbidity in tumor patients, prevention of extravasation reactions is of highest importance. The optimal management of extravasation requires an early diagnosis, the application of specific antidotes and a well-trained oncology team.


Impact of physician-assisted triage on timing of antibiotic delivery in patients admitted to the hospital with community-acquired pneumonia (CAP).
Time to antibiotic delivery in patients with diagnosis of pneumonia is a publicly reported quality measure. We aim to describe the impact of emergency department (ED) physician-assisted triage (PAT) on The Joint Commission (TJC) and Centers for Medicare and Medicaid Services (CMS) pneumonia core quality measures of timing to antibiotic delivery. Retrospective case series studies of patients admitted to the hospital through the ED with diagnosis of community-acquired pneumonia were identified over a period of 48 months. Patients were included in the study if they met TJC/CMS PN-5 (antibiotic timing) criteria. We compared antibiotic delivery timing before and after implementation of PAT in moderate-acuity patients using Wilcoxon rank sum tests. A linear regression analysis was done to account for age, sex, ED volume, and acuity level. A total of 659 patients were identified: 497 patients and 162 patients enrolled pre- and post-implementation of a PAT, respectively. The median antibiotic delivery times for moderate-acuity patients during open hours of operation of PAT were 180min (pre) and 195min (post), p=0.027; this was unchanged when ED volume, age, sex, and acuity level were accounted for. A total of 43 patients (9%) and 13 patients (8%) failed to receive antibiotics within 6h of ED presentation before and after implementation of PAT, respectively. In this study, implementation of PAT did not result in overall decrease in antibiotic delivery time in patients admitted to the hospital with CAP. We postulate several explanations for this delay in antibiotic delivery time.


Influence of fetal gender on the concentration of interleukin-1 receptor antagonist in amniotic fluid and in newborn urine.
IL-1 receptor antagonist (IL-1ra) is a cytokine that blocks the effects of IL-1 by binding to IL-1 receptors without inducing signal transduction. Amniotic fluid contains high concentrations of IL-1ra. The purpose of this study was 1) to analyze whether factors related to the mother or the fetus influence amniotic fluid IL-1ra concentration, and 2) to study whether the fetus is a source of IL-1ra. Two hundred two specimens of amniotic fluid, as well as 21 urine samples from newborn infants, were analyzed. Women carrying a female fetus had a higher concentration of amniotic fluid IL-1ra than those carrying a male fetus (female 136.4 +/- 6.1 micrograms/L, n = 83; male 74.7 +/- 3.7 micrograms/L, n = 119; p < 0.0001, unpaired two-sided t test). Length of gestation, presence or absence of labor signs, or elevated IL-1 beta in amniotic fluid did not affect the concentration of IL-1ra in amniotic fluid. Urine of infants taken during the first 48 h of life contained a high concentration of IL-1ra (91.1 +/- 17.5 micrograms/L). The urinary IL-1ra concentration was higher in female newborns than in male newborns (females 124.0 +/- 25.2 micrograms/L, n = 11; males 54.9 +/- 19.1 micrograms/L, n = 10; p = 0.04). We conclude that 1) the concentration of IL-1ra in amniotic fluid and newborn urine is dependent on the gender of the fetus and of the newborn and 2) fetal urine is a major source of amniotic fluid IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)


Theoretical prediction of ELNES/XANES and chemical bondings of AlN polytypes.
The first principles calculations of ELNES/XANES of AlN polytypes were carried out by the first-principles OLCAO method using large supercells composed of more than 100 atoms. It can quantitatively reproduce the experimental spectra from wurtzite AlN using a 108-atoms supercell. ELNES from rock-salt and zinc-blend AlN were predicted by using 128 atoms supercells. The spectral features of rock-salt phase are different from other phases, whereas that of zinc-blend phase have numerous similarities with that from wurtzite AlN. Characteristic differences between the wurtzite and zinc-blend phases are predicted to appear at the first peak of Al L(2,3) and K edges. The first peak of zinc-blend AlN is broader than that of wurtzite AlN. The same tendency was found in the case of SiC. In order to elucidate the cause of the broadness at the first peak, partial density of states and chemical bondings were investigated. The theoretical analysis revealed that the broadness of the first peak is related to the covalency of the compounds. This result suggests that the spectral features at the first peak of L(2,3) and K edges contain information about the covalency at the illuminated area.


Complementary replica of freeze-fractured human lymphocyte nuclei.
Complementary replicas of freeze-fractured human lymphocyte nuclei were obtained, and were studied with the electron microscope. Complementarity was evident in cross-fractured nuclear pore complexes and in particle-free membrane areas. Explanations for the observed structural peculiarities are considered.


Novel mutation of IFT140 in an infant with Mainzer-Saldino syndrome presenting with retinal dystrophy.
A seven-month-old girl presented with bilateral roving nystagmus, hyperopia, and retinal dystrophy, and was brought to our ophthalmology clinic. Visual-evoked potentials (VEPs) were non-recordable in both the eyes. No other systemic symptoms or abnormalities were observed. Whole exome sequencing (WES) identified a compound heterozygous mutation in the IFT140 gene: c.1990G > A (p. Glu664Lys) and c.2214_2217del (p.Asp738GlufsTer47). The genetic results support a diagnosis of Mainzer-Saldino syndrome (MSS). Importantly, c.2214_2217del is a novel mutation in the IFT140 gene. Although the patient presents with isolated retinal dystrophy, it is crucial to monitor renal function overtime. Taken together, our results reinforce the role of IFT140 in syndromic ciliopathies. This report also highlights the role of combined WES approaches in identifying underlying mutations in infants presenting with isolated retinal dystrophy, considering MSS may present differently over time.


An Application for Exploring Visual Perception: A Pilot Neuroeducational Study.
Neuroeducation of the human brain can be achieved with modern means and even with the use of computer applications. Thus, the idea for a painting application was born. This application focuses on the recreation of a two-dimensional geometric shape with fingers. Users are asked to draw a simple image with geometric shapes, from memory with the primary goal of correctly displaying the shapes of the original one. Based on the Rey-Osterrieth complex figure test, users are confronted with an image for a few seconds and are asked to locate the shapes in that image as well as to represent it as accurately as possible. The main concern is the categorization of users based on their score with the aim of mentally stimulating and training their brain. This categorization depends on how many shapes of the original image they have identified as well as how they have been designed. The main purpose of the application is the neuropsychological evaluation of its users, where it could be used to study information such as the degree of cognitive development in patients.


Vaccine Hesitancy in Pediatrics.
Vaccine hesitancy is a growing complex and multifaceted phenomenon. It encompasses a wide spectrum of context-dependent attitudes and beliefs. Multiple factors influence parental decision-making including knowledge, sources of information, risk perception, trust, and individual experiences among others. This review focuses on describing the most common reasons that contribute to vaccine hesitancy among parents. Social media and the Internet have been described as major elements that can negatively influence parental decision-making regarding vaccines. The next focus is describing effective interventions that clinical providers can apply. Nonconfrontational and open discussions along with trusting and strong relationships between parents and providers seem to create a solid foundation toward vaccine acceptance. In addition, motivational interviewing is a helpful tool that has proven to be effective during these discussions. Ultimately, an individualized approach tailored to a specific community will likely be most effective in addressing vaccine hesitancy.


Complete post-synthetic modification of a spin crossover complex.
The post-synthetic reaction between p-anisaldehyde and the spin-crossover compound [Fe(NH2-trz)3](NO3)2 was explored, obtaining different degrees of transformation from 23% to full conversion by varying the reaction time. The post-synthetic SCO complexes obtained were studied by magnetometry, powder X-ray diffraction (PXRD), elemental analysis, solid state NMR and IR and compared with the corresponding compounds obtained by direct synthetic routes, revealing new spin crossover properties.


Intensive care-treated COVID-19 patients' perception of their illness and remaining symptoms.
The remaining symptoms in patients with coronavirus disease 2019 (COVID-19) treated in intensive care unit are limited described. Therefore, we assessed patient's perception of their COVID-19 disease, stay in intensive care, and remaining symptoms three to six months after intensive care. Prospective cohort study was performed in one intensive care unit of a university hospital in Sweden during the first wave. A questionnaire with open-ended questions and closed-ended questions was used. Data were analyzed using qualitative and quantitative content analysis and descriptive statistics. Out of 123 patients treated for COVID-19, 64 answered the questionnaire 3-6 months after discharge from intensive care. Memories from illness and hospital stay revealed in three categories; awareness of the illness, losing anchor to reality and being cared for in a dynamic environment. Information was perceived as spare by 48% and they wanted the information to be more personal. The diary was perceived as personal and was received by 33% patients. The relationship with family was affected among 39% and 13% of the patients indicated that they had not resumed their daily life. A large amount, 84%, indicated that they had remaining symptoms from COVID-19. The dominated symptoms were impaired strength and energy both physically and mentally. Patients reported a variety of physical and mental symptoms, and revealed memories from the ICU, and specific awareness of other patients' health. It illustrates the need for screening patients for remaining symptoms after COVID-19 disease and ICU care and may affect resuming patients' daily life.


Early-Stage Feasibility of a Mobile Health Intervention (Copilot) to Enhance Exacerbation-Related Self-Management in Patients With Chronic Obstructive Pulmonary Disease: Multimethods Approach.
There is an emergence of mobile health (mHealth) interventions to support self-management in patients with chronic obstructive pulmonary disease (COPD). Recently, an evidence-driven mHealth intervention has been developed to support patients with COPD in exacerbation-related self-management: the Copilot app. Health care providers (HCPs) are important stakeholders as they are the ones who have to provide the app to patients, personalize the app, and review the app. It is, therefore, important to investigate at an early stage whether the app is feasible in the daily practice of the HCPs. The aim of this study is to evaluate the perceived feasibility of the Copilot app in the daily practice of HCPs. A multimethods design was used to investigate how HCPs experience working with the app and how they perceive the feasibility of the app in their daily practice. The feasibility areas described by Bowen et al were used for guidance. HCPs were observed while performing tasks in the app and asked to think aloud. The System Usability Scale was used to investigate the usability of the app, and semistructured interviews were conducted to explore the feasibility of the app. The study was conducted in primary, secondary, and tertiary care settings in the Netherlands from February 2019 to September 2019. In total, 14 HCPs participated in this study-8 nurses, 5 physicians, and 1 physician assistant. The HCPs found the app acceptable to use. The expected key benefits of the app were an increased insight into patient symptoms, more structured patient conversations, and more tailored self-management support. The app especially fits within the available time and workflow of nurses. The use of the app will be influenced by the autonomy of the professional, the focus of the organization on eHealth, costs associated with the app, and compatibility with the current systems used. Most HCPs expressed that there are conditions that must be met to be able to use the app. The app can be integrated into the existing care paths of primary, secondary, and tertiary health care settings. Individual organizational factors must be taken into account when integrating the app into daily practice. This early-stage feasibility study shows that the Copilot app is feasible to use in the daily practice of HCPs and can be integrated into primary, secondary, and tertiary health care settings in the Netherlands. The app was considered to best fit the role of the nurses. The app will be less feasible for those organizations in which many conditions need to be met to use the app. This study provides a new approach to evaluate the perceived feasibility of mHealth interventions at an early stage and provides valuable insights for further feasibility testing.


Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes.
In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities.


The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy.
Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestos-induced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.


Preparation of Mouse Embryonic Fibroblasts as Feeders for iPSC Generation and Maintenance.
Mouse embryonic fibroblasts (MEFs) can be used in co-culture to support generation of induced pluripotent stem cells (iPSCs) and the normal growth and proliferation of human pluripotent stem cells (hPSCs). Here, we describe the necessary steps to derive, expand, harvest, inactivate, plate, and use MEFs as feeders for iPSC generation and maintenance.


Comparison of wood-inhabiting myxomycetes in subalpine and montane coniferous forests in the Yatsugatake Mountains of Central Japan.
To demonstrate altitudinal gradients (and resulting temperatures) that affect myxomycete biodiversity and species composition, we statistically compared myxomycete assemblages between a subalpine coniferous forest and a montane pine forest within the region of the Yatsugatake Mountains, Nagano Prefecture, Central Japan. In summer and autumn field surveys during 2003-2010, 53 myxomycete taxa (with varieties treated as species) were observed from 639 records of fruiting bodies in the subalpine forest and 32 taxa were detected from 613 records in the montane forest. There were 20 species in common between the assemblages and the percentage similarity index was 0.400. Myxomycete biodiversity was higher in the subalpine than in the montane forest. Nine myxomycete species were statistically frequent occurrences in the subalpine forest and appeared in autumn: Lamproderma columbinum, Cribraria macrocarpa, Trichia botrytis, Physarum newtonii, Diderma ochraceum, Enteridium splendens, Elaeomyxa cerifera, Trichia verrucosa, and Colloderma oculatum. Five species were restricted to appear in the subalpine forest: Cribraria purpurea, Cribraria rufa, Cribraria ferruginea, Cribraria piriformis, and Lepidoderma tigrinum. Dead wood in the subalpine forest provided a breeding habitat for specific myxomycetes that inhabit cold areas; that is those areas having geographical features of decreasing temperature and increasing elevation, such as the temperate area of Central Japan.


Antimalarial Efficacy of Hydromethanolic Root Extract and Solvent Fractions of Urtica simensis Hochst. ex. A. Rich. (Urticaceae): An Experimental Study on Plasmodium berghei-Infected Mice.
Despite modern therapeutic armamentariums, malaria remains a 21st century public health menace. The issue of combating malaria is the ever-growing resistance to high-tech medications in which novel phytomedicines are highly demanding, a rapidly expanding research avenue. In Ethiopian folklore medicine, Urtica simensis has been used to treat malaria by drinking its juice after the dry roots have been mashed and combined with water. Hitherto, no in vivo study has been reported in the literature so far. To substantiate this folkloric claim, the present work herein was done. An acute oral toxicity study was conducted as per the standard protocol. To rule out, the extract's inherent potential effects on bodyweight, basal body To, and PCV changes were tracked for two weeks. A four-day suppressive model and a curative assay model were utilized to investigate the antimalarial activity of the plant. Percent parasitemia suppression, packed cell volume, mean survival date, bodyweight, and rectal body temperature were used to determine antimalarial activity. An acute toxicity study reveals that Urtica simensis was atoxic at a dose of 2000 mg/kg. It also affirms that U. simensis is free from intrinsic potential effects of interfering with bodyweight, temperature, and packed cell volume evolution. Both crude extract and its solvent fractions at all test doses exerted significant (P < 0.001) inhibition of parasitemia as compared to the control group. CF400 mg/kg provided the greatest chemosuppressive effect (79.24%). In a curative experiment, crude extract and CF were able to prevent the cardinal indications of P. berghei-induced malaria, such as weight loss, hypothermia, parasitemia, and anemia. Both crude extracts and their solvent fractions prolong survival dates. The antimalarial activity of the crude extract and its solvent fractions was promising, confirming previous assertions. As a result, more research studies into chemical entities may be required.


Impact of Body Mass Index on the Prognosis of Japanese Patients With Non-Valvular Atrial Fibrillation.
Obesity is a risk factor for atrial fibrillation (AF); however, obesity is associated with lower mortality in patients with established AF, a phenomenon known as the obesity paradox. Previous studies reported inconsistent results regarding effects of body weight on risk of cardiogenic embolism in patients with AF. To determine relation between body mass index (BMI) and prognosis among Japanese patients with nonvalvular AF (NVAF), a post hoc analysis was conducted using observational data in the J-RHYTHM Registry. Subjects were categorized as underweight (BMI <18.5), normal (18.5 to 24.9), overweight (25.0 to 29.9), or obese (≥30 kg/m(2)). End points included thromboembolism, major hemorrhaging, all-cause mortality, and cardiovascular mortality. Of the 7,406 patients with NVAF, 6,379 patients (70 ± 10 years old; BMI, 23.6 ± 3.9 kg/m(2)) having baseline BMI data constituted the study group. During the 2-year follow-up period, 111 patients had thromboembolism, 124 experienced major hemorrhage, and 159 died. Multivariate analysis with the Cox proportional hazards model showed that none of the BMI categories were independent predictors of thromboembolism. However, being underweight was an independent predictor of all-cause mortality (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.62 to 3.69; p <0.001) and cardiovascular mortality (HR 3.00, 95% CI 1.52 to 5.91, p = 0.001) when normal weight was used as the reference. Additionally, being overweight was a predictor of lower all-cause mortality (HR 0.60, 95% CI 0.37 to 0.95, p = 0.029). In conclusion, being underweight is associated with higher risks of all-cause and cardiovascular mortality compared with having a normal weight. Being overweight or obese is not associated with increased mortality among Japanese patients with NVAF.


Fabrication, calibration and evaluation of a phosphate ion-selective microelectrode.
To conduct the micro-environment study of flocs in an enhanced biological phosphorus removal (EBPR) process, a phosphate ion-selective microelectrode was developed. The cobalt-based microelectrodes have tip diameters of 5-20μm and respond to all the three forms of phosphate ions, namely, H(2)PO(4)(-), HPO(4)(2-), and PO(4)(3-). The calibration curve at pH 7.5 had a slope of 31.5mV per decade change of concentration and a R(2) value of 0.99. Other characteristics of this microelectrode, such as response time, interferences from pH, ion strength, DO and other anions were also evaluated.


Allergic prostatosis.
The first case of prostatic eosinophilic infiltration treated with antihistaminic therapy is reported. Histological specimens before and after treatment are included.


Effectiveness and Safety of Adalimumab, Etanercept and Ustekinumab for Severe Psoriasis in Children Under 12 Years of Age: A French-Italian Daily Practice Cohort (BiPe Jr).
Biological therapies are valuable treatments for severe psoriasis. Children aged under 12 years are underrepresented in therapeutic trials for these drugs. The objective of the 'BiPe Jr' cohort study was to evaluate the drug survival, effectiveness, tolerance and switching patterns of biological therapies in children under 12 years of age with psoriasis. We conducted a multicentre retrospective study of children with psoriasis who received at least one injection of a biological agent, even off-licence, before the age of 12 years in France and Italy, collecting the data between April and August 2021. The data collected were from March 2012 up to August 2021. In total, 82 children (mean age: 9.1 years; females: 61.0%) received 106 treatments. The drugs administered were adalimumab (n = 49), etanercept (n = 37), ustekinumab (n = 15), anakinra (n = 2), infliximab (n = 2) and secukinumab (n = 1). The most common form of psoriasis was plaque psoriasis (62.9%). The Physician Global Assessment and the Psoriasis Area Severity Index (PASI) scores decreased significantly from baseline to 3 months after treatment initiation for the three main biological drugs; PASI went from 14.1 ± 9.4 to 4.1 ± 11.3 for adalimumab (p = 0.001), 14.9 ± 9.3 to 5.1 ± 4.0 for etanercept (p = 0.002) and 11.6 ± 8.3 to 2.6 ± 2.2 for ustekinumab (p = 0.007). A trend towards higher 2-year maintenance rates was observed for ustekinumab and adalimumab, compared with etanercept (p = 0.06). 52 children discontinued their biological therapy, most frequently due to inefficacy (n = 28) and remission (n = 14). Seven serious adverse events (SAEs) were reported, including four severe infections. Our analyses of drug survival and treatment patterns, combined with those of previous studies conducted in older children, indicate that there is a trend towards higher 2-year survival rates of ustekinumab and adalimumab. The SAEs identified were rare, but highlight the need for increased vigilance concerning infections. Overall, the biological therapies showed good effectiveness and safety profiles when used in daily practice for the treatment of young children with psoriasis.


Magnitude and Severity of Depression and Associated Factors Among Hypertensive Patients Attending Follow-up Treatment at Public Hospitals of Hadiya Zone, Ethiopia.
Co-morbid depression in hypertension leads to non-adherence to anti-hypertensive treatment. To assess the magnitude and severity of depression and associated factors among hypertensive patients attending follow-up treatment at public hospitals of Hadiya zone, Ethiopia, 2022. Hospital-based cross-sectional study was conducted from January 1, to January 31, 2022. The total sample size was 315 and used a systematic random sampling technique. Data were collected through a face-to-face interview. Data were entered using Epi-data Version 4.6 and exported to SPSS Version 25 for analysis. The goodness-of-fit test was done. Binary logistic regression was done, and variables with a p-value of < .25 in the bivariable analysis were taken into the multivariable analysis. Statistically significant was declared at a p-value of < .05 with an adjusted odds ratio and 95% confidence interval. The magnitude of depression among hypertensive patients was 37.1% (95% CI 31.7-43.9). Regarding the severity, 56.1% had no depression, 6.7% had mild, 17.3% had moderate, 14.7% had moderately severe, and 5.1% had severe depression. Body mass index: 19.12-24.9 kg/m2 [AOR 0.06, 95% CI: 0.02-0.23], body mass index: 25-29.9 kg/m2 [AOR 0.08, 95% CI: 0.02-0.35], absence of family history hypertension [AOR 0.39, 95% CI: 0.18-0.85], presence of co-morbidity [AOR 2.43, 95% CI: 1.34-4.42), low perceived stress scale [AOR 0.07, 95% CI: 0.01-0.56], low medication adherence [AOR 2.70, 95% CI: 1.17-6.24], and moderate medication adherence [AOR 0.29, 95% CI: 0.09-0.88] were significantly associated. About four in 10 hypertensive patients attending follow-up treatment were depressed. The mean score of severity of depression was mild. Body mass index, family history of hypertension, co-morbidity, perceived stress scale, and medication adherence were significantly associated with depression. Therefore, maintaining body mass index, screening and treating co-morbid illness, accommodating stress, and educating about medication adherence might minimize the risk of depression.


[Mechanism of IL-6 on acrosome reaction in human sperm].
To explore the mechanism of interleukin-6 (IL-6) on acrosome reaction (AR) in human sperm. Sperm acrosin activity was measured by BAEE/ADH and AR evaluated by FITC-PSA. IL-6 could induce the activity of acrosin and superoxide dismutase (SOD) and enhance AR in human sperm. AR was not induced by extracellular Ca2+, and IL-6-induced AR did not occur in Ca2(+)-free medium. Calphostin C, one inhibitor of the protein kinase C (PKC), could block IL-6-induced AR in human sperm. IL-6 could induce AR by stimulating the activity of acrosin and SOD in human sperm, which also involves the activation of PKC, and requires the presence of extracellular Ca2+.


Activation of Toll-like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP-105) sufficiently enhances immune responses against tumors.
The cell wall skeleton of Mycobacterium bovis BCG has been investigated as an immunopotentiating adjuvant for immuno-therapy of malignant tumors via Toll-like receptor (TLR) 2 and TLR4. However, due to its high molecular weight, highly complicated lipoglycan structure, and complicated purification and isolation procedure, its exact structure-activity relationship has not been well established. We have newly isolated the cell wall skeleton from M. bovis BCG Tokyo (SMP-105) and examined the binding of SMP-105 with TLR. It was revealed that highly purified SMP-105 activates the nuclear factor-kB promoter in a TLR2-dependent manner, not a TLR4-dependent manner, using a reporter gene assay system. Peritoneal exudated cells of TLR2 and MyD88 knockout mice severely reduced the induction of tumor necrosis factor-alpha and interleukin-6 in the presence of SMP-105, whereas cells from TLR4 knockout mice produced similar levels of cytokines to wild-type mice. Dendritic cells and macrophages accumulated in the draining lymph nodes of treated mice. When mice were administered both SMP-105 and mitomycin C-inactivated Lewis lung carcinoma cells simultaneously, interferon-gamma-producing cells reacting to the tumor were increased distinctly in draining lymph nodes. When C57BL/6 mice, into which splenocytes from OT-I transgenic mice had been transferred, were administered with both SMP-105 and E.G7-OVA, OVA-specific cytotoxic T lymphocytes (CTL) increased markedly. Mice treated with SMP-105 and inactivated Lewis lung carcinoma cells suppressed the growth of implanted tumors. These results suggest that the activation of TLR2 by SMP-105 sufficiently enhanced immune responses, such as the number of interferon-gamma-producing cells and CTL, and prevented the growth of tumors without the contribution of TLR4.


Lack of Communication about Medical Marijuana Use between Doctors and Their Patients.
Medical marijuana is now permitted in most states, but it is not clear whether primary care physicians (PCPs) are aware of or recommend its use in their patients. We distributed paired surveys to PCPs and their patients to assess the frequency of patient marijuana use and communication with PCPs about use. Of 242 patients surveyed, 22% reported marijuana use in the past 6 months, and 61% of these identified as medical marijuana users. PCPs did not complete state forms to recommend medical marijuana for any of the surveyed medical marijuana users. PCPs were aware of marijuana use in their patients only 53% of the time. PCPs identified conditions they believed could be adversely affected by marijuana use in 31% of users. There is poor communication between patients and PCPs about medical marijuana use, which is being sanctioned by physicians other than patients' PCPs. We suggest more frequent assessment of and discussion about marijuana use in patients, particularly in states that have approved medical marijuana.


A comparative assessment of efficacy and preference between needleless device INJEX and insulin syringe for anesthetizing primary maxillary teeth in children aged 4-9 years: A split-mouth crossover randomized clinical study.
insulin syringe for anesthetizing primary maxillary teeth in children aged 4-9 years. This randomized clinical study included 46 children aged 4-9 years. The patients were digitally allotted to receive 4% articaine for extractions of primary maxillary teeth, either using needleless device INJEX or insulin syringe on each side of the maxillary arch, in two different appointments after a 1-week washout period. Pain perception was measured by the subjective (Faces Pain Scale-Revised [FPS-R]) and objective pain scores (Face, Legs, Activity, Cry, and Consolability [FLACC]) and hemodynamic parameters (heart rate and oxygen saturation) during LA administration and during extractions. After the second appointment, children were asked about their preference between needleless device INJEX and insulin syringe. On evaluating subjective pain scores with FPS-R, intergroup differences between the INJEX and insulin syringe groups were found statistically insignificant, both during LA administration (P = 0.101) and extraction (P = 0.080). However, on assessing pain objectively during extraction using FLACC, the mean pain score was less with insulin syringe (2.78) as compared to INJEX (4.72) and the difference was statistically significant (P = 0.000). There was no significant difference in patient preference between the two methods. Pain perception was minimal during local anesthesia administration using needleless device INJEX; however, its clinical efficacy during extractions was reported to be lower than insulin syringe. Managing pain in children is the most challenging task as it forms the foundation for instilling positive behavior toward dental treatment. Adequate local anesthesia (LA) is the cornerstone of pain management. However, the fear of needles, particularly in young children, can result in complete avoidance and refusal of treatment. This study aimed to evaluate and compare the efficacy and preference between needleless device INJEX and.


Effect of polyol osmolytes on the structure-function integrity and aggregation propensity of catalase: A comprehensive study based on spectroscopic and molecular dynamic simulation measurements.
Owing to the ability of catalase to function under oxidative stress vis-à-vis its industrial importance, the structure-function integrity of the enzyme is of prime concern. In the present study, polyols (glycerol, sorbitol, sucrose, xylitol), were evaluated for their ability to modulate structure, activity and aggregation of catalase using in vitro and in silico approaches. All polyols were found to increase catalase activity by decreasing Km and increasing Vmax resulting in enhanced catalytic efficiency (kcat/Km) of the enzyme. Glycerol was found to be the most efficient polyol with a kcat/Km increase from 4.38 × 104 mM-1 S-1 (control) to 5.8 × 105 mM-1 S-1. Correlatively with this, enhanced secondary structure with reduced hydrophobic exposure was observed in all polyols. Furthermore, increased stability, with an increase in melting temperature by 15.2 °C, and almost no aggregation was observed in glycerol. Overall, ability to regulate structure-function integrity and aggregation propensity was highest for glycerol and lowest for xylitol. Simulation studies were performed involving structural dynamics measurement, principal component analysis and free energy landscape analysis. Altogether, all polyols were stabilizing in nature and glycerol, in particular, has potential to efficiently prevent not only the aggregation of the antioxidant defense system but might also serve as a stability aid during industrial processing of catalase.


Single-cell transcriptome analysis reveals aberrant stromal cells and heterogeneous endothelial cells in alcohol-induced osteonecrosis of the femoral head.
Alcohol-induced osteonecrosis of the femoral head (ONFH) is a disabling disease with a high incidence and elusive pathogenesis. Here, we used single-cell RNA sequencing to explore the transcriptomic landscape of mid- and advanced-stage alcohol-induced ONFH. Cells derived from age-matched hip osteoarthritis and femoral neck fracture samples were used as control. Our bioinformatics analysis revealed the disorder of osteogenic-adipogenic differentiation of stromal cells in ONFH and altered regulons such as MEF2C and JUND. In addition, we reported that one of the endothelial cell clusters with ACKR1 expression exhibited strong chemotaxis and a weak angiogenic ability and expanded with disease progression. Furthermore, ligand-receptor-based cell-cell interaction analysis indicated that ACKR1+ endothelial cells might specifically communicate with stromal cells through the VISFATIN and SELE pathways, thus influencing stromal cell differentiation in ONFH. Overall, our data revealed single cell transcriptome characteristics in alcohol-induced ONFH, which may contribute to the further investigation of ONFH pathogenesis.


Identification of Immune-Related Breast Cancer Chemotherapy Resistance Genes via Bioinformatics Approaches.
Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.


Elective robotic hysterectomy for placenta accreta spectrum in the second trimester: Case report.
A scheduled pre-viable hysterectomy is a treatment option for women with early diagnosed placenta accreta spectrum who do not wish future fertility. A minimally invasive hysterectomy with pregnancy in situ for placenta accreta spectrum has not been previously reported. A patient with evidence of placenta accreta spectrum on prenatal imaging underwent an elective robot-assisted laparoscopic hysterectomy at 16 weeks of gestation. The procedure was uncomplicated and she was discharged on postoperative day 1. Pathology was consistent with placenta percreta. Robot-assisted laparoscopic hysterectomy with pregnancy in situ is feasible in a patient with placenta accreta spectrum in the second trimester. 1. Early diagnosis of placenta accreta spectrum is important for surgical planning and management. 2. We present a technique for minimally invasive hysterectomy in a patient with placenta accreta spectrum diagnosed before viability.


Rifampicin quinone is an immunosuppressant, but not rifampicin itself.
Rifampicin as a potential immunosuppressive agent was tested in the rat. A freshly made-up solution of this labile antibiotic in a daily dosage of 20 mg/kg iv did not affect mean graft survival time in a heterotopic heart transplant model. However, when stored solutions of rifampicin were used mean graft survival time was significantly prolonged (from 8.2 +/- 0.4 days with the controls to 18.1 +/- 1.2 days). A similar prolongation was observed when rifampicin quinone, the major rifampicin oxidation product, was administered. We conclude that the immunosuppressive effect ascribed to rifampicin is in fact due to its oxidation product, rifampicin quinone.


Connecting the dots: The boons and banes of network modeling.
Network modeling transforms data into a structure of nodes and edges such that edges represent relationships between pairs of objects, then extracts clusters of densely connected nodes in order to capture high-dimensional relationships hidden in the data. This efficient and flexible strategy holds potential for unveiling complex patterns concealed within massive datasets, but standard implementations overlook several key issues that can undermine research efforts. These issues range from data imputation and discretization to correlation metrics, clustering methods, and validation of results. Here, we enumerate these pitfalls and provide practical strategies for alleviating their negative effects. These guidelines increase prospects for future research endeavors as they reduce type I and type II (false-positive and false-negative) errors and are generally applicable for network modeling applications across diverse domains.


[HDL cholesterol and physical training: comparative study of a group of sedentary with a group of athletic young subjects].
Many recent studies have clearly established the anti-atherogenic effect of serum HDL cholesterol. Serum HDL cholesterol was quantified in sedentary young people (less than two weekly hours of moderate physical exercise) and in active young people (average five weekly hours of intense physical exercise). A statistical comparative study indicates that this physical training difference goes with significantly higher HDL cholesterolemia in active young people.


Pseudomeningocele of the lumbar spine.
A patient with a lumbar pseudomeningocele after intervertebral disc surgery is reported and the findings of computed tomography and magnetic resonance imaging are described.


The transition from knowing to doing: teaching junior doctors how to use insulin in the management of diabetes mellitus.
To develop and evaluate a short education programme to improve the skills and confidence of junior doctors in managing the glycaemic control of inpatients with diabetes mellitus. A total of 15 junior doctors completed two 1-hour workshops on the practical skills required to manage the glycaemic control of insulin-treated patients. The workshops were based on simulated case scenarios presented in a workbook format. Pre-workshop performance and levels of confidence were tested, using a set of tasks matched to the learning objectives. Participants were re-tested immediately after the second workshop and again after 3 months. There was a significant overall effect for time of testing for performance and confidence considered together, F(4,11) = 12.67, P = 0.000, power = 1.00. The mean score for performance for the intermediate and 3-month post-tests combined was significantly higher than the mean performance score for the pre-test (11.00 < [17.53 + 15.80]), t(56) = -6.50, P = 0.000 (95% CI -6.15, -3.10). The mean score for confidence for the intermediate and 3 month post-tests combined was higher than the mean for the pre-test (13.20 < [15.33 + 15.20]), t(56) = 2.95, P = 0.011 (95% CI 2.19, 0.46), although this result must be treated with caution. A brief educational intervention can improve and maintain the performance and confidence of junior doctors in managing patients with insulin-treated diabetes in a simulated environment.


Effect of tolbutamide on aminophylline-, 3,5-AMP-dibutyrate- or glucagon-induced insulin release from pancreatic islets after impairment of pyridine nucleotide metabolism caused by 6-aminonicotinamide (6-AN).
The effect of tolbutamide on pyridine nucleotides and insulin secretion stimulated by aminophylline, 3,5-AMP-dibutyrate or glucagon was studied in pancreatic islets of rats previously treated with 6-aminonicotinamide (6-AN), an inhibitor of pyridine nucleotide synthesis. After being incubated for 60 min in a Krebs-Ringer-Bicarbonate-Buffer in the absence of glucose, pancreatic islets of rats i.p. injected with 35 mg/kg of 6-AN 6 hrs before pancreas removal contained about 30% less NADP and NADPH than did islets of control rats. No changes of NDA or NADH were observed in islets of 6-AN-treated animals. Addition of 16.5 mM glucose led to an increase of NADH, NADPH and a decrease of NADP in islets of both groups of animals; NAD levels remained unchanged. In vitro addition of tolbutamide to islets of control rats did not affect the levels of NADPH or NADP in the presence of 5.5 mM glucose. When 16.5 mM glucose were present, a decrease of NADPH and an increase of NADP was obvious. No effect of tolbutamide on insular NADPH or NADP was observed in islets of rats previously treated with 6-AN be it in the presence of 5.5 or 16.5 mM glucose. In islets of 6-AN-treated rats insulin release in response to aminophylline or 3,5-AMP-dibutyrate in the presence of 5.5 mM glucose was significantly depressed, when compared to islets of untreated controls. Addition of tolbutamide increased insulin release due to aminophylline, 3,5-AMP-dibutyrate or glucagon islets of controls. Tolbutamide alone was without effect. In islets of 6-AN-treated rats aminophylline, 3,5-AMP-dibutyrate or glucagon stimulated insulin release only when tolbutamide was present. Our data suggest that there is no direct interference of tolbutamide with pyridine nucleotides of pancreatic islets, and that tolbutamide increases the secretory response of the beta-cell to aminophylline, 3,5-AMP-dibutyrate or glucagon when insulin release due to these agents is inhibited during decrease of insular NADP and NADPH, caused by 6-AN.


Immunohistochemical study of cells positive for glial fibrillary acidic protein (GFAP) in the human pituitary gland, with special reference to folliculo-stellate cells.
The cytology and the distribution of cells which contain glial fibrillary acidic protein (GFAP) were studied immunohistochemically in thick frozen sections of human pituitary glands. Immunoreactive cells were constantly demonstrated in both neuro- and adenohypophysis. In the neural lobe, an irregular network of long GFAP-positive pituicyte processes was revealed. Within this network, some asymmetric pituicytes became visible. A variable number of cells was stained in cell cords and follicles of the pars distalis and the intermediate zone. The morphology of these cells could be studied in detail, providing strong evidence to support the hypothesis that adenohypophyseal GFAP-immunoreactive cells belong to the folliculo-stellate (FS) cell system. Cells with similar cytological features in the pars distalis or the intermediate zone were found to share common immunoreactivities against GFAP and the presumable FS cell markers vimentin and S-100 protein. Our results corroborate the notion that, in the human pituitary, GFAP can be regarded as a marker protein of pituicytes and FS cells, which is expressed at varying degrees.


Haplogroup Structure and Genetic Variation Analyses of 60 Mitochondrial DNA Markers in Southern Shaanxi Han Population.
Mitochondrial DNA (mtDNA) has been widely employed as one tool for the studies of human migration and phylogenetic evolution owing to the characteristics of its lack of recombination and matrilineal inheritance. In this study, we analyze genetic distributions of 60 mtDNA markers in 126 unrelated individuals of Southern Shaanxi Han population and classify their haplogroups. Genetic distribution comparisons between Southern Shaanxi Han and other populations from different continents are conducted based on the same mtDNA markers. The majority of 60 mtDNA markers are polymorphic in Southern Shaanxi Han population. The most common haplogroups observed in Southern Shaanxi Han population are B5, followed by D5, A, D4e, and N9a1'3. Obtained matching probability for these 60 mtDNA markers indicates that the panel could be used as a valuable tool in forensic caseworks. Results of genetic distances (Fst) and multidimensional scaling analysis show that Southern Shaanxi Han population has relatively close genetic relationships with other Han populations in different regions. In conclusion, the panel comprising 60 mtDNA markers could be utilized for forensic applications in Southern Shaanxi Han population.


The occurrence of alpha (1----2) linked N-acetylperosamine--homopolymer in lipopolysaccharides of non-O1 Vibrio cholerae possessing an antigenic factor in common with O1 V. cholerae.
Chemical analysis was carried out on lipopolysaccharides from Vibrio cholerae bio-serogroup Hakata 487-85. The O-specific chain of the phenol-soluble lipopolysaccharides was demonstrated by 13C-NMR spectroscopy and methylation analysis to contain a linear homopolymer of alpha(1----2) linked N-acetylperosamine (4-acetamido-4,6-dideoxy-D-mannopyranose), which was closely similar to but not identical to a linear alpha(1----2) linked N-3-deoxy-L-glycerotetronyl (S-2,4-dihydroxybutyryl) perosamine-homopolymer constituting that of O1 Vibrio cholerae lipopolysaccharides.


Saliva as a diagnostic tool for oral and systemic diseases.
Early disease detection is not only vital to reduce disease severity and prevent complications, but also critical to increase success rate of therapy. Saliva has been studied extensively as a potential diagnostic tool over the last decade due to its ease and non-invasive accessibility along with its abundance of biomarkers, such as genetic material and proteins. This review will update the clinician on recent advances in salivary biomarkers to diagnose autoimmune diseases (Sjogren's syndrome, cystic fibrosis), cardiovascular diseases, diabetes, HIV, oral cancer, caries and periodontal diseases. Considering their accuracy, efficacy, ease of use and cost effectiveness, salivary diagnostic tests will be available in dental offices. It is expected that the advent of sensitive and specific salivary diagnostic tools and the establishment of defined guidelines and results following rigorous testing will allow salivary diagnostics to be used as chair-side tests for several oral and systemic diseases in the near future.


Novel compound heterozygous mutations of the growth hormone-releasing hormone receptor gene in a case of isolated growth hormone deficiency.
To elucidate the pathogenesis of isolated growth hormone (GH) deficiency in a Japanese girl without consanguinity. A 2-year-old girl of height 77.2 cm (-3.0 SD for Japanese girls) was found to have an insulin-like growth factor (IGF)-1 level of 7 ng/mL and IGF binding protein-3 (IGFBP-3) level of 0.41 μg/mL. GH responded modestly to a series of pharmacological stimulants, increasing to 2.81 ng/mL with insulin-induced hypoglycemia, 3.78 ng/mL with arginine, and 3.93 with GH-releasing hormone (GHRH). Following direct sequencing of the GHRH receptor (GHRHR) gene, evaluation by the luciferase reporter assay, immunofluorescence study, and in vitro splicing assay with minigene constructs was conducted. Novel compound heterozygous GHRHR gene mutations were identified in the patient. A p.G136V substitution elicited no luciferase activity increment in response to GHRH stimulation, with normal membranous expression. Splicing assay demonstrated that the IVS2+3a>g mutation would lead to aberrant splicing. A case of isolated GH deficiency due to novel GHRHR gene mutations was identified.


Production of immunoglobulin G and increased antiviral antibody in cerebrospinal fluid of dogs with delayed-onset canine distemper viral encephalitis.
Sera and cerebrospinal fluid (CSF) from four dogs with delayed-onset canine distemper viral (CDV) encephalitis (old dog encephalitis) were compared with samples from dogs with acute CDV and from recently vaccinated controls. Dogs with old dog encephalitis (ODE) had elevated CSF IgG concentrations (122 micrograms/ml) compared to controls (13 micrograms/ml) without elevated CSF albumin; their CSF IgG index was significantly greater. CSF proteins banding in the alkaline region of isoelectric focusing gels were immunochemically identified as IgG. Detectable viral neutralizing antibody was present in ODE CSF, and formed a larger proportion of IgG in CSF than in serum. Serum samples containing 2 mg IgG bound to all viral polypeptides of both R252 and Onderstepoort CDV isolates by immunoblot analysis. CSF samples of ODE patients bound viral antigens when diluted to contain as little as 5-40 micrograms IgG, while patient serum could be diluted to 40-200 micrograms IgG content compared to serum IgG of 100 micrograms/ml in vaccinated controls. Serial CSF dilutions consistently bound to H and NP polypeptides at the highest dilutions, similar to the binding of serums from recently vaccinated dogs. Thus, dogs with delayed-onset CDV encephalitis have elevated concentrations of CSF IgG, much of which is virus-specific, with an antigen binding pattern similar to that of sera of recently immunized dogs.


Chlorinated hydrocarbons in coastal lagoons of the pacific coast of Nicaragua.
A screening for persistent chlorinated hydrocarbons was carried out in December 1995 in the main coastal lagoons on the Pacific side of Nicaragua, where most of the country's agriculture and pesticide use has been taking place for decades. Results for a wide range of organochlorine pesticides in lagoon sediments show levels that generally were very low in Estero Real, Estero Padre Ramos, and estuary of San Juan del Sur. For example, total DDTs in these lagoons averaged 4.5 +/- 3.4 ng g-1 dry weight, which may be considered a baseline level for the region. Other compounds such as HCHs, BHC, endosulfan, heptachlor, endrin, toxaphene, and aroclors were present in concentrations even lower, generally below 1 ng g-1 dry weight. However, sediments of the Esteros Naranjo-Paso Caballos system at Chinandega district contained pesticide residues in much higher levels, attaining maximum values of 1,420 ng g-1 and 270 ng g-1 dry weight, respectively, for toxaphene and total DDTs. Other compounds such as aroclors, chlordane, endosulfan, and dieldrin were also present in the sediments of this lagoon system, but in lower concentrations. The very high concentrations of toxaphene and DDTs in this lagoon are a result of the intensive use of these pesticides in cotton growing in the district of Chinandega. Due to the long environmental half-lives of these compounds (t(1/2) > 10 years in temperate soils), their concentrations in lagoon sediments will likely remain high for years to come. Based on these results, the development of the new shrimp farming activities in the Pacific coastal lagoons should be restricted to selected areas.


Biomimetic scaffolds containing nanofibers coated with willemite nanoparticles for improvement of stem cell osteogenesis.
Nowadays, discovering osteogenesis stimulating effectors is one of the major topics in bone tissue engineering and regenerative medicine. In this study, the proliferation rate and osteogenic differentiation potency of adipose-derived mesenchymal stem cells (AT-MSCs) cultured on poly (l-lactide acid) (PLLA) and willemite-coated PLLA were investigated by MTT assay and common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition and bone-related genes expression. Willemite-coated PLLA showed a higher proliferation support to AT-MSCs in comparison to PLLA and TCPS. During the period of study, AT-MSCs cultured on willemite-coated PLLA scaffolds exhibited the greatest ALP activity and mineralization. Gene expression analysis demonstrated that the highest expression of four important osteogenic-related genes, osteonectin, Runx2, collagen type 1 and osteocalcin was observed in stem cells cultured on willemite-coated PLLA nanofibrous scaffolds. According to the results, willemite-coated PLLA could be a suitable substrate to support the proliferation and osteogenic differentiation of stem cells and holds promising potential for bone tissue engineering and regenerative medicine applications.


Effects of hydrolyzable and condensed tannin on growth and development of two species of polyphagous lepidoptera: Spodoptera eridania and Callosamia promethea.
The effects of tannins on survival, growth, and digestion were compared in two polyphagous species of Lepidoptera (one, the southern armyworm, a forb-feeder; and the other, the promethea silkmoth, a tree-feeder). Two different types of tannins (hydrolyzable and condensed) were incorporated into artificial basal diets in order to determine whether or not differential survival and growth would result between the forb feeder, which normally does not encounter tannins in its natural diet, and the tree-feeder, whose host species include many tanniniferous plants from several different families.Neonate larvae of the forb-feeding armyworms exhibited significantly suppressed 10-day growth rates at all tannin concentrations tested (0.5, 1.0, 1.5, 2.0, 2.5, and 3.0% of wet weight) for both the hydrolyzable and the condensed tannin compared to the control diet, however no dose-effect was detectable. In contrast, there were no detectable differences in neonate survival or growth through the first 10 days for the tree-feeding promethea silkmoth larvae fed diets with either tannic acid or quebracho tree condensed tannin.In order to determine the physiological mechanisms of action of these tannins against armyworms, we conducted detailed physiological bioassays of biomass and nitrogen utilization by penultimate instar larvae. Standard gravimetric feeding studies with both tannic acid and the quebracho tree condensed tannin demonstrated that reduced relative growth rates (RGR's) of Spodoptera eridania Cram. were due to the suppressed relative consumption rates (RCR's) and decreased conversion efficiencies (ECD's) rather than due to digestibility-reduction (as reflected by approximate digestibility, AD). As with the neonate larval growth rate suppression, there were no detectable dose responses at the different concentrations of tannic acid (0.25, 0.50, 0.75, 1.00, 2.50, and 5.0 percent) and condensed tannins from quebracho (0.25, 0.50, 0.75, 1.0, and 2.5 percent) in our penultimate instar studies.


Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription.
The CCAAT displacement protein (CDP-cut/CUTL1/cux) performs a key proliferation-related function as the DNA binding subunit of the cell cycle controlled HiNF-D complex. HiNF-D interacts with all five classes (H1, H2A, H2B, H3, and H4) of the cell-cycle dependent histone genes, which are transcriptionally and coordinately activated at the G(1)/S phase transition independent of E2F. The tumor suppressor pRB/p105 is an intrinsic component of the HiNF-D complex. However, the molecular interactions that enable CDP and pRB to form a complex and thus convey cell growth regulatory information onto histone gene promoters must be further defined. Using transient transfections, we show that CDP represses the H4 gene promoter and that pRB functions with CDP as a co-repressor. Direct physical interaction between CDP and pRB was observed in glutathione-S-transferase (GST) pull-down assays. Furthermore, interactions between these proteins were established by yeast and mammalian two-hybrid experiments and co-immunoprecipitation assays. Confocal microscopy shows that subsets of each protein are co-localized in situ. Using a series of pRB mutants, we find that the CDP/pRB interaction, similar to the E2F/pRB interaction, utilizes the A/B large pocket (LP) of pRB. Thus, several converging lines of evidence indicate that complexes between CDP and pRB repress cell cycle regulated histone gene promoters.


Feasibility of transcaval access TAVI in morbidly obese patients: A single-center experience.
We report a single-center experience in utilizing the transcaval-access transcatheter aortic valve implantation (TAVI) as an alternative approach in morbidly obese patients. Morbidly obese patients present frequently for TAVI. Transfemoral arterial access TAVI in these patients is technically challenging due to deep arterial access, resulting in a higher risk of vascular complications. Transcaval access TAVI is increasingly used in patients with prohibitive iliofemoral arterial access. We used the transcaval approach for eight morbidly obese patients who had otherwise technically feasible femoral arterial access. This technique provides an alternative arterial access point that potentially circumvents some of the challenges relating to femoral arterial access. We report eight morbidly obese patients with a mean body mass index of 42.3 ± 6.2 kg/m2 who underwent transcaval access TAVI at our center (mean EuroScore II 2.47 ± 1.83%). The patient mean age was 70.3 ± 9.8 years; six were female. All eight patients underwent a successful and uncomplicated procedure. The median time to discharge was 2 days and all patients were alive at 30 days. Transcaval access TAVI is a feasible alternative for morbidly obese patients and may reduce vascular complications. Further data are required to evaluate the safety of this approach.


A new model of the mechanism underlying lead poisoning: SNPs in miRNA target region influence the δ-aminolevulinic acid dehydratase expression level.
To determine if SNPs located within the 3'-UTR of δ-aminolevulinic acid dehydratase (ALAD) can alter the risk of lead poisoning and the ALAD gene expression. A case-control study was carried out to find the SNPs in miRNA target region. Luciferase reporter gene assay, qRT-PCR and Western blot was used to determine the relationship between miRNA and SNPs. We found a significant association between rs818708 and the risk of lead poisoning. miR-545-5p was influenced by rs818708 variant and might result in a significant change in ALAD expression. rs818708 T > C can weaken the binding capability between miR-545-5p and 3'-UTR of ALAD and thus may alter the risk of lead poisoning.


Lipoma arborescens - Uncommon Diagnosis for Joint Swelling: Case Report and Review of the Literature.
Soft tissue swelling of the knee joint can be caused by many diseases. Lipomas are one of the most reasonable differential diagnoses we have to consider. Therefore, we now present the uncommon case of a Lipoma arborescens (LA) and differentiate it from a quite similar manifesting spindle cell lipoma as follows. A 49-years old patient reports about progressive knee pain for four years and observes an increasing joint swelling. This swelling is a soft tissue, shiftable tumour, not painful. The magnetic resonance imaging (MRI) with contrast agent brings the diagnosis of an advanced osteoarthritis of the knee joint and classifies the tumour as LA. Subsequently, we treat the osteoarthritis by implanting a total knee arthroplasty with simultaneous intraoperative tumour resection performed as total synovectomy. The histopathological processing confirms the clinically and radiologically made diagnosis of LA. Lipoma arborescens presents an uncommon subgroup of Lipomas, which is characterized by a slowly progressive increasing soft tissue swelling, especially around bigger human joints. Due to its intraarticular location, the LA might become clinically relevant when it reaches a certain tumour size. Looking at the diagnostics, sonography, MRI and especially the histopathological processing give the crucial results. Final proof can only be made by histopathological examination. Additionally, we have some differential diagnoses to exclude. Under these we predominantly find the spindle cell lipoma, synovial haemagioma, vascular synovial malformations and tenosynovial giant-cell tumour. Furthermore, an atypical lipomatous tumour should be excluded by FISH-analysis via determining the MDM2-Genamplification.


Photophysical properties of methyl beta-carboline-3-carboxylate mediated by hydrogen-bonded complexes--a comparative study in different solvents.
The hydrogen bonding interactions of methyl beta-carboline-3-carboxylate (BCCM) in both ground and first singlet excited electronic states have been studied in solvents with different properties in the presence of acetic acid, a hydrogen-bonding donor/acceptor. The methyl ester substituent reduces the pyridinic nitrogen basicity of this beta-carboline derivative. This fact has let us study the hydrogen bonding interactions in a higher range of acetic acid concentrations than for other beta-carboline derivatives previously studied. Steady and non-steady photophysical studies have been carried out in two non-polar solvents, benzene and p-dioxane; and in two polar solvents, acetonitrile and dichloromethane. Six different fluorescence emissions have been isolated corresponding to the uncomplexed BCCM, the protonated species and four different complexes between BCCM and acetic acid whose structures we have tried to elucidate.


[Efficacy observation of fire needle combined with narrow band ultraviolet-B (NB-UVB) for vitiligo].
To compare clinical efficacy difference between fire needle combined with narrow band ultraviolet-B (NB-UVB) and NB-UVB therapy for vitiligo. Ninety-three cases of vitiligo were randomly divided into an observation group (n = 48) and a control group (n = 45). In the observation group, fire needle was applied to ashi points around the damaged skin and Zusanli (ST 36), meanwhile NB-UVB therapy irradiating the local area. The control group was treated by NB-UVB therapy. The clinical efficacy was evaluated after the treatment of 12 weeks. The total effective rate was 79.2% (38/48) in the observation group, which was superior to that 48.9% (22/45, P < 0.05) in the control group. The fire needle combined with NB-UVB for vililigo achieves a more obvious efficacy than NB-UVB therapy.


Aromatic amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid as anti-inflammatory agents free of ulcerogenic liability.
Amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid were synthesized and evaluated for their anti-inflammatory and analgesic activity. Few selected compounds were also screened for their antipyretic, anti-arthritic, and ulcerogenic potential. Most of the compounds exhibited good activity profile and were free of gastrointestinal toxicity of common NSAIDs. However these compounds failed to decrease secondary lesions of adjuvant induced arthritis and also did not inhibit TNF-alpha in lipopolysaccharide induced pyresis.


Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum.
To isolate cDNAs involved in the biosynthesis of acetate-derived naphthoquinones in Drosophyllum lusitanicum, an expressed sequence tag analysis was performed. RNA from callus cultures was used to create a cDNA library from which 2004 expressed sequence tags were generated. One cDNA with similarity to known type III polyketide synthases was isolated as full-length sequence and termed DluHKS. The translated polypeptide sequence of DluHKS showed 51-67% identity with other plant type III PKSs. Recombinant DluHKS expressed in Escherichia coli accepted acetyl-coenzyme A (CoA) as starter and carried out sequential decarboxylative condensations with malonyl-CoA yielding alpha-pyrones from three to six acetate units. However, naphthalenes, the expected products, were not isolated. Since the main compound produced by DluHKS is a hexaketide alpha-pyrone, and the naphthoquinones in D. lusitanicum are composed of six acetate units, we propose that the enzyme provides the backbone of these secondary metabolites. An involvement of accessory proteins in this biosynthetic pathway is discussed.


Percutaneous brachial artery access for coronary artery procedures: Feasible and safe in the current era.
Percutaneous vascular access for coronary intervention is currently achieved predominately via the radial route, the femoral route acting as a backup. Percutaneous trans-brachial access is no longer commonly used due to concerns about vascular complications. This study aimed to investigate the safety and feasibility of percutaneous brachial access when femoral and radial access was not possible. This is a retrospective data analysis of patients who attended a single tertiary cardiology centre in the UK between 2005 and 2014 and had a coronary intervention (coronary angiogram or PCI) via the brachial route. The primary endpoints were procedural success and the occurrence of vascular complications. During the study period 26602 patients had a procedure (15655 underwent PCI and 10947 diagnostic angiography). Of these, 117 (0.44% of total) had their procedure performed via the brachial route. The procedure was successful in 96% (112/117) of cases. 13 (11%) patients experienced post procedural complications, of which 2 (1.7%) were serious. There were no deaths. Percutaneous trans-brachial arterial access is feasible with a high success rate and without evidence of high complication rate in a rare group of patients in whom femoral or sometimes radial attempts have failed.


[Expression Level of Protein Kinase D in Oral Squamous Cell Carcinoma with Diverse Differentiation].
This study aimed to investigate the expression level of protein kinase D (PKD) in oral squamous cell carcinoma (OSCC) and its relationship with differentiation of OSCC. Sample was collected from 10 healthy control subjects and 40 OSCC confirmed by histopathological diagnosis, and the immunohistochemical staining was adopted to detect the expression of PKDs in OSCC tissues. The proportion of stained cell and staining intensity were evaluated to get a score, which used to analyze the difference among PKD1, PKD2 and PKD3 in various differentiation OSCC tissues. The correlations between the staining score of PKDs and differentiation of OSCC were further analyzed. PKD1 and PKD3 were high expression in OSCC tissues. There were statistical significance among the staining score of PKD1, PKD2 and PKD3 in various differentiation OSCC tissues ( P<0.001). In addition, there was a significantly negative correlation between the staining score of PKD1 and PKD2 with the differentiation of OSCC ( r=-0.574, -0.341, P<0.001). In OSCC tissues with different degree of differentiation, there might be some differences among PKDs which play a major role. The expression of PKD1 and PKD2 was correlated with the differentiation of OSCC, the poor differentiation of OSCC, the higher expression of PKD1 and PKD2.