A Trial of Lifestyle Modification on Cardiopulmonary, Inflammatory, and Metabolic Effects among Obese with Chronic Kidney Disease.
The feasibility and benefits of lifestyle intervention in chronic kidney disease (CKD) patients who are obese has not been well studied. We examined the early effects of an exercise plus weight loss intervention on body composition, exercise capacity, metabolic parameters and kidney function in obese subjects with CKD. Nine subjects (median age 57 years, body mass index (BMI) 43.9) underwent a lifestyle intervention program that included supervised aerobic exercise (i.e. ∼85% maximum heart rate) and dietary counseling (500 kcal reduction in daily caloric intake). Body composition (iDXA), exercise capacity (maximal oxygen consumption), quality of life, insulin resistance (Matsuda index), inflammation (high sensitivity C-reactive protein), adipokines (leptin and total adiponectin) and kidney function (iothalamate glomerular filtration rate) were measured at baseline and after 12 weeks of the intervention. Changes in parameters were compared using the Wilcoxon signed-rank test. After 12 weeks of intervention, there was a significant decrease in BMI and fat mass (median -4.9 kg (25th-75th percentile -5.9 to -3.0)). There was a significant increase in exercise capacity (3.7 ml/kg/min (3.0-4.7)), along with improvements in insulin sensitivity (0.55 (0.43-1.2)), total adiponectin (780.9 μg/ml (262.1-1,497.1)) and leptin (-5.1 ng/ml (-14.5 to -3.3)). There were improvements in biomarkers of kidney disease very quality of life measures, but kidney function remained unchanged. Lifestyle modification is feasible in obese patients with CKD and produces weight loss that is related to improvements in exercise capacity, insulin resistance and adipokines. Whether lifestyle-induced weight loss and fitness can be sustained and whether it will mediate improvements in kidney function over time merits further investigation.


Methamphetamine promotes habitual action and alters the density of striatal glutamate receptor and vesicular proteins in dorsal striatum.
Goal-directed actions are controlled by the value of the consequences they produce and so increase when what they produce is valuable and decrease when it is not. With continued invariant practice, however, goal-directed actions can become habits, controlled not by their consequences but by antecedent, reward-related states and stimuli. Here, we show that pre-exposure to methamphetamine (METH) caused abnormally rapid development of habitual control. Furthermore, these drug-induced habits differed strikingly from conventional habits; we found that they were insensitive both to changes in reward value and to the effects of negative feedback. In addition to these behavioral changes, METH exposure produced bidirectional changes to synaptic proteins in the dorsal striatum. In the dorsomedial striatum, a structure critical for goal-directed action, METH exposure was associated with a reduction in glutamate receptor and glutamate vesicular proteins, whereas in the dorsolateral striatum, a region that has previously been implicated in habit learning, there was an increase in these proteins. Together, these results indicate that METH exposure promotes habitual control of action that appears to be the result of bidirectional changes in glutamatergic transmission in the circuits underlying goal-directed and habit-based learning.


Novel TRPM7 inhibitors with potent anti-inflammatory effects in vivo.
TRPM7, a TRP channel with ion conductance and kinase activities, has emerged as an attractive drug target for immunomodulation. Reverse genetics and cell biological studies have already established a key role for TRPM7 in the inflammatory activation of macrophages. Advancing TRPM7 as a viable molecular target for immunomodulation requires selective TRPM7 inhibitors with in vivo tolerability and efficacy. Such inhibitors have the potential to interdict inflammatory cascades mediated by systemic and tissue-specialized macrophages. FTY720, an FDA-approved drug for multiple sclerosis inhibits TRPM7. However, FTY720 is a prodrug and its metabolite, FTY720-phosphate, is a potent agonist of sphingosine 1-phosphate (S1P) receptors. In this study, we tested non-phosphorylatable FTY720 analogs, which are inert against S1PRs and well tolerated in vivo , for activity against TRPM7 and tissue bioavailability. Using patch clamp electrophysiology, we show that VPC01091.4 and AAL-149 block TRPM7 current at low micromolar concentrations. In culture, they act directly on macrophages to blunt LPS-induced inflammatory cytokine expression, an effect that is predominantly but not solely mediated by TRPM7. We found that VPC01091.4 has significant and rapid accumulation in the brain and lungs, along with direct anti-inflammatory action on alveolar macrophages and microglia. Finally, using a mouse model of endotoxemia, we show VPC01091.4 to be an efficacious anti-inflammatory agent that arrests systemic inflammation in vivo . Together, these findings identify novel small molecule inhibitors that allow TRPM7 channel inhibition independent of S1P receptor targeting. These inhibitors exhibit potent anti-inflammatory properties that are mediated by TRPM7 and likely other molecular targets that remain to be identified.


Significant carrier concentration changes in native electrodeposited ZnO.
We show that unintentional hydrogen doping of ZnO during the electrodeposition process can impact the material's carrier concentration as significantly as others have reported for intentional extrinsic doping. Mott-Schottky analyses on the natively n-type electrodeposits show a decrease in the carrier concentrations from 10(21) to 10(18) cm(-3) with increasing overpotential. A strong link exists between larger optical band gaps (determined from diffuse reflectance spectroscopy) and higher carrier concentrations, which suggests that hydrogen-based doping underlies the n-type conductivity (Moss-Burstein effect). We propose that kinetic defects introduced during growth at larger overpotentials compete with hydrogen doping, thereby leading to lower net carrier concentrations. This has important implications for using the deposition potential to tune other electrodeposit properties such as the growth rate and morphology.


Trial of labor after cesarean in the low-risk obstetric population: a retrospective nationwide cohort study.
The purpose of this study was to evaluate the risk of adverse maternal outcomes associated with trial of labor (TOL) after cesarean during subsequent pregnancies in the low-risk population. We conducted a retrospective cohort study using the Nationwide Inpatient Sample and ICD-9 diagnostic and procedure codes from the years 2003 to 2011. A cohort of low-risk pregnant women with a history of previous cesarean delivery were identified and separated into two groups: TOL and no TOL. Logistic regression analysis was used to calculate odds ratios (ORs) comparing adverse maternal outcomes between these two groups. Out of 7 290 474 registered deliveries, there were 685 137 low-risk women who met inclusion criteria. Of these women, 144 066 (21.0%) underwent a TOL, with rates remaining steady over the course of our study. The TOL group was at increased risk of overall morbidity (OR 1.74, 95% confidence interval (CI), 1.66-1.79), most notably uterine rupture (OR 22.52, 95% CI, 19.35-26.20, P<0.01). A secondary analysis showed no apparent correlation between TOL and concomitant adverse maternal outcomes in cases of uterine rupture. Although these outcomes remain rare, low-risk women undergoing a TOL remain at increased risk of adverse maternal events as compared with those who chose elective repeat cesarean delivery.


Reduction of nitrosative stress by methane: Neuroprotection through xanthine oxidoreductase inhibition in a rat model of mesenteric ischemia-reperfusion.
Our aim was to characterize the main components of the nitrosative response with quantitative changes of the nitrergic myenteric neurons in adjacent intestinal segments after transient superior mesenteric artery occlusion. We also tested the hypothesis that exogenous methane may modulate the evolution of nitroxidation by influencing xanthine oxidoreductase (XOR) activity. The microcirculatory consequences of a 50 min ischemia or ischemia-reperfusion were investigated in anesthetized rats (n = 124) inhaling normoxic air with or without 2.2% methane. XOR activities, nitrogen monoxide (NO), nitrite/nitrate (NOx), and nitrotyrosine levels were measured, together with relative nitrergic neuron ratios from duodenum, ileum and colon samples. The effects of methane on XOR were also examined in vitro. The intramural flow stopped only in the ileum during ischemia. The highest baseline XOR activity was found in the duodenum, which increased further during ischemia. NO and nitrotyrosine levels rose, and the nNOS-immunopositive neuron ratio and NOx level both dropped. Reperfusion uniformly elevated XOR activity and nitrotyrosine formation, with the highest level attained in the duodenum, where the nitrergic neuron ratio remained depressed. These alterations were eliminated in methane-treated animals, XOR activity and nitrotyrosine formation decreased in all sites, and the duodenal nitrergic neuron ratio was re-established. The inhibitory effect of methane on XOR-linked nitrate reductase activity was also demonstrated in vitro. With segment-specific microcirculatory alterations, the risk for nitrosative stress is highest in transiently hypoxic tissues with high endogenous XOR activities. The XOR-inhibitory effect of methane can reduce nitroxidation and protects the nitrergic neuron population in such conditions.


Externally readjustable device to regulate sling tension in stress urinary incontinence: preliminary results.
Slings, especially those called "tension free," have low complication rates and good long-term success rates. However, they still have problems with either an excess or a lack of tension, which produces voiding difficulties or urinary leakage persistence, respectively. The effectiveness of a new adjustable sling for the treatment of stress urinary incontinence (SUI) has been evaluated. Between November 1999 and May 2002, 113 consecutive patients were operated for SUI by means of a new adjustable sling. The results were analyzed retrospectively. The average follow-up time was 22 months (range 6-36 months). Objective success was achieved in 108 of 113 patients (95.5%), but subjectively, only 90.3% of the patients were completely satisfied with the procedure because of persistent urge incontinence in 6 cases (5.3%). Morbidity was minimal. This new minimally invasive treatment allows readjustment of sling tension at the immediate or mid-term postoperative period. It is applicable to primary and recurrent SUI and has shown encouraging results.


High-resolution optical coherence tomography in a case of descemetocele managed with amniotic membrane transplantation.
Amniotic membrane transplantation is a useful in the management of corneal melts and descemetocele. We describe high-resolution anterior segment optical coherence tomography (OCT) (Optovue) in a patient with descemetocele who was managed surgically with amniotic membrane transplantation. A 60-year-old female presented with a corneal melt in the right eye. She was a case of rheumatoid arthritis and was on systemic treatment with immunomodulators. Slit lamp examination revealed a severe thinning paracentrally. High-resolution OCT was performed at the site of descemetocele. She underwent amniotic membrane transplantation using fibrin glue and bandage contact lens application. At 6 weeks postoperative, the bandage contact lens was removed. The area of thinning healed with scarring. OCT at the healed site revealed stable surface and an increase in stromal thickness to 281 μ this case describes the utility of amniotic membrane in the healing of sterile corneal melts by providing tectonic support and its integration in the stroma. The stromal healing and increased thickness at the site of descemetocele could be delineated on high-resolution OCT imaging.


14-3-3 proteins participate in light signaling through association with PHYTOCHROME INTERACTING FACTORs.
14-3-3 proteins are regulatory proteins found in all eukaryotes and are known to selectively interact with phosphorylated proteins to regulate physiological processes. Through an affinity purification screening, many light-related proteins were recovered as 14-3-3 candidate binding partners. Yeast two-hybrid analysis revealed that the 14-3-3 kappa isoform (14-3-3κ) could bind to PHYTOCHROME INTERACTING FACTOR3 (PIF3) and CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1). Further analysis by in vitro pull-down assay confirmed the interaction between 14-3-3κ and PIF3. Interruption of putative phosphorylation sites on the 14-3-3 binding motifs of PIF3 was not sufficient to inhibit 14-3-3κ from binding or to disturb nuclear localization of PIF3. It was also indicated that 14-3-3κ could bind to other members of the PIF family, such as PIF1 and PIF6, but not to LONG HYPOCOTYL IN FAR-RED1 (HFR1). 14-3-3 mutants, as well as the PIF3 overexpressor, displayed longer hypocotyls, and a pif3 mutant displayed shorter hypocotyls than the wild-type in red light, suggesting that 14-3-3 proteins are positive regulators of photomorphogenesis and function antagonistically with PIF3. Consequently, our results indicate that 14-3-3 proteins bind to PIFs and initiate photomorphogenesis in response to a light signal.


Efficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn's disease: a single-center experience.
The published experience regarding the use of tacrolimus in Crohn's disease (CD) and ulcerative colitis (UC) refractory to more commonly used medical therapy has been fairly limited. Our objective was to describe our experience with its use in a cohort of patients which, to our knowledge, represents the largest North American cohort described to date. This was a retrospective, single-center chart analysis. Patients were identified by compiling all hospital discharges with principle diagnoses of ICD-9 codes for 555.0-555.9 (regional enteritis) and 556.0-556.9 (ulcerative colitis) from January 1, 2000, to October 31, 2005, and then cross-referencing the electronic charts for tacrolimus serum concentrations ordered during this time period. Additional patients were identified through verbal communication with participating clinicians. Information abstracted included proportion with clinical response and remission (using a modified disease activity index), ability to wean from steroids, need for surgery / time to surgery, and side-effect profile. In all, 32 UC patients and 15 CD patients were identified. The mean disease duration was: UC 81 months (range, 1 month to 37 years), CD 100 months (range, 1 month to 35 years). The disease distribution for UC was: pancolitis 12 (37.5%), extensive colitis 6 (18.8%), left-sided 11 (34.4%), and proctitis 3(9.4%). For CD this was: TI 2 (13.3%), small bowel 2 (13.3%), colonic 3 (20.7%), ileocolonic 7(46.7%), and perianal 1 (6.7%). The duration of tacrolimus treatment for UC was mean, 29 weeks. For CD it was mean, 9.9 weeks. In all, 30/32 UC and 7/15 CD patients were on steroids; 4/30 UC and 0/7 CD patients were able to subsequently wean off steroids. In all, 12/32 UC patients proceeded to colectomy. Mean time to colectomy was 28 weeks and 6/15 CD patients proceeded to a resective surgery. The mean time to surgery was 22 weeks. In all, 22/32 UC patients achieved a clinical response; 3/32 achieved remission and 8/15 CD patients achieved a clinical response; 1/15 achieved remission. Adverse reactions were generally mild. In 6 patients the drug had to be discontinued because of an adverse reaction. There were no opportunistic infections identified, no cases of renal insufficiency related to drug administration, and no deaths while on the medicine. Our experience with tacrolimus in UC and CD indicates that it is safe and relatively well tolerated, although its clinical efficacy is quite variable. More prospective studies assessing its use are necessary.


[Laparoscopic colectomy versus colectomy performed via laparotomy in the treatment of non-metastatic colic adenocarcinomas].
Laparoscopic colectomy is considered with increasing frequency the gold standard treatment for colorectal cancer. Our study aims to show that short-term results and the oncological safety of laparoscopy are at least equivalent to those of laparotomy in the treatment of non-metastatic colic adenocarcinomas. We also highlight the impact of the learning curve on outcomes after laparoscopy in patients with these cancers. We conducted a retrospective study of all patients undergoing surgery for resectable colic adenocarcinomas over a period of 6 years. The study population was divided into 2 groups based on the surgical procedure used initially. The group "OC" included 35 patients who underwent midline laparotomy and the group "LAC" included 30 patients who underwent laparoscopy. All data were analyzed using SPSS software version 19.0. Our study showed that there was no significant difference in short-term outcomes between the 2 groups, namely intraoperative morbidity, hospital stay, intensive care unit stay as well as postoperative morbidity and mortality. Regarding the long-term outcomes, there was also no significant difference in the incidence of late complications, type of recurrence, overall survival and disease-free survival. Oncological safety based on the limits of resection and the number of lymph nodes removed was not significantly different between the two groups. Operative time was significantly longer in the laparoscopic group (p <0.001). Convertion rate was 33%. It went from 67% in the first 2 years of the study to 13% in the last 2 years. The conversion from laparoscopy to laparotomy had no significant impact neither on early postoperative outcomes nor on overall survival and disease-free survival. Laparoscopy is a surgical procedure resulting in at least equivalent short and long term outcomes as laparotomy. The learning curve representing a "prerequisite" has no negative impact on the outcomes of laparoscopic treatment of non-metastatic colic cancers.


Fully automatic multi-atlas segmentation of CTA for partial volume correction in cardiac SPECT/CT.
Anatomical-based partial volume correction (PVC) has been shown to improve image quality and quantitative accuracy in cardiac SPECT/CT. However, this method requires manual segmentation of various organs from contrast-enhanced computed tomography angiography (CTA) data. In order to achieve fully automatic CTA segmentation for clinical translation, we investigated the most common multi-atlas segmentation methods. We also modified the multi-atlas segmentation method by introducing a novel label fusion algorithm for multiple organ segmentation to eliminate overlap and gap voxels. To evaluate our proposed automatic segmentation, eight canine 99mTc-labeled red blood cell SPECT/CT datasets that incorporated PVC were analyzed, using the leave-one-out approach. The Dice similarity coefficient of each organ was computed. Compared to the conventional label fusion method, our proposed label fusion method effectively eliminated gaps and overlaps and improved the CTA segmentation accuracy. The anatomical-based PVC of cardiac SPECT images with automatic multi-atlas segmentation provided consistent image quality and quantitative estimation of intramyocardial blood volume, as compared to those derived using manual segmentation. In conclusion, our proposed automatic multi-atlas segmentation method of CTAs is feasible, practical, and facilitates anatomical-based PVC of cardiac SPECT/CT images.


Genital chlamydial infection in female and male college students.
A review of more than 1,000 medical records of the University of South Florida students screened for gonorrhea, Chlamydia trachomatis, and syphilis during a period of 1 year in 1986-1987 showed genital chlamydial infection to be the most prevalent of these sexually transmitted diseases (STDs). Among normal asymptomatic female students with no known recent STD contact, 6.9% had a positive chlamydial enzyme immunoassay. Female students with vaginal symptoms had a greater tendency to be positive, and 47.8% of those with a recent STD contact tested positive for chlamydia. Males with a clinical diagnosis of nonspecific urethritis had a 50% probability of having a positive chlamydia test. Data from this study clearly support a need for a screening policy and educational program on the campus to improve control of chlamydial infection.


Translational animal models to study endometriosis-associated infertility.
Although there is an apparent association between endometriosis and impaired fertility, the pathophysiology of the reduced fecundity in women with endometriosis still remains unclear. Reproduction is a complex and multifactorial process, and possible factors contributing to the reduced fertility of endometriosis patients include defective function of the ovary, gametes, and endometrium as well as developmental disorders of the embryo. Because controlled experiments in humans are limited due to ethical reasons, experimental animal models have been developed mainly in nonhuman primates and laboratory rodents by induction of endometriosis via autologous transplantation of endometrial tissue. Animals with induced endometriosis reveal an impairment of fecundity similar to the situation described for humans and have been used to identify effects of ectopic endometrial tissue on adhesion formation, peritoneal fluid composition, ovarian function, endometrial gene expression, and embryo implantation. These animal models of endometriosis yield a valuable tool to study the mechanisms of endometriosis-associated infertility especially during the onset of the disease that cannot be investigated in women.


Comparative Analysis of Various Forms of Local Drug Delivery Systems on a Class 2 Furcation - A Systematic Review.
Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar bone remaining intact. There may be involvement of vertical bone loss. Local drug deliveries such as Boric acid, alendronate gel, and other drugs exhibited anti-inflammatory, antibacterial & osteoblastic differentiation activity. The present systematic review compares the drugs based on their outcomes and pharmacological action. To analzse & compare various forms of local drug delivery systems on a class II furcation. A search was conducted using PubMed, Google scholar, science direct, and Pub Med central using MeSH terms - local drug delivery in periodontics, boric acid in the management of class II mandibular furcation, simvastatin in the treatment of furcation. A total of 560 articles were screened; 58 out of 560 were full-text articles accessed for eligibility, and five articles were included in the systematic review. PRISMA guidelines were used for reporting this review. In addition, five randomized controlled trials were enclosed and used in this systematic review. The various local drugs used in treating class II mandibular furcation defects are effective in the prevention of bleeding on probing, bone resorption, gingival bleeding index and increase in the bone fill, and microbial deposit removal. The managing of class II mandibular furcation defect with the drugs mentioned in this review can be effective by reducing several clinical parameters such as bleeding on probing, gingival indices, osteoblastic differentiation, bone fill, etc., Considering the results of the studies, it can be concluded that it can be used as a therapeutic therapy against class II furcation defects with positive outcomes.


Computed tomography and magnetic resonance imaging of nonhemorrhagic, metastatic melanoma of the brain--case report.
Malignant melanoma frequently metastasizes to the central nervous system. Characteristic features of such lesions are increased density on computed tomography (CT) and shortening of the T1 and T2 on magnetic resonance (MR) imaging. Intratumoral hemorrhage, rather than melanin, is considered to be mainly responsible for these unique radiological features. The authors report a case involving a nonhemorrhagic, metastatic intracerebral melanoma. CT revealed a high-density mass, and MR imaging demonstrated a hyperintense mass both on T1- and T2-weighted images. These observations suggest that melanin is in fact a major determinant of the increased density on CT scans and the high signal intensity on T1-weighted MR images. On T2-weighted images, the paramagnetic effect appears to vary according to the melanin content.


Circadian temperature rhythms in clockwise and counter-clockwise rapidly rotating shift schedules.
The purpose of this study was to examine the circadian temperature rhythm in clockwise (CW) and counter-clockwise (CCW) rapidly rotating shift schedules. Arguments against the CCW rotation of shifts are that they result in shortened sleep and promote greater disruption of circadian rhythms. The 3-week study included a week of day shifts (0800-1600) and 2 weeks of shiftwork. The CW 2-2-1 schedule rotated from two early mornings (0600-1400) to two evenings (1400-2200) to one midnight shift (2200-0600) allowing 24 hours off at each shift rotation and a 48-hour weekend. The CCW schedule rotated from two evenings to two early mornings to one midnight shifts allowing only 8 hours off at each shift rotation and an 80-hour weekend. Analysis of the 72-hr periods at the end of each workweek, including the midnight shifts and recovery periods during weeks 2 and 3 were compared to the same 72-hour period at the end of week 1 (baseline). A cosine function that fit the temperature curves by minimizing the sums of squares produced parameters that underwent analysis of covariance procedures. Significant differences were found between rotation conditions for amplitude and acrophase. An attenuation of amplitude and a delay in the acrophase was the found for the counter-clockwise condition. Features inherent in this schedule might explain these effects, particularly, the increased opportunity for "sleeping in" at the beginning of the week and an expanded (2-shift) workday at the end of the week.


Comparison of three empirical force fields for phonon calculations in CdSe quantum dots.
Three empirical interatomic force fields are parametrized using structural, elastic, and phonon dispersion data for bulk CdSe and their predictions are then compared for the structures and phonons of CdSe quantum dots having average diameters of ˜2.8 and ˜5.2 nm (˜410 and ˜2630 atoms, respectively). The three force fields include one that contains only two-body interactions (Lennard-Jones plus Coulomb), a Tersoff-type force field that contains both two-body and three-body interactions but no Coulombic terms, and a Stillinger-Weber type force field that contains Coulombic interactions plus two-body and three-body terms. While all three force fields predict nearly identical peak frequencies for the strongly Raman-active "longitudinal optical" phonon in the quantum dots, the predictions for the width of the Raman peak, the peak frequency and width of the infrared absorption peak, and the degree of disorder in the structure are very different. The three force fields also give very different predictions for the variation in phonon frequency with radial position (core versus surface). The Stillinger-Weber plus Coulomb type force field gives the best overall agreement with available experimental data.


[Demands for a new, patient oriented rehabilitation].
A new orientation of rehabilitation in Germany has been initiated by the social political representatives in legislation and government, based on conceptualizations of self help movements in Europe and Germany. The goal is to form a new rehabilitation which is dedicated to participation and partnership of citizens with disability ("Nothing about us without us"). Empowerment is envisaged and resources supplied by legislation to allow to implement these new concepts (personal budget). To guarantee these new rights they have been codified in a new, 9th book of the German social code (Sozialgesetzbuch IX, SGB IX). This new perspective gives rise to major evolutionary impulses in rehabilitation, notably disabled persons' participation in self-assessment, in formulating their rehabilitation goals, determining and controlling the rehabilitation process, terminating rehabilitation (co-signing their discharge reports), as well as evaluating the outcome (quality control of rehabilitation results). They have the right to get all their medical information (right of informational independence). Seven guidelines of people with disability are formulated to support implementation of the new rehabilitation.


Patterned Arteriole-Scale Vessels Enhance Engraftment, Perfusion, and Vessel Branching Hierarchy of Engineered Human Myocardium for Heart Regeneration.
Heart regeneration after myocardial infarction (MI) using human stem cell-derived cardiomyocytes (CMs) is rapidly accelerating with large animal and human clinical trials. However, vascularization methods to support the engraftment, survival, and development of implanted CMs in the ischemic environment of the infarcted heart remain a key and timely challenge. To this end, we developed a dual remuscularization-revascularization therapy that is evaluated in a rat model of ischemia-reperfusion MI. This study details the differentiation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for engineering cardiac tissue containing patterned engineered vessels 400 μm in diameter. Vascularized engineered human myocardial tissues (vEHMs) are cultured in static conditions or perfused in vitro prior to implantation and evaluated after two weeks. Immunohistochemical staining indicates improved engraftment of hiPSC-CMs in in vitro-perfused vEHMs with greater expression of SMA+ vessels and evidence of inosculation. Three-dimensional vascular reconstructions reveal less tortuous and larger intra-implant vessels, as well as an improved branching hierarchy in in vitro-perfused vEHMs relative to non-perfused controls. Exploratory RNA sequencing of explanted vEHMs supports the hypothesis that co-revascularization impacts hiPSC-CM development in vivo. Our approach provides a strong foundation to enhance vEHM integration, develop hierarchical vascular perfusion, and maximize hiPSC-CM engraftment for future regenerative therapy.


Synthesis of 5-azido-UDP-N-acetylhexosamine photoaffinity analogs and radiolabeled UDP-N-acetylhexosamines.
Nuleotide sugar photoaffinity analogs have proven to be useful in the identification and characterization of glycosyltransferases. A radioenzymatic synthesis of [32P]5-azido-UDP-N-acetylglucosamine has been accomplished using 5-azido-UTP, [gamma-32P]ATP, porcine N-acetylgalactosamine kinase, and Escherichia coli UDP-N-acetylglucosamine pyrophosphorylase, GlmU. This general enzymatic scheme was useful for the synthesis of [32P]5-azido-UDP-N-acetylgalactosamine and high-specific-activity [3H] or [32P]UDP-N-acetylhexosamines. A new chemical synthesis method for generating 5-azido-uridine compounds was also developed. [32P]5-Azido-UDP-N-acetylglucosamine was functionally characterized using different soluble and membrane-associated glycosyltransferases which utilize UDP-GlcNAc as a substrate. Site-specific photoincorporation was observed for partially purified GlmU and porcine UDP-GlcNAc pyrophosphorylase. The photoprobe also effectively photoincorporated into the alpha- and beta-subunits of purified bovine UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. Lastly, the photoprobe was also effective at photolabeling Streptococcus pyogenes hyaluronate synthase in membrane preparations.


Dose-dependent effect of N'-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats.
N'-Nitrosodiethylamine (NDEA) is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is an extensively used experimental model. In the present study, we analysed the dose- and time-dependent effect of NDEA on hepatic damage, RBC rheology and proteomic profile in male Wistar rats. The rats, 5-6 weeks old, were divided into four groups: Group-1 served as control and received normal saline, Group-2 received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p.) and the animals were sacrificed after one week; the rats of Group-3 received a single dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4 received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed. Various biochemical parameters such as ALT, AST, ALP and bilirubin were determined. Further, RBC rheology, histopathology (H&E staining) of liver biopsies and polypeptide profiling (SDS-PAGE) in sera and liver sections were also carried out both in control and NDEA treated groups. Our results showed a significant increase in all the biochemical parameters of the liver function test (p<0.05). In NDEA treated categories dacryocytes (tear drop cells), schistocytes (fragmented cells), codocytes (target cells), acanthocytes (spur cells) and ovalocytes (oval cells) were observed. H & E stained liver biopsies treated with NDEA showed abnormal liver architecture with severe haemorrhage, neutrophilic infiltration and dysplastic hepatocytes manifested in a dose-dependent manner. Software analysis of SDS-PAGE of control and NDEA treated rat sera and liver revealed qualitative and quantitative differences in polypeptide composition. Based on the presence/absence, polypeptides were classified in three different categories: (1) house-keeping, present in all the groups investigated; (2) novel, present in either control or NDEA treated group at any given time; (3) differential expression, showing quantitative differences. Our study indicates a dose and time-dependent hepatocellular damage and proteome profile which is likely due to NDEA-mediated oxidative stress in rats.


Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice.
In human androgen-independent prostate cancer (PCa), epidermal growth factor receptor (EGFR) regulates angiogenesis, tumor growth, and progression. In this study, we evaluated whether the blockade of EGFR by the anti-EGFR antibody ImClone C225 (IMC-C225) inhibited tumor growth and metastasis by inhibiting angiogenesis, and whether paclitaxel enhanced the results of therapy in androgen-independent PCa. PC-3M-LN4 PCa cells were implanted orthotopically in athymic nude mice and treated with i.p. IMC-C225 (1 mg twice a week) and/or paclitaxel (200 microg once a week). In vitro treatment of PC-3M-LN4 with IMC-C225 inhibited EGFR autophosphorylation without any significant antiproliferative effect. In contrast, in vivo therapy with IMC-C225 alone (P < 0.05) or in combination with paclitaxel (P < 0.005) significantly inhibited PCa growth and metastasis. Serum levels of interleukin (IL) 8 were lower after therapy, and IL-8 mRNA expression was down-regulated within the tumors after therapy. The down-regulation of IL-8 correlated with reduced microvessel density. IMC-C225 reduced tumor cell proliferation, enhanced p27(kip1) expression, and induced tumor and endothelial cell apoptosis. These studies indicate that IMC-C225 has significant antitumor effect in this murine model, mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. The simultaneous administration of paclitaxel enhanced this effect.


Protective effects of epigallocatechin gallate on colon preneoplastic lesions induced by 2-amino-3-methylimidazo[4,5-f ] quinoline in mice.
Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has multiple anticarcinogenic effects. The aim of the present study was to investigate if EGCG could prevent the formation of colon aberrant crypt foci (ACF) induced by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) and to explore possible mechanisms for resultant effects. Sixty male BALB/cA nude, immunodeficient mice were divided into six groups including a normal unexposed control, mice induced with IQ alone, three groups treated with varying doses of EGCG post-IQ induction, and a EGCG-treated control population. Six weeks later, the mice were killed, and tissues subjected to hematoxylin-eosin (H&E) and 0.2% methylene blue staining to observe histopathological alterations of colon mucus and the formation of ACF, respectively. Protein expression of NF-E2-related factor 2 (Nrf2) was assessed via immunohistochemistry (IHC) and Western analysis, and mRNA levels of Nrf2 and uridine 5'-diphosphate-glucuronosyltransferase (UGT)1A10 were determined in colon tissues. Our results demonstrate that, compared with IQ-induced controls, the degree of atypical hyperplasia decreased and the number of total ACF and total AC also decreased significantly (P < 0.05 and P < 0.01, respectively) in mice belonging to all EGCG dosing groups. At the same time, the protein levels of Nrf2 detected by IHC and Western blotting increased (both P < 0.01 compared with IQ group), and the mRNA levels of Nrf2 and UGT1A10 increased (both P < 0.01 compared with IQ group). In conclusion, EGCG had preventive effects on preneoplastic lesions induced by IQ. Our observations suggest that this effect may be the result of activation of the Nrf2-UGT1A10 signaling pathway.


Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance.
Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. Here, we investigate BRAFV600E amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that BRAF amplifications acquired de novo are the primary cause of resistance. Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. Most DNA replication and repair genes are re-expressed as cells enter S and G2; however, mRNAs encoding a subset of factors important for error-free replication and chromosome segregation, including TIPIN, PLK2 and PLK3, remain at low abundance. This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. To test the hypothesis that escape from G1 arrest in drug promotes de novo BRAF amplification, we exploited the combination of palbociclib and selumetinib. Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through de novo gene amplification and can be suppressed by impeding cell cycle entry in drug.


Supportive Nursing Care and Satisfaction of Patients Receiving Electroconvulsive Therapy: A Randomized Controlled Clinical Trial.
Patient satisfaction is the most important criterion in evaluating the quality of care. Besides, its assessment in patients with severe mental disorder treated by electroconvulsive therapy (ECT) is highly appropriate. The ECT is accompanied by lower satisfaction and may exacerbate the patients' condition. The current study aimed to determine the effect of supportive nursing care on the satisfaction of patients receiving ECT. This randomized controlled trial was conducted in the education center of Baharan psychiatric hospital, Zahedan, Iran. Seventy hospitalized patients receiving ECT were randomly divided into two groups of control (n = 35) and intervention (n = 35).The socio-personal and Webster Satisfaction Questionnaire were used as data collection tools. The intervention group received supportive nursing care by nurses trained in informational, emotional, and physical aspects. The control group received only regular nursing care. The levels of satisfaction were measured and compared between groups, before and after the intervention. Data were analyzed using the SPSS software, and Chi-square, independent and paired t tests, as well as covariance analysis were performed. The results showed similarities in socio-personal characteristics of both groups. However, there was a significant difference (P < 0.001) between the means of satisfaction in the groups, predominantly for the intervention group. In other words, a significant difference (P < 0.001) was observed between the means of satisfaction of the intervention (54.71 ± 5.27) and control (36.28 ± 7.00) groups after intervention by controlling the effect of socio-personal variables. Results of the current study confirmed the effect of supportive nursing care on increasing the level of satisfaction in ECT receiving patients, recommending the use of this therapeutic method.


Turn up the heat: thermal tolerances of lizards at La Selva, Costa Rica.
Global temperature increases over the next century are predicted to contribute to the extinction of a number of taxa, including up to 40% of all lizard species. Lizards adapted to living in lowland tropical areas are especially vulnerable because of their dependence on specific microhabitats, low vagility, and a reduced capacity to physiologically adjust to environmental change. To assess the potential effects of climate change on lizards in the lowland tropics, we measured the critical thermal maximum (CTmax) of ten species from La Selva, Costa Rica. We also examined how well body size, microhabitat type, and species predicted the CTmax. We used current temperature data along with projected temperature increases for 2080 to predict which species may be at the greatest risk at La Selva. Of the ten species sampled, four are at serious risk of lowland extirpation and three others might also be at risk under the highest predicted temperature-increase models. Forest floor lizards at La Selva have already experienced significant population declines over the past 40 years, and we found that each of the forest floor species we studied is at serious risk of local extirpation. We also found that microhabitat type is the strongest predictor of CTmax, demonstrating the profound impact habitat specialization has on the thermal limits of tropical lizards.


Additional local therapy with primary re-excision or radiation therapy improves survival and local control after incomplete or close surgical excision of mast cell tumors in dogs.
To compare survival and local recurrence outcomes in dogs with mast cell tumors with incomplete or close margins treated with primary re-excision or radiation therapy of the primary site versus no additional local therapy. Retrospective case series. Dogs (n = 64). Outcomes of canine mast cell tumor cases that had incomplete or close surgical resection and presented to the Ontario Veterinary College Health Sciences Centre (2001-2010) were evaluated after additional local therapy (primary re-excision or radiation therapy) or no additional local therapy (comparison). Follow-up was performed through evaluation of medical records and telephone contact with referring veterinarians and owners. Tumors (n = 70) in 64 dogs were studied. Median survival times for the primary re-excision (2930 days) and radiation therapy (2194 days) groups were significantly longer than for the comparison (710 days) group. Local recurrence occurred in 13% of the re-excision group, 8% of the radiation therapy group, and 38% of the comparison group. Although local recurrence rate was not statistically significant for the re-excision group, time to local recurrence was statistically longer for both the re-excision and radiation groups. Adjunctive chemotherapy was not associated with improved survival or local control. There is significant improvement in survival and duration of local control when additional local therapy is performed after incomplete or close resection of mast cell tumors. These follow-up therapies should be recommended to owners when mast cell tumors are incompletely or closely resected.


Cloacal Duplication: Single-center Experience in the Management of a Rare Anomaly.
Cloacal duplication is an exceedingly rare group of anomalies with a limited number of cases reported so far. The anomaly may be confined to partial bladder duplication or it may involve complete duplication of the urogenital tract, hindgut, spine, lower limbs, and vascular structures. Every case is unique and ought to be approached individually. By means of imaging studies and endoscopy, anatomic details should be carefully defined before endorsing surgical correction. A satisfactory outcome can be achieved in the majority of cases. In this report, we describe 3 girls with cloacal duplication, and review pertinent imaging and surgical management.


Mesiodistal crown dimensions of the permanent dentition in North Indian children.
This investigation was conducted on 110 individuals, (40 males and 70 females) in the age range of 12-18 years. The results revealed the mesiodistal crown dimensions of teeth of males to be more than that of the females. Further the ratio of the mesiodistal crown dimension of the maxillary lateral incisors to the maxillary central incisors was 80% in females and 78% in males. The total arch length in males was 117.77 mm in maxilla and 111.60 mm in mandible, while in females, the figures were 113.98 mm in maxilla and 107.10 mm in the mandible.


Cremation and Grief: Are Ways of Commemorating the Dead Related to Adjustment Over Time?
Funeral services are known to serve multiple functions for bereaved persons. There is also a common, intuitively reasonable assumption of positive associations between engaging in funeral activities and adjustment to bereavement. We examined whether restricting ceremonial cremation arrangements to a minimum has a negative association with grief over time. Bereaved persons in the United Kingdom completed questionnaires 2 to 5 months postloss and again a year later (N = 233 with complete data; dropout = 11.4%). Neither type nor elaborateness of the cremation service, nor satisfaction with arrangements (typically high), emerged as significantly related to grief; no major subgroup differences (e.g., according to income level) were found. Results suggested that it does not matter to grief whether a more minimalistic or elaborate funeral ceremony was observed. We concluded that the funeral industry represented in this investigation is offering bereaved people the range of choices regarding cremation arrangements to meet their needs. Limits to generalizability are discussed.


Size- and Chirality-Dependent Structural and Mechanical Properties of Single-Walled Phenine Nanotubes.
Phenine nanotubes (PNTs) have recently been synthesized as a promising new one-dimensional material for high-performance electronics. The periodically distributed vacancy defects in PNTs result in novel semiconducting properties, but may also compromise their mechanical properties. However, the role of these defects in modifying the structural and mechanical properties is not yet well understood. To address this, we conducted systematic molecular dynamics simulations investigating the structural evolution and mechanical responses of PNTs under various conditions. Our results demonstrated that the twisting of linear carbon chains in both armchair and zigzag PNTs led to interesting structural transitions, which were sensitive to chiralities and diameters. Additionally, when subjected to tensile and compressive loading, PNTs' cross-sectional geometry and untwisting of linear carbon chains resulted in distinct mechanical properties compared to carbon nanotubes. Our findings provide comprehensive insights into the fundamental properties of these new structures while uncovering a new mechanism for modifying the mechanical properties of one-dimensional nanostructures through the twisting-untwisting of linear carbon chains.


[Parathion poisoning in cattle (author's transl)].
In a herd of dairy cattle half of the cows showed symptoms of acute poisoning. Blood- and hair samples were taken from seven of the cows, of which two did not show any clinical symptoms. The cholinesterase activities were in all the blood samples decreased to about 10 per cent of normal and parathion was found in all hair samples. The cholinesterase activities rose gradually during a 31/2 month period to the lower part of the normal range. Parathion was found in samples from the inner walls of the cowstable, and it was concluded that the poisoning was probably due to parathion spraying in the stable, while a suspicion of winddrift as a source of poisoning was rejected as less probable.


Identification of at-risk drinkers in an orthopaedic inpatient population.
The prevalence of hazardous drinking of alcohol in orthopaedic inpatients and its impact on patient management was determined. A prospective survey was performed on acute and arranged admissions in the orthopaedic wards at St Vincent's Hospital, Melbourne, over a 3 month period. At-risk drinking was measured by the AUDIT questionnaire, a score of eight or more suggesting hazardous drinking and a score of 20 or more suggesting dependence. A separate questionnaire recorded relevant details of the admission, complications during hospital stay, degree of difficulty nursing the patient and any past history of alcohol problems. Thirty-four (36%) of 94 patients were drinking at hazardous levels. Of these, 62% gave no prior history of problems with alcohol. Thirty-four per cent of 53 acute admissions and 39% of 41 arranged admissions were harmful drinkers suggesting that trauma may not be the only contribution to problem drinking in the orthopaedic setting. Hazardous drinking occurred in both male and female groups aged less than 55 years and in males greater than 55 years. Hazardous drinking was associated with more inpatient complications (chi 2 = 6.6, d.f. = 1, P = 0.01) and greater nursing difficulty (chi 2 = 5.5, d.f. = 1, P = 0.02). A third of the patients in the orthopaedic wards drink alcohol at hazardous levels, whether they are acute or arranged admissions. Hazardous drinking is associated with more complications and greater difficulty in nursing patients.


Herpes simplex virus genes Us3, Us5, and Us12 differentially regulate cytotoxic T lymphocyte-induced cytotoxicity.
Many viruses, including Herpes Simplex Virus (HSV), have developed strategies to avoid detection by cytotoxic T lymphocytes (CTLs). In this article, we evaluated the role of individual HSV-1 genes in preventing cytolysis and apoptosis, and in decreasing viral yield after CTL exposure of HSV-infected fibroblasts, using viruses deleted for the immune evasion gene Us12 or one of the two antiapoptotic genes Us3 and Us5. To evaluate CTL-mediated apoptosis, we used a flow cytometry assay measuring active caspase-3 in target cells. This assay was more sensitive than the chromium release assay used to evaluate cytolysis, and measured a different aspect of CTL cytotoxicity. Although virus with deletion of Us12 was markedly defective in the ability to prevent lysis of target fibroblasts, it retained most of its ability to protect target fibroblasts from CTL-induced apoptosis. Virus with deletion of Us3 was also defective in the ability to prevent lysis of target fibroblasts, yet such virus protected target fibroblasts from CTL-induced apoptosis as well as wild-type viruses. In contrast, Us5-deleted virus showed defects in the ability to protect target fibroblasts from both cytolysis and apoptosis after CTL attack. In addition, the replication of Us12-deleted virus was reduced compared with wild-type virus in fibroblasts subjected to CTL attack 6 h after infection, but showed equivalent replication when CTL attack occurred later. In contrast, Us3- or Us5-deleted virus showed no measurable defect in their ability to replicate in fibroblasts under CTL attack. Our data suggest that cytolysis, apoptosis, and viral yield do not necessarily correlate in infected cells under CTL attack. Furthermore, the Us3, Us5, and Us12 viral genes each have unique inhibitory effects on the different T lymphocyte cytotoxic effects. Taken together, these results suggest that HSV evasion of cellular immunity is multifacterial and complex, and relies on the partially redundant activities of various individual HSV proteins.


NMR-based Stable Isotope Resolved Metabolomics in systems biochemistry.
Metabolism is the basic activity of live cells, and monitoring the metabolic state provides a dynamic picture of the cells or tissues, and how they respond to external changes, for in disease or treatment with drugs. NMR is an extremely versatile analytical tool that can be applied to a wide range of biochemical problems. Despite its modest sensitivity its versatility make it an ideal tool for analyzing biochemical dynamics both in vitro and in vivo, especially when coupled with its isotope editing capabilities, from which isotope distributions can be readily determined. These are critical for any analyses of flux in live organisms. This review focuses on the utility of NMR spectroscopy in metabolomics, with an emphasis on NMR applications in stable isotope-enriched tracer research for elucidating biochemical pathways and networks with examples from nucleotide biochemistry. The knowledge gained from this area of research provides a ready link to genomic, epigenomic, transcriptomic, and proteomic information to achieve systems biochemical understanding of living cells and organisms.


Selecting Female Mice in Estrus and Checking Plugs.
The female mouse estrous cycle is divided into four phases: proestrus (development of ovarian follicles), estrus (ovulation), metestrus (formation of corpora lutea), and diestrus (beginning of follicle development for next ovulation and elimination of previous oocytes). The appearance of the epithelium of the external genitalia is used to identify the stage of the estrous cycle of a female mouse. This is usually easier to see in strains with either no or only light skin pigmentation. By examining the color, moistness, and degree of swelling of the vagina, females in estrus can readily be identified. To set up the matings, females are examined in the afternoon, and those in estrus are placed into the cages with males (one or two females in each cage with one male). Usually, 50% or more of the selected females will mate. The presence of a vaginal copulation plug next morning indicates that mating has occurred, but it does not mean that a pregnancy will result even if proven breeder fertile males were used. It is important to check vaginal plugs early in the morning because they fall out or are no longer detectable ~12 h after mating or sometimes earlier.


High-level expression and preparation of recombinant human fibrinogen as biopharmaceuticals.
Fibrinogen is a large and complex glycoprotein containing two sets of each of three different chains (α, β and γ). There have been no reports of high-level expression of fibrinogen at commercial levels using mammalian cultured cells such as CHO cells because of the difficulty in highly expressing a protein with such a complex structure. We achieved high-level (1.3 g/l or higher) expression of recombinant human fibrinogen using CHO DG44 cells by optimizing the expression system and culture conditions. We also succeeded in establishing a high-recovery preparation method for recombinant fibrinogen that rarely yields degraded products. To characterize the properties of the recombinant human fibrinogen, we performed SDS-PAGE; western blotting of the α, β and γ chains using specific antibodies and scanning electron microscopy observations of fibrin fibres. We also evaluated the functional equivalence between recombinant fibrinogen and plasma fibrinogen with respect to the release of fibrinopeptides initiated by thrombin and its cross-linking properties. The basic properties of recombinant fibrinogen showed no apparent differences from those of plasma fibrinogen. Here, we report the development of methods for the culture and preparation of recombinant human fibrinogen of satisfactory quality that can be scaled up to the commercial level.


Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes.
Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-deficient zebrafish and report that embryonic macrophages emerge followed by their developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. They expressed macrophage-associated genes, but also showed decreased phagocytic gene expression and increased epithelial-associated gene expression, characteristic of metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, csf1r deficiency disrupts embryonic to adult macrophage development. Zebrafish deficient for csf1r are viable and permit analyzing the consequences of macrophage loss throughout life.


Rate-dependent QT shortening mechanism for the LQT3 deltaKPQ mutant.
For the congenital long QT (LQT) syndrome involving mutations of the cardiac sodium channel gene SCN5A, LQT3, the initiation of sudden cardiac death tends to be bradycardia- or pause-dependent, contrary to other LQT syndromes that tend to be adrenergic dependent. Enhanced shortening of the prolonged QT interval with increased heart rate has been reported in LQT3 patients. We hypothesized that the rate-dependent shortening of the QT interval may be attributed to the kinetic properties of inactivation the late sodium current (I(Na)) in LQT3. The deltaKPQ mutant of the human heart voltage-gated sodium channel alpha-subunit was stably transfected into a mammalian cell line (HEK293). I(Na) was recorded using a whole-cell patch-clamp technique. A train of 50 depolarizing pulses or a train of 50 ventricular action potential waveforms was applied with different interpulse durations. Peak I(Na) for the 50th pulse compared with that of I(Na) in the first pulse was decreased <2% for interpulse durations as short as 20 ms, but late I(Na) amplitude measured at the end of the pulse was decreased 95, 78, 68, 56 and 47% with 1000, 500, 200, 100, 20 ms interpulse intervals, respectively. Using the action potential waveform a similar rate-dependent reduction of late I(Na) was found with minimal reduction of peak I(Na). Late I(Na) amplitude in the deltaKPQ mutation is strongly rate dependent. Rate-dependent reductions of late I(Na) may cause shortening the QT interval at higher rates. This provides a mechanism correlating the genotype with the clinical phenotype, and provides a rationale for the effectiveness of pacemaker therapy in LQT3 patients.


Restriction fragment length polymorphism analysis of endogenous avian leukosis viral loci: determination of frequencies in commercial broiler lines.
Four component lines of a commercial broiler stock were analyzed by restriction fragment length polymorphism (RFLP) analysis, for the presence of endogenous avian leukosis virus loci. The resulting RFLP patterns of endogenous virus (ev) loci for the four strains were further characterized in terms of number of loci per animal and frequency. Loci were also analyzed within limits for major structural alterations and deletions to discern whether certain loci were similar to previously identified loci in White Leghorn layer birds. The ev RFLP patterns for these broiler lines were found to be highly complex and contained many loci unreported in White Leghorn layer birds.


Psychometric Properties of the Multidimensional Pain Inventory Applied to Brazilian Patients with Orofacial Pain.
To evaluate the psychometric properties of the Multidimensional Pain Inventory (MPI) in a Brazilian sample of patients with orofacial pain. A total of 1,925 adult patients, who sought dental care in the School of Dentistry of São Paulo State University's Araraquara campus, were invited to participate; 62.5% (n=1,203) agreed to participate. Of these, 436 presented with orofacial pain and were included. The mean age was 39.9 (SD=13.6) years and 74.5% were female. Confirmatory factor analysis was conducted using χ²/df, comparative fit index, goodness of fit index, and root mean square error of approximation as indices of goodness of fit. Convergent validity was estimated by the average variance extracted and composite reliability, and internal consistency by Cronbach's alpha standardized coefficient (α). The stability of the models was tested in independent samples (test and validation; dental pain and orofacial pain). The factorial invariance was estimated by multigroup analysis (Δχ²). Factorial, convergent validity, and internal consistency were adequate in all three parts of the MPI. To achieve this adequate fit for Part 1, item 15 needed to be deleted (λ=0.13). Discriminant validity was compromised between the factors "activities outside the home" and "social activities" of Part 3 of the MPI in the total sample, validation sample, and in patients with dental pain and with orofacial pain. A strong invariance between different subsamples from the three parts of the MPI was detected. The MPI produced valid, reliable, and stable data for pain assessment among Brazilian patients with orofacial pain.


Defining Pediatric Chronic Critical Illness for Clinical Care, Research, and Policy.
Chronically critically ill pediatric patients represent an emerging population in NICUs and PICUs. Chronic critical illness has been recognized and defined in the adult population, but the same attention has not been systematically applied to pediatrics. This article reviews what is currently known about pediatric chronic critical illness, highlighting the unique aspects of chronic critical illness in infants and children, including specific considerations of prognosis, outcomes, and decision-making. We propose a definition that incorporates NICU versus PICU stays, recurrent ICU admissions, dependence on life-sustaining technology, multiorgan dysfunction, underlying medical complexity, and the developmental implications of congenital versus acquired conditions. We propose a research agenda, highlighting existing knowledge gaps and targeting areas of improvement in clinical care, research, and policy.


Evolution of echovirus 11 in a chronically infected immunodeficient patient.
Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate. Extrapolation of mutations accumulation curve into the past suggested that the individual was infected with circulating EV11 in the first half of 1990s. Genomic regions coding for individual viral proteins did not appear to be under strong selective pressure except for protease 3C that was remarkably conserved. This may suggest its important role in maintaining persistent infection.


An electron in a finite-dipole potential.
Some structural properties of the energy eigenfunctions of an electron in a finite-dipole field are analyzed, in particular the asymptotic behavior when the electron is far away, and the coalescence and cusp properties when it is close to the dipole charges. Model wave functions incorporating these properties are developed, which give accurate values for the energies and some other quantities, and a useful insight into the physical structure of the system. Critical radius for the existence of the bound states is obtained from the Wentzel-Kramers-Brillouin approach. These considerations are extended to the description of the system in two dimensions.


Peptide array on cellulose support--a screening tool to identify peptides with dipeptidyl-peptidase IV inhibitory activity within the sequence of α-lactalbumin.
The inhibition of the enzyme dipeptidyl-peptidase IV (DPP-IV) is an effective pharmacotherapeutic approach for the management of type 2 diabetes. Recent findings have suggested that dietary proteins, including bovine α-lactalbumin, could be precursors of peptides able to inhibit DPP-IV. However, information on the location of active peptide sequences within the proteins is far from being comprehensive. Moreover, the traditional approach to identify bioactive peptides from foods can be tedious and long. Therefore, the objective of this study was to use peptide arrays to screen α-lactalbumin-derived peptides for their interaction with DPP-IV. Deca-peptides spanning the entire α-lactalbumin sequence, with a frame shift of 1 amino acid between successive sequences, were synthesized on cellulose membranes using "SPOT" technology, and their binding to and inhibition of DPP-IV was studied. Among the 114 α-lactalbumin-derived decamers investigated, the peptides 60WCKDDQNPHS69 (αK(i) = 76 µM), 105LAHKALCSEK114 (K(i) = 217 µM) and 110LCSEKLDQWL119 (K(i) = 217 µM) were among the strongest DPP-IV inhibitors. While the SPOT- and traditionally-synthesized peptides showed consistent trends in DPP-IV inhibitory activity, the cellulose-bound peptides' binding behavior was not correlated to their ability to inhibit the enzyme. This research showed, for the first time, that peptide arrays are useful screening tools to identify DPP-IV inhibitory peptides from dietary proteins.


Design of a Golf Swing Injury Detection and Evaluation open service platform with Ontology-oriented clustering case-based reasoning mechanism.
Nowadays, people can easily use a smartphone to get wanted information and requested services. Hence, this study designs and proposes a Golf Swing Injury Detection and Evaluation open service platform with Ontology-oritened clustering case-based reasoning mechanism, which is called GoSIDE, based on Arduino and Open Service Gateway initative (OSGi). GoSIDE is a three-tier architecture, which is composed of Mobile Users, Application Servers and a Cloud-based Digital Convergence Server. A mobile user is with a smartphone and Kinect sensors to detect the user's Golf swing actions and to interact with iDTV. An application server is with Intelligent Golf Swing Posture Analysis Model (iGoSPAM) to check a user's Golf swing actions and to alter this user when he is with error actions. Cloud-based Digital Convergence Server is with Ontology-oriented Clustering Case-based Reasoning (CBR) for Quality of Experiences (OCC4QoE), which is designed to provide QoE services by QoE-based Ontology strategies, rules and events for this user. Furthermore, GoSIDE will automatically trigger OCC4QoE and deliver popular rules for a new user. Experiment results illustrate that GoSIDE can provide appropriate detections for Golfers. Finally, GoSIDE can be a reference model for researchers and engineers.


Effects of straits as dispersal barriers for the flightless roving carrion beetle, Silpha perforata (Coleoptera, Silphidae, Silphinae).
Population genetic analyses were conducted for the flightless beetle Silpha perforata in northern Japan to evaluate effects of straits as dispersal barriers. In all, 19 populations on the Hokkaido mainland and one population on each of seven adjacent islands were included in the study. Based on partial sequences (853 bp) of the mitochondrial ND2 gene from 365 individuals, we calculated haplotype diversity (h), nucleotide diversity (pi), Tajima's D, and Fu's F(s) statistics for each population. The genetic distance d(A) and fixation index F(ST) were then estimated between populations, excluding two mainland and two island populations with small sample sizes. The results showed that four island populations (Rebun, Rishiri, Yagishiri, and Teuri) were genetically diverged and isolated from mainland populations, including the closest ones, consistent with the assumption that the straits separating these islands from the mainland have functioned as strong barriers against beetle dispersal. However, some factors other than sea barriers may have resulted in the observed divergence of these island populations, since the straits might be too young to permit such divergence (all are estimated to have been finally established approximately 11,000 to 13,000 years BP). On the other hand, the population on Okushiri Island showed little genetic divergence from the nearest mainland population, suggesting current overseas dispersal across the strait (estimated to have been formed more than 200,000 years BP). The present study thus demonstrated that the effects of straits on dispersal can be diverse, even for species of terrestrial invertebrates with limited dispersal ability.


Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic.
Intracytoplasmic sperm injection (ICSI) is a successful treatment option for severe male infertility, although the aetiology of the disorder remains unclear in most cases. Recently, microdeletions in the AZF region of the Y chromosome have been detected in men with azoospermia or severe oligozoospermia. In this study we investigated the prevalence of microdeletions in the AZF region of the Y chromosome in a population of men undergoing ICSI, and looked for clinical characteristics of men with and without this deletion. Blood was drawn from 164 men, who were on the waiting list for ICSI treatment: 19 were azoospermic, 111 oligozoospermic and 34 normozoospermic (after previous total fertilization failure). A total of 100 men with proven fertility served as a control. Microdeletions in the AZFc region were present in seven of the 111 oligozoospermic men (6.3%). Compared with oligozoospermic men without microdeletions, men with microdeletions had a lower concentration of follicle stimulating hormone (FSH), a lower number of motile spermatozoa and a lower frequency of abnormal findings at andrological history or examination. No microdeletions were found in the azoospermic, normozoospermic and control groups. In conclusion, microdeletions in the AZFc region are relatively frequently found in men with severe unexplained oligozoospermia. In the ICSI era this finding has an important impact because this form of male infertility is now potentially hereditary. Therefore we recommend DNA screening (and genetic counselling) before ICSI, especially in men with normal FSH, severe oligozoospermia and no abnormal clinical andrological findings.


Poloidal rotation dynamics, radial electric field, and neoclassical theory in the jet internal-transport-barrier region.
Results from the first measurements of a core plasma poloidal rotation velocity (upsilontheta) across internal transport barriers (ITB) on JET are presented. The spatial and temporal evolution of the ITB can be followed along with the upsilontheta radial profiles, providing a very clear link between the location of the steepest region of the ion temperature gradient and localized spin-up of upsilontheta. The upsilontheta measurements are an order of magnitude higher than the neoclassical predictions for thermal particles in the ITB region, contrary to the close agreement found between the determined and predicted particle and heat transport coefficients [K.-D. Zastrow, Plasma Phys. Controlled Fusion 46, B255 (2004)]. These results have significant implications for the understanding of transport barrier dynamics due to their large impact on the measured radial electric field profile.


Poly(ethylene glycol)s as Ligands in Calcium-Catalyzed Cyclic Carbonate Synthesis.
Herein the use of CaI2 in combination with poly(ethylene glycol) dimethyl ether (PEG DME 500) as an efficient catalyst system for the addition of CO2 to epoxides is reported. This protocol is based on a nontoxic and abundant metal in conjunction with a polymeric ligand. Fifteen terminal epoxides were converted at room temperature to give the desired products in yields up to 99 %. Notably, this system was also effective for the synthesis of twelve challenging internal carbonates in yields up to 98 %.


Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy.
In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported. The objective of this study was to provide a detailed account of IRs with pegloticase therapy. Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse event or cluster of temporally related events occurring during or within 2 hours of infusion. Infusion-related reactions occurred in 94 (45%) of 208 patients receiving pegloticase; 10 patients reported IRs at first infusion and 84 during subsequent infusions. Chest discomfort (15%), flushing (12%), and dyspnea (11%) were the most common symptoms. Most IRs were rated mild or moderate; 7% were rated severe. All IRs resolved with slowing, interrupting, or stopping the infusion. No patient required blood pressure or ventilatory support. Infusion-related reactions were associated with loss of pegloticase urate-lowering efficacy: 91% of all IRs occurred in patients with preinfusion serum uric acid concentrations (sUA) greater than 6 mg/dL. For patients sustaining preinfusion sUA of less than 6 mg/dL, IRs occurred in fewer than 1 per 100 infusions. Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.


BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.
In a prospective study of 5384 older men, hip BMD was a very strong predictor of hip fracture, much stronger than spine BMD. The relationship between hip BMD and hip fracture risk seemed to be stronger than observed in a large prospective study of women. Hip BMD is an excellent test for predicting fracture risk in men. There have been few studies of the relationship between BMD and risk of fractures in men and none for the association between lumbar spine BMD and risk of hip and nonvertebral fractures. There is also controversy about whether the associations between BMD and risk of fracture are the same in men and women. We measured proximal femur and lumbar spine BMD in 5384 men, 5384 men, >or= 65 years of age. We compared the results to the very similar cohort of 7871 women >or=65 of age. During 4.4 years of 99% complete follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169 nonvertebral (208 hip) fractures in women. Total hip BMD was very strongly associated with risk hip fracture in men (3.2-fold increased risk per sex-specific SD decrease in BMD; 95% CI, 2.4-4.1). The association was stronger than observed in SOF (2.1; 95% CI, 1.8, 2.4; p < 0.001 for interaction). Among the men, lumbar spine BMD was weakly associated with risk of hip fracture (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0). The association between total hip BMD and risk of nonvertebral fractures was somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p = 0.01 for interaction). The risk of nonvertebral fracture was substantially higher in women than in men for all T scores of hip BMD, regardless of whether sex-specific or female reference values were used. Hip BMD is strongly associated with risk of nonvertebral, and especially hip fracture, in older men. These associations are at least as strong as in women. As in women, lumbar spine BMD in men is only weakly associated with risk of hip fracture. Regardless of whether sex-specific or female reference values were used, T scores indicated different risks of fractures in men than in women.


The neglected pathogen: case reports of severe lower respiratory tract infection by human coronavirus 229E.
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues, other previously ignored viruses must be taken into account as causes of severe acute respiratory distress, influenza-like illness and pneumonia. In this article, we report two cases of pneumonia in chronic liver disease patients where human coronavirus (HCoV) 229E was identified as the only infecting pathogen. Both the patients presented with fever, cough and respiratory distress, along with radiological findings suggestive of pneumonia. Multiplex real-time PCR for various respiratory viruses (FilmArray Respiratory Panel 2 plus) detected HCoV-229E in both cases. Both cases were managed with prophylactic antibiotics, steroids and supplemental oxygen therapy, after which they recovered completely and were discharged.


Information literacy: educating for life-long learning.
Creating information-literate nurses is a challenging and complex task for nurse educators. It requires expertise on the part of the instructor, and a solid commitment to the importance of acquiring information skills and a willingness to demand quality work from the students. A librarian shares her views on information literacy.


Practical partnered research to improve weight loss among overweight/obese veterans: lessons from the trenches.
Obesity and obesity-related conditions, such as type 2 diabetes, are a major issue for Veteran health. Veterans Health Administration (VA) researchers and health systems leaders have worked separately and together to provide more effective weight management programs for Veterans. Although randomized clinical trials are often considered the gold standard for establishing efficacy of interventions in controlled circumstances, pragmatic clinical trials (PCTs) provide agility for translation. VA researchers and health system leaders collaboratively designed a PCT to compare the Diabetes Prevention Program (VA-DPP) to usual care (MOVE!®) in promoting weight loss and glycemic control among overweight/obese Veterans with prediabetes. Together, they navigated the tensions that exist between quality improvement and research activities, facing challenges but reaping significant rewards. Early findings led to updated national guidance for delivering obesity treatment in VA. Partnered research and the use of PCTs can be powerful strategies for accelerating evidence-based findings into practice. Collaborative partnerships between researchers and health systems leaders can help enhance and sustain translation in real-world settings.


Effects of battlefield display frames of reference on navigation tasks, spatial judgements, and change detection.
This paper describes an experiment which illustrates the cause of 'cognitive tunnelling' as it affects information gathering and perception-based task performance in computer-generated terrain displays of varying frames of reference. Cognitive tunnelling refers to the effect where observers focus attention on information from specific areas of a display to the exclusion of information presented outside these areas. Previous research suggests that cognitive tunnelling is induced by more immersive or egocentric visual displays. Results from our preceding study suggested that an immersed split-screen display induces cognitive tunnelling and results in poorer information extraction and situation awareness than an exocentric display of the same information. The current study determined that failure of the observers to integrate information across the two views of the immersed display led to the cognitive tunnelling effect. Cognitive tunnelling was also affected by primacy of information initially presented within the larger egocentric view in the immersed display.


Tumor regulation of hepatic glutamine metabolism.
Fast-growing tumors are major glutamine consumers and may alter host glutamine metabolism to benefit the tumor. Previous studies from our laboratory have demonstrated that the liver switches from an organ of glutamine balance to one of glutamine release with progressive malignant growth. However, the regulation of this change is unclear. This study examined tumor modulation of hepatic glutamine metabolism by determining the activities of glutaminase, the principle enzyme of glutamine degradation, and glutamine synthetase, the principal enzyme of glutamine synthesis. Hepatic glutamine content was also determined. Rats with a fast-growing subcutaneous fibrosarcoma (TBR) and pair-fed controls were studied at 2 and 3 weeks after tumor or sham implantation, when the tumors comprised approximately 5% and 20% of total body weight. Arterial glutamine fell with progressive tumor growth (608 +/- 26 mumol/L in controls vs 494 +/- 15 in TBR, p less than 0.005) and was not attributable to a diminished food intake. Hepatic glutamine content was increased 45% (p less than 0.01) in tumor rats at 2 weeks due in part to a 35% fall in liver glutaminase activity. At 3 weeks, glutamine synthetase activity increased by 43% (0.58 +/- 0.07 mumol/mg of protein/hr in controls vs 0.83 +/- 0.04 in TBR, p less than 0.01) whereas glutaminase remained depressed (2.68 +/- 0.12 mumol/mg of protein/hr in controls vs 2.22 +/- 0.15 in TBR, p less than 0.05) and glutamine content fell compared to 2 week tumor-bearing rats, consistent with accelerated hepatic glutamine release. Tumors may alter liver glutamine metabolism by modulating hepatic enzyme activity in order to provide circulating glutamine for the growing malignancy.


Efficacy of using three-tesla magnetic resonance imaging diagnosis of capsule invasion for decision-making about neurovascular bundle preservation in robotic-assisted radical prostatectomy.
To evaluate the efficacy of using 3-tesla (T) magnetic resonance imaging (MRI) diagnosis of extracapsular extension (ECE) for decision-making about neurovascular bundle (NVB) preservation in robot-assisted radical prostatectomy (RARP) for prostate cancer (PC). We prospectively collected data on PC patients (n=67) who underwent preoperative 3-T MRI before RARP. The choice between nerve sparing or resection was based on 3-T MRI findings of ECE. We compared the MRI findings with the pathological data on surgical margins. Our clinical staging in this study was defined only by MRI. When the data were divided by prostate lobe (right lobe or left lobe, n=134), 3-T MRI showed 28 positive cases of ECE in 134 prostate lobes, allowing NVB preservation in 42 cases (31.3%). Nerve-sparing surgery was achieved in 38.7% of cases in which clinical T2 staging by MRI was reported. The pathological data revealed that 10 of 134 prostate lobes had positive ECE. The overall sensitivity, specificity, positive predictive value, and negative predictive value for predicting stage T3 (positive ECE) by side were 60.0% (12 of 20 sides), 86.0% (98 of 114 sides), 42.9% (12 of 28 sides), and 92.5% (98 of 106 sides), respectively. Three-T MRI prior to RARP enables the use of ECE diagnosis to guide decision-making about NVB preservation, with comparatively high specificity and negative predictive value. Further prospective studies are underway to reach more definitive conclusions.


Real-Time Gender Recognition for Juvenile and Adult Faces.
Facial gender recognition is a crucial research topic due to its comprehensive use cases, including a demographic gender survey, visitor profile identification, targeted advertisement, access control, security, and surveillance from CCTV. For these real-time applications, the face of a person can be oriented to any angle from the camera axis, and the person can be of any age group, including juveniles. A child's face consists of immature craniofacial feature points in texture and edge compared to an adult face, making it very hard to recognize gender using the child's face. Real-word faces captured in an unconstrained environment make the gender prediction system more complex to identify correctly due to orientation. These factors reduce the accuracy of the existing state-of-the-art models developed so far for real-time facial gender prediction. This paper presents the novelty of facial gender recognition for juveniles, adults, and unconstrained-oriented faces. The progressive calibration network (PCN) detects rotation-invariant faces in the proposed model. Then, a Gabor filter is applied to extract unique edge and texture features from the detected face. The Gabor filter is invariant to illumination and produces texture and edge features with redundant feature coefficients in large dimensions. Gabor has drawbacks such as redundancy and a large dimension resolved by the proposed meanDWT feature optimization method, which optimizes the system's accuracy, the size of the model, and computational timing. The proposed feature engineering model is classified with different classifiers such as Naïve Bayes, Logistic Regression, SVM with linear, and RBF kernel. Its results are compared with the state-of-the-art techniques; detailed experimental analysis is presented and concluded to support the argument. We also present a review of approaches based on conventional and deep learning methods with their pros and cons for facial gender recognition on different datasets available for facial gender recognition.


Myths, Fallacies and Misconceptions: Applying Social Marketing for Promoting Appropriate Health Seeking Behavior in Pakistan.
Myths and fallacies have existed ever since societies began, influencing the perceptions about health, and the cause and cure of health related problems. The role of such myths in governing the health and health seeking behavior of people is quite explicit. Misconceptions about breast-feeding, pre-lacteal feed, weaning, dietary habits and other health related matters are commonly heard in the cultures of developing countries. False perceptions have undoubtedly an impact on the health seeking behavior. People coming from the low socio-economic strata in rural areas suffer the most. They lack access to formal health care services and are unable to afford specialized medical care. This gives rise to alternative health seeking behaviors. A considerable majority of people prefer to go to spiritual healers, quacks and other non-formal health providers for the treatment of their ailments. This paper has reviewed a variety of myths, fallacies and misconceptions collectively in the cultural context and has attempted to relate them to the health seeking behaviors of Pakistani people. The paper is based on the contemporary literature review and library work, focusing on finding the feasible strategies to address a variety of myths and misconceptions. Since myths have many adverse implications on the health of the people, an effective way of motivating low income and high risk people to adopt healthy behavior is 'social marketing'. Creating 'health promotion committees' at village level sounds like another doable strategy to ameliorate the situation in order to educate people to take care of not only their own health but of the future generations as well.


Autologous lymphocyte-mediated cytotoxicity against monocytes in canine ehrlichiosis.
The 51Cr-release technique for detecting cytotoxicity had been adapted to immunologic studies of canine ehrlichiosis. Lymphocytes from dogs infected with Ehrlichia canis, cause of canine ehrlichiosis, were shown to be cytotoxic for autologous monocytes. The effect was dependent on the concentraton of lymphocytes, being optimal at 100:1 lymphocyte:monocyte ratio. Neither immune serum and complement, nor anti-canine globulin had any observable effect on cytotoxicity. The monocytotoxicity bore a temporal relationship to the thrombocytopenia. It is suggested that T lymphocyte activation accompanying ehrlichiosis contributes to pathogenesis of the disease and that the specific immune elimination of parasitized monocytes is antibody independent.


Use of computed tomography and histopathologic review for lung lesions produced by the interaction between Mycoplasma hyopneumoniae and fumonisin mycotoxins in pigs.
Mycoplasma hyopneumoniae has a primary role in the porcine respiratory disease complex (PRDC). The objective of this study was to determine whether fumonisin mycotoxins influence the character and/or the severity of pathological processes induced in the lungs of pigs by Mycoplasma hyopneumoniae. Four groups of pigs (n = 7/group) were used, one fed 20 ppm fumonisin B1 (FB1) from 16 days of age (group F), one only infected with M. hyopneumoniae on study day 30 (group M), and a group fed FB1 and infected with M. hyopneumoniae (group MF), along with an untreated control group (group C). Computed tomography (CT) scans of infected pigs (M and MF) on study day 44 demonstrated lesions extending to the cranial and middle or in the cranial third of the caudal lobe of the lungs. The CT images obtained on study day 58 showed similar but milder lesions in 5 animals from group M, whereas lungs from 2 pigs in group MF appeared progressively worse. The evolution of average pulmonary density calculated from combined pixel frequency values, as measured by quantitative CT, was significantly influenced by the treatment and the age of the animals. The most characteristic histopathologic lesion in FB1-treated pigs was pulmonary edema, whereas the pathomorphological changes in Mycoplasma-infected pigs were consistent with catarrhal bronchointerstitial pneumonia. FB1 aggravated the progression of infection, as demonstrated by severe illness requiring euthanasia observed in 1 pig and evidence of progressive pathology in 2 pigs (group MF) between study days 44 and 58.


[Resistance to P. falciparum malaria in tropical Africa: congenital and genetic factors. General review (author's transl)].
During the first months of life, maternal antibodies and foetal haemoglobine reduce the parasitical multiplication and allow the development of an effective immunological defense. In addition, the foetal defense structures receive a useful information from the malarial antigens passing in through the placenta. Genetic erythrocytic factors also, operate in some individuals, who, as a rule, are homozygotic. Various genes control the development of a premunition-type immunization giving an almost perfect balance between host and parasite, in individuals as well as for populations as a whole. It is likely that selective mutation has increased the frequency of favourable genes.


[Intramedullary interlocking of humeral fractures and nonunions with Seidel nail].
The advantages and disadvantages of interlocking Seidel's nails determined by their construction and the way of insertion were presented on the basis of own experience and literature. The advantages are strength and shape of the nails which are conductive to fragments stability and make insertion into humerus medullar canal easier. The tools set for insertion and locking of distal part. It doesn't truly protect from torsion displacements. Locking takes place by draw for a few weeks by external immobilization. The Seidel's nail has also disadvantages associated with proximal insertion. Unavoidable injury of supraspinatus tendon insertion can be the reason of loss of shoulder function. The antegrade fixation can cause pushing distal fragment downward by tip of the nail. It is necessary to control it's insertion under image intensifier. Presented disadvantages of Seidel's nail fixation didn't result in any problems in humerus fractures or pseudoarthroses healing. In one case it was necessary to perform additional decortication and space of fracture fulfillment with bone grafts.


[Pseudolinitis plastica of breast origin].
The most common type of gastric metastases secondary to carcinoma of the breast is the one showing a linitis plastica appearance. The roentgenologic aspect when performing an upper gastrointestinal examination with barium contrast is typical and allows the differential diagnosis with the primitive linitis. The linitis plastica type of metastatic breast carcinoma results from transmural infiltration of the stomach wall with initial deposit of tumor cells in the submucosal or subserosal regions. CT provide valuable information concerning the metastatic spread.


Nitrate behaviors and source apportionment in an aquatic system from a watershed with intensive agricultural activities.
Nitrate pollution in aquatic systems caused by intensive agricultural activities is a serious problem in the Sanjiang Plain. In this study, a dual isotope approach (δ(15)N-NO3(-) and δ(18)O-NO3(-)) was employed to identify potential nitrate sources (atmospheric deposition, AD; NO3(-) derived from soil organic matter nitrification, NS; NO3(-) derived from chemical fertilizer nitrification, NF; and manure and sewage, M&S) and transformation processes occurring in the Abujiao River watershed located in the Sanjiang Plain. The Bayesian model (stable isotope analysis in R, SIAR) was utilized to apportion the contribution of the potential sources. In this watershed, the nitrate concentrations in the surface water were low (mean ± SD = 1.15 ± 0.84 mg L(-1)), and were greatly influenced by precipitation and land use conditions during the two sampling periods (the high flow period, September; the low flow period, November). On the contrary, in the ground water, high NO3(-) concentrations were observed (7.84 ± 5.83 mg L(-1)) and no significant temporal variation in NO3(-) was found during the sampling periods. The sampled water δ(18)O-NO3(-) values suggest that the nitrification process was not the main N cycling process, because most of the measured δ(18)O-NO3(-) values were above the expected δ(18)O-NO3(-) from nitrification throughout the sampling periods. Both the chemical and isotopic characteristics indicated that the signs of de-nitrification were absent in the surface water. However, significant de-nitrification processes were observed in the ground water for all sample periods. Results from the SIAR model showed that source contributions differed significantly during the two sampling periods. During the high flow period, chemical fertilizers and soil N fertilizer equally contributed to the major sources of nitrate in the surface water. In contrast, manure and sewage sources dominated the source contribution during the low flow period (November). This study suggested that with the assessment of the behaviors and sources of NO3(-), effective nitrate reduction strategies and better management practices can be implemented to protect water quality.


Influence of film structure on the dewetting kinetics of thin polymer films in the solvent annealing process.
On a non-wetting solid substrate, the solvent annealing process of a thin polymer film includes the swelling process and the dewetting process. Owing to difficulties in the in situ analysis of the two processes simultaneously, a quantitative study on the solvent annealing process of thin polymer films on the non-wetting solid substrate is extremely rare. In this paper, we design an experimental method by combining spectroscopic ellipsometry with optical microscopy to achieve the simultaneous in situ study. Using this method, we investigate the influence of the structure of swollen film on its dewetting kinetics during the solvent annealing process. The results show that for a thin PS film with low Mw (Mw = 4.1 kg mol(-1)), acetone molecules can form an ultrathin enriched layer between the PS film and the solid substrate during the swelling process. The presence of the acetone enriched layer accounts for the exponential kinetic behavior in the case of a thin PS film with low Mw. However, the acetone enriched layer is not observed in the case of a thin PS film with high Mw (Mw = 400 kg mol(-1)) and the slippage effect of polymer chains is valid during the dewetting process.


Rare Case of Endoscopic Treatment for Bevacizumab-Related Gastric Perforation in a Patient with Ovarian Cancer.
Antiangiogenic chemotherapy is a common treatment option for patients with advanced ovarian cancer (OC) and has been proven to be effective and generally safe. Nevertheless, in rare cases, these drugs can give serious complications such as gastrointestinal perforations that can be even mortal or very difficult to treat and can heavily impact the clinical management. We present a rare case of bevacizumab-induced gastric perforation in a patient with advanced OC occurred during bevacizumab-including chemotherapy in an adjuvant setting. Surgical treatment was not possible due to the frailty of the clinical condition of the patient and the gastric perforation was successfully treated with endoscopic suturing.