Resting metabolic rate and postprandial thermogenesis in vegetarians and nonvegetarians.
Resting metabolic rate (RMR), thermic effect of a meal (TEM), and associated hormonal changes were studied in vegetarians and nonvegetarians. RMR was established by indirect calorimetry in 12 male vegetarians (VEG) and 11 nonvegetarians (NVEG) of similar body fat and aerobic fitness. Subjects ingested a liquid meal and TEM was measured for 180 min postprandially. Plasma concentrations of glucose, insulin and thyroid hormones (T3 and T4) were determined before and after meal ingestion. Absolute RMR was comparable between VEG and NVEG. However, TEM was lower (p less than 0.01) in VEG (55.8 +/- 3.3 kcal/180 min) vs NVEG (76.4 +/- 3.6). Plasma levels of glucose and insulin were similar between the two groups whereas plasma T3 was slightly but nonsignificantly lower in vegetarians. A vegetarian diet may decrease the postprandial thermic response; this does not support the supposition that an elevated TEM is a factor contributing to the lower body weight in vegetarians than in omnivores.


[Effect of TGF-beta1 stimulation on the smad signal transduction pathway of human peritoneal mesothelial cells].
To explore whether the Smad signal transduction pathway in human peritoneal mesothelial cells (HPMCs) influences the process of human peritoneal fibrosis stimulated by TGF-beta1. HPMCs were isolated from normal human omentum and 95% of the primary cultured cells was confirmed to be HPMCs. The third generation of cultured cells was stimulated by 5 ng/ml TGF-beta1. Immunohistochemistry, Western blotting, ELISA, and RT-PCR were employed to investigate the follows: the protein expression of p-Smad2/3 and its migration in HPMCs; the protein and mRNA expressions of SMAD 7 in cells; and the expressions of extracellular fibronectin (FN) protein, intracellular FN mRNA, as well as intracellular collenge-I (COL1) protein and mRNA. The protein expression of p-Smad2/3 in HPMCs obviously increased 15 min (29% p-Smad2/3-positive cells) after TGF-beta1 stimulation, peaking from 30 min (81% ) to 1 h (84%) and dropping after 2 h (37%); Meanwhile, p-Smad2/3 mainly distributed in cytoplasm at 15 min, concentrated in cell nucleus and peri-nucleus from 30 min to 1 h, and distributed in cytoplasm again at 2 h. The protein expression of SMAD7 in cells obviously increased 24 h after TGF-beta1 stimulation, peaking at 48 h. The mRNA expression of SMAD7 time-dependently increased. The expressions of extracellular FN protein, intracellular FN mRNA, as well as intracellular COL1 protein and mRNA significantly increased and all of them displayed time dependency. The SMAD signal transduction pathway of HPMCs can be specifically activated by TGF-beta1 and influence the process of human peritoneal fibrosis. With the stimulation of TGF-beta1, the protein and mRNA expressions of SMAD 7 (an inhibitor of SMAD pathway) significantly increase as a result of feedback.


Totally tubeless percutaneous nephrolithotomy is feasible in morbidly obese patients.
Regarding technical difficulties that obese body habitus might impose to percutaneous nephrolithotomy (PNL) success and higher risk of peri-operative complications in this group of patients, we decided to retrospectively gather data from our patients during past 8 years to determine the stone free and complication rates. Between January 2007-December 2015, seventy-eight obese patients with body mass index over 35 who had indication for PNL including stones larger than 2 cm in pelvi-calyceal system or smaller extracorporeal shock wave lithotripsy (ESWL) resistant stones or who were not a fit candidate for ESWL due to increased skin to target distance, with no contraindication of PNL (including bleeding diathesis, inability to be positioned in prone) were enrolled. They were randomly assigned to group 1 (standard PNL with nephrostomy and ureteral stent) or group 2 (totally tubeless PNL with no ureteral stent and no nephrostomy). The outcomes were compared. The transfusion rate, operation time, and the hemoglobin drop were same across the groups (p>0.05). Total analgesic use was equivalent of 33.8 vs. 14.7 mgs of morphine sulfate (18-77 mg) and was significantly lower in total tubeless group (p=0.001). Return to normal activity was described as total number of in-patient and outpatient days from time of admission to the point which the patients returns to normal life activity such as going to job or school and was 19.4 vs. 9.3 days (6-30 days, p=0.001). Totally tubeless PNL in obese subjects would have lower analgesic use and return to normal activity versus standard PNL. Totally tubeless PNL is recommended for obese patients.


Screening for Rare Coding Variants That Associate With the QTc Interval in Iceland.
Background Long-QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1, KCNH2, and SCN5A. The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ1, 3 in KCNH2, 2 in cardiomyopathy genes MYBPC3 and PKP2, and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms (P=4.2×10-7; odds ratio [OR], 38.6; P=8.4×10-10, OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (P=0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (P=1.8×10-44; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.


[The Keel Mesh prosthesis: an innovative surgical device for a modern Bassini inguino-crural hernia operation without limits].
Accepting the therapeutic rational underlying laparoscopic and suprapubic laparotomy access, the same therapeutic goal is achieved through direct inguinal access. In this way, using just one prosthesis, inguinal-crural hernias of the Fruchaud pectineus orifice can be treated. The patented three-dimensional pre-cut Keel Mesh prosthesis made of polypropylene monofilament interwoven in a mesh, is tension-free and endowed with plastic memory. It is applied using a slightly modified Lichtenstein technique and is composed of two assembled elements (A and B-C) of different shapes and sizes. From May 2000 to December 2005, the Keel Mesh prosthesis was used in 358 surgical inguino-crural alloplasty operations according to Lichtenstein-De Pascale in 328 patients. Thirty patients were treated with bilateral allo-plasties. Coexistence of a crural hernia was found in 13 male and 4 female patients (5%). At the present time all the patients who are entering into follow-up at different times show perfect compliance of the prosthesis with no relapses. The theoretical and practical considerations regarding the production of the Keel Mesh prosthesis and its easy application suggest it is an extremely valid, rational device for the initial and combined treatment of inguinal and crural hernia.


A 2D coordination polymer assembled from a nickel(II) tetraazamacrocyclic cation and 4,4'-(dimethylsilanediyl)diphthalate(3-) linker.
The preformed nickel(II) complex of the 14-membered macrocyclic ligand 1,4,8,11-tetraazacyclotetradecane (cyclam, L), when treated with 4,4'-(dimethylsilanediyl)diphthalic acid (H4A) in a DMF/H2O mixture (4:1 v/v) under heating, leads to [Ni(L)]3(HA)2·3DMF (I·DMF). Redissolution of this compound in a DMF/H2O/MeOH mixture (4:1:30 v/v/v) with mild acidification under gentle heating results in the formation of a similar compound but containing water and methanol molecules of crystallization, [Ni(L)]3(HA)2·5H2O·2MeOH (II·H2O). At lower temperature and concentration of reactants and longer reaction time, single crystals of composition {[{Ni(L)}3(HA)2]·4CH3OH}n (II·MeOH) were isolated. Single-crystal X-ray diffraction analysis of this compound, which, according to PXRD is isostructural with II·H2O but different from I·DMF, revealed its two-dimensional (2D) polymeric structure, i.e. poly[[bis{μ3-4-[(4-carboxy-3-carboxylatophenyl)dimethylsilyl]benzene-1,2-dicarboxylato-κ3O1:O2:O3'}tris(1,4,8,11-tetraazacyclotetradecane-κ4N)trinickel(II)] methanol tetrasolvate], {[Ni3(C18H13O8Si)2(C10H24N4)3]·4CH3OH}n. It is built up of the monoprotonated tricarboxylate HA3- ligand coordinated in a monodentate manner in the axial positions of two crystallographically independent NiII cations, one of which is located on a crystallographic inversion centre. Both metal ions adopt a slightly tetragonally elongated trans-N4O2 octahedral geometry. The compound has a lamellar structure with polymeric layers oriented parallel to the (10-2) plane, which are in turn linked via hydrogen bonds involving protonated carboxylic acid groups of the ligand. Bulk compounds I·DMF and II·H2O were characterized by FT-IR and diffuse reflectance spectroscopy and thermogravimetry, which provide evidence of their structural differences.


Curing potential of experimental resin composites filled with bioactive glass: A comparison between Bis-EMA and UDMA based resin systems.
To evaluate the degree of conversion, light transmittance, and depth of cure of two experimental light-curable bioactive glass (BG)-containing composite series based on different resin systems. Experimental composite series based on either Bis-EMA or UDMA resin were prepared. Each series contained 0, 5, 10, 20, and 40wt% of BG 45S5. Reinforcing fillers were added up to a total filler load of 70wt%. The degree of conversion was evaluated using Raman spectroscopy, while light transmittance was measured using visible light spectroscopy. The depth of cure was estimated from the degree of conversion data and using the ISO 4049 scraping test. Replacement of reinforcing fillers with BG can diminish the degree of conversion, light transmittance, and depth of cure. The effect of BG on the aforementioned properties was highly variable between the experimental series. While in the Bis-EMA series, the degree of conversion was significantly impaired by BG, all of the composites in the UDMA series attained clinically acceptable degree of conversion values. The reduction of the degree of conversion in the Bis-EMA series occurred independently of the changes in light transmittance. The UDMA series showed better light transmittance and consequently higher depth of cure than the Bis-EMA series. The depth of cure for all composites in the UDMA series was above 2mm. While the Bis-EMA series demonstrated clinically acceptable curing potential only for 0-10wt% of BG loading, an excellent curing potential in the UDMA series was observed for a wide range (0-40wt%) of BG loadings.


Inner-City Asthma in Children.
Asthma in inner-city children is often severe and difficult to control. Residence in poor and urban areas confers increased asthma morbidity even after adjusting for ethnicity, age, and gender. Higher exposure to household pests, such as cockroaches and mice, pollutants and tobacco smoke exposure, poverty, material hardship, poor-quality housing, differences in health care quality, medication compliance, and heath care access also contribute to increased asthma morbidity in this population. Since 1991, the National Institutes of Allergy and Infectious Diseases established research networks: the National Cooperative Inner-City Asthma Study (NCICAS), the Inner-City Asthma Study (ICAS), and the Inner-City Asthma Consortium (ICAC), to improve care for this at risk population. The most striking finding of the NCICAS is the link between asthma morbidity and the high incidence of allergen sensitization and exposure, particularly cockroach. The follow-up ICAS confirmed that reductions in household cockroach and dust mite were associated with reduction in the inner-city asthma morbidity. The ICAC studies have identified that omalizumab lowered fall inner-city asthma exacerbation rate; however, the relationship between inner-city asthma vs immune system dysfunction, respiratory tract infections, prenatal environment, and inner-city environment is still being investigated. Although challenging, certain interventions for inner-city asthma children have shown promising results. These interventions include family-based interventions such as partnering families with asthma-trained social workers, providing guidelines driven asthma care as well as assured access to controller medication, home-based interventions aim at elimination of indoor allergens and tobacco smoke exposure, school-based asthma programs, and computer/web-based asthma programs.


Evaluation of antegonial notch depth for growth prediction.
In recent years, some researchers have proposed that the depth of the mandibular antegonial notch can be used as a predictor of facial growth. However, the data for those studies were derived from populations with extreme morphologic characteristics. The purpose of this investigation was to test the hypothesis that the antegonial notch depth is a useful predictor of facial growth in a longitudinal sample of untreated growing patients selected at random. Lateral cephalometric radiographs were obtained from 20 males and 20 females at 3 times, approximating prepubescence (8.5 years), adolescence (12 years), and adulthood (> or = 17 years). These 40 subjects were randomly chosen from a longitudinal sample of untreated growing patients. Prepubescent and adolescent antegonial notch depths were correlated with vertical and horizontal growth changes of the jaws from the age of 8.5 years to adulthood. Correlation analysis revealed a statistically (but not clinically) significant negative relationship (0.40 < or = r < or = 0.47; P < or =.05) between adolescent antegonial notch depth and horizontal growth of the maxilla and the mandible from adolescence to adulthood. Previous investigators have proposed that antegonial notch depth, when extreme in magnitude, might be used to predict facial growth. We concluded that antegonial notch depth fails to provide sufficient indication of future facial growth to warrant its application as a growth predictor in a nonextreme population.


[Ultrasonography and anencephaly].
On the basis of a personal clinical case, an analysis is made of the most recent data of medical literature concerning the pathogenesis and diagnosis of anencephaly. Emphasis is laid on the primary role of ultrasonography for an antenatal diagnosis of such fetal malformation.


Multi-dimensional fractionation and characterization of crude protein mixtures: toward establishment of a database of protein purification process development parameters.
A multi-dimensional fractionation and characterization scheme was developed for fast acquisition of the relevant molecular properties for protein separation from crude biological feedstocks by ion-exchange chromatography (IEX), hydrophobic interaction chromatography (HIC), and size-exclusion chromatography. In this approach, the linear IEX isotherm parameters were estimated from multiple linear salt-gradient IEX data, while the nonlinear IEX parameters as well as the HIC isotherm parameters were obtained by the inverse method under column overloading conditions. Collected chromatographic fractions were analyzed by gel electrophoresis for estimation of molecular mass, followed by mass spectrometry for protein identification. The usefulness of the generated molecular properties data for rational decision-making during downstream process development was equally demonstrated. Monoclonal antibody purification from crude hybridoma cell culture supernatant was used as case study. The obtained chromatographic parameters only apply to the employed stationary phases and operating conditions, hence prior high throughput screening of different chromatographic resins and mobile phase conditions is still a prerequisite. Nevertheless, it provides a quick, knowledge-based approach for rationally synthesizing purification cascades prior to more detailed process optimization and evaluation.


[Arterial hypertension as a risk factor for multifocal atherosclerosis].
It is well known that atherosclerosis as systemic disease have a significant correlation with score of multiple risk factors (MRF). Atherosclerosis as a multifocal disease, produces multisegmental stenotic changes of various arterial segments which arises simultaneously as a pre-existing asymptomatic disease. Aim of this study is to evaluate the presence of multifocal atherosclerotic disease among pts. with predominant arterial occlusive disease (AOD), and to correlate arterial hypertension as a major independent risk factor and multifocal atherosclerotic disease. We included 109 consecutive patients treated at our Institute in the period Dec 1999--Dec 2000, all with clear arterial occlusive disease (AOD). According to Fontaine clinical staging of their AOD, we made three groups--group FII, clinical stage Fontaine II 63 pts, group FIII, clinical stage Fontaine III 32 pts, and group FIV, clinical stage Fontaine IV 14 pts. We evaluated clinical variables: age, gender, arterial hypertension (HTA), tobacco, hyperlipidemia (HLP), obesity (BMI), diabetes mellitus, coronary heart disease (CHD), and cerebrovascular disease (CVD). Score of MRF is calculated as x/9. Special focus has been made to pts. with positive HTA. All pts. were evaluated according to clinical evidence of CHD and CVD, respectively. We had 109 pts, 89 males and 20 females, average age of 62 yrs, males 63 and females 60 yrs. In the FII group were 63 pts. with average MRF 4.27, in the FIII group 32 pts. with MRF 3.97, in the FIV group 14 pts. with MRF 3.93. Out of the total number of pts. 52 were hypertensive (47.7%), 41 males, and 11 females, with average age 64.8 yrs, males, and 61.8 yrs, females. Isolated systolic HTA had 33 pts. (63.5%), and 19 pts. (36.5%) systolic and diastolic HTA. In whole group (n-109), multifocal disease, AOD + CHD, had 22 (20.21%) pts. (MRF score 4.86), AOD + CVD had (5.5%) 6 pts. (MRF score 3.66) and AOD + CHD + CVD had 8 (7.33%) patients (MRF score 6.13). In hypertensive pts. multifocal atherosclerotic disease, AOD + CHD, had 12 pts. (23.1%), and AOD + CHD + CVD, 2 pts (7.6%). Among clinical variables, tobacco was of high risk, 97 pts. positive (89.9%), what is of high significance, p < 0.001. We have a clear connection of multifocal disease with elevated MRF score, especially clinical variables, smoking (p < 0.001) and arterial hypertension (p < 0.01). Multifocal atherosclerotic disease was present in 36 pts. (33.1%), and among hypertensive pts. multifocal atherosclerotic disease was present in 14 pts. (26.9%). There is a high positive correlation rank of multifocal disease, HTA and score of MRF, r = .70, and borderline correlation rank of multifocal disease and score of MRF, r = .40.


[Structure of recombinant human serum albumin from Pichia pastoris].
The structure of recombinant human serum albumin derived from Pichia pastoris (rHSA) was analyzed in detail. Complete amino acid analysis was performed by the phenyl isothiocyanate precolumn labeling method. The amino terminal sequence was determined by the Edman degradation. The carboxyl terminal amino acid was determined by digestion with carboxypeptidase, and the carboxyl terminal peptide fragment was analyzed by electrospray mass spectrometry. The peptide fragments of rHSA digested with Lysylendopeptidase, Endoproteinase Glu-C, or Endoproteinase Asp-N were analyzed by electrospray mass spectrometry. The complete amino acid composition, the terminal sequences and the complete amino acid sequence of rHSA agreed with the primary structure deduced from its cDNA. The elution pattern of reduced and carboxymethylated rHSA digested with Lysylendopeptidase and the elution pattern of intact rHSA digested with pepsin were respectively similar to those of plasma-derived human serum albumin (pHSA). The pattern of CD spectrum of rHSA was identical in both shape and magnitude to that of pHSA. 1H-NMR spectra of rHSA and pHSA in deuterium oxide showed the same signal patterns in the observed region (delta 10.5-0.5 ppm). Cross peaks assigned to the alpha proton-beta proton of Asp-1 (delta 4.2/2.8 ppm) and the delta proton-epsilon proton of lysine residues (delta 2.8-3.2/1.4-2.0) showed the same cross peak patterns and chemical shifts in two-dimensional phase sensitive double-quantum filtered 1H-1H correlation spectra of rHSA and pHSA.


Defective neutrophil and lymphocyte function in leucocyte adhesion deficiency.
We report a Chinese girl with the moderate phenotype of leucocyte adhesion deficiency (LAD), presenting with persistent omphalitis and recurrent soft tissue infections. She had subnormal adhesion-dependent neutrophil functions, such as chemotaxis and chemiluminescence response to a particulate stimulant (opsonised zymosan). Despite her adequate humoral response to documented herpes simplex virus type 1, parainfluenza type 2 and adenovirus infection in vivo, there was marked impairment in the generation of plaque-forming cells (PFC) driven by pokeweed mitogen (PWM) in vitro. IgM PFC were less severely affected than IgG and IgA PFC, probably because IgM production is less dependent on T cell help than IgA and IgG production. The patient's B cells and accessory cells had reduced function compared with the control subsets, while helper function of her CD4+ cells was virtually absent in the PWM-driven PFC assay. She also had marked defect in natural killer cell activity. The proliferation of her lymphocytes was normal to several plant lectins, including phytohaemagglutinin, concanavalin A and PWM, but markedly defective to OKT3.


Resistance status of the carmine spider mite, Tetranychus cinnabarinus and the twospotted spider mite, Tetranychus urticae to selected acaricides on strawberries.
The carmine spider mite, Tetranychus cinnabarinus (Boisduval) and the twospotted spider mite, Tetranychus urticae Koch, are serious pests of strawberries and many other horticultural crops. Control of these pests has been heavily dependent upon chemical acaricides. Objectives of this study were to determine the resistance status of these two pest species to commonly used acaricides on strawberries in a year-round intensive horticultural production region. LC90 of abamectin for adult carmine spider mites was 4% whereas that for adult twospotted spider mites was 24% of the top label rate. LC90s of spiromesifen, etoxazole, hexythiazox and bifenazate were 0.5%, 0.5%, 1.4% and 83% of their respective highest label rates for carmine spider mite eggs, 0.7%, 2.7%, 12.1% and 347% of their respective highest label rates for the nymphs. LC90s of spiromesifen, etoxazole, hexythiazox and bifenazate were 4.6%, 11.1%, 310% and 62% of their respective highest label rates for twospotted spider mite eggs, 3%, 13%, 432,214% and 15% of their respective highest label rates for the nymphs. Our results suggest that T. cinnabarinus have developed resistance to bifenazate and that the T. urticae have developed resistance to hexythiazox. These results strongly emphasize the need to develop resistance management strategies in the region.


Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications.
Although breathing disorders are often found in patients with chronic heart failure, exertional oscillatory ventilation (EOV) has been occasionally described. The aim of this study was to determine the prevalence, clinical characteristics, and outcome of patients with chronic heart failure and EOV. Cardiology division at tertiary-care hospital. We studied 323 patients with chronic heart failure and left ventricular ejection fraction (LVEF) < or = 40%. All patients performed a symptom-limited cardiopulmonary exercise test and were followed up for 22 +/- 11 months (mean +/- SD). EOV was defined as cyclic fluctuations in minute ventilation (E) at rest that persist during effort lasting > or = 60% of the exercise duration, with an amplitude > or = 15% of the average resting value. Patients with EOV (12%), as compared to those without, showed higher New York Heart Association (NYHA) class (p < 0.05) and lower LVEF (p < 0.0001) and peak oxygen consumption (O(2)) [p < 0.0001]. During the follow-up period, 53 patients died or underwent urgent cardiac transplantation; this group showed higher NYHA class (p < 0.05) and E/CO(2) slope (p < 0.0001) and lower LVEF (p < 0.0001), mitral Doppler early deceleration time (p < 0.01), and peak O(2) (p < 0.0001). EOV was more frequent in nonsurvivors than in survivors (28% vs 9%, p < 0.01). Multivariate analysis revealed peak O(2) (chi(2), 51.5; p < 0.0001), EOV (chi(2), 45.4; p < 0.0001), and LVEF (chi(2), 20.6; p < 0.0001) as independent predictors of major cardiac events. EOV is not unusual in patients with chronic heart failure, and is associated with worse clinical status, cardiac function, and exercise capacity. EOV is a powerful predictor of poor prognosis and, consequently, it may be considered a valuable guide in the management of patients with chronic heart failure and should suggest a more aggressive medical treatment policy when detected.


Determinants of prolonged length of hospital stay after coronary bypass surgery.
The length of hospital stay after coronary surgery was studied in 4,683 patients undergoing cardiac catheterization followed by coronary surgery at Emory University Hospital or Crawford Long Hospital between the years 1981 and 1986. Length of stay after coronary surgery had a median and modal value of 7 days. There was, however, a long statistical tail of patients with a prolonged length of stay extending out to more than 180 days. Prolonged length of stay (greater than 10 days) could be correlated with preprocedural variables such as age, elective versus emergency status, angina class, ejection fraction, and gender. Length of stay increased from a mean of 6.9 +/- 1.4 days under the age of 40 years to 10.9 +/- 12.1 days over the age of 70 years (p less than 0.0001). Length of stay was correlated with the periprocedural variables of wound infection, neurologic event, arrhythmias, pneumonia, postoperative myocardial infarction, mortality, and pericarditis. Length of stay increased from 8.8 +/- 9.6 days without a neurologic event to 21.1 +/- 17.9 days with a neurologic event (p less than 0.0001). Similarly, without a wound infection, the average stay was 8.7 +/- 8.9 days; with a wound infection, the average stay was 32.2 +/- 25.8 days (p less than 0.0001). The correlates of prolonged stay were tested in another population comprising 781 patients undergoing cardiac catheterization followed by coronary artery bypass grafting in 1987. The predictors of prolonged stay in the 1987 population were wound infection, pneumonia, arrhythmias, age, neurologic events, postoperative infarction, and ejection fraction. Thus, length of hospital stay after coronary surgery may be predicted by multiple preprocedural and periprocedural variables.(ABSTRACT TRUNCATED AT 250 WORDS)


Vitamin D Level and Vitamin D Receptor Genetic Variation Were Involved in the Risk of Non-Alcoholic Fatty Liver Disease: A Case-Control Study.
It has been demonstrated that vitamin D receptor (VDR), a key gene in the metabolism of vitamin D (VD), may affect the development of Non-alcoholic fatty liver disease (NAFLD) by regulating VD level and its biological effects. To investigate the effects of serum VD level, VDR variation, and a combination of VDR SNP and environmental behavior factor on the risk of NAFLD. A total of 3023 subjects from a community in Nanjing were enrolled, including 1120 NAFLD cases and 1903 controls. Serum 25(OH)D3 levels were measured and eight single nucleotide polymorphisms (SNPs) in VDR gene were genotyped. Logistic regression analyses indicated that VD sufficiency and VD insufficiency were significantly associated with a low risk of NAFLD (all P<0.05; all Ptrend<0.05, in a locus-dosage manner). After adjusting for gender and age, VDR rs2228570-A and rs11168287-A alleles were all reduced the risk of NAFLD (all PFDR=0.136, in dominant model; Ptrend =0.039, combined effects in a locus-dosage manner). The protective effects of two favorable alleles were more evident among subjects ≤40 years, non-hypertension, non-hyperglycemia and non-low high density lipoprotein-cholesterol (all P<0.05). The area under the receiver operating curve of the combination of VDR SNP and exercise time for assessing NAFLD risk was slightly higher than that of only including exercise time or neither (all P<0.05). High serum VD levels and VDR variants (rs2228570-A and rs11168287-A) might contribute to a low risk of NAFLD in Chinese Han population. The inclusion of VDR SNP and exercise time could improve the efficiency in assessment of NAFLD risk, which might provide a novel perspective for early screening and preventing NAFLD.


Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour.
Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology-controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve-sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs.


Detection of bloodstream infections in adults: how many blood cultures are needed?
Although several reports have shown that two to three 20-ml blood cultures are adequate for the detection of bacteremia and fungemia in adults, a recent study (F. R. Cockerill et al., Clin. Infect. Dis. 38:1724-1730, 2004) found that two blood cultures detected only 80% of bloodstream infections and that three blood cultures detected 96% of episodes. We reviewed data at two university hospitals to determine whether the recent observations by Cockerill et al. are applicable more widely. We assessed all blood cultures obtained from adult inpatients from 1 January 2004 through 31 December 2005 at Robert Wood Johnson University Hospital and Duke University Medical Center. All instances in which > or =3 blood cultures per patient were obtained during a 24-h period were included. The medical records of patients who met the inclusion criteria were reviewed retrospectively to determine the clinical significance of the positive blood culture (true infection versus contamination). Data were analyzed to determine the cumulative sensitivity of blood cultures obtained sequentially during the 24-h time period. Of 629 unimicrobial episodes with > or =3 blood cultures obtained during the 24-h period, 460 (73.1%) were detected with the first blood culture, 564 (89.7%) were detected with the first two blood cultures, 618 (98.2%) were detected with the first three blood cultures, and 628 (99.8%) were detected with the first four blood cultures. Of 351 unimicrobial episodes with > or =4 blood cultures obtained during the 24-h period, 257 (73.2%) were detected with the first blood culture, 308 (93.9%) were detected with the first two blood cultures, 340 (96.9%) were detected with the first three blood cultures, and 350 (99.7%) were detected with the first four blood cultures. Among unimicrobial episodes, Staphylococcus aureus was more likely to be detected with the first blood culture (approximately 90% detected with the first blood culture). There were 58 polymicrobial episodes in which > or =3 blood cultures were obtained. Forty-seven (81.0%) were detected with the first blood culture, 54 (93.1%) were detected with the first two blood cultures, and 58 (100%) were detected with the first three blood cultures. The results of this study indicate that two blood cultures in a 24-h period will detect approximately 90% of bloodstream infections in adults. To achieve a detection rate of >99%, as many as four blood cultures may be needed. The previously held axiom that virtually all bloodstream infections can be detected with two to three blood cultures may no longer be valid but may also depend on the definition of the "first" blood culture obtained (see Materials and Methods and Discussion in the text).


Criteria for pacemaker explant in patients without a precise indication for pacemaker implantation.
Unnecessary pacemaker implantation may cause significant social and psychological consequences, the inconvenience of periodic office visits, and the expense of pulse generator replacement. Establishing adequate criteria for explantingpacemakers is crucial and has notyet been described. This study presents the results of a study protocol for explanting the pacemaker in patients without a clear indication for pacemaker implantation. Seventy pacemaker users without a clear reason for the implantation were included in the study conducted from August 1986 to November 1998 and were prospectively followed. The investigation consisted of clinical and neurological evaluations, echocardiogram, exercise testing, and tilt table testing. When these tests were negative, the pulse generator energy and stimulation rates were reprogrammed to the lowest values. Periodic Holter monitoring was conducted during follow-up. When asymptomatic for 1 year, patients underwent an electrophysiological evaluation of sinus and atrioventricular junction function and ventricular vulnerability. When the electrophysiological study was negative, pacemaker explantation was performed. Of the 70 patients, 35 had their pacemaker explanted; 3 were excluded due to a positive tilt table test and electrophysiological study, and 3 are waitingfor pacemaker explantation. Mean follow-up after pacemaker explantation was 30.3 months, and all patients remained asymptomatic, exceptfor one patient who died of a noncardiac cause. Critical analysis of pacemaker users without a well-established indication is justified because it may allowpacemaker explant in a significant proportion of these patients, and it may bring considerable social, economic, and psychological benefits.


Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
Basal cell carcinoma (BCC) is the most common malignant tumor of the eyelid and its incidence is increasing. It remains to be established which is the best treatment in terms of safety and cost-effectiveness. Our purpose was to analyze the long-term treatment results and possible side effects of cryosurgery of eyelid BCC. During the last 14 years 219 patients (222 tumors) treated for eyelid BCC with cryosurgery were followed up prospectively for up to 10 years. The tumors cleared completely after treatment in all patients with no recurrence observed to date. Ninety-two patients were followed up for 5 years or more. Complications were few and minor. In 26 treated eyelids conjunctival overgrowth was noted. We conclude that cryosurgery of BCC of the eyelid has a high cure rate, is cost-effective, and is well tolerated.


Grazing in the dark: A behavioural adjustment in a population of the black sea urchin Arbacia lixula.
In Mediterranean rocky shores, the black sea urchin Arbacia lixula is often associated with communities dominated by encrusting corallines, devoid of fleshy algae. While it is commonly known as a diurnal herbivore, this species also migrates at night from hidden to more exposed habitats. Here, we provide the first experimental evidence of an adjustment to a predominant nocturnal behaviour in a population of A. lixula. Sea urchin densities changed from nearly zero during daytime to more than 16 urchins m-2 at night in treatment plots where the sea urchins were removed. We suggest that the observed behaviour was triggered by our experimental manipulations and was a response to the presence of dead conspecifics and small predatory fishes attracted by the urchin culling. Further research is needed to assess whether our findings can be generalised to the behaviour of A. lixula in areas where sea urchins are under strong pressure from diurnal predators. In these cases, it is important to perform sea urchin density counts at night to avoid misleading assessments about the herbivore pressure in a littoral area.


SEASONAL VARIATION IN SEXUAL SELECTION IN THE MOTTLED SCULPIN.
Seasonal variation in sexual and natural selection in male mottled sculpins (Cottus bairdi) can be evaluated by calculating selection differentials, which measure the magnitude of phenotypic change resulting from selection, and by calculating indices of the opportunity for selection, which indicate the potential for phenotypic selection in a given interval. Selection differentials are high at the beginning of the breeding season and decline throughout the breeding season. The magnitude and direction of selection differentials depend on when spawning occurs and are independent of the size or age of the females that spawn. Annual selection differentials due to differences in mating success (female choice) are nearly constant between years. Annual selection differentials associated with hatching success are variable. Opportunities for selection (I = fitness variance/[mean fitness]2 ) show clear seasonal patterns. They are highest at the beginning and at the end of the spawning season. However, this variation is dependent on the mean used to calculate I, and hence variation in I values does not indicate a significant change in the variance of male fitness.


Topographic customized photorefractive keratectomy for regular and irregular astigmatism after penetrating keratoplasty using the LIGI CIPTA/LaserSight platform.
To evaluate the use of a software ablation program (Corneal Interactive Programmed Topographic Ablation [CIPTA]) that provides customized photorefractive keratectomy (PRK) to correct astigmatism after keratoplasty. In this prospective, noncomparative, consecutive case series, 44 eyes underwent CIPTA for correction of astigmatism after penetrating keratoplasty. Eighteen eyes were treated for regular astigmatism and 26 eyes were treated for irregular astigmatism after penetrating keratoplasty. Orbscan II topography (Bausch & Lomb) and a flying-spot laser (LaserScan 2000; LaserSight) were used. Epithelial debridement with alcohol was performed before PRK in 16 eyes and transepithelial PRK was performed in 28 eyes. Mean target-induced astigmatism was 8.19 +/- 2.68 diopters (D) and 7.68 +/- 4.50 D in the regular and irregular astigmatism groups, respectively. Mean follow-up was 25.4 +/- 13 months. At last postoperative follow-up, 13 (72.2%) and 18 (69.2%) eyes in the regular and irregular astigmatism groups, respectively, had uncorrected visual acuity (UCVA) better than 20/40. Four (22.2%) and 8 (30.7%) eyes in the regular and irregular astigmatism groups, respectively, had UCVA of 20/20. Fourteen (77.7%) and 18 (69.2%) eyes in the regular and irregular astigmatism groups, respectively, were within 1.00 D of attempted correction in spherical equivalent manifest refraction. No eye lost Snellen lines of best spectacle-corrected visual acuity. Mean surgically induced astigmatism was 7.66 +/- 2.70 D and 6.99 +/- 3.80 D for the regular and irregular astigmatism groups, respectively. Index of success of astigmatic correction was 0.138 and 0.137 for the regular and irregular astigmatism groups, respectively. Haze developed in three eyes. Topography-driven PRK using CIPTA software is a suitable solution for correcting regular and irregular astigmatism after penetrating keratoplasty.


Using curcumin to prevent structural and behavioral changes of medial prefrontal cortex induced by sleep deprivation in rats.
Sleep Deprivation (SD) is known to result in a range of neurological consequences in chronically-afflicted subjects. Curcumin, a natural substance, has neuroprotective properties. This study aimed to evaluate the effects of curcumin on the medial Prefrontal Cortex (mPFC) of SD rats. Male rats were arbitrarily assigned to nine groups, including control, curcumin (100 mg/kg/day), olive oil, SD, SD+curcumin, SD+olive oil, grid, grid+curcumin, and grid+olive oil groups. SD was induced by a multiplatform box containing water. After a period of 21 days, the learning and memory of the rats were tested in an eight-arm radial maze. Afterwards, their brains were evaluated using stereological methods. Concomitant treatment of curcumin during SD caused fewer errors during evaluation of the working and reference memory errors in the acquisition and retention phases. The overall volume of the mPFC, Infralimbic Cortex (ILC), Prelimbic Cortex (PLC), Anterior Cingulate Cortex (ACC) and the total number of neurons and glial cells reduced by 20 %-40 % on average in the SD animals in comparison to the control group. This indicated atrophic changes and cell loss in these areas (p < 0.01). The dendrites' length and the number of spines per dendrite also reduced by 35 %-55 % in the SD rats compared to the ones in the control group (p < 0.01). Yet, treatment of the SD animals with curcumin prevented the atrophic changes of the mPFC, cell loss, and dendritic changes (p < 0.05). SD induced structural changes in the mPFC and memory impairment in the rats. However, curcumin could protect their PFC.


GABAergic neurones in the rat periaqueductal grey matter express alpha4, beta1 and delta GABAA receptor subunits: plasticity of expression during the estrous cycle.
Immunoreactivity for alpha4, beta1 and delta GABAA receptor subunits on neurones in the periaqueductal gray matter was investigated at different stages of the estrous cycle in Wistar rats. Immunostaining for alpha4, beta1 and delta GABAA receptor subunits was present on neurones throughout the periaqueductal gray matter. The numbers of subunit-immunoreactive neurones remained constant during the early phases of the estrous cycle (proestrus to early diestrus) but increased significantly in late diestrus. Dual immunolabeling for the GABA synthesizing enzyme glutamic acid decarboxylase revealed that almost 90% of the subunit-positive cells contained immunoreactivity for glutamic acid decarboxylase. During the early phases of the estrous cycle (proestrus to early diestrus), approximately one third of the glutamic acid decarboxylase-positive population co-localized alpha4, beta1 and delta GABAA receptor subunits. When the number of subunit positive cells increased during late diestrus, the proportion of the glutamic acid decarboxylase-containing population that expressed alpha4, beta1 and delta GABAA receptor subunits almost doubled. We propose that GABAA receptors with the alpha4beta1delta configuration are expressed by GABAergic neurones in the periaqueductal gray matter and that the numbers of cells expressing these subunits are increased in late diestrus in line with falling plasma progesterone levels. Changes in GABAA receptor expression may lead to changes in the excitability of the neural circuitry in the periaqueductal gray matter.


Self-similar structures near boundaries in strained systems.
We study the buckling of thin elastic plates caused by residual strains concentrated near a free edge. This is a model for plant leaves and torn plastic sheet morphologies. We derive new governing equations explaining self-similar patterns reported earlier in experiments. We reveal the cascade mechanism, determine the bounds for its wavelengths, and predict a similarity factor of 3 in agreement with experiments. This is confirmed by numerical solutions with up to five generations of wrinkles.


Determinants of Reduced Genetic Capacity for Butyrate Synthesis by the Gut Microbiome in Crohn's Disease and Ulcerative Colitis.
Alterations in short chain fatty acid metabolism, particularly butyrate, have been reported in inflammatory bowel disease, but results have been conflicting because of small study numbers and failure to distinguish disease type, activity or other variables such as diet. We performed a comparative assessment of the capacity of the microbiota for butyrate synthesis, by quantifying butyryl-CoA:acetate CoA-transferase [BCoAT] gene content in stool from patients with Crohn's disease [CD; n = 71], ulcerative colitis [UC; n = 58] and controls [n = 75], and determined whether it was related to active vs inactive inflammation, microbial diversity, and composition and/or dietary habits. BCoAT gene content was quantified by quantitative polymerase chain reaction [qPCR]. Disease activity was assessed clinically and faecal calprotectin concentration measured. Microbial composition was determined by sequencing 16S rRNA gene. Dietary data were collected using an established food frequency questionnaire. Reduced butyrate-synthetic capacity was found in patients with active and inactive CD [p < 0.001 and p < 0.01, respectively], but only in active UC [p < 0.05]. In CD, low BCoAT gene content was associated with ileal location, stenotic behaviour, increased inflammation, lower microbial diversity, greater microbiota compositional change, and decreased butyrogenic taxa. Reduced BCoAT gene content in patients with CD was linked with a different regimen characterised by lower dietary fibre. Reduced butyrate-synthetic capacity of the microbiota is more evident in CD than UC and may relate to reduced fibre intake. The results suggest that simple replacement of butyrate per se may be therapeutically inadequate, whereas manipulation of microbial synthesis, perhaps by dietary means, may be more appropriate.


Specific interactions between ATPase subunits of the 26 S protease.
The regulatory complex of the 26 S protease contains at least 15 distinct subunits. Six of these subunits (S4, S6, S6', S7, S8, and S10b) belong to a novel subfamily of presumptive nucleotidases that we call subunit 4 (S4)-like ATPases. Each of these putative ATPases was synthesized in reticulocyte lysate containing [35S]methionine, and the radiolabeled proteins were used in binding studies. S4, S6, S10b, and S6' displayed specific binding to components of the regulatory complex separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) or two-dimensional PAGE. S4 bound to S7, and S6 bound two proteins: S8 and centractin, a component of the dynactin complex. S10b bound to S6' and bound much more weakly to S1 and p50, another component of the dynactin complex. S6' bound to S10b. Two subunits, S7 and S8, did not bind any components present on nitrocellulose membranes, presumably because S7 and S8 are already oligomeric following synthesis. Co-translation and sucrose gradient sedimentation of 35S-labeled ATPases demonstrated the formation of S6'-S10b dimers in solution but revealed more complex associations, namely the formation of trimers and tetramers, among S4, S6, S7, and S8. Progressive COOH-terminal deletions that removed as much as 300 amino acids from S4 had no effect on the binding of S4 to S7. In striking contrast, truncation of 85 NH2-terminal amino acids from S4 abrogated binding, clearly implicating the NH2 terminus of S4 in its specific interaction with S7. Since S4-like ATPases contain putative coiled-coils within the first 150 NH2-terminal amino acids, we propose that coiled-coil interactions are responsible for the specificity of the observed subunit associations and that these associations are important for self-assembly of the regulatory complex.


Spatially resolved images of reactive ions in the Orion Bar,★★.
We report high angular resolution (4.9″×3.0″) images of reactive ions SH+, HOC+, and SO+ toward the Orion Bar photodissociation region (PDR). We used ALMA-ACA to map several rotational lines at 0.8 mm, complemented with multi-line observations obtained with the IRAM 30 m telescope. The SH+ and HOC+ emission is restricted to a narrow layer of 2″- to 10″-width (≈800 to 4000 AU depending on the assumed PDR geometry) that follows the vibrationally excited [Formula: see text] emission. Both ions efficiently form very close to the H/H2 transition zone, at a depth of Av≲1 mag into the neutral cloud, where abundant C+, S+, and [Formula: see text] coexist. SO+ peaks slightly deeper into the cloud. The observed ions have low rotational temperatures (Trot≈10-30 K≪Tk) and narrow line-widths (~2-3 km s-1), a factor of ≃2 narrower that those of the lighter reactive ion CH+. This is consistent with the higher reactivity and faster radiative pumping rates of CH+ compared to the heavier ions, which are driven relatively faster toward smaller velocity dispersion by elastic collisions and toward lower Trot by inelastic collisions. We estimate column densities and average physical conditions from an excitation model (n(H2)≈105-106 cm-3, n(e-)≈10 cm-3, and Tk≈200 K). Regardless of the excitation details, SH+ and HOC+ clearly trace the most exposed layers of the UV-irradiated molecular cloud surface, whereas SO+ arises from slightly more shielded layers.


Melanoma circulating tumor cells: Benefits and challenges required for clinical application.
The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.


Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at Weaning.
Gastrointestinal nematodes (GIN) pose a severe threat to sheep production worldwide. Anthelmintic drug resistance coupled with growing concern regarding potential environmental effects of drug use have demonstrated the necessity of implementing other methods of GIN control. The aim of this study was to test for genetic variants associated with resistance or susceptibility to GIN in Katahdin sheep to improve the current understanding of the genetic mechanisms responsible for host response to GIN. Linear regression and case-control genome-wide association studies were conducted with high-density genotype data and cube-root transformed weaning fecal egg counts (tFEC) of 583 Katahdin sheep. The case-control GWAS identified two significant SNPs (P-values 1.49e-08 to 1.01e-08) within introns of the gene adhesion G protein-coupled receptor B3 (ADGRB3) associated with lower fecal egg counts. With linear regression, four significant SNPs (P-values 7.82e-08 to 3.34e-08) were identified within the first intron of the gene EGF-like repeats and discoidin domains 3 (EDIL3). These identified SNPs were in very high linkage disequilibrium (r 2 of 0.996-1), and animals with alternate homozygous genotypes had significantly higher median weaning tFEC phenotypes compared to all other genotypes. Significant SNPs were queried through public databases to identify putative transcription factor binding site (TFBS) and potential lncRNA differences between reference and alternate alleles. Changes in TFBS were predicted at two SNPs, and one significant SNP was found to be within a predicted lncRNA sequence with greater than 90% similarity to a known lncRNA in the bovine genome. The gene EDIL3 has been described in other species for its roles in the inhibition and resolution of inflammation. Potential changes of EDIL3 expression mediated through lncRNA expression and/or transcription factor binding may impact the overall immune response and reduce the ability of Katahdin sheep to control GIN infection. This study lays the foundation for further research of EDIL3 and ADGRB3 towards understanding genetic mechanisms of susceptibility to GIN, and suggests these SNPs may contribute to genetic strategies for improving parasite resistance traits in sheep.


Detection of Yersinia pestis in sputum by real-time PCR.
A 5' nuclease PCR assay for detection of the Yersinia pestis plasminogen activator (pla) gene in human respiratory specimens with simulated Y. pestis infection was developed. An internal positive control was added to the reaction mixture in order to detect the presence of PCR inhibitors that are often found in biological samples. The assay was 100% specific for Y. pestis. In the absence of inhibitors, a sensitivity of 10(2) CFU/ml of respiratory fluid was obtained. When inhibitors were present, detection of Y. pestis DNA required a longer sample treatment time and an initial concentration of bacteria of at least 10(4) CFU/ml. The test's total turnaround time was less than 5 h. The assay described here is well suited to the rapid diagnosis of pneumonic plague, the form of plague most likely to result from a bioterrorist attack.


Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL clinical audit.
Current COPD management recommendations indicate that pharmacological treatment can be stepped up or down, but there are no recommendations on how to make this adjustment. We aimed to describe pharmacological prescriptions during a routine clinical visit for COPD and study the determinants of changing therapy. EPOCONSUL is a Spanish nationwide observational cross-sectional clinical audit with prospective case recruitment including 4,508 COPD patients from outpatient respiratory clinics for a period of 12 months (May 2014-May 2015). Prescription patterns were examined in 4,448 cases and changes analyzed in stepwise backward, binomial, multivariate, logistic regression models. Patterns of prescription of inhaled therapy groups were no treatment prescribed, 124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502 (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and triple therapy cases, 2,428 (53.9%) cases. Incorrect prescriptions of inhaled therapies were observed in 261 (5.9%) cases. After the clinical visit was audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307 (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme, 182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified change. Stepping-up strategies were associated with clinical presentation (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive bronchodilator test, and specific inhaled medication groups. Stepping down was associated with lung function impairment, ICS containing regimens, and nonexacerbator phenotype. The EPOCONSUL study shows a comprehensive evaluation of pharmacological treatments in COPD care, highlighting strengths and weaknesses, to help us understand how physicians use available drugs.


Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein.
The role of the endothelium in modulating cyclic nucleotide levels and intrinsic smooth muscle tone was studied in isolated rings of bovine intrapulmonary artery and vein. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were threefold to fourfold higher in unrubbed artery and vein than in vessels that had been denuded of endothelium. Cyclic 3',5'-adenosine monophosphate (cAMP) levels were twofold higher in unrubbed than in endothelium-denuded artery, but no differences were observed in veins. Methylene blue, an inhibitor of guanylate cyclase, decreased cGMP but not cAMP levels, and this was accompanied by increases in smooth muscle tone. M&B 22,948, an inhibitor of cGMP-phosphodiesterase, increased cGMP but not cAMP levels, and this was accompanied by decreases in smooth muscle tone. Unrubbed vessels were more sensitive than endothelium-denuded vessels to the actions of both methylene blue and M&B 22,948, and this may be attributed to endothelium-dependent increases in cGMP turnover. Moreover, unrubbed vessels were more sensitive than endothelium-denuded vessels to contractile responses to phenylephrine and potassium, and these responses were potentiated by methylene blue and attenuated by M&B 22,948. Although indomethacin lowered cAMP levels in unrubbed artery, no changes in tone or contractile responsiveness were observed. A consistent observation was that the smaller branches of unrubbed but not endothelium-denuded intrapulmonary artery and vein had higher levels of cGMP but not cAMP, were sensitive to endothelium-dependent vasodilators, were more sensitive to methylene blue, and would not maintain a steady level of submaximal tone to phenylephrine when compared with larger branches from a common vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)


Possible role of histamine in rheumatoid arthritis. Treatment with cimetidine and mepyramine.
Basophilocytes from patients with rheumatoid arthritis (RA) responded to leukocyte nuclei from normal persons with histamine release; a similar histamine release induced by the nuclear components RNA and DNA has been demonstrated previously. A role of histamine in RA is also supported by the findings of clinical improvement during treatment with H1 and H2 antihistamines in six of 12 patients with RA in active phase, whereas four showed definite deterioration.


Clinical SYNTAX score predicts outcomes of patients undergoing coronary artery bypass grafting.
The SYNTAX score (SS) is a determinant of outcome in patients undergoing percutaneous coronary intervention. In addition, it has been recently shown that the clinical SYNTAX score (cSS), obtained by adding clinical variables to the SS, improves the predictive power of the resulting risk model. We assessed the hypothesis that the use of the cSS may predict outcomes of patients undergoing coronary artery bypass grafting (CABG). We measured the SYNTAX score in 874 patients undergoing isolated first time on-pump CABG. The clinical SYNTAX score was calculated at the time of the study using age, creatinine clearance and ejection fraction, the modified ACEF score, and analyses performed for major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality at 3-year follow-up. The mean age of the study population was 70.9 ± 8.1 years, and the median cSS 14.2 (range 2.1-286.5). The ROC curve analysis showed that a cSS >14.5 (81.4% sensitivity and 67.8% specificity) was a reliable tool in discrimination of patients for the occurrence of MACCE (AUC 0.78) and all-cause mortality (AUC 0.74). Kaplan-Meier survival analysis confirmed that patients belonging to higher cSS quartiles have poorer 3-year survival (P = .0001) and MACCE-free survival (P = .0001), with respect to those with lower cSS. This observational study has shown that the clinical SYNTAX score, incorporating the lesion-based SS and clinical-based ACEF score, predicted mid-term adverse outcomes of patients undergoing CABG and may play an important role in the risk stratification of this population. Further studies are needed to confirm these findings.


The Accuracy of Noninvasive Imaging Techniques in Diagnosis of Carotid Plaque Morphology.
The stroke is leading cause of death and severe disability worldwide. Atherosclerosis is responsible for over 30% of all ischemic strokes. It has been recently discovered that plaque morphology may help predict the clinical behavior of carotid atherosclerosis and determine the risk of stroke. The noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify "vulnerable plaques". The purpose is to investigate the diagnostic accuracy of ultrasound, multidetector computed tomography and magnetic resonance imaging in the identification of plaque components associated with plaque vulnerability. One hundred patients were admitted for carotid endarterectomy for high grade carotid stenosis. We defined the diagnostic value of B-mode ultrasound of carotid plaque in a half, and the accuracy of multidetector computed tomography and magnetic resonance imaging, in the other group, for detection of unstable carotid plaque. The reference standard was histology. Sensitivity of ultrasound, multidetector computed tomography and magnetic resonance imaging is 94%, 83% and 100%, and the specificity is 93%, 73% and 89% for detection of unstable carotid plaque. The ultrasound has high accuracy for diagnostics of carotid plaque morphology, magnetic resonance imaging has high potential for tissue differentiation and multidetector computed tomography determines precisely degree of stenosis and presence of ulceration and calcifications. The three noninvasive imaging modalities are complementary for optimal evaluation of the morphology of carotid plaque. This will help to determine the risk of stroke and to decide on the best treatment - carotid endarterectomy or carotid stenting.


Facile S(N)2 reaction in protic solvent: quantum chemical analysis.
We study the effects of protic solvent (water, methanol, ethanol, and tert-butyl alcohol) and cation (Na+, K+, Cs+) on the unsymmetrical SN2 reaction X- + RY --> RX + Y- (X = F, Br; R = CH3,C3H7;Y = Cl, OMs). We describe a series of calculations for the S(N)2 reaction mechanism under the influence of cation and protic solvent, presenting the structures of pre- and postreaction complexes and transition states and the magnitude of the activation barrier. An interesting mechanism is proposed, in which the protic solvent molecules that are shielded from the nucleophile by the intervening cation act as a Lewis base to reduce the unfavorable Coulombic influence of the cation on the nucleophile. We predict that the reaction barrier for the S(N)2 reaction is significantly lowered by the cooperative effects of cation and protic solvent. We show that the cation and protic solvent, each of which has been considered to retard the SN2 reactivity of the nucleophile, can accelerate the reaction tremendously when they interact with the fluoride ion in an intricate, combined fashion. This alternative S(N)2 mechanism is discussed in relation to the recently observed phenomenal efficiency of fluorination in tert-alcohol media [Kim, D. W.; et al. J. Am. Chem. Soc. 2006, 128, 16394].


Outcomes of Partnered Individuals Undergoing Bariatric Surgery Together: A Single Institution Case Series.
There exists marked variation in weight loss among the 200,000 annual bariatric patients, and many of these patients struggle with weight regain. Several studies have suggested that positive social support may significantly impact bariatric surgery outcomes, leading to more excess weight loss and maintenance of this weight loss through appropriate lifestyle changes. We sought to understand this by assessing clinical and behavioral outcomes among married couples whereby both spouses underwent bariatric surgery at our institution. In our case series, we found evidence that married couples meet or exceed postoperative weight loss milestones at 12, 18, and 24 months and did not show signs of weight regain as a group at 18 or 24 months. Among partners who underwent the same clinical pathway at our single institution, women tended to lose more weight than men at 12 months. Additionally, while there was significant variation in postoperative follow-up among patients, we found that partners within couples typically exhibited the same behavior with respect to postoperative visits when they had their surgeries within a year of each other. This case series suggests that partnered patients undergoing bariatric surgery can meet or exceed weight loss outcomes and may practice similar follow-up adherence.


Maternal touch moderates sex differences in juvenile social play behavior.
Additional somatosensory contact of preterm human infants improves a variety of developmental assessment scores, but less is known about its lasting consequences. In rodents, maternal contact may influence the programming of juvenile social play behavior. Therefore, we used a paradigm where we can control the levels of somatosensory contact associated with maternal care. We find that additional somatosensory contact of offspring can have lasting consequences on juvenile social play behavior in a sex-dependent manner. Specifically, additional somatosensory stimuli reduced male social play behavior, but did not change female play behavior. We then examined if this additional infant contact altered some neurobiological substrates associated with play within the juvenile amygdala. Control males had lower levels of 5HT2a receptor mRNA levels contrasted to females; however, similar to its sex-dependent effect on juvenile social play, males that received additional somatosensory contact had higher serotonin 5HT2a receptor mRNA levels than control males. No difference was found in females. As serotonin signaling typically opposes juvenile play behavior, these data suggest that maternal touch can program lasting differences in juvenile social play and 5HT2a receptors mRNA levels within the juvenile amygdala.


Bladder outflow obstruction treated with phenoxybenzamine.
Sixty-one male patients took part in a study of phenoxybenzamine (PBZ), the initial phase of which was double-blind (41 patients). All patients had urodynamically proven outflow obstruction. The double-blind phase of the trial showed an overall symptomatic improvement in the PBZ patients. The symptoms of slow stream and hesitancy were significantly improved. The urethral pressure profile features of prostatic plateau height and prostatic plateau area were significantly decreased in the PBZ group. Dizziness was the most common side effect of PBZ but was well tolerated by most patients. This study shows that PBZ has an effect on bladder outflow obstruction by reducing pressure in the proximal urethra and that the drug is suitable for the treatment of patients with symptoms attributable to obstruction.


Sartorius Muscle Flaps: Perioperative Outcomes Based on Surgical Specialty.
Complicated groin wounds often require repair by sartorius muscle flap (SMF). Operating surgical specialty differs based on SMF indication, hospital, and operating surgeon preference. We aim to assess the effect of operating surgical specialty, indication for SMF, and other patient-level factors on 30-day outcomes. We collected data on all patients undergoing SMF performed at our institution from 2005 to 2015, including age, sex, body mass index, comorbidity index (hypertension, diabetes, dyslipidemia, peripheral arterial disease, coronary artery disease), smoking status, history of malignancy, indication for SMF (infection, noninfectious complication, prophylaxis), and operating surgeon's specialty (vascular, plastic, general, other). Primary outcome was any 30-day complications (wound infection, seroma, dehiscence, or bleeding). Secondary outcome included 30-day surgical reintervention rate. Univariate analysis and multivariate logistic regression modeling were used to evaluate primary outcomes. A total of 170 SMFs were performed during the study period (mean patient age 58 years; 49% male). Primary indication for SMF was prophylaxis in 116 cases (68%), followed by infection in 36 cases (21%) and noninfectious complications in 18 cases (11%). General surgeons performed the highest proportion of SMF (45%) followed by vascular surgeons (26%), "other specialties" (15%), and plastic surgeons (14%). Compared with all specialties, vascular surgeons operated on the severely ill patients (77% of vascular patients had ≥3 comorbidities, P < 0.001). Surgical reintervention within 30 days was required in 7 patients (4.1%): 3 by vascular surgeons (6.8% of total cases by vascular surgery) and 4 by plastic surgeons (17.4% of total cases by plastic surgery, P < 0.001). Any 30-day complications occurred in 47 patients (28%): 30 general surgery cases (39%), 7 plastic surgery cases (30%), 7 other specialty cases (27%), and 3 vascular surgery cases (7%) (P < 0.001). Of all vascular disease-related cases (56), plastic surgeons performed 21% of SMF, while vascular surgeons performed 79%. On logistic regression correcting for baseline differences between groups, vascular surgeon SMF outcomes were compared favorably with those done by other specialties. Overall, SMFs have low perioperative reintervention rates but high complication rates. Vascular surgeons perform SMF on high-risk patients with more comorbidities compared with other specialties. Although overall morbidity associated with this procedure is high, perioperative outcomes for SMF performed by vascular surgeons are favorable.


Fluctuating nematic elastomer membranes.
We study the flat phase of nematic elastomer membranes with rotational symmetry spontaneously broken by an in-plane nematic order. Such a state is characterized by a vanishing elastic modulus for simple shear and soft transverse phonons. At harmonic level, the in-plane orientational (nematic) order is stable to thermal fluctuations that lead to short-range in-plane translational (phonon) correlations. To treat thermal fluctuations and relevant elastic nonlinearities, we introduce two generalizations of two-dimensional membranes in a three-dimensional space to arbitrary D-dimensional membranes embedded in a d-dimensional space and analyze their anomalous elasticities in an expansion about D=4. We find a stable fixed point that controls long-scale properties of nematic elastomer membranes. It is characterized by singular in-plane elastic moduli that vanish as a power law eta(lambda)=4-D of a relevant inverse length scale (e.g., wave vector) and a finite bending rigidity. Our predictions are asymptotically exact near four dimensions.


[Mass spectrometry combined with gene analysis for prenatal diagnosis of glutaric acidemia type Ⅰ].
Objective: To investigate the value of amniotic fluid metabolite detection by mass spectrometry combined with gene mutation analysis in the prenatal diagnosis of glutaric acidemia type Ⅰ (GA-Ⅰ). Method: From January 2009 to December 2016, Department of Pediatric Endocrinology and Genetic, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine carried out prenatal diagnosis for 24 cases of pregnant women with GA-Ⅰproband. 24 pregnant women without organic acidemia proband for conventional prenatal diagnosis at the same period were used as the control group. The pregnant women of the two groups had the amniocentesis at 16 to 20 weeks of gestation.The levels of glutaryl carnitine (C5DC) and octanoylcarnitine (C8) in amniotic fluid were detected by tandem mass spectrometry, and the levels of glutaric acid was determined by gas chromatography-mass spectrometry. All the amniotic fluid cells underwent GCDH gene testing. Result: A total of 4 cases of fetuses were diagnosed by gene mutation analysis combined with mass spectrometry detection, the levels of C5DC (1.58(0.89-2.85) μmol/L), C5DC/C8 (19.74(12.40-25.93))and glutaric acid (129.96 (90.09-66.02) mmol/mol Cr) were significantly higher than the upper limit of the reference, of which in one case with the proband only on mutation was detected, and in the amniotic fluid cells also only one mutation was detected, the diagnosis was made according to the significantly increased levels of amniotic fluid C5DC, C5DC/C8 and glutaric acid. Twenty cases of fetuses were identified as non-GA-Ⅰchildren, of whom in 2 cases of proband only one mutation was detected, and also in amniotic fluid cells one mutation was detected, in 2 cases the diagnosis was excluded because the normal levels of C5DC, C5DC/C8 and glutaric acid. There were 2 cases whose levels of C5DC or glutaric acid were slightly higher than the upper limit of the reference, but the diagnosis was excluded according to genetic testing. Conclusion: Prenatal diagnosis cannot be made by gene analysis when the proband mutation is not clear, and it cannot determine whether the fetus is patient when the mass spectrometry detection of amniotic fluid metabolite is mildly abnormal, while mass spectrometry detection of amniotic fluid C5DC, C5DC/C8 and glutaric acid levels combined with GCDH gene analysis can make up the deficiencies, and make the prenatal diagnosis of GA-Ⅰ more reliably.


A Community Hospital's Response to the COVID-19 Pandemic.
The novel coronavirus 2019-nCoV (COVID-19) has disrupted and altered the way health care is delivered in the United States and across the world. Patient care guidelines and isolation recommendations continue to hastily change, demonstrating the key role of nursing professional development practitioners in educating and preparing frontline staff to provide safe patient care during the COVID-19 pandemic. This article describes a community hospital's strategic educational response to a highly contagious respiratory pandemic. Initiatives to increase staff education and conserve personal protective equipment are discussed.


[Effect of diffuse light and heat on 8 BCG vaccines prepared from 4 different strains].
In order to improve our knowledge of the effect of daylight on freeze-dried and rehydrated BCG, 8 BCG vaccines prepared with four BCG strains--Danish 1331, French 1173-P2, English (Glaxo-1077) and Japanese 172--were studied. Four of them were in amber-coloured ampoules manufactured in Copenhagen (K. Bunch -Christensen) and four were in colourless ampoules manufactured by Institut Pasteur Production (Paris). Samples of these vaccines, both freeze-dried and rehydrated for use in children, were exposed to both factors and checked regularly for their viability. Daylight had a deleterious effect on the viability of both freeze-dried and (especially) rehydrated BCG vaccines. The fall in viability began after 2-h exposure of rehydrated vaccines and after 8-h exposure of freeze-dried ones. BCG survival was improved by coloured ampoules. Differences were observed between BCG strains in terms of the light effect, with the French strain being most resistant, the Danish least resistant and the others intermediate. UV irradiation was even more deleterious: 50% survival after 30-min exposure at 20 microW /cm2. In conclusion, since BCG vaccines are sensitive to these factors, they must therefore be protected and their viability checked during BCG vaccination campaigns.


Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: a cohort study from Stockholm County.
The Swedish National Patient Register offers unique possibilities for identification of large cohorts, such as patients with rheumatoid arthritis (RA). Although the overall diagnostic validity in the register has been reported as good, the aims of this study were to a) specifically validate the RA diagnosis from contemporary outpatient specialist care in this register, and b) assess the proportion of patients identified via algorithms to define incident RA in the register who in clinical practice also have new-onset disease. 211 individuals with prevalent or incident RA in the National Patient Register were included. By extracting diagnosis-related parameters from their medical records, we determined if the patient fulfilled the 2010 ACR/EULAR- and the 1987 ACR-classification criteria for RA. We also determined whether clinical diagnosis was synchronous with disease onset as defined through register-based algorithms. For 91% of the prevalent patients, the RA diagnosis in the National Patient Register fulfilled classification criteria or clinical diagnosis for RA. Among individuals identified with incident RA using a strict algorithm for new-onset disease, the RA diagnosis was substantiated in 91%, of whom 92% also represented new-onset disease. The validity of the RA diagnosis in the National Patient Register was high and, by using specific algorithms, new-onset RA can be defined. These findings strengthen the notion that the National Patient Register may be used to define RA populations with high validity to allow for high-quality epidemiological studies.


Inappropriate fetal sinus tachycardia at 9 weeks of gestation.
Inappropriate sinus tachycardia (IST) is characterized by an inexplicably elevated sinus heart rate (HR) at rest, with an exaggerated response to physical activity. Its etiology is unknown, and IST is more common in the middle-aged population, being rare in children and adolescents. Although a favorable long-term prognosis has been described in a small series, tachycardia-induced cardiomyopathy has rarely been associated with IST. In this report, we describe an extremely rare case of IST detected in the first trimester of gestation, focusing on reviewing important features to improve the diagnosis of the different types of tachycardia by applying fetal cardiac ultrasonography. In the case reported, the diagnosis of IST was suspected in a fetus from a pregnant woman with celiac disease, who was referred at 9 weeks of gestation with fetal tachycardia. The fetus remained hemodynamically stable until term, and the female neonate was born unremarkably. Electrocardiography in the newborn showed sinus tachycardia (ST) with normal PR and QTc intervals. Possible causes of ST were excluded, thus confirming the fetal diagnosis. The patient presented with a fast HR at rest with an exaggerated increase with minimal physical activity accompanied by irritability. Beta-adrenergic blocker therapy was initiated, and the female neonate has progressed well.


Efficacy of ethyl nitrite in reversing surgical vasospasm.
Vasospasm leading to thrombosis is a major cause of free flap failure. Flap blood flow may improve by application of vasodilating agents to the pedicle. The purpose of this study is to evaluate the effect of a novel S-nitrosylating agent, O-ethyl nitrite, on flap blood flow and pedicle vessels diameter in a rat model, after induction of vasospasm. Two hours after surgery, the arterial diameter was significantly (P < .05) dilated by treatment with O-ethyl nitrite, lidocaine, or lidocaine + O-ethyl nitrite. None of these treatments had a statistically significant effect on blood flow or venous diameter. Twenty-four hours following surgery, both O-ethyl nitrite- and lidocaine-treated groups had larger arteries than the control group (P < .05). The O-ethyl nitrite-treated animals also had significantly (P < .05) elevated blood flow compared with control animals, but lidocaine-treated animals did not demonstrate any improved flow at 24 hours. O-Ethyl nitrite may become clinically useful in microvascular surgery procedures.


[Combined effect of interferons alpha, beta and gamma on tumor growth in vitro].
The antiproliferative effect of human recombinant interferon alpha, beta and gamma was studied in vitro in combination. Growth of human gastric cancer cell lines and a pancreatic cancer cell line was inhibited markedly by combination of interferons beta and gamma or a combination of all three interferon types. Combination of low-dose interferons (50-100 units/ml) was more effective than a high dose of single interferon. Moreover, human pancreatic cancer cells were completely eliminated after incubation with 5-fluorouracil (0.001 microgram/ml) or methotrexate (0.1 microgram/ml) combined with interferons beta and gamma (50 units/ml each). These results suggested that combination of interferons beta and gamma could be the most effective interferon therapy for cancer.


A stable hippocampal code in freely flying bats.
Neural activity in the hippocampus is known to reflect how animals move through an environment1,2. Although navigational behaviour may show considerable stability3-6, the tuning stability of individual hippocampal neurons remains unclear7-12. Here we used wireless calcium imaging to longitudinally monitor the activity of dorsal CA1 hippocampal neurons in freely flying bats performing highly reproducible flights in a familiar environment. We find that both the participation and the spatial selectivity of most neurons remain stable over days and weeks. We also find that apparent changes in tuning can be largely attributed to variations in the flight behaviour of the bats. Finally, we show that bats navigating in the same environment under different room lighting conditions (lights on versus lights off) exhibit substantial changes in flight behaviour that can give the illusion of neuronal instability. However, when similar flight paths are compared across conditions, the stability of the hippocampal code persists. Taken together, we show that the underlying hippocampal code is highly stable over days and across contexts if behaviour is taken into account.


The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes.
We have recently shown that (a) human melanocytes express the p75 nerve growth factor (NGF) receptor in vitro; (b) that melanocyte dendricity and migration, among other behaviors, are regulated at least in part by NGF; and (c) that cultured human epidermal keratinocytes produce NGF. We now report that melanocyte stimulation with phorbol 12-tetra decanoate 13-acetate (TPA), previously reported to induce p75 NGF receptor, also induces trk in melanocytes, and TPA effect is further potentiated by the presence of keratinocytes in culture. Moreover, trk in melanocytes becomes phosphorylated within minutes after NGF stimulation. As well, cultures of dermal fibroblasts express neurotrophin-3 (NT-3) mRNA; NT-3 mRNA levels in cultured fibroblasts are modulated by mitogenic stimulation, UV irradiation, and exposure to melanocyte-conditioned medium. Moreover, melanocytes constitutively express low levels of trk-C, and its expression is downregulated after TPA stimulation. NT-3 supplementation to cultured melanocytes maintained in Medium 199 alone prevents cell death. These combined data suggest that melanocyte behavior in human skin may be influenced by neurotrophic factors, possibly of keratinocyte and fibroblast origin, which act through high affinity receptors.


Effects of inertia and gravity on liquid plug splitting at a bifurcation.
Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. During inspiration the plug may split at airway bifurcations and lead to a nonuniform final liquid distribution, which can adversely affect treatment outcomes. In this paper, a combination of bench top experimental and theoretical studies is presented to study the effects of inertia and gravity on plug splitting in an airway bifurcation model to simulate the liquid distributions in large airways. The splitting ratio, Rs, is defined as the ratio of the plug volume entering the upper (gravitationally opposed) daughter tube to the lower (gravitationally favored) one. Rs is measured as a function of parent tube Reynolds number, Rep; gravitational orientations for roll angle, phi, and pitch angle, gamma; parent plug length LP; and the presence of pre-existing plug blockages in downstream daughter tubes. Results show that increasing Rep causes more homogeneous splitting. A critical Reynolds number Rec is found to exist so that when Rep < or = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases while Rs decreases with increasing the gravitational effect, i.e., increasing phi and gamma. When a blockage exists in the lower daughter, Rec is only found at phi = 60 deg in the range of Rep studied, and the resulting total mass ratio can be as high as 6, which also asymptotes to a finite value for different phi as Rep increases. Inertia is further demonstrated to cause more homogeneous plug splitting from a comparison study of Rs versus Cap (another characteristic speed) for three liquids: water, glycerin, and LB-400X. A theoretical model based on entrance flow for the plug in the daughters is developed and predicts Rs versus Rep. The frictional pressure drop, as a part of the total pressure drop, is estimated by two fitting parameters and shows a linear relationship with Rep. The theory provides a good prediction on liquid plug splitting and well simulates the liquid distributions in the large airways of human lungs.


Stromal miR-20a controls paracrine CXCL8 secretion in colitis and colon cancer.
Inflammatory bowel disease (IBD) affects one million people in the US. Ulcerative colitis (UC) is a subtype of IBD that can lead to colitis-associated cancer (CAC). In UC, the rate of CAC is 3-5-fold greater than the rate of sporadic colorectal cancer (CRC). The pathogenesis of UC and CAC are due to aberrant interactions between host immune system and microenvironment, but precise mechanisms are still unknown. In colitis and CAC, microenvironmental fibroblasts exhibit an activated, inflammatory phenotype that contributes to tumorigenesis accompanied by excessive secretion of the chemokine CXCL8. However, mechanisms regulating CXCL8 secretion are unclear. Since it is known that miRNAs regulate chemokines such as CXCL8, we queried a microRNA library for mimics affecting CXCL8 secretion. Among the identified microRNAs, miR-20a/b was further investigated as its stromal expression levels inversely correlated with the amounts of CXCL8 secreted and predicted fibroblast tumor-promoting activity. Indeed, miR-20a directly bound to the 3'UTR of CXCL8 mRNA and regulated its expression by translational repression. In vivo co-inoculation studies with CRC stem cells demonstrated that fibroblasts characterized by high miR-20a expression had reduced tumor-promoting activities. These studies reveal that in stromal fibroblasts, miR-20a modulates CXCL8 function, therefore influencing tumor latency.


Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.
PET/CT using 68Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. 203 consecutive PC patients with biochemical failure referred to 68Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUVmax) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUVmax: 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUVmax: 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUVmax of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUVmax value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUVmax: 5.9 vs. 1.9, 4.0 and 2.4, respectively). Performance of early imaging in 68Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.


Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa.
Polyphenolic compounds present in rosemary were found to have antioxidant properties, anticarcinogenic activity, and to increase the detoxification of pro-carcinogens. The aim of the study was to determine the effect the aqueous extract of rosemary (AER) on mutagenicity induced by methylmethane sulfonate in meristematic cells of Allium cepa, as well as to describe its mode of action. Anti-mutagenicity experiments were carried out with 3 different concentrations of AER, which alone showed no mutagenic effects. In antimutagenicity experiments, AER showed chemopreventive activity in cultured meristematic cells of A. cepa against exposure to methylmethane sulfonate. Additionally, post-treatment and simultaneous treatment using pre-incubation protocols were the most effective. Evaluation of different protocols and the percent reduction in DNA indicated bioantimutagenic as well desmutagenic modes of action for AER. AER may be chemopreventive and antimutagenic.


The efficacy of parenteral fish oil in critical illness patients with sepsis: a prospective, non-randomized, observational study.
To investigate the clinical outcomes in septic patients receiving parenteral fish oil. A prospective, non-randomized, observational clinical study was carried out in 112 patients with sepsis from March, 2013 to May, 2015 in the surgical intensive care unit (SICU) of a tertiaryreferral hospital. The patients were put into one of two groups; either the control or the study group. Patients received the standard treatment of sepsis based on guidelines in the control group. In the study group, patients received parenteral nutrition (PN) containing fish oil. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the length of ICU and hospital stay, duration of mechanical ventilation, mortality, and readmission into the ICU were recorded. Tumor necrosis factor (TNF)-α and procalcitonin (PCT) levels were also evaluated. The study group showed a significant reduction for all-cause mortality (20.0% vs 10.0% in study and control groups, p=0.034) and APACHE II score on day 5 (p=0.015), day 7 (p=0.036) and day out of SICU (p=0.045) compared with the control group. The study group tended to show a shortened length of stay in the ICU compared to the control group. However, TNF-α and PCT level, 28 d mortality, the length of hospital stay and the duration of mechanical ventilation did not show statistical differences between the two groups. There were no drug-related adverse effects shown during the study. PN with fish oil is probably safe and may improve clinical outcome in critical ill patients with sepsis.


Temporary Single Palatal Implant for Denture Stabilization During Augmentation and Implant Procedure: A Case Report.
This case report introduces a temporary denture with reduced extension stabilized in the edentulous maxilla as a possible treatment method for patients with a severe gag reflex, allowing them to test the function, esthetics, and tolerance of the denture prior to hard tissue augmentation and implant placement. A 4-mm implant was placed in the central anterior palate and allowed to heal for 3 months. During the complete treatment period, a denture with reduced extension can be delivered on a fixed Locator abutment. This method was successfully applied in three patients, and the palatal implant remained stable until the final removable prosthesis could be delivered.


Observation of molecular hyperfine structure in the extreme ultraviolet: The HF C-X spectrum.
Clearly resolved hyperfine structure has been observed in the extreme ultraviolet (XUV) spectra of the C (1)Pi, v=0-X (1)Sigma(+), v=0 transition of H(19)F obtained through 1 XUV+1 UV resonance enhanced multiphoton ionization spectroscopy. The hyperfine splitting within the R-branch lines shows significant perturbations, which we attribute to mixing with the rotational levels of the nearby v=29 level of the B (1)Sigma(+) ion-pair state. A deperturbation analysis quantitatively explains the apparent variation of the fluorine magnetic hyperfine parameter a(F), for which a value of 4034(83) MHz was obtained by averaging over the values derived from the R(0)-R(4) lines, after correcting for the effects of the perturbations.


Dinitrogen activation in sterically-hindered three-coordinate transition metal complexes.
Dinuclear metal systems based on sterically-hindered, three-coordinate transition metal complexes of the type ML3 where the ancillary ligands L comprise bulky organic substituents, hold great promise synthetically for the activation and scission of small, multiply-bonded molecules such as N2, NO and N2O. In this study we have employed density functional methods to identify the metal/ligand combinations which achieve optimum activation and/or cleavage of N2. Strong pi donor ligands such as NH2 and OH are found to produce the greatest level of activation based on N-N bond lengths in the intermediate dimer complex, L3Mo(mu-N2)MoL3, whereas systems containing the weak or non-pi donor ligands NH3, PH3, OH2 and SH2 are found to be thermodynamically unfavourable for N2 activation. In the case of the Mo-NH2 and W-NH2 systems, a fragment bonding analysis reveals that the orientation of the amide ligands around the metal is important in determining both the spin state and the extent of dinitrogen activation in the intermediate dimer. For both systems, an intermediate dimer structure where one of the NH2 ligands on each metal is rotated 90 degrees relative to the other ligands, is more activated than the structure in which the NH2 ligands are trigonally disposed around the metals. The level of activation is found to be very sensitive to the electronic configuration of the metal with d3 metal ions delivering the best activation along any one transition series. In particular, strong activation or cleavage of N2 was calculated for the third row d3 metals systems involving Ta(II), W(III) and Re(IV), with the level of activation decreasing as the nuclear charge on the metal increases. This trend in activation reflects the size of the valence 5d orbitals and consequently, the capacity of the metal to back donate into the dinitrogen pi* orbitals.


Hormone replacement therapy in women with past history of endometriosis.
Endometriosis is a common clinical condition and its treatment will often lead to an estrogen deficiency status. As most of these patients are young, they will need to consider hormone replacement therapy. Endometriosis is a hormone-dependent disease and estrogen replacement can be associated with a risk of recurrence or malignant transformation. Only a few studies have addressed this problem. With the use of hormone replacement therapy (HRT), there is an increased, although undefined, risk of recurrence of endometriosis, especially in known severe cases and in obese patients. Unopposed estrogen appears to carry a higher risk than combined preparations. Delay in starting HRT after pelvic clearance is not of any benefit. After radical surgery for severe endometriosis, women often have much to gain from HRT, particularly in the early years. Benefits of HRT in terms of control of menopausal symptoms, prevention of urogenital atrophy and loss of libido and bone protection are of particular importance. HRT may still have a role in prevention of cardiovascular disease in early menopause, but this remains unproven. Although there is no firm evidence, continuous combined preparations or tibolone would appear to be the optimum choice.


Bevacizumab Regulates Cancer Cell Migration by Activation of STAT3.
There are numerous clinical cases indicating that long-term use of bevacizumab may increase the invasiveness of tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purpose of our study was to investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27, Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6 and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide and S3I-201 inhibited the STAT3 signal pathway, which is activated by bevacizumab. These inhibitors also substantially blocked bevacizumab-induced migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6 and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose that bevacizumab has differential effects on the migration of different cancer cell lines and promotes migration via the IL-6/STAT3 signaling pathway.